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More on Calcium Supplements
From MEDLINE PLUS
http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202108.html
Calcium Supplements (Systemic)
Contents of this page:
Description
Importance of Diet
Before Using This Medicine
Proper Use of This Medicine
Precautions While Using This Medicine
Side Effects of This Medicine
Additional Information
Brand Names
Category
DescriptionReturn to top
Calcium supplements are taken by individuals who are unable to get enough calcium in their regular diet or who have a need for more calcium. They are used to prevent or treat several conditions that may cause hypocalcemia (not enough calcium in the blood). The body needs calcium to make strong bones. Calcium is also needed for the heart, muscles, and nervous system to work properly.
The bones serve as a storage site for the body's calcium. They are continuously giving up calcium to the bloodstream and then replacing it as the body's need for calcium changes from day to day. When there is not enough calcium in the blood to be used by the heart and other organs, your body will take the needed calcium from the bones. When you eat foods rich in calcium, the calcium will be restored to the bones and the balance between your blood and bones will be maintained.
Pregnant women, nursing mothers, children, and adolescents may need more calcium than they normally get from eating calcium-rich foods. Adult women may take calcium supplements to help prevent a bone disease called osteoporosis. Osteoporosis, which causes thin, porous, easily broken bones, may occur in women after menopause, but may sometimes occur in elderly men also. Osteoporosis in women past menopause is thought to be caused by a reduced amount of ovarian estrogen (a female hormone). However, a diet low in calcium for many years, especially in the younger adult years, may add to the risk of developing it. Other bone diseases in children and adults are also treated with calcium supplements.
Calcium supplements may also be used for other conditions as determined by your health care professional.
Injectable calcium is administered only by or under the supervision of your health care professional. Other forms of calcium are available without a prescription.
Calcium supplements are available in the following dosage forms:
Oral
Calcium Carbonate
Capsules (U.S. and Canada)
Oral suspension (U.S.)
Tablets (U.S. and Canada)
Chewable tablets (U.S. and Canada)
Calcium Citrate
Tablets (U.S.)
Tablets for solution (U.S.)
Calcium Glubionate
Syrup (U.S. and Canada)
Calcium Gluceptate and Calcium Gluconate
Oral solution (Canada)
Calcium Gluconate
Tablets (U.S. and Canada)
Chewable tablets (U.S.)
Calcium Lactate
Tablets (U.S. and Canada)
Calcium Lactate-Gluconate and Calcium Carbonate
Tablets for solution (Canada)
Dibasic Calcium Phosphate
Tablets (U.S.)
Tribasic Calcium Phosphate
Tablets (U.S.)
Parenteral
Calcium Acetate
Injection (U.S.)
Calcium Chloride
Injection (U.S. and Canada)
Calcium Glubionate
Injection (Canada)
Calcium Gluceptate
Injection (U.S.)
Calcium Gluconate
Injection (U.S. and Canada)
Calcium Glycerophosphate and Calcium Lactate
Injection (U.S.)
A calcium ``salt'' contains calcium along with another substance, such as carbonate or gluconate. Some calcium salts have more calcium (elemental calcium) than others. For example, the amount of calcium in calcium carbonate is greater than that in calcium gluconate. To give you an idea of how different calcium supplements vary in calcium content, the following chart explains how many tablets of each type of supplement will provide 1000 milligrams of elemental calcium. When you look for a calcium supplement, be sure the number of milligrams on the label refers to the amount of elemental calcium, and not to the strength of each tablet.
Calcium supplement Strength of each tablet (in milligrams) Amount of elemental calcium per tablet (in milligrams) Number of tablets to provide 1000 milligrams of calcium
Calcium carbonate 625 250 4
650 260 4
750 300 4
835 334 3
1250 500 2
1500 600 2
Calcium citrate 950 200 5
Calcium gluconate 500 45 22
650 58 17
1000 90 11
Calcium lactate 325 42 24
650 84 12
Calcium phosphate, dibasic 500 115 9
Calcium phosphate, tribasic 800 304 4
1600 608 2
Importance of DietReturn to top
For good health, it is important that you eat a balanced and varied diet. Follow carefully any diet program your health care professional may recommend. For your specific dietary vitamin and/or mineral needs, ask your health care professional for a list of appropriate foods. If you think that you are not getting enough vitamins and/or minerals in your diet, you may choose to take a dietary supplement. The daily amount of calcium needed is defined in several different ways.
For U.S.—
Recommended Dietary Allowances (RDAs) are the amount of vitamins and minerals needed to provide for adequate nutrition in most healthy persons. RDAs for a given nutrient may vary depending on a person's age, sex, and physical condition (e.g., pregnancy).
Daily Values (DVs) are used on food and dietary supplement labels to indicate the percent of the recommended daily amount of each nutrient that a serving provides. DV replaces the previous designation of United States Recommended Daily Allowances (USRDAs).
For Canada—
Recommended Nutrient Intakes (RNIs) are used to determine the amounts of vitamins, minerals, and protein needed to provide adequate nutrition and lessen the risk of chronic disease.
Normal daily recommended intakes in milligrams (mg) for calcium are generally defined as follows:
Persons U.S. (mg) Canada (mg)
Infants and children
Birth to 3 years of age 400–800 250–550
4 to 6 years of age 800 600
7 to 10 years of age 800 700–1100
Adolescent and adult males 800–1200 800–1100
Adolescent and adult females 800–1200 700–1100
Pregnant females 1200 1200–1500
Breast-feeding females 1200 1200–1500
Getting the proper amount of calcium in the diet every day and participating in weight-bearing exercise (walking, dancing, bicycling, aerobics, jogging), especially during the early years of life (up to about 35 years of age) is most important in helping to build and maintain bones as dense as possible to prevent the development of osteoporosis in later life.
The following table includes some calcium-rich foods. The calcium content of these foods can supply the daily RDA or RNI for calcium if the foods are eaten regularly in sufficient amounts.
Food (amount) Milligrams of calcium
Nonfat dry milk, reconstituted (1 cup) 375
Lowfat, skim, or whole milk (1 cup) 290 to 300
Yogurt (1 cup) 275 to 400
Sardines with bones (3 ounces) 370
Ricotta cheese, part skim (½ cup) 340
Salmon, canned, with bones (3 ounces) 285
Cheese, Swiss (1 ounce) 272
Cheese, cheddar (1 ounce) 204
Cheese, American (1 ounce) 174
Cottage cheese, lowfat (1 cup) 154
Tofu (4 ounces) 154
Shrimp (1 cup) 147
Ice milk (¾ cup) 132
Vitamin D helps prevent calcium loss from your bones. It is sometimes called ``the sunshine vitamin'' because it is made in your skin when you are exposed to sunlight. If you get outside in the sunlight every day for 15 to 30 minutes, you should get all the vitamin D you need. However, in northern locations in winter, the sunlight may be too weak to make vitamin D in the skin. Vitamin D may also be obtained from your diet or from multivitamin preparations. Most milk is fortified with vitamin D.
Do not use bonemeal or dolomite as a source of calcium . The Food and Drug Administration has issued warnings that bonemeal and dolomite could be dangerous because these products may contain lead.
Before Using This MedicineReturn to top
If you are taking this dietary supplement without a prescription, carefully read and follow any precautions on the label. For calcium supplements, the following should be considered:
Pregnancy—It is especially important that you are receiving enough calcium when you become pregnant and that you continue to receive the right amount of calcium throughout your pregnancy. The healthy growth and development of the fetus depend on a steady supply of nutrients from the mother. However, taking large amounts of a dietary supplement during pregnancy may be harmful to the mother and/or fetus and should be avoided.
Breast-feeding—It is especially important that you receive the right amount of calcium so that your baby will also get the calcium needed to grow properly. However, taking large amounts of a dietary supplement while breast-feeding may be harmful to the mother and/or baby and should be avoided.
Children—Problems in children have not been reported with intake of normal daily recommended amounts. Injectable forms of calcium should not be given to children because of the risk of irritating the injection site.
Older adults—Problems in older adults have not been reported with intake of normal daily recommended amounts. It is important that older people continue to receive enough calcium in their daily diets. However, some older people may need to take extra calcium or larger doses because they do not absorb calcium as well as younger people. Check with your health care professional if you have any questions about the amount of calcium you should be taking in each day.
Other medicines—Medicines or other dietary supplements
Although certain medicines or dietary supplements should not be used together at all, in other cases they may be used together even if an interaction might occur. In these cases, your health care professional may want to change the dose, or other precautions may be necessary. When you are taking calcium supplements, it is especially important that your health care professional know if you are taking any of the following:
Calcium-containing medicines, other—Taking excess calcium may cause too much calcium in the blood or urine and lead to medical problems
Cellulose sodium phosphate (e.g., Calcibind)—Use with calcium supplements may decrease the effects of cellulose sodium phosphate
Digitalis glycosides (heart medicine)—Use with calcium supplements by injection may increase the chance of irregular heartbeat
Etidronate (e.g., Didronel)—Use with calcium supplements may decrease the effects of etidronate; etidronate should not be taken within 2 hours of calcium supplements
Gallium nitrate (e.g., Ganite)—Use with calcium supplements may cause gallium nitrate to not work properly
Magnesium sulfate (for injection)—Use with calcium supplements may cause either medicine to be less effective
Phenytoin (e.g., Dilantin)—Use with calcium supplements may decrease the effects of both medicines; calcium supplements should not be taken within 1 to 3 hours of phenytoin
Tetracyclines (medicine for infection) taken by mouth—Use with calcium supplements may decrease the effects of tetracycline; calcium supplements should not be taken within 1 to 3 hours of tetracyclines
Other medical problems—The presence of other medical problems may affect the use of calcium supplements. Make sure you tell your health care professional if you have any other medical problems, especially:
Diarrhea or
Stomach or intestinal problems—Extra calcium or specific calcium preparations may be necessary in these conditions
Heart disease—Calcium by injection may increase the chance of irregular heartbeat
Hypercalcemia (too much calcium in the blood) or
Hypercalciuria (too much calcium in the urine)—Calcium supplements may make these conditions worse
Hyperparathyroidism or
Sarcoidosis—Calcium supplements may increase the chance of hypercalcemia (too much calcium in the blood)
Hypoparathyroidism—Use of calcium phosphate may cause high blood levels of phosphorus which could increase the chance of side effects
Kidney disease or stones—Too much calcium may increase the chance of kidney stones
Proper Use of This MedicineReturn to top
Dosing—
The amount of calcium needed to meet normal daily recommended intakes will be different for different individuals. The following information includes only the average amounts of calcium.
For oral dosage form (capsules, chewable tablets, lozenges, oral solution, oral suspension, syrup, tablets, extended-release tablets, tablets for solution):
To prevent deficiency, the amount taken by mouth is based on normal daily recommended intakes (Note that the normal daily recommended intakes are expressed as an actual amount of calcium. The salt form [e.g., calcium carbonate, calcium gluconate, etc.] has a different strength):
For the U.S.
Adults and teenagers—800 to 1200 milligrams (mg) per day.
Pregnant and breast-feeding females—1200 mg per day.
Children 4 to 10 years of age—800 mg per day.
Children birth to 3 years of age—400 to 800 mg per day.
For Canada
Adult and teenage males—800 to 1100 mg per day.
Adult and teenage females—700 to 1100 mg per day.
Pregnant and breast-feeding females—1200 to 1500 mg per day.
Children 7 to 10 years of age—700 to 1100 mg per day.
Children 4 to 6 years of age—600 mg per day.
Children birth to 3 years of age—250 to 550 mg per day.
To treat deficiency:
Adults, teenagers, and children—Treatment dose is determined by prescriber for each individual based on severity of deficiency.
Drink a full glass (8 ounces) of water or juice when taking a calcium supplement. However, if you are taking calcium carbonate as a phosphate binder in kidney dialysis, it is not necessary to drink a glass of water.
This dietary supplement is best taken 1 to 1½ hours after meals, unless otherwise directed by your health care professional. However, patients with a condition known as achlorhydria may not absorb calcium supplements on an empty stomach and should take them with meals.
For individuals taking the chewable tablet form of this dietary supplement:
Chew the tablets completely before swallowing.
For individuals taking the syrup form of this dietary supplement:
Take the syrup before meals. This will allow the dietary supplement to work faster.
Mix in water or fruit juice for infants or children.
Take this dietary supplement only as directed. Do not take more of it and do not take it more often than recommended on the label. To do so may increase the chance of side effects.
Missed dose—
If you are taking this dietary supplement on a regular schedule and you miss a dose, take it as soon as possible, then go back to your regular dosing schedule.
Storage—
To store this dietary supplement:
Keep out of the reach of children.
Store away from heat and direct light.
Do not store in the bathroom, near the kitchen sink, or in other damp places. Heat or moisture may cause the dietary supplement to break down.
Keep the liquid form of this dietary supplement from freezing.
Do not keep outdated dietary supplements or those no longer needed. Be sure that any discarded dietary supplement is out of the reach of children.
Precautions While Using This MedicineReturn to top
If this dietary supplement has been ordered for you by your health care professional and you will be taking it in large doses or for a long time, your health care professional should check your progress at regular visits. This is to make sure the calcium is working properly and does not cause unwanted effects.
Do not take calcium supplements within 1 to 2 hours of taking other medicine by mouth. To do so may keep the other medicine from working properly.
Unless you are otherwise directed by your health care professional, to make sure that calcium is used properly by your body:
Do not take other medicines or dietary supplements containing large amounts of calcium, phosphates, magnesium, or vitamin D unless your health care professional has told you to do so or approved.
Do not take calcium supplements within 1 to 2 hours of eating large amounts of fiber-containing foods, such as bran and whole-grain cereals or breads, especially if you are being treated for hypocalcemia (not enough calcium in your blood).
Do not drink large amounts of alcohol or caffeine-containing beverages (usually more than 8 cups of coffee a day), or use tobacco.
Some calcium carbonate tablets have been shown to break up too slowly in the stomach to be properly absorbed into the body. If the calcium carbonate tablets you purchase are not specifically labeled as being ``USP,'' check with your pharmacist. He or she may be able to help you determine which tablets are best.
Side Effects of This MedicineReturn to top
Side Effects of This Dietary SupplementAlong with its needed effects, a dietary supplement may cause some unwanted effects. Although the following side effects occur very rarely when the calcium supplement is taken as recommended, they may be more likely to occur if:
It is taken in large doses.
It is taken for a long time.
It is taken by patients with kidney disease.
Check with your health care professional as soon as possible if any of the following side effects occur:
More common (for injection form only)
Dizziness; flushing and/or sensation of warmth or heat; irregular heartbeat; nausea or vomiting; skin redness, rash, pain, or burning at injection site; sweating; tingling sensation
Rare
Difficult or painful urination; drowsiness ; nausea or vomiting (continuing); weakness
Early signs of overdose
Constipation (severe) ; dryness of mouth ; headache (continuing) ; increased thirst ; irritability ; loss of appetite ; mental depression ; metallic taste ; unusual tiredness or weakness
Late signs of overdose
Confusion ; drowsiness (severe) ; high blood pressure ; increased sensitivity of eyes or skin to light ; irregular, fast, or slow heartbeat; unusually large amount of urine or increased frequency of urination
Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your health care professional.
Additional InformationReturn to top
Once a medicine or dietary supplement has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although this use is not included in product labeling, calcium supplements are used in certain patients with the following medical condition:
Hyperphosphatemia (too much phosphate in the blood)
Other than the above information, there is no additional information relating to proper use, precautions, or side effects for this use.
Brand NamesReturn to top
Some commonly used brand names are:
In the U.S.—
Alka-Mints2
Amitone2
Calcarb 6002
Calci-Chew2
Calciday 6672
Calcilac2
Calci-Mix2
Calcionate5
Calcium 6002
Calglycine2
Calphosan8
Cal-Plus2
Caltrate 6002
Caltrate Jr2
Chooz2
Citracal4
Citracal Liquitabs4
Dicarbosil2
Gencalc 6002
Liquid-Cal2
Liquid Cal-6002
Maalox Antacid Caplets2
Mallamint2
Neo-Calglucon5
Nephro-Calci2
Os-Cal 5002
Os-Cal 500 Chewable2
Oysco2
Oysco 500 Chewable2
Oyst-Cal 5002
Oystercal 5002
Posture12
Rolaids Calcium Rich2
Titralac2
Tums2
Tums 5002
Tums E-X2
In Canada—
Apo-Cal2
Calciject3
Calcite 5002
Calcium-Sandoz5
Calcium-Sandoz Forte10
Calcium Stanley6
Calsan2
Caltrate 6002
Gramcal10
Nu-Cal2
Os-Cal2
Os-Cal Chewable2
Tums Extra Strength2
Tums Regular Strength2
Note:
For quick reference, the following calcium supplements are numbered to match the corresponding brand names.
This information applies to the following:
1. Calcium Acetate (KAL-see-um ASa-tate)†
2. Calcium Carbonate (KAL-see-um KAR-boh-nate)‡
3. Calcium Chloride (KAL-see-um KLOR-ide)‡
4. Calcium Citrate (KAL-see-um SIH-trayt)‡†
5. Calcium Glubionate (KAL-see-um gloo-BY-oh-nate)§
6. Calcium Gluceptate and Calcium Gluconate (KAL-see-um gloo-SEP-tate and KAL-see-um GLOO-coh-nate)*
7. Calcium Gluconate (KAL-see-um GLOO-coh-nate)‡
8. Calcium Glycerophosphate and Calcium Lactate (KAL-see-um gliss-er-o-FOS-fate and KAL-see-um LAK-tate)†
9. Calcium Lactate (KAL-see-um LAK-tate)‡
10. Calcium Lactate-Gluconate and Calcium Carbonate (KAL-see-um LAK-tate GLOO-coh-nate and KAL-see-um KAR-boh-nate)*
11. Dibasic Calcium Phosphate (dy-BAY-sic KAL-see-um FOS-fate)‡†
12. Tribasic Calcium Phosphate (try-BAY-sic KAL-see-um FOS-fate)†
13. Calcium Gluceptate (KAL-see-um gloo-SEP-tate)‡†
‡ Generic name product may be available in the U.S.
§ Generic name product may be available in Canada
* Not commercially available in the U.S.
† Not commercially available in Canada
CategoryReturn to top
Antacid --Calcium Carbonate
Antihyperkalemic --Calcium Chloride ; Calcium Gluconate Injection
Antihypermagnesemic -- Calcium Chloride; Calcium Gluceptate; Calcium Gluconate Injection
Antihyperphosphatemic --Calcium Carbonate ; Calcium Citrate
Antihypocalcemic --Calcium Acetate ; Calcium Carbonate; Calcium Chloride; Calcium Citrate; Calcium Glubionate; Calcium Gluceptate; Calcium Gluconate; Calcium Glycerophosphate and Calcium Lactate; Calcium Lactate; Calcium Lactate-Gluconate and Calcium Carbonate; Calcium Phosphate, Dibasic; Calcium Phosphate, Tribasic
Cardiotonic --Calcium Chloride; Calcium Gluconate Injection
Electrolyte replenisher --Calcium Acetate; Calcium Chloride; Calcium Gluceptate; Calcium Gluconate Injection
Nutritional supplement, mineral --Calcium Carbonate; Calcium Citrate; Calcium Glubionate, Oral ; Calcium Gluceptate and Calcium Gluconate ; Calcium Gluconate, Oral; Calcium Lactate; Calcium Lactate-Gluconate and Calcium Carbonate; Calcium Phosphate, Dibasic; Calcium Phosphate, Tribasic
Revised: 07/18/1995
http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202108.html
Calcium Supplements (Systemic)
Contents of this page:
Description
Importance of Diet
Before Using This Medicine
Proper Use of This Medicine
Precautions While Using This Medicine
Side Effects of This Medicine
Additional Information
Brand Names
Category
DescriptionReturn to top
Calcium supplements are taken by individuals who are unable to get enough calcium in their regular diet or who have a need for more calcium. They are used to prevent or treat several conditions that may cause hypocalcemia (not enough calcium in the blood). The body needs calcium to make strong bones. Calcium is also needed for the heart, muscles, and nervous system to work properly.
The bones serve as a storage site for the body's calcium. They are continuously giving up calcium to the bloodstream and then replacing it as the body's need for calcium changes from day to day. When there is not enough calcium in the blood to be used by the heart and other organs, your body will take the needed calcium from the bones. When you eat foods rich in calcium, the calcium will be restored to the bones and the balance between your blood and bones will be maintained.
Pregnant women, nursing mothers, children, and adolescents may need more calcium than they normally get from eating calcium-rich foods. Adult women may take calcium supplements to help prevent a bone disease called osteoporosis. Osteoporosis, which causes thin, porous, easily broken bones, may occur in women after menopause, but may sometimes occur in elderly men also. Osteoporosis in women past menopause is thought to be caused by a reduced amount of ovarian estrogen (a female hormone). However, a diet low in calcium for many years, especially in the younger adult years, may add to the risk of developing it. Other bone diseases in children and adults are also treated with calcium supplements.
Calcium supplements may also be used for other conditions as determined by your health care professional.
Injectable calcium is administered only by or under the supervision of your health care professional. Other forms of calcium are available without a prescription.
Calcium supplements are available in the following dosage forms:
Oral
Calcium Carbonate
Capsules (U.S. and Canada)
Oral suspension (U.S.)
Tablets (U.S. and Canada)
Chewable tablets (U.S. and Canada)
Calcium Citrate
Tablets (U.S.)
Tablets for solution (U.S.)
Calcium Glubionate
Syrup (U.S. and Canada)
Calcium Gluceptate and Calcium Gluconate
Oral solution (Canada)
Calcium Gluconate
Tablets (U.S. and Canada)
Chewable tablets (U.S.)
Calcium Lactate
Tablets (U.S. and Canada)
Calcium Lactate-Gluconate and Calcium Carbonate
Tablets for solution (Canada)
Dibasic Calcium Phosphate
Tablets (U.S.)
Tribasic Calcium Phosphate
Tablets (U.S.)
Parenteral
Calcium Acetate
Injection (U.S.)
Calcium Chloride
Injection (U.S. and Canada)
Calcium Glubionate
Injection (Canada)
Calcium Gluceptate
Injection (U.S.)
Calcium Gluconate
Injection (U.S. and Canada)
Calcium Glycerophosphate and Calcium Lactate
Injection (U.S.)
A calcium ``salt'' contains calcium along with another substance, such as carbonate or gluconate. Some calcium salts have more calcium (elemental calcium) than others. For example, the amount of calcium in calcium carbonate is greater than that in calcium gluconate. To give you an idea of how different calcium supplements vary in calcium content, the following chart explains how many tablets of each type of supplement will provide 1000 milligrams of elemental calcium. When you look for a calcium supplement, be sure the number of milligrams on the label refers to the amount of elemental calcium, and not to the strength of each tablet.
Calcium supplement Strength of each tablet (in milligrams) Amount of elemental calcium per tablet (in milligrams) Number of tablets to provide 1000 milligrams of calcium
Calcium carbonate 625 250 4
650 260 4
750 300 4
835 334 3
1250 500 2
1500 600 2
Calcium citrate 950 200 5
Calcium gluconate 500 45 22
650 58 17
1000 90 11
Calcium lactate 325 42 24
650 84 12
Calcium phosphate, dibasic 500 115 9
Calcium phosphate, tribasic 800 304 4
1600 608 2
Importance of DietReturn to top
For good health, it is important that you eat a balanced and varied diet. Follow carefully any diet program your health care professional may recommend. For your specific dietary vitamin and/or mineral needs, ask your health care professional for a list of appropriate foods. If you think that you are not getting enough vitamins and/or minerals in your diet, you may choose to take a dietary supplement. The daily amount of calcium needed is defined in several different ways.
For U.S.—
Recommended Dietary Allowances (RDAs) are the amount of vitamins and minerals needed to provide for adequate nutrition in most healthy persons. RDAs for a given nutrient may vary depending on a person's age, sex, and physical condition (e.g., pregnancy).
Daily Values (DVs) are used on food and dietary supplement labels to indicate the percent of the recommended daily amount of each nutrient that a serving provides. DV replaces the previous designation of United States Recommended Daily Allowances (USRDAs).
For Canada—
Recommended Nutrient Intakes (RNIs) are used to determine the amounts of vitamins, minerals, and protein needed to provide adequate nutrition and lessen the risk of chronic disease.
Normal daily recommended intakes in milligrams (mg) for calcium are generally defined as follows:
Persons U.S. (mg) Canada (mg)
Infants and children
Birth to 3 years of age 400–800 250–550
4 to 6 years of age 800 600
7 to 10 years of age 800 700–1100
Adolescent and adult males 800–1200 800–1100
Adolescent and adult females 800–1200 700–1100
Pregnant females 1200 1200–1500
Breast-feeding females 1200 1200–1500
Getting the proper amount of calcium in the diet every day and participating in weight-bearing exercise (walking, dancing, bicycling, aerobics, jogging), especially during the early years of life (up to about 35 years of age) is most important in helping to build and maintain bones as dense as possible to prevent the development of osteoporosis in later life.
The following table includes some calcium-rich foods. The calcium content of these foods can supply the daily RDA or RNI for calcium if the foods are eaten regularly in sufficient amounts.
Food (amount) Milligrams of calcium
Nonfat dry milk, reconstituted (1 cup) 375
Lowfat, skim, or whole milk (1 cup) 290 to 300
Yogurt (1 cup) 275 to 400
Sardines with bones (3 ounces) 370
Ricotta cheese, part skim (½ cup) 340
Salmon, canned, with bones (3 ounces) 285
Cheese, Swiss (1 ounce) 272
Cheese, cheddar (1 ounce) 204
Cheese, American (1 ounce) 174
Cottage cheese, lowfat (1 cup) 154
Tofu (4 ounces) 154
Shrimp (1 cup) 147
Ice milk (¾ cup) 132
Vitamin D helps prevent calcium loss from your bones. It is sometimes called ``the sunshine vitamin'' because it is made in your skin when you are exposed to sunlight. If you get outside in the sunlight every day for 15 to 30 minutes, you should get all the vitamin D you need. However, in northern locations in winter, the sunlight may be too weak to make vitamin D in the skin. Vitamin D may also be obtained from your diet or from multivitamin preparations. Most milk is fortified with vitamin D.
Do not use bonemeal or dolomite as a source of calcium . The Food and Drug Administration has issued warnings that bonemeal and dolomite could be dangerous because these products may contain lead.
Before Using This MedicineReturn to top
If you are taking this dietary supplement without a prescription, carefully read and follow any precautions on the label. For calcium supplements, the following should be considered:
Pregnancy—It is especially important that you are receiving enough calcium when you become pregnant and that you continue to receive the right amount of calcium throughout your pregnancy. The healthy growth and development of the fetus depend on a steady supply of nutrients from the mother. However, taking large amounts of a dietary supplement during pregnancy may be harmful to the mother and/or fetus and should be avoided.
Breast-feeding—It is especially important that you receive the right amount of calcium so that your baby will also get the calcium needed to grow properly. However, taking large amounts of a dietary supplement while breast-feeding may be harmful to the mother and/or baby and should be avoided.
Children—Problems in children have not been reported with intake of normal daily recommended amounts. Injectable forms of calcium should not be given to children because of the risk of irritating the injection site.
Older adults—Problems in older adults have not been reported with intake of normal daily recommended amounts. It is important that older people continue to receive enough calcium in their daily diets. However, some older people may need to take extra calcium or larger doses because they do not absorb calcium as well as younger people. Check with your health care professional if you have any questions about the amount of calcium you should be taking in each day.
Other medicines—Medicines or other dietary supplements
Although certain medicines or dietary supplements should not be used together at all, in other cases they may be used together even if an interaction might occur. In these cases, your health care professional may want to change the dose, or other precautions may be necessary. When you are taking calcium supplements, it is especially important that your health care professional know if you are taking any of the following:
Calcium-containing medicines, other—Taking excess calcium may cause too much calcium in the blood or urine and lead to medical problems
Cellulose sodium phosphate (e.g., Calcibind)—Use with calcium supplements may decrease the effects of cellulose sodium phosphate
Digitalis glycosides (heart medicine)—Use with calcium supplements by injection may increase the chance of irregular heartbeat
Etidronate (e.g., Didronel)—Use with calcium supplements may decrease the effects of etidronate; etidronate should not be taken within 2 hours of calcium supplements
Gallium nitrate (e.g., Ganite)—Use with calcium supplements may cause gallium nitrate to not work properly
Magnesium sulfate (for injection)—Use with calcium supplements may cause either medicine to be less effective
Phenytoin (e.g., Dilantin)—Use with calcium supplements may decrease the effects of both medicines; calcium supplements should not be taken within 1 to 3 hours of phenytoin
Tetracyclines (medicine for infection) taken by mouth—Use with calcium supplements may decrease the effects of tetracycline; calcium supplements should not be taken within 1 to 3 hours of tetracyclines
Other medical problems—The presence of other medical problems may affect the use of calcium supplements. Make sure you tell your health care professional if you have any other medical problems, especially:
Diarrhea or
Stomach or intestinal problems—Extra calcium or specific calcium preparations may be necessary in these conditions
Heart disease—Calcium by injection may increase the chance of irregular heartbeat
Hypercalcemia (too much calcium in the blood) or
Hypercalciuria (too much calcium in the urine)—Calcium supplements may make these conditions worse
Hyperparathyroidism or
Sarcoidosis—Calcium supplements may increase the chance of hypercalcemia (too much calcium in the blood)
Hypoparathyroidism—Use of calcium phosphate may cause high blood levels of phosphorus which could increase the chance of side effects
Kidney disease or stones—Too much calcium may increase the chance of kidney stones
Proper Use of This MedicineReturn to top
Dosing—
The amount of calcium needed to meet normal daily recommended intakes will be different for different individuals. The following information includes only the average amounts of calcium.
For oral dosage form (capsules, chewable tablets, lozenges, oral solution, oral suspension, syrup, tablets, extended-release tablets, tablets for solution):
To prevent deficiency, the amount taken by mouth is based on normal daily recommended intakes (Note that the normal daily recommended intakes are expressed as an actual amount of calcium. The salt form [e.g., calcium carbonate, calcium gluconate, etc.] has a different strength):
For the U.S.
Adults and teenagers—800 to 1200 milligrams (mg) per day.
Pregnant and breast-feeding females—1200 mg per day.
Children 4 to 10 years of age—800 mg per day.
Children birth to 3 years of age—400 to 800 mg per day.
For Canada
Adult and teenage males—800 to 1100 mg per day.
Adult and teenage females—700 to 1100 mg per day.
Pregnant and breast-feeding females—1200 to 1500 mg per day.
Children 7 to 10 years of age—700 to 1100 mg per day.
Children 4 to 6 years of age—600 mg per day.
Children birth to 3 years of age—250 to 550 mg per day.
To treat deficiency:
Adults, teenagers, and children—Treatment dose is determined by prescriber for each individual based on severity of deficiency.
Drink a full glass (8 ounces) of water or juice when taking a calcium supplement. However, if you are taking calcium carbonate as a phosphate binder in kidney dialysis, it is not necessary to drink a glass of water.
This dietary supplement is best taken 1 to 1½ hours after meals, unless otherwise directed by your health care professional. However, patients with a condition known as achlorhydria may not absorb calcium supplements on an empty stomach and should take them with meals.
For individuals taking the chewable tablet form of this dietary supplement:
Chew the tablets completely before swallowing.
For individuals taking the syrup form of this dietary supplement:
Take the syrup before meals. This will allow the dietary supplement to work faster.
Mix in water or fruit juice for infants or children.
Take this dietary supplement only as directed. Do not take more of it and do not take it more often than recommended on the label. To do so may increase the chance of side effects.
Missed dose—
If you are taking this dietary supplement on a regular schedule and you miss a dose, take it as soon as possible, then go back to your regular dosing schedule.
Storage—
To store this dietary supplement:
Keep out of the reach of children.
Store away from heat and direct light.
Do not store in the bathroom, near the kitchen sink, or in other damp places. Heat or moisture may cause the dietary supplement to break down.
Keep the liquid form of this dietary supplement from freezing.
Do not keep outdated dietary supplements or those no longer needed. Be sure that any discarded dietary supplement is out of the reach of children.
Precautions While Using This MedicineReturn to top
If this dietary supplement has been ordered for you by your health care professional and you will be taking it in large doses or for a long time, your health care professional should check your progress at regular visits. This is to make sure the calcium is working properly and does not cause unwanted effects.
Do not take calcium supplements within 1 to 2 hours of taking other medicine by mouth. To do so may keep the other medicine from working properly.
Unless you are otherwise directed by your health care professional, to make sure that calcium is used properly by your body:
Do not take other medicines or dietary supplements containing large amounts of calcium, phosphates, magnesium, or vitamin D unless your health care professional has told you to do so or approved.
Do not take calcium supplements within 1 to 2 hours of eating large amounts of fiber-containing foods, such as bran and whole-grain cereals or breads, especially if you are being treated for hypocalcemia (not enough calcium in your blood).
Do not drink large amounts of alcohol or caffeine-containing beverages (usually more than 8 cups of coffee a day), or use tobacco.
Some calcium carbonate tablets have been shown to break up too slowly in the stomach to be properly absorbed into the body. If the calcium carbonate tablets you purchase are not specifically labeled as being ``USP,'' check with your pharmacist. He or she may be able to help you determine which tablets are best.
Side Effects of This MedicineReturn to top
Side Effects of This Dietary SupplementAlong with its needed effects, a dietary supplement may cause some unwanted effects. Although the following side effects occur very rarely when the calcium supplement is taken as recommended, they may be more likely to occur if:
It is taken in large doses.
It is taken for a long time.
It is taken by patients with kidney disease.
Check with your health care professional as soon as possible if any of the following side effects occur:
More common (for injection form only)
Dizziness; flushing and/or sensation of warmth or heat; irregular heartbeat; nausea or vomiting; skin redness, rash, pain, or burning at injection site; sweating; tingling sensation
Rare
Difficult or painful urination; drowsiness ; nausea or vomiting (continuing); weakness
Early signs of overdose
Constipation (severe) ; dryness of mouth ; headache (continuing) ; increased thirst ; irritability ; loss of appetite ; mental depression ; metallic taste ; unusual tiredness or weakness
Late signs of overdose
Confusion ; drowsiness (severe) ; high blood pressure ; increased sensitivity of eyes or skin to light ; irregular, fast, or slow heartbeat; unusually large amount of urine or increased frequency of urination
Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your health care professional.
Additional InformationReturn to top
Once a medicine or dietary supplement has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although this use is not included in product labeling, calcium supplements are used in certain patients with the following medical condition:
Hyperphosphatemia (too much phosphate in the blood)
Other than the above information, there is no additional information relating to proper use, precautions, or side effects for this use.
Brand NamesReturn to top
Some commonly used brand names are:
In the U.S.—
Alka-Mints2
Amitone2
Calcarb 6002
Calci-Chew2
Calciday 6672
Calcilac2
Calci-Mix2
Calcionate5
Calcium 6002
Calglycine2
Calphosan8
Cal-Plus2
Caltrate 6002
Caltrate Jr2
Chooz2
Citracal4
Citracal Liquitabs4
Dicarbosil2
Gencalc 6002
Liquid-Cal2
Liquid Cal-6002
Maalox Antacid Caplets2
Mallamint2
Neo-Calglucon5
Nephro-Calci2
Os-Cal 5002
Os-Cal 500 Chewable2
Oysco2
Oysco 500 Chewable2
Oyst-Cal 5002
Oystercal 5002
Posture12
Rolaids Calcium Rich2
Titralac2
Tums2
Tums 5002
Tums E-X2
In Canada—
Apo-Cal2
Calciject3
Calcite 5002
Calcium-Sandoz5
Calcium-Sandoz Forte10
Calcium Stanley6
Calsan2
Caltrate 6002
Gramcal10
Nu-Cal2
Os-Cal2
Os-Cal Chewable2
Tums Extra Strength2
Tums Regular Strength2
Note:
For quick reference, the following calcium supplements are numbered to match the corresponding brand names.
This information applies to the following:
1. Calcium Acetate (KAL-see-um ASa-tate)†
2. Calcium Carbonate (KAL-see-um KAR-boh-nate)‡
3. Calcium Chloride (KAL-see-um KLOR-ide)‡
4. Calcium Citrate (KAL-see-um SIH-trayt)‡†
5. Calcium Glubionate (KAL-see-um gloo-BY-oh-nate)§
6. Calcium Gluceptate and Calcium Gluconate (KAL-see-um gloo-SEP-tate and KAL-see-um GLOO-coh-nate)*
7. Calcium Gluconate (KAL-see-um GLOO-coh-nate)‡
8. Calcium Glycerophosphate and Calcium Lactate (KAL-see-um gliss-er-o-FOS-fate and KAL-see-um LAK-tate)†
9. Calcium Lactate (KAL-see-um LAK-tate)‡
10. Calcium Lactate-Gluconate and Calcium Carbonate (KAL-see-um LAK-tate GLOO-coh-nate and KAL-see-um KAR-boh-nate)*
11. Dibasic Calcium Phosphate (dy-BAY-sic KAL-see-um FOS-fate)‡†
12. Tribasic Calcium Phosphate (try-BAY-sic KAL-see-um FOS-fate)†
13. Calcium Gluceptate (KAL-see-um gloo-SEP-tate)‡†
‡ Generic name product may be available in the U.S.
§ Generic name product may be available in Canada
* Not commercially available in the U.S.
† Not commercially available in Canada
CategoryReturn to top
Antacid --Calcium Carbonate
Antihyperkalemic --Calcium Chloride ; Calcium Gluconate Injection
Antihypermagnesemic -- Calcium Chloride; Calcium Gluceptate; Calcium Gluconate Injection
Antihyperphosphatemic --Calcium Carbonate ; Calcium Citrate
Antihypocalcemic --Calcium Acetate ; Calcium Carbonate; Calcium Chloride; Calcium Citrate; Calcium Glubionate; Calcium Gluceptate; Calcium Gluconate; Calcium Glycerophosphate and Calcium Lactate; Calcium Lactate; Calcium Lactate-Gluconate and Calcium Carbonate; Calcium Phosphate, Dibasic; Calcium Phosphate, Tribasic
Cardiotonic --Calcium Chloride; Calcium Gluconate Injection
Electrolyte replenisher --Calcium Acetate; Calcium Chloride; Calcium Gluceptate; Calcium Gluconate Injection
Nutritional supplement, mineral --Calcium Carbonate; Calcium Citrate; Calcium Glubionate, Oral ; Calcium Gluceptate and Calcium Gluconate ; Calcium Gluconate, Oral; Calcium Lactate; Calcium Lactate-Gluconate and Calcium Carbonate; Calcium Phosphate, Dibasic; Calcium Phosphate, Tribasic
Revised: 07/18/1995
posted by bakerchiropractic at 9:13 PM
links to this post
A brief guide to calcium supplements
People often ask me, "What kind of calcium should I take as a supplement?"
The most commonly taken form of calcium supplement is calcium carbonate, but that is not the only form of calcium supplement that is available. Here are a few of the others:
From http://www.earlymenopause.com/calcium.htm
"Calcium citrate is the form of calcium most often recommended by doctors, chiefly because it is the most easily absorbed. This claim to fame may not apply to you since it is older women who tend to have more problems with digestion as their stomach acid production goes down, not women in their 20s and 30s. But if you have any problems with digestion -- or just want a calcium that isn’t hard on your stomach, calcium citrate probably makes sense. There is one drawback to this type of calcium: it contains only about 21% elemental calcium, so to get enough calcium, you usually have to take more tablets. . . . which winds up costing more. In addition, in spite of its stomach-friendly reputation, it may cause stomach upset or diarrhea. If you choose the type of calcium, you should take it between meals or just before bedtime.
Calcium Carbonate is the other most widely-used form of calcium. It is not as easily absorbed as calcium citrate, but is the most concentrated form of calcium with 40 percent elemental calcium (which also makes it the cheapest!) In other words, if you take a 1250 mg of calcium carbonate tablet, you’re getting 500 mg of elemental calcium. This is also the form of calcium that has been studied the most -- and there’s another side benefit: It also can act as an antacid. On the negative side, though, it can cause constipation and bloating. If you take this, it’s a good idea to drink more water than usual -- and take it in two or more doses, rather than all at one time. You may also want to chew it to make easily absorbed into your system. Unlike calcium citrate, you should take this with meals.
Tribasic Calcium Phosphate contains roughly 39% elemental calcium -- and is another easily digested form of calcium. It’s also the type of calcium used to fortify many foods such as orange juice and soy milk. The only problem? It’s among the most expensive forms of calcium.
Like calcium citrate, Calcium Lactate and Calcium Gluconate are less concentrated forms of calcium (containing about 15 percent elemental calcium), and are similar to calcium citrate in terms of absorbability and lack of side effects. But they usually cost more than calcium citrate -- as much as three to ten times more -- so you’re better off avoiding these and opting for another form of calcium.
Calcium supplements made of bone meal and dolomite are high in elemental calcium, but are not a good choice as they may contain lead and other toxic metals.
Finally, there are calcium-based antacids -- products like Tums and Rolaids Calcium Rich, which are probably one of the cheapest ways of getting calcium. These contain calcium carbonate, so usually offer you about 40% elemental calcium. For example, if you chew a regular Tums tablet (which contains 500 mg of calcium), you’ll get about 200 mg of elemental calcium. Many women like them because you can chew them instead of swallowing. If you opt for this form of calcium, you should take them between meals. And be sure to read the label carefully. You don’t want to get an antacid that includes aluminum because that can leach calcium from your system.
Calcium Supplements Rules of Thumb
It is a good idea to take your calcium twice a day, inside of in one dose, because your body can absorb only 600 milligrams of elemental calcium at a time.
Do not take calcium with iron, because it interferes with its absorption.
Also avoid taking calcium supplements with high-fiber meals or bulk laxatives, as they can cut down on the amount of calcium you absorb.
Be sure that your calcium is actually doing what you’re paying for by putting your tablets through this simple absorbability test.. Drop one tablet in a small glass or bowl with white vinegar and stir it every few minutes. After fifteen minutes to half an hour has passed, the pill should have disintegrated. If it hasn’t dissolved in the vinegar, it won’t dissolve in your stomach either -- making it essentially useless. In this case, you should get another brand or try another form.
Where calcium is concerned, you can get too much of a good thing. Over 2,000 milligrams a day of elementalcalcium may pose problems for your kidneys. So if you have had kidney stones or have a family history of them, talk to your doctor before taking calcium supplements.
Calcium Helpers
To make calcium work well, you need other vitamins and minerals to help it along. Some of these are available in combination with calcium; others are in multi-vitamins or trace mineral compounds, or you can take them individually -- or, of course, can get them through a well-balanced diet. Where you get them isn’t really the issue; the key is being sure you are getting them to get the most out of your calcium intake. The calcium helpers, then are:
Vitamin D -- which is essential for helping your body absorb calcium. While you can get Vitamin D from the sun, it’s not considered the best way since you can’t be sure you’re getting enough (and it’s tough to get if you live in a very cloudy area or use sunscreen.) In fact, according to a recent study, Vitamin D deficiency is much more common then previously thought. Most interestingly, thirty seven percent of the women in the study who had low Vitamin D levels reported that they were consuming at least the minimum requirement of Vitamin D. Since Vitamin D is so vital in the fight against osteoporosis, it’s probably best to take supplementation, then, to be sure you’re getting what you need. Most doctors agree that you need 400 I U s for maximum benefit, and can safely take up to 800 I U s daily. But more than this amount is toxic -- so be sure not to overdo. You can get Vitamin D in your diet from fatty fish (salmon, sardines, herring); fortified milk and other dairy products; egg yolks; and fortified cereals and breads.
Magnesium -- which is very commonly found in calcium supplements -- is also crucial for optimum skeletal health. In addition, it appears to hep fight fatigue and boost energy levels, as well as helping protect against heart disease. Generally, you should take a dosage equal to half of the calcium dosage you’re taking. The usual dosage is about 200 to 750 I Us depending on how much calcium you take. Some good natural sources of magnesium include: whole grains; dark-green leafy vegetables; milk and dairy products; nuts; meat and fish; dried cooked beans, especially soy beans.
Boron-- another mineral that helps prevent bone loss, it is often included in calcium supplements. It’s generally recommended you get about 3 to 6 mg of boron daily. Good natural sources of boron include fruits (including apples and pears); green and dark-yellow vegetables (including broccoli and carrots); and nuts (including almonds and hazelnuts).
Vitamin K -- another key player where bone health is concerned. Most women, however, get enough Vitamin K through their diet -- since it’s found in many vegetables.
You also need trace amounts of the following minerals: copper, zinc, manganese, and silicon (all of which are usually included in multi-vitamins or multi-mineral supplement. "
I do not agree with the admonition in the above passage about calcium lactacte and calcium gluconate. I urge folks to consider these forms.
Here is a link to more on calcium lactate
http://www.drugs.com/mtm/calcium_lactate.html
But, this is a much better information page on Calcium lactate
http://www.jtbaker.com/msds/englishhtml/c0429.htm
"Calcium Lactate, 5-Hydrate
--------------------------------------------------------------------------------
1. Product Identification
Synonyms: 2-Hydroxypropanoic acid, calcium salt, pentahydrate; Lactic acid, calcium salt (2:1), pentahydrate
CAS No.: 814-80-2 (Anhydrous) 63690-56-2 (Pentahydrate)
Molecular Weight: 308.3
Chemical Formula: (CH3CHOHCOOH)2Ca . 5H2O
Product Codes:
J.T. Baker: 1390, 1391
Mallinckrodt: 4208
--------------------------------------------------------------------------------
2. Composition/Information on Ingredients
Ingredient CAS No Percent Hazardous
--------------------------------------- ------------ ------------ ---------
Calcium Lactate (anhydrous) 814-80-2 98 - 100% Yes
--------------------------------------------------------------------------------
3. Hazards Identification
Emergency Overview
--------------------------
As part of good industrial and personal hygiene and safety procedure, avoid all unnecessary exposure to the chemical substance and ensure prompt removal from skin, eyes and clothing.
J.T. Baker SAF-T-DATA(tm) Ratings (Provided here for your convenience)
-----------------------------------------------------------------------------------------------------------
Health Rating: 0 - None
Flammability Rating: 0 - None
Reactivity Rating: 0 - None
Contact Rating: 0 - None
Lab Protective Equip: GOGGLES; LAB COAT
Storage Color Code: Orange (General Storage)
-----------------------------------------------------------------------------------------------------------
Potential Health Effects
----------------------------------
Inhalation:
Not expected to be a health hazard. Can cause breathing difficulty if inhaled in large amounts.
Ingestion:
Not expected to be a health hazard via ingestion. Large amounts may produce gastric upset.
Skin Contact:
No adverse effects expected. May cause mild irritation and redness.
Eye Contact:
No adverse effects expected but dust may cause mechanical irritation.
Chronic Exposure:
No information found.
Aggravation of Pre-existing Conditions:
No information found.
--------------------------------------------------------------------------------
4. First Aid Measures
Inhalation:
Not expected to require first aid measures. Remove to fresh air. Get medical attention for any breathing difficulty.
Ingestion:
Not expected to require first aid measures. If large amounts were swallowed, give water to drink and get medical advice.
Skin Contact:
Not expected to require first aid measures. Wash exposed area with soap and water. Get medical advice if irritation develops.
Eye Contact:
Wash thoroughly with running water. Get medical advice if irritation develops.
--------------------------------------------------------------------------------
5. Fire Fighting Measures
Fire:
Not expected to be a fire hazard.
Explosion:
No information found.
Fire Extinguishing Media:
Use any means suitable for extinguishing surrounding fire.
Special Information:
In the event of a fire, wear full protective clothing and NIOSH-approved self-contained breathing apparatus with full facepiece operated in the pressure demand or other positive pressure mode.
--------------------------------------------------------------------------------
6. Accidental Release Measures
Ventilate area of leak or spill. Wear appropriate personal protective equipment as specified in Section 8. Spills: Sweep up and containerize for reclamation or disposal. Vacuuming or wet sweeping may be used to avoid dust dispersal.
--------------------------------------------------------------------------------
7. Handling and Storage
Keep in a tightly closed container, stored in a cool, dry, ventilated area. Protect against physical damage. Containers of this material may be hazardous when empty since they retain product residues (dust, solids); observe all warnings and precautions listed for the product.
--------------------------------------------------------------------------------
8. Exposure Controls/Personal Protection
Airborne Exposure Limits:
None established.
Ventilation System:
A system of local and/or general exhaust is recommended to keep employee exposures as low as possible. Local exhaust ventilation is generally preferred because it can control the emissions of the contaminant at its source, preventing dispersion of it into the general work area. Please refer to the ACGIH document, Industrial Ventilation, A Manual of Recommended Practices, most recent edition, for details.
Personal Respirators (NIOSH Approved):
For conditions of use where exposure to dust or mist is apparent and engineering controls are not feasible, a particulate respirator (NIOSH type N95 or better filters) may be worn. If oil particles (e.g. lubricants, cutting fluids, glycerine, etc.) are present, use a NIOSH type R or P filter. For emergencies or instances where the exposure levels are not known, use a full-face positive-pressure, air-supplied respirator. WARNING: Air-purifying respirators do not protect workers in oxygen-deficient atmospheres.
Skin Protection:
Wear protective gloves and clean body-covering clothing.
Eye Protection:
Use chemical safety goggles. Maintain eye wash fountain and quick-drench facilities in work area.
--------------------------------------------------------------------------------
9. Physical and Chemical Properties
Appearance:
White crystalline powder.
Odor:
Faint odor.
Solubility:
Moderate (1-10%)
Specific Gravity:
No information found.
pH:
No information found.
% Volatiles by volume @ 21C (70F):
0
Boiling Point:
No information found.
Melting Point:
No information found.
Vapor Density (Air=1):
Not applicable.
Vapor Pressure (mm Hg):
Not applicable.
Evaporation Rate (BuAc=1):
No information found.
--------------------------------------------------------------------------------
10. Stability and Reactivity
Stability:
Stable under ordinary conditions of use and storage.
Hazardous Decomposition Products:
Carbon dioxide and carbon monoxide may form when heated to decomposition.
Hazardous Polymerization:
Will not occur.
Incompatibilities:
No information found.
Conditions to Avoid:
No information found.
--------------------------------------------------------------------------------
11. Toxicological Information
No LD50/LC50 information found relating to normal routes of occupational exposure.
--------\Cancer Lists\------------------------------------------------------
---NTP Carcinogen---
Ingredient Known Anticipated IARC Category
------------------------------------ ----- ----------- -------------
Calcium Lactate (anhydrous) No No None
(814-80-2)
--------------------------------------------------------------------------------
12. Ecological Information
Environmental Fate:
No information found.
Environmental Toxicity:
No information found.
--------------------------------------------------------------------------------
13. Disposal Considerations
Whatever cannot be saved for recovery or recycling should be managed in an appropriate and approved waste disposal facility. Processing, use or contamination of this product may change the waste management options. State and local disposal regulations may differ from federal disposal regulations. Dispose of container and unused contents in accordance with federal, state and local requirements.
--------------------------------------------------------------------------------
14. Transport Information
Not regulated.
--------------------------------------------------------------------------------
15. Regulatory Information
--------\Chemical Inventory Status - Part 1\---------------------------------
Ingredient TSCA EC Japan Australia
----------------------------------------------- ---- --- ----- ---------
Calcium Lactate (anhydrous) (814-80-2) Yes Yes Yes Yes
--------\Chemical Inventory Status - Part 2\---------------------------------
--Canada--
Ingredient Korea DSL NDSL Phil.
----------------------------------------------- ----- --- ---- -----
Calcium Lactate (anhydrous) (814-80-2) Yes Yes No Yes
--------\Federal, State & International Regulations - Part 1\----------------
-SARA 302- ------SARA 313------
Ingredient RQ TPQ List Chemical Catg.
----------------------------------------- --- ----- ---- --------------
Calcium Lactate (anhydrous) (814-80-2) No No No No
--------\Federal, State & International Regulations - Part 2\----------------
-RCRA- -TSCA-
Ingredient CERCLA 261.33 8(d)
----------------------------------------- ------ ------ ------
Calcium Lactate (anhydrous) (814-80-2) No No No
Chemical Weapons Convention: No TSCA 12(b): No CDTA: No
SARA 311/312: Acute: No Chronic: No Fire: No Pressure: No
Reactivity: No (Pure / Solid)
Australian Hazchem Code: None allocated.
Poison Schedule: None allocated.
WHMIS:
This MSDS has been prepared according to the hazard criteria of the Controlled Products Regulations (CPR) and the MSDS contains all of the information required by the CPR.
--------------------------------------------------------------------------------
16. Other Information
NFPA Ratings: Health: 1 Flammability: 0 Reactivity: 0
Label Hazard Warning:
As part of good industrial and personal hygiene and safety procedure, avoid all unnecessary exposure to the chemical substance and ensure prompt removal from skin, eyes and clothing.
Label Precautions:
None.
Label First Aid:
Not applicable.
Product Use:
Laboratory Reagent.
Revision Information:
MSDS Section(s) changed since last revision of document include: 8.
Disclaimer:
************************************************************************************************
Mallinckrodt Baker, Inc. provides the information contained herein in good faith but makes no representation as to its comprehensiveness or accuracy. This document is intended only as a guide to the appropriate precautionary handling of the material by a properly trained person using this product. Individuals receiving the information must exercise their independent judgment in determining its appropriateness for a particular purpose. MALLINCKRODT BAKER, INC. MAKES NO REPRESENTATIONS OR WARRANTIES, EITHER EXPRESS OR IMPLIED, INCLUDING WITHOUT LIMITATION ANY WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE WITH RESPECT TO THE INFORMATION SET FORTH HEREIN OR THE PRODUCT TO WHICH THE INFORMATION REFERS. ACCORDINGLY, MALLINCKRODT BAKER, INC. WILL NOT BE RESPONSIBLE FOR DAMAGES RESULTING FROM USE OF OR RELIANCE UPON THIS INFORMATION.
************************************************************************************************
Prepared by: Environmental Health & Safety
Phone Number: (314) 654-1600 (U.S.A.) "
Here's another source page on calcium supplements
"The Myth of Calcium Supplements:
which one is the best?
Written by: Gloria Tsang, RD
The role of calcium in bone health is indisputable. We've previously talked about food sources of calcium (Calcium Nutrition), we will spend some time discussing the different forms of calcium supplements.
The Dietary Reference Intake DRI for calcium for adults is 1000mg -1300mg depending on age and gender. As one serving of dairy product provides ~300mg of calcium, those who do not consume enough calcium from food sources may need calcium supplements to meet their daily requirement.
Calcium Supplements
discounted Calcium Supplements from drugstore.com
When purchasing calcium supplements, ensure to look for the elemental calcium content, not the total content. For instance, a pill containing 500mg of Calcium Carbonate provides 200mg of elemental calcium. Hence one pill in this example only provides 200mg of calcium, not 500mg.
Calcium is absorbed in small intestines. Not all calcium we consume will be absorbed. The amount of calcium absorbed is dependent on a number of factors such as the acidic condition in our intestines, Vitamin D level, estrogen level and the type of calcium supplement.
Different Types of Calcium Supplements
One important factor affecting calcium absorption is how well the pill dissolves. Try buying calcium pills of US Pharmacopeia's standards. The "USP" on the label indicates that the calcium pill meets the USP standards of supplying adequate elemental calcium and how well it dissolves in our intestines.
Calcium Citrate e.g. Citracal or Solgar: Calcium is best absorbed in an acidic environment, hence calcium citrate is the best absorbed supplemental form of calcium. It does not require extra stomach acid for absorption, hence we may take it anytime in a day, even on an empty stomach. However Calcium Citrate usually provides less elemental calcium per pill, therefore one may need to take a relatively more numbers of pills per day depending to the needs. Cautions for people with acid reflux.
Calcium Carbonate e.g. Tums or Caltrate: Most calcium pills in the market are in the form of calcium carbonate. It requires extra stomach acid for better absorption, hence it is best taken after meals.
Dolomite, Bone Meal or Oyster Shell: These naturally occurring calcium pills may contain heavy metal or lead. At the moment, calcium supplements are not tested by any regulatory agency for lead content. Therefore, it's best to avoid.
Calcium Gluconate and Calcium Lactate: These types of calcium pills contain low content of elemental calcium. Hence, one may need to take a large amount of tablets to meet the calcium requirement!
Coral Calcium: This type of calcium is marketed for more than bone health. Its infomercial claimed that it can cure 200 human diseases. It's indeed only Calcium Carbonate. Read Alert! Coral Calcium Supplement Scam
Calcium Pill Warning: do not consume more than 2500mg of elemental calcium daily."
The most commonly taken form of calcium supplement is calcium carbonate, but that is not the only form of calcium supplement that is available. Here are a few of the others:
From http://www.earlymenopause.com/calcium.htm
"Calcium citrate is the form of calcium most often recommended by doctors, chiefly because it is the most easily absorbed. This claim to fame may not apply to you since it is older women who tend to have more problems with digestion as their stomach acid production goes down, not women in their 20s and 30s. But if you have any problems with digestion -- or just want a calcium that isn’t hard on your stomach, calcium citrate probably makes sense. There is one drawback to this type of calcium: it contains only about 21% elemental calcium, so to get enough calcium, you usually have to take more tablets. . . . which winds up costing more. In addition, in spite of its stomach-friendly reputation, it may cause stomach upset or diarrhea. If you choose the type of calcium, you should take it between meals or just before bedtime.
Calcium Carbonate is the other most widely-used form of calcium. It is not as easily absorbed as calcium citrate, but is the most concentrated form of calcium with 40 percent elemental calcium (which also makes it the cheapest!) In other words, if you take a 1250 mg of calcium carbonate tablet, you’re getting 500 mg of elemental calcium. This is also the form of calcium that has been studied the most -- and there’s another side benefit: It also can act as an antacid. On the negative side, though, it can cause constipation and bloating. If you take this, it’s a good idea to drink more water than usual -- and take it in two or more doses, rather than all at one time. You may also want to chew it to make easily absorbed into your system. Unlike calcium citrate, you should take this with meals.
Tribasic Calcium Phosphate contains roughly 39% elemental calcium -- and is another easily digested form of calcium. It’s also the type of calcium used to fortify many foods such as orange juice and soy milk. The only problem? It’s among the most expensive forms of calcium.
Like calcium citrate, Calcium Lactate and Calcium Gluconate are less concentrated forms of calcium (containing about 15 percent elemental calcium), and are similar to calcium citrate in terms of absorbability and lack of side effects. But they usually cost more than calcium citrate -- as much as three to ten times more -- so you’re better off avoiding these and opting for another form of calcium.
Calcium supplements made of bone meal and dolomite are high in elemental calcium, but are not a good choice as they may contain lead and other toxic metals.
Finally, there are calcium-based antacids -- products like Tums and Rolaids Calcium Rich, which are probably one of the cheapest ways of getting calcium. These contain calcium carbonate, so usually offer you about 40% elemental calcium. For example, if you chew a regular Tums tablet (which contains 500 mg of calcium), you’ll get about 200 mg of elemental calcium. Many women like them because you can chew them instead of swallowing. If you opt for this form of calcium, you should take them between meals. And be sure to read the label carefully. You don’t want to get an antacid that includes aluminum because that can leach calcium from your system.
Calcium Supplements Rules of Thumb
It is a good idea to take your calcium twice a day, inside of in one dose, because your body can absorb only 600 milligrams of elemental calcium at a time.
Do not take calcium with iron, because it interferes with its absorption.
Also avoid taking calcium supplements with high-fiber meals or bulk laxatives, as they can cut down on the amount of calcium you absorb.
Be sure that your calcium is actually doing what you’re paying for by putting your tablets through this simple absorbability test.. Drop one tablet in a small glass or bowl with white vinegar and stir it every few minutes. After fifteen minutes to half an hour has passed, the pill should have disintegrated. If it hasn’t dissolved in the vinegar, it won’t dissolve in your stomach either -- making it essentially useless. In this case, you should get another brand or try another form.
Where calcium is concerned, you can get too much of a good thing. Over 2,000 milligrams a day of elementalcalcium may pose problems for your kidneys. So if you have had kidney stones or have a family history of them, talk to your doctor before taking calcium supplements.
Calcium Helpers
To make calcium work well, you need other vitamins and minerals to help it along. Some of these are available in combination with calcium; others are in multi-vitamins or trace mineral compounds, or you can take them individually -- or, of course, can get them through a well-balanced diet. Where you get them isn’t really the issue; the key is being sure you are getting them to get the most out of your calcium intake. The calcium helpers, then are:
Vitamin D -- which is essential for helping your body absorb calcium. While you can get Vitamin D from the sun, it’s not considered the best way since you can’t be sure you’re getting enough (and it’s tough to get if you live in a very cloudy area or use sunscreen.) In fact, according to a recent study, Vitamin D deficiency is much more common then previously thought. Most interestingly, thirty seven percent of the women in the study who had low Vitamin D levels reported that they were consuming at least the minimum requirement of Vitamin D. Since Vitamin D is so vital in the fight against osteoporosis, it’s probably best to take supplementation, then, to be sure you’re getting what you need. Most doctors agree that you need 400 I U s for maximum benefit, and can safely take up to 800 I U s daily. But more than this amount is toxic -- so be sure not to overdo. You can get Vitamin D in your diet from fatty fish (salmon, sardines, herring); fortified milk and other dairy products; egg yolks; and fortified cereals and breads.
Magnesium -- which is very commonly found in calcium supplements -- is also crucial for optimum skeletal health. In addition, it appears to hep fight fatigue and boost energy levels, as well as helping protect against heart disease. Generally, you should take a dosage equal to half of the calcium dosage you’re taking. The usual dosage is about 200 to 750 I Us depending on how much calcium you take. Some good natural sources of magnesium include: whole grains; dark-green leafy vegetables; milk and dairy products; nuts; meat and fish; dried cooked beans, especially soy beans.
Boron-- another mineral that helps prevent bone loss, it is often included in calcium supplements. It’s generally recommended you get about 3 to 6 mg of boron daily. Good natural sources of boron include fruits (including apples and pears); green and dark-yellow vegetables (including broccoli and carrots); and nuts (including almonds and hazelnuts).
Vitamin K -- another key player where bone health is concerned. Most women, however, get enough Vitamin K through their diet -- since it’s found in many vegetables.
You also need trace amounts of the following minerals: copper, zinc, manganese, and silicon (all of which are usually included in multi-vitamins or multi-mineral supplement. "
I do not agree with the admonition in the above passage about calcium lactacte and calcium gluconate. I urge folks to consider these forms.
Here is a link to more on calcium lactate
http://www.drugs.com/mtm/calcium_lactate.html
But, this is a much better information page on Calcium lactate
http://www.jtbaker.com/msds/englishhtml/c0429.htm
"Calcium Lactate, 5-Hydrate
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1. Product Identification
Synonyms: 2-Hydroxypropanoic acid, calcium salt, pentahydrate; Lactic acid, calcium salt (2:1), pentahydrate
CAS No.: 814-80-2 (Anhydrous) 63690-56-2 (Pentahydrate)
Molecular Weight: 308.3
Chemical Formula: (CH3CHOHCOOH)2Ca . 5H2O
Product Codes:
J.T. Baker: 1390, 1391
Mallinckrodt: 4208
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2. Composition/Information on Ingredients
Ingredient CAS No Percent Hazardous
--------------------------------------- ------------ ------------ ---------
Calcium Lactate (anhydrous) 814-80-2 98 - 100% Yes
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3. Hazards Identification
Emergency Overview
--------------------------
As part of good industrial and personal hygiene and safety procedure, avoid all unnecessary exposure to the chemical substance and ensure prompt removal from skin, eyes and clothing.
J.T. Baker SAF-T-DATA(tm) Ratings (Provided here for your convenience)
-----------------------------------------------------------------------------------------------------------
Health Rating: 0 - None
Flammability Rating: 0 - None
Reactivity Rating: 0 - None
Contact Rating: 0 - None
Lab Protective Equip: GOGGLES; LAB COAT
Storage Color Code: Orange (General Storage)
-----------------------------------------------------------------------------------------------------------
Potential Health Effects
----------------------------------
Inhalation:
Not expected to be a health hazard. Can cause breathing difficulty if inhaled in large amounts.
Ingestion:
Not expected to be a health hazard via ingestion. Large amounts may produce gastric upset.
Skin Contact:
No adverse effects expected. May cause mild irritation and redness.
Eye Contact:
No adverse effects expected but dust may cause mechanical irritation.
Chronic Exposure:
No information found.
Aggravation of Pre-existing Conditions:
No information found.
--------------------------------------------------------------------------------
4. First Aid Measures
Inhalation:
Not expected to require first aid measures. Remove to fresh air. Get medical attention for any breathing difficulty.
Ingestion:
Not expected to require first aid measures. If large amounts were swallowed, give water to drink and get medical advice.
Skin Contact:
Not expected to require first aid measures. Wash exposed area with soap and water. Get medical advice if irritation develops.
Eye Contact:
Wash thoroughly with running water. Get medical advice if irritation develops.
--------------------------------------------------------------------------------
5. Fire Fighting Measures
Fire:
Not expected to be a fire hazard.
Explosion:
No information found.
Fire Extinguishing Media:
Use any means suitable for extinguishing surrounding fire.
Special Information:
In the event of a fire, wear full protective clothing and NIOSH-approved self-contained breathing apparatus with full facepiece operated in the pressure demand or other positive pressure mode.
--------------------------------------------------------------------------------
6. Accidental Release Measures
Ventilate area of leak or spill. Wear appropriate personal protective equipment as specified in Section 8. Spills: Sweep up and containerize for reclamation or disposal. Vacuuming or wet sweeping may be used to avoid dust dispersal.
--------------------------------------------------------------------------------
7. Handling and Storage
Keep in a tightly closed container, stored in a cool, dry, ventilated area. Protect against physical damage. Containers of this material may be hazardous when empty since they retain product residues (dust, solids); observe all warnings and precautions listed for the product.
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8. Exposure Controls/Personal Protection
Airborne Exposure Limits:
None established.
Ventilation System:
A system of local and/or general exhaust is recommended to keep employee exposures as low as possible. Local exhaust ventilation is generally preferred because it can control the emissions of the contaminant at its source, preventing dispersion of it into the general work area. Please refer to the ACGIH document, Industrial Ventilation, A Manual of Recommended Practices, most recent edition, for details.
Personal Respirators (NIOSH Approved):
For conditions of use where exposure to dust or mist is apparent and engineering controls are not feasible, a particulate respirator (NIOSH type N95 or better filters) may be worn. If oil particles (e.g. lubricants, cutting fluids, glycerine, etc.) are present, use a NIOSH type R or P filter. For emergencies or instances where the exposure levels are not known, use a full-face positive-pressure, air-supplied respirator. WARNING: Air-purifying respirators do not protect workers in oxygen-deficient atmospheres.
Skin Protection:
Wear protective gloves and clean body-covering clothing.
Eye Protection:
Use chemical safety goggles. Maintain eye wash fountain and quick-drench facilities in work area.
--------------------------------------------------------------------------------
9. Physical and Chemical Properties
Appearance:
White crystalline powder.
Odor:
Faint odor.
Solubility:
Moderate (1-10%)
Specific Gravity:
No information found.
pH:
No information found.
% Volatiles by volume @ 21C (70F):
0
Boiling Point:
No information found.
Melting Point:
No information found.
Vapor Density (Air=1):
Not applicable.
Vapor Pressure (mm Hg):
Not applicable.
Evaporation Rate (BuAc=1):
No information found.
--------------------------------------------------------------------------------
10. Stability and Reactivity
Stability:
Stable under ordinary conditions of use and storage.
Hazardous Decomposition Products:
Carbon dioxide and carbon monoxide may form when heated to decomposition.
Hazardous Polymerization:
Will not occur.
Incompatibilities:
No information found.
Conditions to Avoid:
No information found.
--------------------------------------------------------------------------------
11. Toxicological Information
No LD50/LC50 information found relating to normal routes of occupational exposure.
--------\Cancer Lists\------------------------------------------------------
---NTP Carcinogen---
Ingredient Known Anticipated IARC Category
------------------------------------ ----- ----------- -------------
Calcium Lactate (anhydrous) No No None
(814-80-2)
--------------------------------------------------------------------------------
12. Ecological Information
Environmental Fate:
No information found.
Environmental Toxicity:
No information found.
--------------------------------------------------------------------------------
13. Disposal Considerations
Whatever cannot be saved for recovery or recycling should be managed in an appropriate and approved waste disposal facility. Processing, use or contamination of this product may change the waste management options. State and local disposal regulations may differ from federal disposal regulations. Dispose of container and unused contents in accordance with federal, state and local requirements.
--------------------------------------------------------------------------------
14. Transport Information
Not regulated.
--------------------------------------------------------------------------------
15. Regulatory Information
--------\Chemical Inventory Status - Part 1\---------------------------------
Ingredient TSCA EC Japan Australia
----------------------------------------------- ---- --- ----- ---------
Calcium Lactate (anhydrous) (814-80-2) Yes Yes Yes Yes
--------\Chemical Inventory Status - Part 2\---------------------------------
--Canada--
Ingredient Korea DSL NDSL Phil.
----------------------------------------------- ----- --- ---- -----
Calcium Lactate (anhydrous) (814-80-2) Yes Yes No Yes
--------\Federal, State & International Regulations - Part 1\----------------
-SARA 302- ------SARA 313------
Ingredient RQ TPQ List Chemical Catg.
----------------------------------------- --- ----- ---- --------------
Calcium Lactate (anhydrous) (814-80-2) No No No No
--------\Federal, State & International Regulations - Part 2\----------------
-RCRA- -TSCA-
Ingredient CERCLA 261.33 8(d)
----------------------------------------- ------ ------ ------
Calcium Lactate (anhydrous) (814-80-2) No No No
Chemical Weapons Convention: No TSCA 12(b): No CDTA: No
SARA 311/312: Acute: No Chronic: No Fire: No Pressure: No
Reactivity: No (Pure / Solid)
Australian Hazchem Code: None allocated.
Poison Schedule: None allocated.
WHMIS:
This MSDS has been prepared according to the hazard criteria of the Controlled Products Regulations (CPR) and the MSDS contains all of the information required by the CPR.
--------------------------------------------------------------------------------
16. Other Information
NFPA Ratings: Health: 1 Flammability: 0 Reactivity: 0
Label Hazard Warning:
As part of good industrial and personal hygiene and safety procedure, avoid all unnecessary exposure to the chemical substance and ensure prompt removal from skin, eyes and clothing.
Label Precautions:
None.
Label First Aid:
Not applicable.
Product Use:
Laboratory Reagent.
Revision Information:
MSDS Section(s) changed since last revision of document include: 8.
Disclaimer:
************************************************************************************************
Mallinckrodt Baker, Inc. provides the information contained herein in good faith but makes no representation as to its comprehensiveness or accuracy. This document is intended only as a guide to the appropriate precautionary handling of the material by a properly trained person using this product. Individuals receiving the information must exercise their independent judgment in determining its appropriateness for a particular purpose. MALLINCKRODT BAKER, INC. MAKES NO REPRESENTATIONS OR WARRANTIES, EITHER EXPRESS OR IMPLIED, INCLUDING WITHOUT LIMITATION ANY WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE WITH RESPECT TO THE INFORMATION SET FORTH HEREIN OR THE PRODUCT TO WHICH THE INFORMATION REFERS. ACCORDINGLY, MALLINCKRODT BAKER, INC. WILL NOT BE RESPONSIBLE FOR DAMAGES RESULTING FROM USE OF OR RELIANCE UPON THIS INFORMATION.
************************************************************************************************
Prepared by: Environmental Health & Safety
Phone Number: (314) 654-1600 (U.S.A.) "
Here's another source page on calcium supplements
http://www.healthcastle.com/calciumpill.shtml
"The Myth of Calcium Supplements:
which one is the best?
Written by: Gloria Tsang, RD
The role of calcium in bone health is indisputable. We've previously talked about food sources of calcium (Calcium Nutrition), we will spend some time discussing the different forms of calcium supplements.
The Dietary Reference Intake DRI for calcium for adults is 1000mg -1300mg depending on age and gender. As one serving of dairy product provides ~300mg of calcium, those who do not consume enough calcium from food sources may need calcium supplements to meet their daily requirement.
Calcium Supplements
discounted Calcium Supplements from drugstore.com
When purchasing calcium supplements, ensure to look for the elemental calcium content, not the total content. For instance, a pill containing 500mg of Calcium Carbonate provides 200mg of elemental calcium. Hence one pill in this example only provides 200mg of calcium, not 500mg.
Calcium is absorbed in small intestines. Not all calcium we consume will be absorbed. The amount of calcium absorbed is dependent on a number of factors such as the acidic condition in our intestines, Vitamin D level, estrogen level and the type of calcium supplement.
Different Types of Calcium Supplements
One important factor affecting calcium absorption is how well the pill dissolves. Try buying calcium pills of US Pharmacopeia's standards. The "USP" on the label indicates that the calcium pill meets the USP standards of supplying adequate elemental calcium and how well it dissolves in our intestines.
Calcium Citrate e.g. Citracal or Solgar: Calcium is best absorbed in an acidic environment, hence calcium citrate is the best absorbed supplemental form of calcium. It does not require extra stomach acid for absorption, hence we may take it anytime in a day, even on an empty stomach. However Calcium Citrate usually provides less elemental calcium per pill, therefore one may need to take a relatively more numbers of pills per day depending to the needs. Cautions for people with acid reflux.
Calcium Carbonate e.g. Tums or Caltrate: Most calcium pills in the market are in the form of calcium carbonate. It requires extra stomach acid for better absorption, hence it is best taken after meals.
Dolomite, Bone Meal or Oyster Shell: These naturally occurring calcium pills may contain heavy metal or lead. At the moment, calcium supplements are not tested by any regulatory agency for lead content. Therefore, it's best to avoid.
Calcium Gluconate and Calcium Lactate: These types of calcium pills contain low content of elemental calcium. Hence, one may need to take a large amount of tablets to meet the calcium requirement!
Coral Calcium: This type of calcium is marketed for more than bone health. Its infomercial claimed that it can cure 200 human diseases. It's indeed only Calcium Carbonate. Read Alert! Coral Calcium Supplement Scam
Calcium Pill Warning: do not consume more than 2500mg of elemental calcium daily."
posted by bakerchiropractic at 8:47 PM
links to this post
RESTLESS LEG SYNDROIME - PART 3
How to help patients with restless legs syndrome
Discerning the indescribable and relaxing the restless
Virgilio Gerald H. Evidente, MD Charles H. Adler, MD, PhD
VOL 105 / NO 3 / MARCH 1999 / POSTGRADUATE MEDICINE
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CME learning objectives
To familiarize primary care physicians with diagnostic criteria for restless legs syndrome
To elucidate secondary, and often curable, causes of restless legs syndrome
To describe current treatment options for restless legs syndrome
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This page is best viewed with a browser that supports tables
Preview: Few conditions are characterized by the difficulty encountered in trying to depict their symptoms, but such is the case in restless legs syndrome. Patients report sensations that are not painful yet are distinctly bothersome and can lead to significant physical and emotional disability. Once correctly diagnosed, restless legs syndrome can usually be effectively treated symptomatically, and in some secondary cases, it can even be cured. In this article, the authors focus on clinical features that enable timely identification of the condition and on current management strategies.
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In the mid-1940s, Swedish neurologist Karl A. Ekbom described a disorder characterized by sensory symptoms and motor disturbance of the limbs, mainly during rest. He named the condition restless legs syndrome (1). Although the syndrome affects about 10% to 15% of the US population (2), it is often unrecognized and misdiagnosed. It may begin at any age (1-3), even as early as infancy, but most patients who are severely affected are middle-aged or older. Symptoms progress over time in about two thirds of patients and may be severe enough to be disabling.
Diagnostic criteria and common features
In 1995, the newly formed International Restless Legs Syndrome Study Group developed criteria for diagnosing restless legs syndrome (3). Four basic elements must be present to make the diagnosis: (1) a desire to move the limbs, often associated with paresthesia or dysesthesia, (2) symptoms exacerbated by rest and relieved by activity, (3) motor restlessness, and (4) nocturnal worsening of symptoms. These and several additional features commonly seen in restless legs syndrome are discussed in the following paragraphs.
Desire to move the limbs, paresthesia, dysesthesia. Patients often describe an unpleasant sensation in the calves and occasionally in the thighs, feet, or upper limbs. Although the study group refers to dysesthesia or paresthesia (which implies abnormal sensations) (3), most patients simply relate vague, nonpainful, indescribable, bilateral (rarely unilateral) discomfort in the limbs, using such terms as crawling, creeping, tingling, burning, itching, and aching.
Symptoms are similar to those described by patients with akathisia (which is usually caused by use of neuroleptic drugs). However, in contrast to patients with restless legs syndrome, those with akathisia have an inner feeling of restlessness, gain the most relief by resting in a recumbent position, and do not experience paresthesia or nocturnal worsening of symptoms.
Symptoms exacerbated by rest, relieved by activity. The unpleasant limb sensations of restless legs syndrome are precipitated by rest or inactivity (eg, lying in bed at night, riding in a car or airplane, sitting in a theater). The discomfort is usually relieved by motor activity (eg, moving the legs, walking).
Motor restlessness. Patients describe a buildup of discomfort and involuntary limb jerking if they remain still. There is an urge to move the legs and relief after moving (much like the sensation of tics). Compelling motor restlessness can manifest as tossing and turning in bed, needing to pace the floor, stretching or shaking the legs, or needing to exercise (3). Limb movements in restless legs syndrome are partly voluntary, in that patients choose to move to relieve the discomfort, and partly involuntary, since patients are compelled to move. Such partly voluntary, partly involuntary movements are sometimes referred to as "unvoluntary" or "semivoluntary."
Nocturnal worsening of symptoms. All patients notice worsening of symptoms at night (usually as they lie in bed before sleep or when they are awakened in the middle of the night) and improve-ment early in the morning. Nocturnal worsening is caused by lack of motor activity at night and is also thought to be due to an independent circadian rhythm (3). In severe cases, patients experience symptoms both day and night.
Periodic limb movements of sleep. About 80% of patients with restless legs syndrome have unilateral or bilateral periodic limb movements of sleep, also called nocturnal myoclonus (1,3). These movements are stereotyped, repetitive, slow flexion of the limbs (legs alone or legs more than arms) during stage 1 or 2 sleep. They occur semirhythmically at intervals of 5 to 60 seconds and last about 1.5 to 2.5 seconds. In the lower limbs, repetitive dorsiflexion of the big toe with fanning of the small toes is seen, along with flexion of the ankles, knees, and thighs.
Dyskinesias while awake. These motions, also called periodic limb movements while awake, are seen in 30% to 50% of patients with restless legs syndrome (3). They are similar to periodic limb movements of sleep but occur only during wakefulness. They can be fast or slow and periodic or nonperiodic.
Sleep disturbance. Because of limb discomfort and jerking, most patients with restless legs syndrome have disturbances of sleep onset or maintenance (1,3). The result is excessive daytime sleepiness and fatigability, although not to the same degree as that caused by narcolepsy.
Primary disease
In most cases, restless legs syndrome is idiopathic. Such idiopathic disease can be familial (in 25% to 75% of cases) and, if so, is transmitted in an autosomal-dominant fashion (1,3,4). Progressive decrease in age at onset with subsequent generations (ie, genetic anticipation) has been described in some families. Patients with familial restless legs syndrome tend to have an earlier age at onset and slower progression (5).
Secondary disease
Restless legs syndrome can develop as a result of certain conditions or factors (table 1), particularly iron deficiency and peripheral neuropathy (6-12). These two conditions should be ruled out on clinical grounds before restless legs syndrome is labeled primary (13). Because of the prevalence of these conditions in the general population, their association with restless legs syndrome needs to be interpreted with considerable caution.
Table 1. Factors and conditions that may contribute to secondary restless legs syndrome (in order of frequency)
Deficiency of iron, folate, or magnesium
Polyneuropathy caused by alcohol abuse, amyloidosis, diabetes mellitus, idiopathic polyneuropathy, lumbosacral radiculopathy, Lyme disease, monoclonal gammopathy of undetermined significance, rheumatoid arthritis, Sjögren's syndrome, uremia, or vitamin B12 deficiency
Pregnancy
Anemia
Parkinson's disease
Gastric surgery
Chronic obstructive pulmonary disease
Carcinoma
Chronic venous insufficiency or varicose veins
Intake of certain substances or drugs: alcohol, caffeine, anticonvulsants (eg, methsuximide [Celontin Kapseals], phenytoin [Dilantin]), antidepressants (eg, amitriptyline HCl [Elavil], paroxetine HCl [Paxil]), beta blockers, histamine2 antagonists, lithium, neuroleptics
Withdrawal from vasodilators, sedatives, or imipramine HCl (Tofranil)
Cigarette smoking
Myelopathy or myelitis
Hypothyroidism or hyperthyroidism
Acute intermittent porphyria
Fibromyalgia syndrome
Arborizing telangiectasia of the lower limbs
Peripheral microemboli made of cholesterol
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Restless legs syndrome can be the initial manifestation of iron deficiency (1,14). A low serum ferritin level may precede a drop in serum iron level. Depletion of iron stores, in the absence of overt iron deficiency, can lead to restless legs syndrome. How this occurs in unknown. Treatment with ferrous sulfate may bring improvement.
About 5% of patients with sensory neuropathy (especially caused by uremia, rheumatoid arthritis, and diabetes) have restless legs syndrome (8). Treatment of the polyneuropathy may improve symptoms.
Diagnosis
Diagnosis of restless legs syndrome is founded mainly on clinical history. If a secondary cause is suspected on the basis of history, abnormal findings on neurologic examination, or poor response to treatment, a laboratory workup should be done. Testing should measure levels of blood urea nitrogen, creatinine, fasting blood glucose, ferritin, magnesium, thyrotropin, and folate and should include a glucose tolerance test and a complete blood cell count.
Needle electromyography and nerve-conduction studies should be considered if polyneuropathy is suspected on clinical grounds, even if results of neurologic examination are apparently normal (13). Polysomnography is rarely necessary but may be used to quantify periodic limb movements of sleep or to characterize sleep architecture, especially in patients who continue to have significant sleep disturbance despite relief of sensory symptoms with treatment.
Nonpharmacologic management
Patients with suspected restless legs syndrome who are sensitive to caffeine, alcohol, or nicotine should avoid these substances (1,6). Offending medications (table 1) also should be discontinued. In general, physical measures are only partially or temporarily helpful. Some patients benefit from hot or cold baths, whirlpool baths, rubbing of the limbs, or vibratory or electrical stimulation of the feet and toes before bedtime.
Supplementation to correct deficiencies in vitamins (eg, folate) (15), electrolytes (eg, magnesium) (7), or iron may improve symptoms. Patients with prominent varicose veins in the legs may benefit from use of sclerosing agents (9). Those with uremia may have relief after kidney transplantation or correction of anemia with erythropoietin (Epogen, Procrit) (6).
Pharmacologic management
Drug therapy for primary restless legs syndrome is largely symptomatic, since cure is only possible in secondary disease. Medications should be initiated at a low dose and be taken an hour or two before bedtime to allow sufficient absorption and onset of action. Additional doses can be taken if symptoms cause awakening in the middle of the night. If tolerance to one drug develops, another class of drugs may be substituted. Monthly rotation of two or three agents found to be effective may help prevent tolerance. A combination of drugs may be beneficial in severe cases.
Levodopa with carbidopa Levodopa with carbidopa (Sinemet) can improve sensory symptoms and periodic limb movements of sleep in primary restless legs syndrome and that associated with uremia (1-3,16). For symptoms that start before sleep, one 25/100-mg carbidopa/levodopa tablet can be taken 1 to 2 hours before bedtime. If symptoms occur during the night, one 25/100-mg controlled-release carbidopa/levodopa (Sinemet CR) tablet can be used. In patients who have symptoms both before sleep and during the night, a combination of short-acting and controlled-release tablets can be given. Most patients experience benefits when the levodopa portion of carbidopa/levodopa totals 100 to 500 mg daily, although some may need 1,000 to 1,500 mg. Nausea and constipation are the most common side effects of levodopa.
The major drawback in prescribing levodopa for restless legs syndrome is that in about 80% of patients, augmentation of symptoms occurs as early as a few months after initiation of therapy (17). It can manifest as earlier onset during the evening or after assuming a restful position, as increased intensity in the morning (ie, rebound), or as extension of symptoms to the upper body. Augmentation is more likely in patients with severe pretreatment symptoms and in those taking 200 mg or more of levodopa daily. If augmentation or rebound develops, adjunctive therapy with reduction of the levodopa dose or discontinuation of levodopa and substitution of another drug may help.
Dopamine agonists Dopamine agonists are less likely to produce augmentation or rebound and can be useful alone or along with levodopa in patients in whom one of these conditions develops (2,17,18). Side effects of dopamine agonists include nausea, light-headedness, drowsiness, and postural hypotension.
Pergolide mesylate (Permax) is a potent, long-acting dopamine D1 and D2 receptor agonist that has been shown to be effective in restless legs syndrome (1-3,16), even in patients who are unresponsive to levodopa (18). The dose is 0.05 mg before bedtime initially, and it can be increased by 0.05 mg every 3 to 5 days until relief is obtained or side effects develop. The usual effective daily total is 0.1 to 0.75 mg, given in divided doses; some patients may need up to 1.5 mg.
Bromocriptine mesylate (Parlodel), a dopamine D2 receptor agonist, also has been found to be effective in restless legs syndrome (1-3,18). Bromocriptine can be started at a dose of 1.25 mg at bedtime and increased by 1.25 mg every few days until benefits or side effects are noted. The effective daily dose ranges from 5 to 15 mg.
Pramipexole (Mirapex), a dopamine D2 and D3 receptor agonist, and ropinirole hydrochloride (Requip), a dopamine D2 receptor agonist, were recently approved by the Food and Drug Administration for treating Parkinson's disease. Pramipexole is started at 0.125 mg at bedtime and gradually increased to a maximum of 1.5 mg three times daily. Ropinirole is started at 0.25 mg and increased to 3 to 8 mg three times daily (19,20).
Benzodiazepines Benzodiazepines may be used as monotherapy in patients with mild or intermittent symptoms or as add-on therapy in severe cases. Clonazepam (Klonopin) has been shown to ease the sensory symptoms and periodic limb movements of sleep in restless legs syndrome (1-3,16). The agent can be started at 0.25 mg at bedtime and increased by 0.25 mg every week to a maximum of 3 to 4 mg daily in divided doses. Anecdotal reports indicate that other benzodiazepines, such as temazepam (Restoril) and alprazolam (Xanax), are also effective. The major side effects of benzodiazepines include daytime drowsiness and confusion, unsteadiness and falls, and aggravation of sleep apnea.
Opioids Low-potency opioids, such as codeine and propoxyphene (Darvon, Dolene), can benefit patients with mild and intermittent symptoms, and higher-potency agents, such as oxycodone hydrochloride (Roxicodone), methadone (Dolophine) hydrochloride, and levorphanol tartrate (Levo-Dromoran), may have a role in refractory cases (1-3,16). In a double-blind, placebo-controlled study, oxycodone (mean daily dose, 15.9 mg) was found to be more effective than placebo (21). However, most physicians are hesitant to use opioids in restless legs syndrome because of the perceived risk of addiction and do so only in refractory cases.
Anticonvulsants Double-blind studies have shown that carbamazepine (Tegretol), at a dose of 200 to 400 mg daily, is effective in reducing sensory manifestations of restless legs syndrome (1-3,16), especially among young patients with recent onset of disease and severe symptoms. Unfortunately, subsequent clinical experience has not shown convincing efficacy of carbamazepine.
Open-label studies have found gabapentin (Neurontin) to be effective in relieving sensory symptoms (22) and periodic limb movements of sleep, even in refractory cases. The drug can be initiated at a dose of 100 to 300 mg at bedtime and increased by 100 to 300 mg every 3 days to a maximum of 2,400 mg daily in divided doses. Gabapentin is usually well tolerated but may cause transient or mild side effects, such as somnolence, dizziness, ataxia, and fatigue.
Presynaptic alpha2-adrenergic agonist Clonidine hydrochloride (Catapres) may be effective in primary restless legs syndrome and that associated with uremia (1-3,16). The drug should be started at 0.1 mg at bedtime and can be increased every week by 0.1 mg to a maximum of 1 mg daily (average effective daily dose, 0.5 mg). Among the common side effects are dry mouth, decreased cognition, light-headedness, sleepiness, and constipation.
Summary
Restless legs syndrome is a common, potentially disabling condition that affects about 10% to 15% of the general population and yet is often unrecognized and misdiagnosed. It is mainly diagnosed clinically and only rarely requires polysomnography. The condition is usually primary and treatable. First, however, secondary causes should be sought, especially iron deficiency and peripheral neuropathy, because when the source is an accompanying factor or condition, the syndrome may be curable. The most effective drugs are dopaminergic agents, clonazepam, opioids, gabapentin, and clonidine. Additional agents are available that may be beneficial as add-on or alternative therapy.
References
Trenkwalder C, Walters AS, Hening W. Periodic limb movements and restless legs syndrome. Neurol Clin 1996;14(3):629-50
Silber MH. Restless legs syndrome. Mayo Clin Proc 1997;72(3):261-4
Walters AS, for the International Restless Legs Syndrome Study Group. Toward a better definition of the restless legs syndrome. Mov Disord 1995;10(5):634-42
Trenkwalder C, Seidel VC, Gasser T, et al. Clinical symptoms and possible anticipation in a large kindred of familial restless legs syndrome. Mov Disord 1996;11(4):389-94
Ondo W, Jankovic J. Restless legs syndrome: clinicoetiologic correlates. Neurology 1996;47(6):1435-41
O'Keeffe ST. Restless legs syndrome: a review. Arch Intern Med 1996;156(3):243-8
Popoviciu L, Asgian B, Delast-Popoviciu D, et al. Clinical, EEG, electromyographic and polysomnographic studies in restless legs syndrome caused by magnesium deficiency. Rom J Neurol Psychiatry 1993;31(1):55-61
Rutkove SB, Matheson JK, Logigian EL. Restless legs syndrome in patients with polyneuropathy. Muscle Nerve 1996;19(5):670-2
Kanter AH. The effect of sclerotherapy on restless legs syndrome. Dermatol Surg 1995;21(4):328-32
Sanz-Fuentenebro FJ, Huidobro A, Tejadas-Rivas A, et al. Restless legs syndrome and paroxetine. Acta Psychiatr Scand 1996;94(6):482-4
Drake ME. Restless legs with anti-epileptic drug therapy. Clin Neurol Neurosurg 1988;90(2):151-4
Metcalfe RA, MacDermott N, Chalmers RJ. Restless red legs: an association of the restless legs syndrome with arborizing telangiectasia of the lower limbs. J Neurol Neurosurg Psychiatry 1986;49(7):820-3
Iannaccone S, Zucconi M, Marchettini P, et al. Evidence of peripheral axonal neuropathy in primary restless legs syndrome. Mov Disord 1995;10(1):2-9
O'Keeffe ST, Gavin K, Lavan JN. Iron status and restless legs syndrome in the elderly. Age Ageing 1994;23(3):200-3
Botez MI, Lambert B. Folate deficiency and restless-legs syndrome in pregnancy. N Engl J Med 1977;297(12):670
Krueger BR. Restless legs syndrome and periodic movements of sleep. Mayo Clin Proc 1990;65(7):999-1006
Allen RP, Earley CJ. Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep 1996;19(3):205-13
Earley CJ, Allen RP. Pergolide and carbidopa/levodopa treatment of the restless legs syndrome and periodic leg movements in sleep in a consecutive series of patients. Sleep 1996;19(10):801-10
Ondo W. Ropinirole for restless legs syndrome. Mov Disord 1999;14(1):138-40
Lin SC, Kaplan J, Burger CD, et al. Effect of pramipexole in treatment of resistant restless legs syndrome. Mayo Clin Proc 1998;73(6):497-500
Walters AS, Wagner ML, Hening WA, et al. Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo. Sleep 1993;16(4):327-32
Adler CH. Treatment of restless legs syndrome with gabapentin. Clin Neuropharmacol 1997;20(2):148-51
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What are the mechanisms that cause restless legs syndrome?
Pathogenesis of the syndrome is unclear. Karl A. Ekbom originally proposed that it was mainly the result of accumulation of metabolites in the legs from venous congestion (1-3). Peripheral nerve abnormalities have also been proposed, but no structural changes in nerve endings have been seen (4). Many experts believe that the syndrome is generated centrally (1,3,5). Periodic limb movements of sleep, in particular, are thought to be caused by sleep-related disruption of descending inhibitory reticulospinal pathways that are normally active at the brain stem or spinal cord level.
On the basis of treatment response, restless legs syndrome has been linked to dopaminergic or opiate abnormalities (3). Dopamine blockers and opiate blockers reactivate symptoms when given to patients with the syndrome. Results of single-photon emission computed tomography have suggested deficiency of dopamine D2 receptors (6). Sympathetic hyperactivity has also been implicated (5) on the basis of observations that sympathetic nerve blockade relieves periodic limb movements of sleep and that alpha-adrenergic blockers improve symptoms of restless legs syndrome. Studies also have suggested possible underactivity of the serotonin and gamma-aminobutyric acid neurotransmitter systems.
References
Trenkwalder C, Walters AS, Hening W. Periodic limb movements and restless legs syndrome. Neurol Clin 1996;14(3):629-50
Silber MH. Restless legs syndrome. Mayo Clin Proc 1997;72(3):261-4
Walters AS, for the International Restless Legs Syndrome Study Group. Toward a better definition of the restless legs syndrome. Mov Disord 1995;10(5):634-42
Rutkove SB, Matheson JK, Logigian EL. Restless legs syndrome in patients with polyneuropathy. Muscle Nerve 1996;19(5):670-2
O'Keeffe ST. Restless legs syndrome: a review. Arch Intern Med 1996;156(3):243-8
Staedt J, Stoppe G, Kogler A, et al. Dopamine D2 receptor alteration in patients with periodic movements in sleep (nocturnal myoclonus). J Neural Transm Gen Sect 1993;93(1):71-4
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Dr Evidente was a fellow in movement disorders and Dr Adler is associate professor of neurology, Parkinson's Disease and Movement Disorders Center, Mayo Clinic Scottsdale, Scottsdale, Arizona. Dr Evidente is now at St Lukes Medical Center, Quezon City, Philippines. Correspondence: Charles H. Adler, MD, PhD, Parkinson's Disease and Movement Disorders Center, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259.
Discerning the indescribable and relaxing the restless
Virgilio Gerald H. Evidente, MD Charles H. Adler, MD, PhD
VOL 105 / NO 3 / MARCH 1999 / POSTGRADUATE MEDICINE
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CME learning objectives
To familiarize primary care physicians with diagnostic criteria for restless legs syndrome
To elucidate secondary, and often curable, causes of restless legs syndrome
To describe current treatment options for restless legs syndrome
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Preview: Few conditions are characterized by the difficulty encountered in trying to depict their symptoms, but such is the case in restless legs syndrome. Patients report sensations that are not painful yet are distinctly bothersome and can lead to significant physical and emotional disability. Once correctly diagnosed, restless legs syndrome can usually be effectively treated symptomatically, and in some secondary cases, it can even be cured. In this article, the authors focus on clinical features that enable timely identification of the condition and on current management strategies.
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In the mid-1940s, Swedish neurologist Karl A. Ekbom described a disorder characterized by sensory symptoms and motor disturbance of the limbs, mainly during rest. He named the condition restless legs syndrome (1). Although the syndrome affects about 10% to 15% of the US population (2), it is often unrecognized and misdiagnosed. It may begin at any age (1-3), even as early as infancy, but most patients who are severely affected are middle-aged or older. Symptoms progress over time in about two thirds of patients and may be severe enough to be disabling.
Diagnostic criteria and common features
In 1995, the newly formed International Restless Legs Syndrome Study Group developed criteria for diagnosing restless legs syndrome (3). Four basic elements must be present to make the diagnosis: (1) a desire to move the limbs, often associated with paresthesia or dysesthesia, (2) symptoms exacerbated by rest and relieved by activity, (3) motor restlessness, and (4) nocturnal worsening of symptoms. These and several additional features commonly seen in restless legs syndrome are discussed in the following paragraphs.
Desire to move the limbs, paresthesia, dysesthesia. Patients often describe an unpleasant sensation in the calves and occasionally in the thighs, feet, or upper limbs. Although the study group refers to dysesthesia or paresthesia (which implies abnormal sensations) (3), most patients simply relate vague, nonpainful, indescribable, bilateral (rarely unilateral) discomfort in the limbs, using such terms as crawling, creeping, tingling, burning, itching, and aching.
Symptoms are similar to those described by patients with akathisia (which is usually caused by use of neuroleptic drugs). However, in contrast to patients with restless legs syndrome, those with akathisia have an inner feeling of restlessness, gain the most relief by resting in a recumbent position, and do not experience paresthesia or nocturnal worsening of symptoms.
Symptoms exacerbated by rest, relieved by activity. The unpleasant limb sensations of restless legs syndrome are precipitated by rest or inactivity (eg, lying in bed at night, riding in a car or airplane, sitting in a theater). The discomfort is usually relieved by motor activity (eg, moving the legs, walking).
Motor restlessness. Patients describe a buildup of discomfort and involuntary limb jerking if they remain still. There is an urge to move the legs and relief after moving (much like the sensation of tics). Compelling motor restlessness can manifest as tossing and turning in bed, needing to pace the floor, stretching or shaking the legs, or needing to exercise (3). Limb movements in restless legs syndrome are partly voluntary, in that patients choose to move to relieve the discomfort, and partly involuntary, since patients are compelled to move. Such partly voluntary, partly involuntary movements are sometimes referred to as "unvoluntary" or "semivoluntary."
Nocturnal worsening of symptoms. All patients notice worsening of symptoms at night (usually as they lie in bed before sleep or when they are awakened in the middle of the night) and improve-ment early in the morning. Nocturnal worsening is caused by lack of motor activity at night and is also thought to be due to an independent circadian rhythm (3). In severe cases, patients experience symptoms both day and night.
Periodic limb movements of sleep. About 80% of patients with restless legs syndrome have unilateral or bilateral periodic limb movements of sleep, also called nocturnal myoclonus (1,3). These movements are stereotyped, repetitive, slow flexion of the limbs (legs alone or legs more than arms) during stage 1 or 2 sleep. They occur semirhythmically at intervals of 5 to 60 seconds and last about 1.5 to 2.5 seconds. In the lower limbs, repetitive dorsiflexion of the big toe with fanning of the small toes is seen, along with flexion of the ankles, knees, and thighs.
Dyskinesias while awake. These motions, also called periodic limb movements while awake, are seen in 30% to 50% of patients with restless legs syndrome (3). They are similar to periodic limb movements of sleep but occur only during wakefulness. They can be fast or slow and periodic or nonperiodic.
Sleep disturbance. Because of limb discomfort and jerking, most patients with restless legs syndrome have disturbances of sleep onset or maintenance (1,3). The result is excessive daytime sleepiness and fatigability, although not to the same degree as that caused by narcolepsy.
Primary disease
In most cases, restless legs syndrome is idiopathic. Such idiopathic disease can be familial (in 25% to 75% of cases) and, if so, is transmitted in an autosomal-dominant fashion (1,3,4). Progressive decrease in age at onset with subsequent generations (ie, genetic anticipation) has been described in some families. Patients with familial restless legs syndrome tend to have an earlier age at onset and slower progression (5).
Secondary disease
Restless legs syndrome can develop as a result of certain conditions or factors (table 1), particularly iron deficiency and peripheral neuropathy (6-12). These two conditions should be ruled out on clinical grounds before restless legs syndrome is labeled primary (13). Because of the prevalence of these conditions in the general population, their association with restless legs syndrome needs to be interpreted with considerable caution.
Table 1. Factors and conditions that may contribute to secondary restless legs syndrome (in order of frequency)
Deficiency of iron, folate, or magnesium
Polyneuropathy caused by alcohol abuse, amyloidosis, diabetes mellitus, idiopathic polyneuropathy, lumbosacral radiculopathy, Lyme disease, monoclonal gammopathy of undetermined significance, rheumatoid arthritis, Sjögren's syndrome, uremia, or vitamin B12 deficiency
Pregnancy
Anemia
Parkinson's disease
Gastric surgery
Chronic obstructive pulmonary disease
Carcinoma
Chronic venous insufficiency or varicose veins
Intake of certain substances or drugs: alcohol, caffeine, anticonvulsants (eg, methsuximide [Celontin Kapseals], phenytoin [Dilantin]), antidepressants (eg, amitriptyline HCl [Elavil], paroxetine HCl [Paxil]), beta blockers, histamine2 antagonists, lithium, neuroleptics
Withdrawal from vasodilators, sedatives, or imipramine HCl (Tofranil)
Cigarette smoking
Myelopathy or myelitis
Hypothyroidism or hyperthyroidism
Acute intermittent porphyria
Fibromyalgia syndrome
Arborizing telangiectasia of the lower limbs
Peripheral microemboli made of cholesterol
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Restless legs syndrome can be the initial manifestation of iron deficiency (1,14). A low serum ferritin level may precede a drop in serum iron level. Depletion of iron stores, in the absence of overt iron deficiency, can lead to restless legs syndrome. How this occurs in unknown. Treatment with ferrous sulfate may bring improvement.
About 5% of patients with sensory neuropathy (especially caused by uremia, rheumatoid arthritis, and diabetes) have restless legs syndrome (8). Treatment of the polyneuropathy may improve symptoms.
Diagnosis
Diagnosis of restless legs syndrome is founded mainly on clinical history. If a secondary cause is suspected on the basis of history, abnormal findings on neurologic examination, or poor response to treatment, a laboratory workup should be done. Testing should measure levels of blood urea nitrogen, creatinine, fasting blood glucose, ferritin, magnesium, thyrotropin, and folate and should include a glucose tolerance test and a complete blood cell count.
Needle electromyography and nerve-conduction studies should be considered if polyneuropathy is suspected on clinical grounds, even if results of neurologic examination are apparently normal (13). Polysomnography is rarely necessary but may be used to quantify periodic limb movements of sleep or to characterize sleep architecture, especially in patients who continue to have significant sleep disturbance despite relief of sensory symptoms with treatment.
Nonpharmacologic management
Patients with suspected restless legs syndrome who are sensitive to caffeine, alcohol, or nicotine should avoid these substances (1,6). Offending medications (table 1) also should be discontinued. In general, physical measures are only partially or temporarily helpful. Some patients benefit from hot or cold baths, whirlpool baths, rubbing of the limbs, or vibratory or electrical stimulation of the feet and toes before bedtime.
Supplementation to correct deficiencies in vitamins (eg, folate) (15), electrolytes (eg, magnesium) (7), or iron may improve symptoms. Patients with prominent varicose veins in the legs may benefit from use of sclerosing agents (9). Those with uremia may have relief after kidney transplantation or correction of anemia with erythropoietin (Epogen, Procrit) (6).
Pharmacologic management
Drug therapy for primary restless legs syndrome is largely symptomatic, since cure is only possible in secondary disease. Medications should be initiated at a low dose and be taken an hour or two before bedtime to allow sufficient absorption and onset of action. Additional doses can be taken if symptoms cause awakening in the middle of the night. If tolerance to one drug develops, another class of drugs may be substituted. Monthly rotation of two or three agents found to be effective may help prevent tolerance. A combination of drugs may be beneficial in severe cases.
Levodopa with carbidopa Levodopa with carbidopa (Sinemet) can improve sensory symptoms and periodic limb movements of sleep in primary restless legs syndrome and that associated with uremia (1-3,16). For symptoms that start before sleep, one 25/100-mg carbidopa/levodopa tablet can be taken 1 to 2 hours before bedtime. If symptoms occur during the night, one 25/100-mg controlled-release carbidopa/levodopa (Sinemet CR) tablet can be used. In patients who have symptoms both before sleep and during the night, a combination of short-acting and controlled-release tablets can be given. Most patients experience benefits when the levodopa portion of carbidopa/levodopa totals 100 to 500 mg daily, although some may need 1,000 to 1,500 mg. Nausea and constipation are the most common side effects of levodopa.
The major drawback in prescribing levodopa for restless legs syndrome is that in about 80% of patients, augmentation of symptoms occurs as early as a few months after initiation of therapy (17). It can manifest as earlier onset during the evening or after assuming a restful position, as increased intensity in the morning (ie, rebound), or as extension of symptoms to the upper body. Augmentation is more likely in patients with severe pretreatment symptoms and in those taking 200 mg or more of levodopa daily. If augmentation or rebound develops, adjunctive therapy with reduction of the levodopa dose or discontinuation of levodopa and substitution of another drug may help.
Dopamine agonists Dopamine agonists are less likely to produce augmentation or rebound and can be useful alone or along with levodopa in patients in whom one of these conditions develops (2,17,18). Side effects of dopamine agonists include nausea, light-headedness, drowsiness, and postural hypotension.
Pergolide mesylate (Permax) is a potent, long-acting dopamine D1 and D2 receptor agonist that has been shown to be effective in restless legs syndrome (1-3,16), even in patients who are unresponsive to levodopa (18). The dose is 0.05 mg before bedtime initially, and it can be increased by 0.05 mg every 3 to 5 days until relief is obtained or side effects develop. The usual effective daily total is 0.1 to 0.75 mg, given in divided doses; some patients may need up to 1.5 mg.
Bromocriptine mesylate (Parlodel), a dopamine D2 receptor agonist, also has been found to be effective in restless legs syndrome (1-3,18). Bromocriptine can be started at a dose of 1.25 mg at bedtime and increased by 1.25 mg every few days until benefits or side effects are noted. The effective daily dose ranges from 5 to 15 mg.
Pramipexole (Mirapex), a dopamine D2 and D3 receptor agonist, and ropinirole hydrochloride (Requip), a dopamine D2 receptor agonist, were recently approved by the Food and Drug Administration for treating Parkinson's disease. Pramipexole is started at 0.125 mg at bedtime and gradually increased to a maximum of 1.5 mg three times daily. Ropinirole is started at 0.25 mg and increased to 3 to 8 mg three times daily (19,20).
Benzodiazepines Benzodiazepines may be used as monotherapy in patients with mild or intermittent symptoms or as add-on therapy in severe cases. Clonazepam (Klonopin) has been shown to ease the sensory symptoms and periodic limb movements of sleep in restless legs syndrome (1-3,16). The agent can be started at 0.25 mg at bedtime and increased by 0.25 mg every week to a maximum of 3 to 4 mg daily in divided doses. Anecdotal reports indicate that other benzodiazepines, such as temazepam (Restoril) and alprazolam (Xanax), are also effective. The major side effects of benzodiazepines include daytime drowsiness and confusion, unsteadiness and falls, and aggravation of sleep apnea.
Opioids Low-potency opioids, such as codeine and propoxyphene (Darvon, Dolene), can benefit patients with mild and intermittent symptoms, and higher-potency agents, such as oxycodone hydrochloride (Roxicodone), methadone (Dolophine) hydrochloride, and levorphanol tartrate (Levo-Dromoran), may have a role in refractory cases (1-3,16). In a double-blind, placebo-controlled study, oxycodone (mean daily dose, 15.9 mg) was found to be more effective than placebo (21). However, most physicians are hesitant to use opioids in restless legs syndrome because of the perceived risk of addiction and do so only in refractory cases.
Anticonvulsants Double-blind studies have shown that carbamazepine (Tegretol), at a dose of 200 to 400 mg daily, is effective in reducing sensory manifestations of restless legs syndrome (1-3,16), especially among young patients with recent onset of disease and severe symptoms. Unfortunately, subsequent clinical experience has not shown convincing efficacy of carbamazepine.
Open-label studies have found gabapentin (Neurontin) to be effective in relieving sensory symptoms (22) and periodic limb movements of sleep, even in refractory cases. The drug can be initiated at a dose of 100 to 300 mg at bedtime and increased by 100 to 300 mg every 3 days to a maximum of 2,400 mg daily in divided doses. Gabapentin is usually well tolerated but may cause transient or mild side effects, such as somnolence, dizziness, ataxia, and fatigue.
Presynaptic alpha2-adrenergic agonist Clonidine hydrochloride (Catapres) may be effective in primary restless legs syndrome and that associated with uremia (1-3,16). The drug should be started at 0.1 mg at bedtime and can be increased every week by 0.1 mg to a maximum of 1 mg daily (average effective daily dose, 0.5 mg). Among the common side effects are dry mouth, decreased cognition, light-headedness, sleepiness, and constipation.
Summary
Restless legs syndrome is a common, potentially disabling condition that affects about 10% to 15% of the general population and yet is often unrecognized and misdiagnosed. It is mainly diagnosed clinically and only rarely requires polysomnography. The condition is usually primary and treatable. First, however, secondary causes should be sought, especially iron deficiency and peripheral neuropathy, because when the source is an accompanying factor or condition, the syndrome may be curable. The most effective drugs are dopaminergic agents, clonazepam, opioids, gabapentin, and clonidine. Additional agents are available that may be beneficial as add-on or alternative therapy.
References
Trenkwalder C, Walters AS, Hening W. Periodic limb movements and restless legs syndrome. Neurol Clin 1996;14(3):629-50
Silber MH. Restless legs syndrome. Mayo Clin Proc 1997;72(3):261-4
Walters AS, for the International Restless Legs Syndrome Study Group. Toward a better definition of the restless legs syndrome. Mov Disord 1995;10(5):634-42
Trenkwalder C, Seidel VC, Gasser T, et al. Clinical symptoms and possible anticipation in a large kindred of familial restless legs syndrome. Mov Disord 1996;11(4):389-94
Ondo W, Jankovic J. Restless legs syndrome: clinicoetiologic correlates. Neurology 1996;47(6):1435-41
O'Keeffe ST. Restless legs syndrome: a review. Arch Intern Med 1996;156(3):243-8
Popoviciu L, Asgian B, Delast-Popoviciu D, et al. Clinical, EEG, electromyographic and polysomnographic studies in restless legs syndrome caused by magnesium deficiency. Rom J Neurol Psychiatry 1993;31(1):55-61
Rutkove SB, Matheson JK, Logigian EL. Restless legs syndrome in patients with polyneuropathy. Muscle Nerve 1996;19(5):670-2
Kanter AH. The effect of sclerotherapy on restless legs syndrome. Dermatol Surg 1995;21(4):328-32
Sanz-Fuentenebro FJ, Huidobro A, Tejadas-Rivas A, et al. Restless legs syndrome and paroxetine. Acta Psychiatr Scand 1996;94(6):482-4
Drake ME. Restless legs with anti-epileptic drug therapy. Clin Neurol Neurosurg 1988;90(2):151-4
Metcalfe RA, MacDermott N, Chalmers RJ. Restless red legs: an association of the restless legs syndrome with arborizing telangiectasia of the lower limbs. J Neurol Neurosurg Psychiatry 1986;49(7):820-3
Iannaccone S, Zucconi M, Marchettini P, et al. Evidence of peripheral axonal neuropathy in primary restless legs syndrome. Mov Disord 1995;10(1):2-9
O'Keeffe ST, Gavin K, Lavan JN. Iron status and restless legs syndrome in the elderly. Age Ageing 1994;23(3):200-3
Botez MI, Lambert B. Folate deficiency and restless-legs syndrome in pregnancy. N Engl J Med 1977;297(12):670
Krueger BR. Restless legs syndrome and periodic movements of sleep. Mayo Clin Proc 1990;65(7):999-1006
Allen RP, Earley CJ. Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep 1996;19(3):205-13
Earley CJ, Allen RP. Pergolide and carbidopa/levodopa treatment of the restless legs syndrome and periodic leg movements in sleep in a consecutive series of patients. Sleep 1996;19(10):801-10
Ondo W. Ropinirole for restless legs syndrome. Mov Disord 1999;14(1):138-40
Lin SC, Kaplan J, Burger CD, et al. Effect of pramipexole in treatment of resistant restless legs syndrome. Mayo Clin Proc 1998;73(6):497-500
Walters AS, Wagner ML, Hening WA, et al. Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo. Sleep 1993;16(4):327-32
Adler CH. Treatment of restless legs syndrome with gabapentin. Clin Neuropharmacol 1997;20(2):148-51
--------------------------------------------------------------------------------
What are the mechanisms that cause restless legs syndrome?
Pathogenesis of the syndrome is unclear. Karl A. Ekbom originally proposed that it was mainly the result of accumulation of metabolites in the legs from venous congestion (1-3). Peripheral nerve abnormalities have also been proposed, but no structural changes in nerve endings have been seen (4). Many experts believe that the syndrome is generated centrally (1,3,5). Periodic limb movements of sleep, in particular, are thought to be caused by sleep-related disruption of descending inhibitory reticulospinal pathways that are normally active at the brain stem or spinal cord level.
On the basis of treatment response, restless legs syndrome has been linked to dopaminergic or opiate abnormalities (3). Dopamine blockers and opiate blockers reactivate symptoms when given to patients with the syndrome. Results of single-photon emission computed tomography have suggested deficiency of dopamine D2 receptors (6). Sympathetic hyperactivity has also been implicated (5) on the basis of observations that sympathetic nerve blockade relieves periodic limb movements of sleep and that alpha-adrenergic blockers improve symptoms of restless legs syndrome. Studies also have suggested possible underactivity of the serotonin and gamma-aminobutyric acid neurotransmitter systems.
References
Trenkwalder C, Walters AS, Hening W. Periodic limb movements and restless legs syndrome. Neurol Clin 1996;14(3):629-50
Silber MH. Restless legs syndrome. Mayo Clin Proc 1997;72(3):261-4
Walters AS, for the International Restless Legs Syndrome Study Group. Toward a better definition of the restless legs syndrome. Mov Disord 1995;10(5):634-42
Rutkove SB, Matheson JK, Logigian EL. Restless legs syndrome in patients with polyneuropathy. Muscle Nerve 1996;19(5):670-2
O'Keeffe ST. Restless legs syndrome: a review. Arch Intern Med 1996;156(3):243-8
Staedt J, Stoppe G, Kogler A, et al. Dopamine D2 receptor alteration in patients with periodic movements in sleep (nocturnal myoclonus). J Neural Transm Gen Sect 1993;93(1):71-4
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Dr Evidente was a fellow in movement disorders and Dr Adler is associate professor of neurology, Parkinson's Disease and Movement Disorders Center, Mayo Clinic Scottsdale, Scottsdale, Arizona. Dr Evidente is now at St Lukes Medical Center, Quezon City, Philippines. Correspondence: Charles H. Adler, MD, PhD, Parkinson's Disease and Movement Disorders Center, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259.
posted by bakerchiropractic at 8:42 PM
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RESTLESS LEG SYNDROME - PART 2
TREATMENT
Treatment
The goal of treatment for RLS is to eliminate or minimize associated symptoms and increase normal functioning, thereby improving overall quality of life. Treatment is directed toward eliminating troublesome symptoms during rest, sleep, or sedentary activities, with the goal of reducing sleep disturbances, preventing daytime fatigue or somnolence, and improving the patient's ability to participate in work and leisure activities.
The clearly established therapies for RLS and PLMD are all pharmacologic, with only one drug, ropinirole (Requip®), currently approved by the U.S. Food and Drug Administration with labeling for RLS. Therefore the use of any drugs, other than ropinirole, in the treatment of RLS is considered to be off label in the United States. In Germany and Switzerland, Restex® (carbidopa-benserazide) and, in Australia, Repreve® (ropinirole) have appropriate regulatory approval for the treatment of RLS.
Before embarking on pharmacotherapy, the treating physician typically explores the possibility that lifestyle changes may alleviate or lessen the symptoms of RLS. In addition, treating any associated conditions that exacerbate the symptoms of RLS may lessen the need for pharmacologic intervention for the RLS.
Two publications provide guidance for the treatment of RLS. The Standards of Practice Committee of the American Academy of Sleep Medicine published practice parameters for the treatment of RLS and PLMD in 1999; in 2004, the Committee updated these guidelines regarding dopaminergic treatment, with recommendations centered upon evidence classified according to study design. Based on a review of the medical literature and expert opinion, the Medical Advisory Board of the Restless Legs Syndrome Foundation developed "An algorithm for the management of restless legs syndrome."277 This algorithm, published in July 2004 in The Mayo Clinic Proceedings, is available in PDF format from the web site of the Proceedings (http://www.mayoclinicproceedings.com/pdf/7907/7907Crc.pdf).
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Nonpharmacologic Treatment
The first step in the treatment of RLS is to assess the patient's lifestyle for factors that may exacerbate the condition. As mentioned in previous sections, a variety of factors, including medications and substances such as caffeine and alcohol (Table 6) and iron deficiency (with or without anemia) may worsen the symptoms of RLS. Having the patient thoroughly review his or her eating and drinking habits and ingestion of over-the-counter medications or illicit substances, with use of a diary, may help to identify these factors.
Causes of decreased iron stores should be elicited during the clinical interview and treated appropriately. Serum ferritin levels have been shown to be inversely correlated with RLS symptoms; however, even patients with hemochromatosis have also been shown to have symptoms of RLS.278 Therefore serum ferritin levels should be obtained in all patients with a new onset of RLS symptoms or who have not previously had levels checked before commencing with iron supplementation. The symptoms of RLS in patients with low-normal levels (i.e., less than 40-50 ng/dL) may respond to treatment with iron supplementation. Typical oral supplementation includes 325 mg of ferrous sulfate three times daily, given with 100 to 200 mg of vitamin C to enhance absorption. Serum ferritin levels should be followed at three- to six-month intervals until iron therapy is discontinued, typically when serum ferritin levels reach 50 ng/dL or greater. Periodic rechecks may be necessary to determine the need for further iron treatment or when symptoms escalate. Recently published studies have shown the effectiveness of the intravenous administration of iron dextran in patients with primary and ESRD-related RLS45,207; however, this treatment remains experimental at this time. Often overlooked in the list of factors that may exacerbate symptoms of RLS is a history of frequent blood donation.49,51,248,279 Patients with RLS should be encouraged to have their serum ferritin levels checked before donating blood.
Remaining physically active in the evening hours, although not strenuous exercise, may delay the need for pharmacologic intervention into a time later in the evening. During times of forced immobilization, such as airplane flights, patients may find that mentally alerting activities such as playing computer games, performing intricate needlework, or reading an engaging novel may lessen their symptoms of RLS.
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Pharmacologic Treatment
With optimization of lifestyle and treatment for comorbid conditions, in combination with removal of exacerbating substances and medications, many patients with RLS avoid the need for pharmacologic intervention; however for those patients whose symptoms negatively impact their ability to actively engage in employment, leisure, and family pursuits and who desire treatment, pharmacologic intervention has been shown to significantly improve quality of life.22,24,30,116,127,163,165-167,169-171,280-282 No currently available drugs can cure RLS; they aim only at providing symptomatic relief. Because RLS is a chronic condition, therapy must usually be continued indefinitely.
Symptoms of RLS that occur only intermittently, i.e., not daily, can often be managed with medications administered on an as-needed basis. Any of the primary medications in the following sections, with the possible exception of gabapentin, may be used in this manner; however, the onset of action of each drug will determine the timing of the appropriate dose.
Key Points to Achieving Optimal Pharmacologic Treatment of RLS
Treatment of comorbid conditions may alter the pharmacologic treatment of RLS
Drugs should be initiated at the lowest possible dosage and gradually upwardly titrated
Onset of action and half-life of medications, in combination with the patient's personal schedule, determine the appropriate timing of treatment
Drugs are often given at lower doses in the treatment of RLS than in the treatment of the condition for which the drug is indicated
Intractable RLS may require the use of polytherapy
Effective long-term therapy may be difficult; when one drug loses its effectiveness, another drug in the same or a different class may prove to be effective
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Dopaminergic Agents
Dopaminergic drugs were developed and have been approved for the treatment of Parkinson's disease. Their safety and efficacy have been established in this population.
Dopaminergic agents are first-line therapy in the treatment of moderate to severe RLS and are also effective in the treatment of mild or intermittent RLS that is not responsive to nonpharmacologic intervention.
Table 8
Dopaminergic Agents
Drug Typical starting dose, mg Usual therapeutic range, mg Peak concentration, h Half-life, h Side effects
Nonergot dopamine receptor agonists Mild N/V; sedation; orthostatic hypotension;
Pramipexole 0.125 0.25-1.0 2 8-12
Ropinirole 0.25 0.5-8.0 1-2 6
Ergot-derived dopamine receptor agonists Severe N/V; sedation; orthostatic hypotension; cardiac valvulopathy; nasal congestion
Pergolide 0.025 0.5-1.0 1-3 12-27
Dopamine precursor Augmentation; N/V; headache
Carbidopa-levodopa 12.5/50 12.5/50-75/300 .5 1.5-2.0
Carbidopa-levodopa CR 25/100 25/100-100/400 2 3-8
N/V refers to nausea and vomiting; CR, continuous release
Augmentation is a phenomenon unique to the use of dopaminergic agents in the treatment of RLS.87,283,284 Augmentation occurs in temporal relationship to the ingestion of dopaminergic drugs; it is most commonly encountered with the use of levodopa-carbidopa284-286 but has also recently been shown with the use of dopamine receptor agonists.153,155,287,288 When augmentation develops, the symptoms of RLS occur at a time at least two hours before they occurred before the initiation of drug therapy. The symptoms frequently intensify and spread to previously noninvolved parts of the body (particularly the arms). In addition, the time from onset of quiescence to onset of symptoms is typically shortened. Because the rate of augmentation is highest with the use of levodopa, dopamine receptor agonists are the preferred drug for the treatment of RLS that occurs on a daily basis.277
Key Features of Augmentation
Temporal relationship exists between
↑ daily medication ↑ symptom intensity
↓ daily medication ↓ symptom intensity
Sensations spread to previously uninvolved parts of the body.
The duration of treatment effect is shorter than the duration with initial therapeutic response.
Periodic limb movements while awake either occur for the first time or are worse than with initial therapeutic response or before treatment was instituted.
Augmentation should be discussed with all patients treated with dopaminergic agents; patients should be cautioned that if augmentation occurs, they should not increase their dosage of medication but, instead, should return to the prescribing physician for consultation. The treatment of augmentation may involve adjusting the timing or the dose of the medication or switching to another agent.
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Dopamine Receptor Agonists
Dopaminergic receptor agonists are first-line therapy in the treatment of moderate to severe RLS; these drugs are also effective in the treatment of mild or intermittent RLS that is not responsive to nonpharmacologic intervention (Table 8). Dopamine receptor agonists bind to dopamine receptors, producing dopamine-like effects. The medications studied most thoroughly for use in RLS include the nonergot derivatives pramipexole dihydrochloride (Mirapex®) and ropinirole hydrochloride (Requip® or, in Australia, Repreve®) and the ergot derivative pergolide mesylate (Permax®); these drugs are included in both the algorithm published in the "Mayo Clinic Proceedings" and the American Academy of Sleep Medicine's practice parameters. Several other ergot derivatives have also been used in the treatment of RLS but have either only recently been studied (apomorphine289-291 [Apokyn®], rotigitine,115 and the partial agonist-antagonist terguride129 [Mysalfon]) or are no longer frequently used (bromocriptine [Parlodel®]) in the treatment of RLS. Cabergoline (Dostinex,® in the United States, or Cabaser, in Europe) has recently been studied for the treatment of RLS119,128,133,136,292,293; however, in the United States, it is packaged only for use in the treatment of hyperprolactinemia. Reports have indicated that long-term therapy with dopamine agonists remains effective for many RLS patients.
Recent reports have raised awareness about excessive daytime somnolence in patients taking dopamine agonists (particularly in those with Parkinson's disease and with higher doses).292,294-305 Patients should be cautioned to refrain from driving a motor vehicle or operating heavy machinery when therapy is instituted with these medications and until the patients can assess whether they will be adversely affected.
Nonergot Derivatives
Pramipexole
Pramipexole, which stimulates D2 and D3 receptors in the striatum and substantia nigra, has been shown to alleviate the sensory and motor symptoms in patients with primary and secondary RLS in a retrospective chart review,288 open-label trials,120,125,140,150,306-308 a double-blind placebo-controlled crossover trial,147 and a single-blind placebo-controlled crossover trials.309 These studies have found that the use of pramipexole greatly reduces periodic limb movements during sleep125,147,309 and wakefulness,125,310 in addition to alleviating the subjective symptoms of RLS. Identified rates of augmentation with the use of pramipexole vary from 0% to 33% over a mean of 7 to 30 months. A survey by Stiasny et al. of patients taking pramipexole at a mean dose of 0.37 mg found that none of the 24 patients had had an unexpected sleep attack; 11 patients did acknowledge that they experienced daytime sleepiness and usually napped during the day.
Ropinirole
Ropinirole stimulates D2 and D3 receptors, such as postsynaptic D2 receptors in the caudate and putamen. The effectiveness of this drug on the subjective symptoms of RLS has been shown in a case series,311 an open-label study,148 and two large116,127 and one small312 double-blind, randomized, placebo-controlled trials. Several additional studies that employed polysomnography—including open-label131,313 and double-blind, placebo-controlled trials114,314,315—have shown the efficacy of ropinirole in reducing the number of PLMS. In addition, Pellecchia et al.316 showed the efficacy of ropinirole over sustained-release levodopa in the treatment of RLS in a 14-week open-label, randomized, crossover trial in 10 patients who were on chronic hemodialysis for ESRD. Augmentation was not assessed in any of these studies, and no studies have evaluated the rate of sleep attacks in patients with RLS. Ropinirole was approved by the U. S. Food and Drug Administration for the treatment of moderate to severe RLS in May 2005.
Ergot Derivatives
Pergolide is the ergot-derived dopamine receptor agonist used most frequently in the United States for the treatment of RLS; in Europe, however, cabergoline is also frequently used. Pergolide, a semisynthetic ergot alkaloid derivative, is an agonist at D1, D2, and D3 receptors, stimulating postsynaptic dopamine receptors in the nigrostriatal system. With evidence from open-label trials151,152; long-term clinical case series139,153,317; and randomized double-blind, placebo-controlled crossover trials,154,318 including a multicenter trial with 100 patients,124 the practice parameters of the American Academy of Sleep Medicine designated pergolide as a standard in the treatment of RLS.121,122,143,319 However, recent reports of the development of cardiac valvulopathy in patients taking pergolide will likely limit the use of this drug.320-328 If ergot-derived dopamine receptor agonists are used, patients should be informed of the risks, and cardiac function should be monitored
Pergolide is best given in two equal divided doses, one taken with the evening meal and the other approximately one hour before bedtime. Temporarily discontinuing and then reinstating pergolide therapy may help to minimize associated side effects. A nasal decongestant may relieve the congestion that is often caused with the use of this drug. The few studies that have assessed augmentation with the use of pergolide have found the rate to vary from 15% to 27%.153,155 Bassetti et al.305 have reported the occurrence of a "sleep attack" in one patient with RLS who was treated with pergolide.
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Dopamine Precursor
Levodopa primarily acts by increasing dopamine concentrations in the brain. Carbidopa or benserazide, which are decarboxylase inhibitors that do not cross the blood-brain barrier, retard the peripheral breakdown of levodopa. The addition of decarboxylase inhibitors, therefore, increases the availability of levodopa for transport to the brain and the bioavailability of dopamine in the CNS. Concurrent administration of carbidopa allows a decrease in levodopa dosage, thus reducing potential side effects, such as nausea and vomiting.
Sinemet® is available in the United States in several strengths, with carbidopa and levodopa in varying ratios. In extended-release formulations, such as Sinemet CR, levodopa and carbidopa are contained in a polymeric-based delivery system that releases the drug over a four- to six-hour period in the gastrointestinal tract. Because amino acid transport mechanisms carry levodopa across gastrointestinal membranes, a high-protein diet may interfere with the absorption of levodopa formulations.
Levodopa medications are administered orally as needed or on a regular schedule. Such medications should be taken approximately 1 to 2 hours before bedtime on an empty stomach, if possible. Open-label trials155,329-331; longitudinal case series159,332; and randomized, double-blind, placebo-controlled trials156,157,333-338 provided the evidence for the Standards of Practice Committee of the American Academy of Sleep Medicine to make levodopa with a decarboxylase inhibitor a standard treatment. In selected patients, long-term therapy may remain effective for several years, with tolerable side effects. This is usually true of patients with mild RLS symptoms who require low doses or for those with isolated PLMD. However, because of its short half-life and the potential for augmentation to occur at higher doses,155,284 the use of levodopa preparation is typically reserved for those patients who have intermittent or rare symptoms of RLS that require treatment.277
Augmentation has been shown to occur in up to 80% of patients with RLS who are treated with levodopa. The occurrence of augmentation typically correlates with high daily dosages of levodopa equal to or more than 200 mg and administration of initial daily doses before 6 PM. Once daytime augmentation develops, levodopa therapy is usually discontinued and replaced with an appropriate agent, such as a dopamine receptor agonist. It is recommended that the total daily dose of carbidopa/levodopa not exceed 75/300 mg and should only be used in doses above 50/200 mg with considerable caution. In addition, patients with RLS may experience end-of-dose rebound during the middle of the night or early the next morning, particularly with short-acting formulations of levodopa preparations.339 Switching to a controlled-release formulation or adding a dose in the middle of the night may help to alleviate rebound; however, in such cases, problems of augmentation are also likely to occur.
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Benzodiazepines
Benzodiazepines act upon the hypothalamic, thalamic, and limbic regions, causing varying levels of depression in the CNS. This action is thought to be mediated through GABA receptors (i.e., increasing the affinity GABA for its receptors) or through serotonergic mechanisms (Table 9).
Table 9
Benzodiazepines
Drug Usual therapeutic range, mg/day Half-life, h
Clonazepam 0.5-2.0 18-40
Temazepam 7.5-30.0 1.5-5.5
Diazepam 5-15 30-60
Triazolam 0.125-0.5 8-15
Benzodiazepine therapy may improve sleep and reduce arousals due to PLMS, yet may be less effective in eliminating movement and sensory abnormalities associated with RLS. However, in some patients with severe RLS, benzodiazepine therapy significantly decreases the total number of abnormal leg movements during rest. Overall, long-term nightly benzodiazepine therapy has been shown to remain effective with a low risk of adverse effects, tolerance, or abuse. Patients with mild or intermittent symptoms of RLS, particularly young individuals, may receive the most benefit from such therapy. If combined with carbidopa/levodopa or dopamine receptor agonists, benzodiazepines may assist in the management of severe RLS symptoms and are usually administered orally shortly before or at bedtime.
Several clinical studies have documented the efficacy of clonazepam in alleviating RLS symptoms.340-348 Other benzodiazepines, such as temazepam, diazepam, and triazolam, may be effective alternatives but have not been formally studied in the treatment of RLS. Such benzodiazepine agents are Schedule C-IV controlled substances.
Potential adverse effects associated with benzodiazepine therapy for RLS include somnolence, especially with the use of long-acting medications (e.g., clonazepam); decreased libido; a risk of falls during the night, particularly in elderly patients; and exacerbation of comorbid obstructive sleep apnea. Depending upon dosage levels, therapy with such agents may result in tolerance and dependency; in addition, if therapy is discontinued abruptly rather than through gradually tapered dosages, there may be precipitation of withdrawal. However, in patients receiving long-term therapy for RLS, there is usually a low risk of such phenomena. Patients should be advised not to take benzodiazepines in combination with alcohol or other CNS depressants. In addition, physicians should carefully monitor benzodiazepine therapy in those patients who are currently receiving additional pharmacologic agents that may potentiate the effects of benzodiazepines and further depress CNS activities.
Other benzodiazepines may be considered as possible alternatives in the treatment of RLS. Such agents include alprazolam (Xanax®), lorazepam (Ativan®), chlordiazepoxide (Librium®), or flurazepam (Dalmane®), all of which are schedule C-IV controlled substances.
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Opioids
Though the specific physiologic action of opioids remains unclear, stimulation of opiate receptors serves to decrease the release of neurotransmitters, producing analgesic effects in the CNS. Opioid agents vary greatly in potency, ranging from mild (e.g., codeine), to moderate (e.g., oxycodone), to extremely strong (e.g., methadone) (Table 10).
Table 10
Opioids
Drug Typical starting dose, mg/day Usual therapeutic range, mg/day Potency Half-life, h Schedule class Receptor
Codeine 15-30 15-120 Low 3-4 C-II µ, Κ
Propoxyphene 65-130 130-520 Low 6-12 C-IV µ
Oxycodone 4.5-5.0 5-20 Moderate 3-6 C-II µ, Κ
Methadone 5-10 5-30 High 13-47 C-II µ, Κ
In clinical studies, with a relatively small number of patients,349,350 the use of opioids has been shown to alleviate paresthesias or dysesthesias, motor restlessness, and sleep disturbances associated with RLS. A recent review of long-term monotherapy for RLS with opioids in 20 patients found that one patient developed problems related to addiction or tolerance; two of the seven patients who were followed with polysomnography subsequently developed sleep apnea, and one had a worsening of apnea. Although opioid therapy produces minimal side effects and appears to carry little risk of tolerance or dependency, some patients with RLS have become addicted to opioids.
Opioids are administered orally and may be taken with food to help minimize gastrointestinal upset. Most physicians report that they prefer to prescribe a regimen consisting of one dose (e.g., codeine, propoxyphene, or oxycodone) shortly before or at bedtime. However, for some RLS patients who do not respond to a single-dose regimen or who require higher dosage levels, it may be necessary to administer one dose 2 hours before bedtime, one at bedtime, and another dose during the middle of the night (should patients awaken).
The major adverse effects of opioid therapy include nausea and constipation. In some patients, mental changes such as confusion may also occur. As with the benzodiazepines, patients should be cautioned not to take opioids in combination with alcohol or other CNS depressants. In addition, opioid therapy should be monitored in patients taking tricyclic antidepressants, sedatives, hypnotics, or other agents that may potentiate the effects of opioids, further depressing CNS activity. Opioids rarely cause daytime augmentation. However, RLS symptoms may reemerge after such therapy has been discontinued; in addition, there may be a temporary intensification of symptoms during withdrawal from opioid therapy.
The use of hydrocodone and the synthetic opioid, µ-receptor agonist, tramadol,351 may be considered as possible alternatives for the treatment of RLS.
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Anticonvulsants
Anticonvulsant medications inhibit neuronal activity and are primarily prescribed for the treatment of disease states that are characterized by abnormally increased CNS activity. The anticonvulsant agents carbamazepine352-356 and gabapentin (Neurontin®131,331,357-364 have been used most often in the treatment of RLS.
The exact mechanism of anticonvulsant action by carbamazepine is not completely understood. Carbamazepine is known to block use-dependent sodium channels, preventing repetitive firing, and to decrease posttetanic potentiation of synaptic transmission, limiting seizure dissemination. Carbamazepine has a slow variable rate of absorption from the gastrointestinal tract and a bioavailability of approximately 85%. The plasma half-life of carbamazepine is initially approximately 25 to 65 hours and 12 to 17 hours after ongoing therapy. Effective dosages have ranged from 100 to 600 mg per day, with increases up to 800 to 1,000 mg per day in individuals in whom the symptoms of RLS have not responded to lower doses.
The anticonvulsant gabapentin, a drug that is structurally related to the principal inhibitory CNS neurotransmitter GABA, has also shown promise as a treatment for RLS.131,331,357-364 The anticonvulsant mechanisms of gabapentin are unknown; however, they do not appear to be associated with its development as a structural analog of GABA. Gabapentin does not appear to bind with GABA receptors, act as a GABA precursor, or affect GABA reuptake. However, animal studies have demonstrated that the drug protects against GABA antagonist or GABA synthesis inhibitor-induced seizure or tonic extensions. Gabapentin is administered orally and is rapidly absorbed. The bioavailability of the drug ranges from 60% (for a 300-mg dose) to 35% (for a 1,600-mg dose). In patients with renal impairment who may or may not be receiving dialysis, dose levels and the frequency of gabapentin administration should be adjusted in response to the degree of impaired renal function. Gabapentin appears to be most effective in patients with mild or moderate RLS symptoms who experience actual pain. Average effective dosages may range from 300 to 2,700 mg per day, taken in divided doses.
The use of other anticonvulsant medications such as valproate (Depakene®) or lamotrigine (Lamictal®) may be considered as possible alternatives, although they have not been demonstrated to reduce RLS symptoms in clinical studies. Valproate, a carboxylic acid derivative, is thought to increase GABA concentrations in the brain. The medication is reported to have an elimination half-life of 5 to 20 hours. Drug clearance may be reduced in patients with renal impairment. Lamotrigine may serve to block voltage-sensitive sodium channels, inhibiting the presynaptic release of excitatory neurotransmitters (e.g., aspartate, glutamate). After oral administration, lamotrigine is rapidly absorbed and its bioavailability is approximately 98%. The plasma half-life ranges from approximately 14 to 59 hours. However, if no other medications are being administered, its half-life may decrease by approximately 25% and its plasma clearance may increase by 37%. Dosage adjustments may be required for patients with hepatic impairment.
Anticonvulsant medications should be taken with food to help minimize potential gastrotoxicity. Additional adverse effects include fatigue, drowsiness, or dizziness. Lamotrigine has rarely been associated with severe rashes and Stevens-Johnson syndrome. These have primarily occurred in patients receiving rapid dose escalation and with concomitant administration of other agents that block metabolism (such as valproate).
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Other Medications
Other pharmacologic agents may be effective in relieving symptoms associated with RLS. Clonidine hydrochloride (Catapres®), an imidazoline-derivative hypotensive agent, appears to stimulate postsynaptic α2-receptors in the CNS, primarily in the medulla, inhibiting sympathetic vasomotor centers. Clonidine is also a partial agonist at presynaptic α2-adrenergic receptors, although peripheral venous pressure typically remains unchanged. Large oral doses (or intravenous administration) of the drug may also stimulate α1-receptors in peripheral vascular smooth muscle, resulting in transient increases in blood pressure. Following oral administration, clonidine is rapidly absorbed; its bioavailability may be up to 100%. The elimination half-life of clonidine is approximately 6 to 24 hours. Because its half-life may be increased in patients with renal failure, a dose reduction may be required in such patients. Discontinuation of clonidine therapy requires gradual tapering of dosage levels over 2 to 4 days to prevent withdrawal effects.
Several studies have shown the efficacy of clonidine in the treatment of RLS.365-371 In two double-blind placebo-controlled studies, each with 10 patients, 9 uremic patients had complete or significant relief of symptoms, and 7 patients with primary RLS felt clonidine was more effective than placebo, although sleep parameters were unchanged. Relatively low dosages, such as 0.1 to 0.3 mg at bedtime, may be effective in some patients. In addition, RLS symptoms that have not responded to treatment with other medications have shown significant improvement with clonidine given in dosages up to 0.9 mg per day in divided doses. Common side effects include dry mouth, dizziness, lightheadedness, or decreased cognition.
The use of baclofen may also alleviate some symptoms associated with RLS. Baclofen, a skeletal muscle relaxant, is a GABA derivative. Although the exact mechanism of action is not fully understood, it appears to primarily inhibit spinal polysynaptic efferent pathways (as well as monosynaptic afferent pathways to a lesser extent) by functioning as an inhibitory neurotransmitter. The primary site of action is the spinal cord, where baclofen also reduces the release of excitatory neurotransmitters. When administered orally, baclofen is rapidly absorbed; however, bioavailability varies from case to case. Its serum half-life ranges from approximately 2.5 to 4.0 hours. Because clearance is primarily renal, a dose reduction may be required in patients with impaired renal function.
In some patients, other medications, such as sedative-hypnotics (e.g., zolpidem tartrate [Ambien®]), appear to have been efficacious in some patients with RLS. However, no controlled studies have been conducted to evaluate such medications in the treatment of RLS.
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Pharmacologic Therapy During Pregnancy
None of the drugs used to treat RLS are known to be safe in pregnancy; in many cases, no information at all is available. Nonpharmacologic measures, therefore, are the safest treatments for women who experience RLS during pregnancy. In addition, if such patients are experiencing symptomatic RLS associated with iron or folate deficiency, appropriate supplementation may be helpful. Obtaining serum ferritin levels in pregnant women with symptoms of RLS may assist in identifying iron deficiency and may guide therapy. Because RLS typically becomes more severe as the pregnancy progresses, drug therapy, if used at all, may often be withheld until the third trimester, at which time such medications have the least risk of causing teratogenic effects. Carbamazepine, especially, is contraindicated in the first semester. (Please refer to the package information for use of these drugs in pregnancy.) Educating the pregnant woman that RLS is temporary and that symptoms will typically resolve with delivery may allay her concerns.
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Pharmacologic Therapy for Children with RLS
The typical first course of action in children with RLS is nonpharmacologic. Many affected children have mild symptoms and eventually may experience remission during adolescence; however, in such cases, RLS symptoms may recur in adulthood. Appropriate lifestyle changes including regular exercise, strict sleep hygiene, appropriate sleep routines, and dietary adjustments, such as restrictions on all caffeinated food and drinks, are usually recommended. Assessing serum ferritin levels in children will assist in identifying iron deficiency, which may lead to or exacerbate symptoms of RLS.47,209 If lifestyle interventions and supplementation are not effective, the use of appropriately age- and weight-adjusted dosages of clonidine, carbidopa/levodopa, and dopamine receptor agonists might be cautiously considered. In some children with RLS and coexisting ADHD, such medications may effectively treat symptoms of both disorders.80
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Treatment
The goal of treatment for RLS is to eliminate or minimize associated symptoms and increase normal functioning, thereby improving overall quality of life. Treatment is directed toward eliminating troublesome symptoms during rest, sleep, or sedentary activities, with the goal of reducing sleep disturbances, preventing daytime fatigue or somnolence, and improving the patient's ability to participate in work and leisure activities.
The clearly established therapies for RLS and PLMD are all pharmacologic, with only one drug, ropinirole (Requip®), currently approved by the U.S. Food and Drug Administration with labeling for RLS. Therefore the use of any drugs, other than ropinirole, in the treatment of RLS is considered to be off label in the United States. In Germany and Switzerland, Restex® (carbidopa-benserazide) and, in Australia, Repreve® (ropinirole) have appropriate regulatory approval for the treatment of RLS.
Before embarking on pharmacotherapy, the treating physician typically explores the possibility that lifestyle changes may alleviate or lessen the symptoms of RLS. In addition, treating any associated conditions that exacerbate the symptoms of RLS may lessen the need for pharmacologic intervention for the RLS.
Two publications provide guidance for the treatment of RLS. The Standards of Practice Committee of the American Academy of Sleep Medicine published practice parameters for the treatment of RLS and PLMD in 1999; in 2004, the Committee updated these guidelines regarding dopaminergic treatment, with recommendations centered upon evidence classified according to study design. Based on a review of the medical literature and expert opinion, the Medical Advisory Board of the Restless Legs Syndrome Foundation developed "An algorithm for the management of restless legs syndrome."277 This algorithm, published in July 2004 in The Mayo Clinic Proceedings, is available in PDF format from the web site of the Proceedings (http://www.mayoclinicproceedings.com/pdf/7907/7907Crc.pdf).
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Nonpharmacologic Treatment
The first step in the treatment of RLS is to assess the patient's lifestyle for factors that may exacerbate the condition. As mentioned in previous sections, a variety of factors, including medications and substances such as caffeine and alcohol (Table 6) and iron deficiency (with or without anemia) may worsen the symptoms of RLS. Having the patient thoroughly review his or her eating and drinking habits and ingestion of over-the-counter medications or illicit substances, with use of a diary, may help to identify these factors.
Causes of decreased iron stores should be elicited during the clinical interview and treated appropriately. Serum ferritin levels have been shown to be inversely correlated with RLS symptoms; however, even patients with hemochromatosis have also been shown to have symptoms of RLS.278 Therefore serum ferritin levels should be obtained in all patients with a new onset of RLS symptoms or who have not previously had levels checked before commencing with iron supplementation. The symptoms of RLS in patients with low-normal levels (i.e., less than 40-50 ng/dL) may respond to treatment with iron supplementation. Typical oral supplementation includes 325 mg of ferrous sulfate three times daily, given with 100 to 200 mg of vitamin C to enhance absorption. Serum ferritin levels should be followed at three- to six-month intervals until iron therapy is discontinued, typically when serum ferritin levels reach 50 ng/dL or greater. Periodic rechecks may be necessary to determine the need for further iron treatment or when symptoms escalate. Recently published studies have shown the effectiveness of the intravenous administration of iron dextran in patients with primary and ESRD-related RLS45,207; however, this treatment remains experimental at this time. Often overlooked in the list of factors that may exacerbate symptoms of RLS is a history of frequent blood donation.49,51,248,279 Patients with RLS should be encouraged to have their serum ferritin levels checked before donating blood.
Remaining physically active in the evening hours, although not strenuous exercise, may delay the need for pharmacologic intervention into a time later in the evening. During times of forced immobilization, such as airplane flights, patients may find that mentally alerting activities such as playing computer games, performing intricate needlework, or reading an engaging novel may lessen their symptoms of RLS.
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Pharmacologic Treatment
With optimization of lifestyle and treatment for comorbid conditions, in combination with removal of exacerbating substances and medications, many patients with RLS avoid the need for pharmacologic intervention; however for those patients whose symptoms negatively impact their ability to actively engage in employment, leisure, and family pursuits and who desire treatment, pharmacologic intervention has been shown to significantly improve quality of life.22,24,30,116,127,163,165-167,169-171,280-282 No currently available drugs can cure RLS; they aim only at providing symptomatic relief. Because RLS is a chronic condition, therapy must usually be continued indefinitely.
Symptoms of RLS that occur only intermittently, i.e., not daily, can often be managed with medications administered on an as-needed basis. Any of the primary medications in the following sections, with the possible exception of gabapentin, may be used in this manner; however, the onset of action of each drug will determine the timing of the appropriate dose.
Key Points to Achieving Optimal Pharmacologic Treatment of RLS
Treatment of comorbid conditions may alter the pharmacologic treatment of RLS
Drugs should be initiated at the lowest possible dosage and gradually upwardly titrated
Onset of action and half-life of medications, in combination with the patient's personal schedule, determine the appropriate timing of treatment
Drugs are often given at lower doses in the treatment of RLS than in the treatment of the condition for which the drug is indicated
Intractable RLS may require the use of polytherapy
Effective long-term therapy may be difficult; when one drug loses its effectiveness, another drug in the same or a different class may prove to be effective
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Dopaminergic Agents
Dopaminergic drugs were developed and have been approved for the treatment of Parkinson's disease. Their safety and efficacy have been established in this population.
Dopaminergic agents are first-line therapy in the treatment of moderate to severe RLS and are also effective in the treatment of mild or intermittent RLS that is not responsive to nonpharmacologic intervention.
Table 8
Dopaminergic Agents
Drug Typical starting dose, mg Usual therapeutic range, mg Peak concentration, h Half-life, h Side effects
Nonergot dopamine receptor agonists Mild N/V; sedation; orthostatic hypotension;
Pramipexole 0.125 0.25-1.0 2 8-12
Ropinirole 0.25 0.5-8.0 1-2 6
Ergot-derived dopamine receptor agonists Severe N/V; sedation; orthostatic hypotension; cardiac valvulopathy; nasal congestion
Pergolide 0.025 0.5-1.0 1-3 12-27
Dopamine precursor Augmentation; N/V; headache
Carbidopa-levodopa 12.5/50 12.5/50-75/300 .5 1.5-2.0
Carbidopa-levodopa CR 25/100 25/100-100/400 2 3-8
N/V refers to nausea and vomiting; CR, continuous release
Augmentation is a phenomenon unique to the use of dopaminergic agents in the treatment of RLS.87,283,284 Augmentation occurs in temporal relationship to the ingestion of dopaminergic drugs; it is most commonly encountered with the use of levodopa-carbidopa284-286 but has also recently been shown with the use of dopamine receptor agonists.153,155,287,288 When augmentation develops, the symptoms of RLS occur at a time at least two hours before they occurred before the initiation of drug therapy. The symptoms frequently intensify and spread to previously noninvolved parts of the body (particularly the arms). In addition, the time from onset of quiescence to onset of symptoms is typically shortened. Because the rate of augmentation is highest with the use of levodopa, dopamine receptor agonists are the preferred drug for the treatment of RLS that occurs on a daily basis.277
Key Features of Augmentation
Temporal relationship exists between
↑ daily medication ↑ symptom intensity
↓ daily medication ↓ symptom intensity
Sensations spread to previously uninvolved parts of the body.
The duration of treatment effect is shorter than the duration with initial therapeutic response.
Periodic limb movements while awake either occur for the first time or are worse than with initial therapeutic response or before treatment was instituted.
Augmentation should be discussed with all patients treated with dopaminergic agents; patients should be cautioned that if augmentation occurs, they should not increase their dosage of medication but, instead, should return to the prescribing physician for consultation. The treatment of augmentation may involve adjusting the timing or the dose of the medication or switching to another agent.
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Dopamine Receptor Agonists
Dopaminergic receptor agonists are first-line therapy in the treatment of moderate to severe RLS; these drugs are also effective in the treatment of mild or intermittent RLS that is not responsive to nonpharmacologic intervention (Table 8). Dopamine receptor agonists bind to dopamine receptors, producing dopamine-like effects. The medications studied most thoroughly for use in RLS include the nonergot derivatives pramipexole dihydrochloride (Mirapex®) and ropinirole hydrochloride (Requip® or, in Australia, Repreve®) and the ergot derivative pergolide mesylate (Permax®); these drugs are included in both the algorithm published in the "Mayo Clinic Proceedings" and the American Academy of Sleep Medicine's practice parameters. Several other ergot derivatives have also been used in the treatment of RLS but have either only recently been studied (apomorphine289-291 [Apokyn®], rotigitine,115 and the partial agonist-antagonist terguride129 [Mysalfon]) or are no longer frequently used (bromocriptine [Parlodel®]) in the treatment of RLS. Cabergoline (Dostinex,® in the United States, or Cabaser, in Europe) has recently been studied for the treatment of RLS119,128,133,136,292,293; however, in the United States, it is packaged only for use in the treatment of hyperprolactinemia. Reports have indicated that long-term therapy with dopamine agonists remains effective for many RLS patients.
Recent reports have raised awareness about excessive daytime somnolence in patients taking dopamine agonists (particularly in those with Parkinson's disease and with higher doses).292,294-305 Patients should be cautioned to refrain from driving a motor vehicle or operating heavy machinery when therapy is instituted with these medications and until the patients can assess whether they will be adversely affected.
Nonergot Derivatives
Pramipexole
Pramipexole, which stimulates D2 and D3 receptors in the striatum and substantia nigra, has been shown to alleviate the sensory and motor symptoms in patients with primary and secondary RLS in a retrospective chart review,288 open-label trials,120,125,140,150,306-308 a double-blind placebo-controlled crossover trial,147 and a single-blind placebo-controlled crossover trials.309 These studies have found that the use of pramipexole greatly reduces periodic limb movements during sleep125,147,309 and wakefulness,125,310 in addition to alleviating the subjective symptoms of RLS. Identified rates of augmentation with the use of pramipexole vary from 0% to 33% over a mean of 7 to 30 months. A survey by Stiasny et al. of patients taking pramipexole at a mean dose of 0.37 mg found that none of the 24 patients had had an unexpected sleep attack; 11 patients did acknowledge that they experienced daytime sleepiness and usually napped during the day.
Ropinirole
Ropinirole stimulates D2 and D3 receptors, such as postsynaptic D2 receptors in the caudate and putamen. The effectiveness of this drug on the subjective symptoms of RLS has been shown in a case series,311 an open-label study,148 and two large116,127 and one small312 double-blind, randomized, placebo-controlled trials. Several additional studies that employed polysomnography—including open-label131,313 and double-blind, placebo-controlled trials114,314,315—have shown the efficacy of ropinirole in reducing the number of PLMS. In addition, Pellecchia et al.316 showed the efficacy of ropinirole over sustained-release levodopa in the treatment of RLS in a 14-week open-label, randomized, crossover trial in 10 patients who were on chronic hemodialysis for ESRD. Augmentation was not assessed in any of these studies, and no studies have evaluated the rate of sleep attacks in patients with RLS. Ropinirole was approved by the U. S. Food and Drug Administration for the treatment of moderate to severe RLS in May 2005.
Ergot Derivatives
Pergolide is the ergot-derived dopamine receptor agonist used most frequently in the United States for the treatment of RLS; in Europe, however, cabergoline is also frequently used. Pergolide, a semisynthetic ergot alkaloid derivative, is an agonist at D1, D2, and D3 receptors, stimulating postsynaptic dopamine receptors in the nigrostriatal system. With evidence from open-label trials151,152; long-term clinical case series139,153,317; and randomized double-blind, placebo-controlled crossover trials,154,318 including a multicenter trial with 100 patients,124 the practice parameters of the American Academy of Sleep Medicine designated pergolide as a standard in the treatment of RLS.121,122,143,319 However, recent reports of the development of cardiac valvulopathy in patients taking pergolide will likely limit the use of this drug.320-328 If ergot-derived dopamine receptor agonists are used, patients should be informed of the risks, and cardiac function should be monitored
Pergolide is best given in two equal divided doses, one taken with the evening meal and the other approximately one hour before bedtime. Temporarily discontinuing and then reinstating pergolide therapy may help to minimize associated side effects. A nasal decongestant may relieve the congestion that is often caused with the use of this drug. The few studies that have assessed augmentation with the use of pergolide have found the rate to vary from 15% to 27%.153,155 Bassetti et al.305 have reported the occurrence of a "sleep attack" in one patient with RLS who was treated with pergolide.
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Dopamine Precursor
Levodopa primarily acts by increasing dopamine concentrations in the brain. Carbidopa or benserazide, which are decarboxylase inhibitors that do not cross the blood-brain barrier, retard the peripheral breakdown of levodopa. The addition of decarboxylase inhibitors, therefore, increases the availability of levodopa for transport to the brain and the bioavailability of dopamine in the CNS. Concurrent administration of carbidopa allows a decrease in levodopa dosage, thus reducing potential side effects, such as nausea and vomiting.
Sinemet® is available in the United States in several strengths, with carbidopa and levodopa in varying ratios. In extended-release formulations, such as Sinemet CR, levodopa and carbidopa are contained in a polymeric-based delivery system that releases the drug over a four- to six-hour period in the gastrointestinal tract. Because amino acid transport mechanisms carry levodopa across gastrointestinal membranes, a high-protein diet may interfere with the absorption of levodopa formulations.
Levodopa medications are administered orally as needed or on a regular schedule. Such medications should be taken approximately 1 to 2 hours before bedtime on an empty stomach, if possible. Open-label trials155,329-331; longitudinal case series159,332; and randomized, double-blind, placebo-controlled trials156,157,333-338 provided the evidence for the Standards of Practice Committee of the American Academy of Sleep Medicine to make levodopa with a decarboxylase inhibitor a standard treatment. In selected patients, long-term therapy may remain effective for several years, with tolerable side effects. This is usually true of patients with mild RLS symptoms who require low doses or for those with isolated PLMD. However, because of its short half-life and the potential for augmentation to occur at higher doses,155,284 the use of levodopa preparation is typically reserved for those patients who have intermittent or rare symptoms of RLS that require treatment.277
Augmentation has been shown to occur in up to 80% of patients with RLS who are treated with levodopa. The occurrence of augmentation typically correlates with high daily dosages of levodopa equal to or more than 200 mg and administration of initial daily doses before 6 PM. Once daytime augmentation develops, levodopa therapy is usually discontinued and replaced with an appropriate agent, such as a dopamine receptor agonist. It is recommended that the total daily dose of carbidopa/levodopa not exceed 75/300 mg and should only be used in doses above 50/200 mg with considerable caution. In addition, patients with RLS may experience end-of-dose rebound during the middle of the night or early the next morning, particularly with short-acting formulations of levodopa preparations.339 Switching to a controlled-release formulation or adding a dose in the middle of the night may help to alleviate rebound; however, in such cases, problems of augmentation are also likely to occur.
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Benzodiazepines
Benzodiazepines act upon the hypothalamic, thalamic, and limbic regions, causing varying levels of depression in the CNS. This action is thought to be mediated through GABA receptors (i.e., increasing the affinity GABA for its receptors) or through serotonergic mechanisms (Table 9).
Table 9
Benzodiazepines
Drug Usual therapeutic range, mg/day Half-life, h
Clonazepam 0.5-2.0 18-40
Temazepam 7.5-30.0 1.5-5.5
Diazepam 5-15 30-60
Triazolam 0.125-0.5 8-15
Benzodiazepine therapy may improve sleep and reduce arousals due to PLMS, yet may be less effective in eliminating movement and sensory abnormalities associated with RLS. However, in some patients with severe RLS, benzodiazepine therapy significantly decreases the total number of abnormal leg movements during rest. Overall, long-term nightly benzodiazepine therapy has been shown to remain effective with a low risk of adverse effects, tolerance, or abuse. Patients with mild or intermittent symptoms of RLS, particularly young individuals, may receive the most benefit from such therapy. If combined with carbidopa/levodopa or dopamine receptor agonists, benzodiazepines may assist in the management of severe RLS symptoms and are usually administered orally shortly before or at bedtime.
Several clinical studies have documented the efficacy of clonazepam in alleviating RLS symptoms.340-348 Other benzodiazepines, such as temazepam, diazepam, and triazolam, may be effective alternatives but have not been formally studied in the treatment of RLS. Such benzodiazepine agents are Schedule C-IV controlled substances.
Potential adverse effects associated with benzodiazepine therapy for RLS include somnolence, especially with the use of long-acting medications (e.g., clonazepam); decreased libido; a risk of falls during the night, particularly in elderly patients; and exacerbation of comorbid obstructive sleep apnea. Depending upon dosage levels, therapy with such agents may result in tolerance and dependency; in addition, if therapy is discontinued abruptly rather than through gradually tapered dosages, there may be precipitation of withdrawal. However, in patients receiving long-term therapy for RLS, there is usually a low risk of such phenomena. Patients should be advised not to take benzodiazepines in combination with alcohol or other CNS depressants. In addition, physicians should carefully monitor benzodiazepine therapy in those patients who are currently receiving additional pharmacologic agents that may potentiate the effects of benzodiazepines and further depress CNS activities.
Other benzodiazepines may be considered as possible alternatives in the treatment of RLS. Such agents include alprazolam (Xanax®), lorazepam (Ativan®), chlordiazepoxide (Librium®), or flurazepam (Dalmane®), all of which are schedule C-IV controlled substances.
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Opioids
Though the specific physiologic action of opioids remains unclear, stimulation of opiate receptors serves to decrease the release of neurotransmitters, producing analgesic effects in the CNS. Opioid agents vary greatly in potency, ranging from mild (e.g., codeine), to moderate (e.g., oxycodone), to extremely strong (e.g., methadone) (Table 10).
Table 10
Opioids
Drug Typical starting dose, mg/day Usual therapeutic range, mg/day Potency Half-life, h Schedule class Receptor
Codeine 15-30 15-120 Low 3-4 C-II µ, Κ
Propoxyphene 65-130 130-520 Low 6-12 C-IV µ
Oxycodone 4.5-5.0 5-20 Moderate 3-6 C-II µ, Κ
Methadone 5-10 5-30 High 13-47 C-II µ, Κ
In clinical studies, with a relatively small number of patients,349,350 the use of opioids has been shown to alleviate paresthesias or dysesthesias, motor restlessness, and sleep disturbances associated with RLS. A recent review of long-term monotherapy for RLS with opioids in 20 patients found that one patient developed problems related to addiction or tolerance; two of the seven patients who were followed with polysomnography subsequently developed sleep apnea, and one had a worsening of apnea. Although opioid therapy produces minimal side effects and appears to carry little risk of tolerance or dependency, some patients with RLS have become addicted to opioids.
Opioids are administered orally and may be taken with food to help minimize gastrointestinal upset. Most physicians report that they prefer to prescribe a regimen consisting of one dose (e.g., codeine, propoxyphene, or oxycodone) shortly before or at bedtime. However, for some RLS patients who do not respond to a single-dose regimen or who require higher dosage levels, it may be necessary to administer one dose 2 hours before bedtime, one at bedtime, and another dose during the middle of the night (should patients awaken).
The major adverse effects of opioid therapy include nausea and constipation. In some patients, mental changes such as confusion may also occur. As with the benzodiazepines, patients should be cautioned not to take opioids in combination with alcohol or other CNS depressants. In addition, opioid therapy should be monitored in patients taking tricyclic antidepressants, sedatives, hypnotics, or other agents that may potentiate the effects of opioids, further depressing CNS activity. Opioids rarely cause daytime augmentation. However, RLS symptoms may reemerge after such therapy has been discontinued; in addition, there may be a temporary intensification of symptoms during withdrawal from opioid therapy.
The use of hydrocodone and the synthetic opioid, µ-receptor agonist, tramadol,351 may be considered as possible alternatives for the treatment of RLS.
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Anticonvulsants
Anticonvulsant medications inhibit neuronal activity and are primarily prescribed for the treatment of disease states that are characterized by abnormally increased CNS activity. The anticonvulsant agents carbamazepine352-356 and gabapentin (Neurontin®131,331,357-364 have been used most often in the treatment of RLS.
The exact mechanism of anticonvulsant action by carbamazepine is not completely understood. Carbamazepine is known to block use-dependent sodium channels, preventing repetitive firing, and to decrease posttetanic potentiation of synaptic transmission, limiting seizure dissemination. Carbamazepine has a slow variable rate of absorption from the gastrointestinal tract and a bioavailability of approximately 85%. The plasma half-life of carbamazepine is initially approximately 25 to 65 hours and 12 to 17 hours after ongoing therapy. Effective dosages have ranged from 100 to 600 mg per day, with increases up to 800 to 1,000 mg per day in individuals in whom the symptoms of RLS have not responded to lower doses.
The anticonvulsant gabapentin, a drug that is structurally related to the principal inhibitory CNS neurotransmitter GABA, has also shown promise as a treatment for RLS.131,331,357-364 The anticonvulsant mechanisms of gabapentin are unknown; however, they do not appear to be associated with its development as a structural analog of GABA. Gabapentin does not appear to bind with GABA receptors, act as a GABA precursor, or affect GABA reuptake. However, animal studies have demonstrated that the drug protects against GABA antagonist or GABA synthesis inhibitor-induced seizure or tonic extensions. Gabapentin is administered orally and is rapidly absorbed. The bioavailability of the drug ranges from 60% (for a 300-mg dose) to 35% (for a 1,600-mg dose). In patients with renal impairment who may or may not be receiving dialysis, dose levels and the frequency of gabapentin administration should be adjusted in response to the degree of impaired renal function. Gabapentin appears to be most effective in patients with mild or moderate RLS symptoms who experience actual pain. Average effective dosages may range from 300 to 2,700 mg per day, taken in divided doses.
The use of other anticonvulsant medications such as valproate (Depakene®) or lamotrigine (Lamictal®) may be considered as possible alternatives, although they have not been demonstrated to reduce RLS symptoms in clinical studies. Valproate, a carboxylic acid derivative, is thought to increase GABA concentrations in the brain. The medication is reported to have an elimination half-life of 5 to 20 hours. Drug clearance may be reduced in patients with renal impairment. Lamotrigine may serve to block voltage-sensitive sodium channels, inhibiting the presynaptic release of excitatory neurotransmitters (e.g., aspartate, glutamate). After oral administration, lamotrigine is rapidly absorbed and its bioavailability is approximately 98%. The plasma half-life ranges from approximately 14 to 59 hours. However, if no other medications are being administered, its half-life may decrease by approximately 25% and its plasma clearance may increase by 37%. Dosage adjustments may be required for patients with hepatic impairment.
Anticonvulsant medications should be taken with food to help minimize potential gastrotoxicity. Additional adverse effects include fatigue, drowsiness, or dizziness. Lamotrigine has rarely been associated with severe rashes and Stevens-Johnson syndrome. These have primarily occurred in patients receiving rapid dose escalation and with concomitant administration of other agents that block metabolism (such as valproate).
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Other Medications
Other pharmacologic agents may be effective in relieving symptoms associated with RLS. Clonidine hydrochloride (Catapres®), an imidazoline-derivative hypotensive agent, appears to stimulate postsynaptic α2-receptors in the CNS, primarily in the medulla, inhibiting sympathetic vasomotor centers. Clonidine is also a partial agonist at presynaptic α2-adrenergic receptors, although peripheral venous pressure typically remains unchanged. Large oral doses (or intravenous administration) of the drug may also stimulate α1-receptors in peripheral vascular smooth muscle, resulting in transient increases in blood pressure. Following oral administration, clonidine is rapidly absorbed; its bioavailability may be up to 100%. The elimination half-life of clonidine is approximately 6 to 24 hours. Because its half-life may be increased in patients with renal failure, a dose reduction may be required in such patients. Discontinuation of clonidine therapy requires gradual tapering of dosage levels over 2 to 4 days to prevent withdrawal effects.
Several studies have shown the efficacy of clonidine in the treatment of RLS.365-371 In two double-blind placebo-controlled studies, each with 10 patients, 9 uremic patients had complete or significant relief of symptoms, and 7 patients with primary RLS felt clonidine was more effective than placebo, although sleep parameters were unchanged. Relatively low dosages, such as 0.1 to 0.3 mg at bedtime, may be effective in some patients. In addition, RLS symptoms that have not responded to treatment with other medications have shown significant improvement with clonidine given in dosages up to 0.9 mg per day in divided doses. Common side effects include dry mouth, dizziness, lightheadedness, or decreased cognition.
The use of baclofen may also alleviate some symptoms associated with RLS. Baclofen, a skeletal muscle relaxant, is a GABA derivative. Although the exact mechanism of action is not fully understood, it appears to primarily inhibit spinal polysynaptic efferent pathways (as well as monosynaptic afferent pathways to a lesser extent) by functioning as an inhibitory neurotransmitter. The primary site of action is the spinal cord, where baclofen also reduces the release of excitatory neurotransmitters. When administered orally, baclofen is rapidly absorbed; however, bioavailability varies from case to case. Its serum half-life ranges from approximately 2.5 to 4.0 hours. Because clearance is primarily renal, a dose reduction may be required in patients with impaired renal function.
In some patients, other medications, such as sedative-hypnotics (e.g., zolpidem tartrate [Ambien®]), appear to have been efficacious in some patients with RLS. However, no controlled studies have been conducted to evaluate such medications in the treatment of RLS.
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Pharmacologic Therapy During Pregnancy
None of the drugs used to treat RLS are known to be safe in pregnancy; in many cases, no information at all is available. Nonpharmacologic measures, therefore, are the safest treatments for women who experience RLS during pregnancy. In addition, if such patients are experiencing symptomatic RLS associated with iron or folate deficiency, appropriate supplementation may be helpful. Obtaining serum ferritin levels in pregnant women with symptoms of RLS may assist in identifying iron deficiency and may guide therapy. Because RLS typically becomes more severe as the pregnancy progresses, drug therapy, if used at all, may often be withheld until the third trimester, at which time such medications have the least risk of causing teratogenic effects. Carbamazepine, especially, is contraindicated in the first semester. (Please refer to the package information for use of these drugs in pregnancy.) Educating the pregnant woman that RLS is temporary and that symptoms will typically resolve with delivery may allay her concerns.
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Pharmacologic Therapy for Children with RLS
The typical first course of action in children with RLS is nonpharmacologic. Many affected children have mild symptoms and eventually may experience remission during adolescence; however, in such cases, RLS symptoms may recur in adulthood. Appropriate lifestyle changes including regular exercise, strict sleep hygiene, appropriate sleep routines, and dietary adjustments, such as restrictions on all caffeinated food and drinks, are usually recommended. Assessing serum ferritin levels in children will assist in identifying iron deficiency, which may lead to or exacerbate symptoms of RLS.47,209 If lifestyle interventions and supplementation are not effective, the use of appropriately age- and weight-adjusted dosages of clonidine, carbidopa/levodopa, and dopamine receptor agonists might be cautiously considered. In some children with RLS and coexisting ADHD, such medications may effectively treat symptoms of both disorders.80
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Restless Leg Syndrome - What is it ? (Part 1)
There are various ideas about restless leg syndrome. During WW II, American prisoners in the hands of the Japanese military, were given a diet that was very vitamin and mineral deficient. Some of the men started developing a syndrome in which they would feel as if they had to move their legs. One of the POWs started gathering grasses and made a hot tea which the soldiers with the "restles legs" drank, and the "restless legs" syndrome started going away.
Nowadays, there are various websites devoted to RLS.
For example
http://www.ninds.nih.gov/disorders/restless_legs/restless_legs.htm#What_is
What is Restless Legs Syndrome?
Restless legs syndrome (RLS) is a common neurological disorder characterized by unpleasant sensations of the legs and an urge to move them for relief. Individuals affected with the disorder describe the sensations as pulling, drawing, crawling, wormy, boring, tingling, pins and needles, prickly, and sometimes painful sensations that are usually accompanied by an overwhelming urge to move the legs. Movement provides temporary relief from the discomfort.
Is there any treatment?
Massage and application of cold compresses may provide temporary relief. Medications such as temazepam, levodopa/carbidopa, bromocriptine, pergolide mesylate, oxycodone, propoxyphene, and codeine are effective in relieving the symptoms. Current research suggests that correction of iron deficiency may improve symptoms for some patients.
What is the prognosis?
RLS is a life-long condition for which there is no cure. Symptoms may gradually worsen with age. Because symptoms are intensified by inactivity and lying down, RLS patients often have difficulty falling asleep and staying asleep. Left untreated, RLS causes exhaustion and fatigue, which can affect occupational performance, social activities, and family life.
What research is being done?
The National Institute of Neurological Disorders and Stroke (NINDS) and other institutes of the National Institutes of Health (NIH) conduct RLS research in laboratories at the NIH and also support research through grants to major medical institutions across the country. NINDS-supported research is aimed at discovering the mechanisms responsible for motor disorders such as RLS, especially those associated with sleep changes. The goal of this research is to discover ways to prevent, diagnose, treat, and ultimately find cures for motor disorders including RLS.
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Also
http://www.wemove.org/rls/rls.html
What are the symptoms of restless legs syndrome?
In 1995, the International Restless Legs Syndrome Study Group, then comprising 28 investigators from seven countries, defined the four primary features of RLS.
The desire to move the legs in association with unusual or uncomfortable sensations (paresthesias/dysesthesias) deep within the legs, usually in the calves; in some cases, the arms may also be affected. These sensations are described as creeping, burning, tingling, cramping, aching, itching, pulling, crawling, or "water flowing" deep within the affected extremities. Patients with mild or moderate RLS characterize these sensations as uncomfortable; for the most part, they are not perceived as painful. In rare cases, unusual sensations occur in the feet. In even rarer cases, these sensations may also be present in the trunk or genital area. These feelings may move from one part of the body to another or may affect only one side of the body (asymmetric). For example, one leg may have unusual sensations whereas the other does not.
Motor restlessness in response to or in an effort to relieve unusual sensations or discomfort. To the extent that a patient feels a compelling urge to move, these movements may be termed involuntary; however, in so far as a patient chooses which type of movement to perform, these movements are voluntary. Such movements are often repetitive and may include pacing, rocking, shaking, tossing and turning in bed, stretching, bending, marching in place, or engaging in certain repetitive exercises, such as riding an exercise bike or walking on a treadmill. Many individuals develop their own routine of stereotypical movements and tend to repeat these same movements in response to uncomfortable sensations.
Symptoms become obvious or worse while at rest (during periods of inactivity or relaxation) and may be temporarily diminished by voluntary movements of the affected limb(s). This restlessness is sometimes mistaken as "fidgetiness" or "nervousness." The unusual sensations and motor restlessness associated with RLS may also be provoked by prolonged periods of inactivity such as occurs during travel in a plane, train, or car.
Symptoms occur most frequently during the evening or the early part of the night (e.g., between 6 p.m. and 4 a.m.). Individuals with even the most severe RLS symptoms typically obtain some measure of relief during the early morning hours. Worsening of symptoms while at rest and at nighttime may be a very distinctive pattern that is unique to restless legs syndrome.
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And from http://www.mdvu.org/library/disease/rls/ this :
Restless Legs Syndrome
This... ailment... occurs most often when the legs get warm in bed, and prevents going to sleep... A curious unlocalized restlessness is felt in one or both legs. It is not quite a pain, but is distinctly unpleasant. A combination of voluntary movement and involuntary jerks of the affected limb fails to find rest. In ten minutes to an hour the "jitters" depart and sleep comes... The disagreeable sensation stops at once on chewing 1/100 grain of nitroglycerine, suggesting that the cause is vascular.1
Introduction
Known in the common vernacular as the heebie jeebies, Elvis legs, the fidgets, and simply the leg thing, restless legs syndrome (RLS)—a term coined by Swedish neurologist Karl-Axel Ekbom2—is a sensory and movement disorder with a profound impact on sleep. The pulling, tugging, creepy-crawly, electric shock-like, bubbling, or jittery and not infrequently painful sensations are often difficult for patients to describe, leading to reports of sometimes bizarre-sounding symptoms such as Coca-Cola in the veins, insects crawling deep in the tissue, and itching bones. Relief with movement of the affected limb—typically the legs and, not uncommonly, the arms—is one of the distinguishing features. Because of the exacerbation in symptoms with quiescence and the circadian properties of the condition, when people with RLS do seek medical attention, it is often because of their difficulty initiating and maintaining sleep. It is common for people with RLS—after enduring the symptoms for many years—to hear about the disorder in the media and recognize for the first time that their odd sensations indeed constitute a real and treatable condition.
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Primary and Secondary RLS
Primary RLS has been identified as having a more insidious onset of symptoms, which occur at an earlier age (usually before 40 years); patients with primary RLS are more likely to have affected family members than are people in the general population or even those patients with the secondary form of RLS.3-6 In secondary RLS, the onset is usually more precipitous and typically occurs after age 40 years.3-5,7 In this case, RLS occurs in relationship to other conditions, such as pregnancy,8-20 end-stage renal disease (ESRD),21-42 and iron deficiency (with or without anemia)43-56 or with the use of medications, such as dopamine receptor antagonists,57-60 histamine-receptor antagonists,61 selective serotonin reuptake inhibitors,62-70 and other antidepressant drugs.71 Any drugs that cause sedation may prove to be problematic for patients with RLS, particularly if the drugs are taken during the daytime.72
Patients with a late age of onset of symptoms are also less likely to have decreased serum ferritin levels, as compared with patients with early-onset RLS.7 Children and adults with RLS often exhibit symptoms of attention-deficit hyperactivity disorder (ADHD). Whether this occurs because of the impact of RLS on sleep or an overlapping dopaminergic dysfunction is not known.73-80 In children, symptoms of RLS are frequently mislabeled as growing pains.4,6,73,79,81-85
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Diagnostic Criteria
Essential Criteria
Conforming with Ekbom's original description of RLS, the International RLS Study Group developed and published four essential diagnostic criteria for RLS in adults 50 years after Ekbom's original 1945 dissertation86; members of the Study Group and other interested parties revised these criteria in 2002 at a workshop held at the National Institutes of Health (Table 1).87 To support a diagnosis of RLS, all four of these criteria—the sensations and urge to move, relief with movement, exacerbation during quiescence, and worsening of symptoms in the evening and at night—must have been met at some time throughout the course of the patient's condition.
Table 1
Essential Diagnostic Criteria
An urge to move the legs is present, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs.
Sometimes the urge to move is present without the uncomfortable sensations, and sometimes the arms or other body parts are involved in addition to the legs.
The urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity such as lying or sitting.
The urge to move or unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues.
The urge to move or unpleasant sensations are worse in the evening or night than during the day or only occur in the evening or night.
When symptoms are severe, the worsening at night may not be noticeable but must have been previously present.
Modified from Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4(2):101-119.87
The first criterion requires that the patient has an urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs. Some patients, however, are unable to delineate a specific sensation and only relate an overwhelming urge to move the limbs. Typically, these sensations occur in the legs; however, they may also occur in the arms6,88-91 and, very rarely, the trunk or face.92
Criterion two relates to the role of quiescence in increasing the sensations and urge to move. This criterion is supported by the recent work of Michaud et al.,93 who, through the use of the Suggested Immobilization Test (SIT), have verified that patients with RLS, as compared with matched controls, experience more discomfort and have more periodic limb movements during a one-hour testing period.
Criterion three requires that the urge to move or unpleasant sensations be partially or totally relieved by movement. Patients employ a variety of techniques to relieve the sensations and urge to move. These techniques range from simply stretching or rubbing the leg, to pounding the leg and performing deep knee bends, to executing convoluted contortions. The critical factor in this criterion is that the relief is experienced almost as soon as the patient begins the movement and persists as long as the patient continues performing the sensation-relieving movement.
Intrinsic circadian factors define criterion four, with a worsening of symptoms during the evening and night relative to daytime levels94; however, patients with severe RLS may not exhibit a diurnal variation in symptoms. Evidence supports the finding of increased symptoms, both sensory and limb movement, occurring on the falling phase of core body temperature95-98; however, both differences99 and no differences100,101 have been found between daytime and nighttime excretion of melatonin or pulses of prolactin, growth hormone, and cortisol. Recent studies following nighttime treatment with levodopa, as compared with baseline levels before treatment, have shown changes in prolactin release and secretion of growth hormone102 and in the dim-light melatonin onset in patients with RLS but not controls.103
Supportive Clinical Features
In situations with diagnostic uncertainty, the supportive clinical features (Table 2) may assist the clinician in delineating cases of RLS. These features are not required for the diagnosis of RLS, but their presence does lend reinforcement to the diagnosis.
Table 2
Supportive Clinical Features of Restless Legs Syndrome
More than 50% of patients with primary RLS have affected family members.
A positive response to dopaminergic therapy is almost universal.
As many as 85% of people with RLS have periodic limb movements during wakefulness or sleep.
Modified from Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4(2):101-119.87
A variety of research studies have verified the clinical impression that approximately 50% of patients with RLS have a family history of the disorder.3,5,7,104-111 A person with RLS is three to six times more likely to have another family member with RLS than is someone without RLS.7,104
Another clinical feature of both primary and secondary RLS is the almost universal response to dopaminergic therapy.43,103,112-160 The vast majority of people with RLS will have an initial positive response to treatment with either levodopa or a dopamine receptor agonist. If the patient's symptoms do not respond to dopaminergic therapy, the diagnosis may need to be reevaluated.
More than 85% of people with RLS have periodic limb movements during sleep (PLMS), during wakefulness, or during both sleep and wakefulness.161 (Thanks to the popular television program Seinfeld, this condition is also known as jimmy legs162 George Constanza's mother has a derivation known as jimmy arms). Montplaisir and his colleagues have studied the prevalence of both arm and leg movements during sleep, using polysomnography (which in a typical clinical scenario does not include the assessment of arm movements), and during wakefulness, using the SIT.88 During the SIT, patients remain in bed in a semirecumbent position for one hour before their typical sleep time; they are instructed to keep their limbs still. During this test, objective electromyography of leg movements is recorded, as are subjective patient reports of the sensory component.
Associated Features
Associated features of RLS include that those are frequently found in affected individuals but are not specific to the diagnosis of RLS (Table 3).
Table 3
Associated Features of Restless Legs Syndrome
The natural clinical course varies between primary and secondary forms.
Sleep onset and sleep maintenance may be impacted, resulting in severe sleep loss.
Normal findings are present on physical examination in primary RLS; abnormal findings of associated conditions in secondary RLS may be present and may impact the presentation of RLS.
Modified from Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4(2):101-119.87
The natural clinical course of RLS is dependent upon whether the RLS is a primary or a secondary form of the disorder. As mentioned previously, in primary RLS, the onset of symptoms typically occurs at a younger age, is insidious and slowly progressive, and is not related to any secondary etiology. The onset of symptoms in secondary RLS typically begins after age 40 years. The course is one of more-rapid onset and escalation of symptoms coinciding with the causative factor, i.e., ESRD, pregnancy, neuropathy, and iron deficiency—with or without anemia.
The second associated feature of RLS—the disturbance of sleep onset and maintenance of sleep—reflects both the circadian and quiescegenic features of RLS. As the primary precipitating event leading patients to seek treatment, the negative impact of RLS on sleep is at least partially responsible for the reduced quality of life in patients with RLS.24,38,127,163-171
Finally, unless the RLS is related to a secondary condition, the findings on physical examination are typically normal. Identifying and treating relevant secondary causes of RLS will assist in guiding treatment and lead to improved outcome.
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Pathophysiology
Although the underlying cause of RLS has not been determined with certainty, multiple etiologies likely impact the dopaminergic, opioidergic, or both the dopaminergic and opioidergic systems, leading to the symptoms of RLS.
Genetics
The increase of RLS among first-degree relatives, as compared with the prevalence among the general population,104,106,111 has led researchers to investigate the genetic basis of RLS. In 2001, Desautels and his colleagues in Montreal identified a major susceptibility locus on a 14.71-cM region between D12S1044 and D12S78 on chromosome 12q in their large population of French-speaking Canadians.172 Study of a three-generation Italian family subsequently identified another locus—the 14q13-21 region173; this locus was further confirmed by Desautels' group in one of their kindred.174 With the assumption that the RLS in their 15-family, multigenerational pedigrees was inherited in an autosomal-dominant fashion, Chen et al.175 performed a genomewide scan and found evidence suggestive of linkage at 9p24-22 in two families.
Desautels and his colleagues have also examined candidate genes, including those for neurotensin176 and tyrosine hydroxylase, dopamine transporter, dopamine receptors D1 to D5, and dopamine β-hydroxylase177; they found no evidence of genetic linkage to support the role of the dopamine system in the etiology of RLS symptoms. Li et al178 also did not find evidence of linkage when they examined genes responsible for dopamine and iron metabolism in a Chinese Han population with RLS.178 Using complex segregation analysis, Winkelmann et al.108 found evidence supporting the role of a single gene transmitted in an autosomal-dominant pattern in their patients with early-onset RLS; no evidence was found for a major gene in those patients with late-onset RLS.
In studying almost 2000 twin pairs—933 of whom were monozygotic—Desai et al.179 found that 54% of RLS and 60% of PLMS cases were due to heritability. Ondo and his colleagues,180 when examining 12 monozygotic twin pairs with RLS, found a concordance rate of 83%; all of the 10 concordant pairs had at least one affected parent, as did one of the discordant pairs. The age of onset varied by as much as 42 years between the members of the pairs; the severity of symptoms, according to the International RLS Rating Scale, ranged from a low of a two-point difference to a high of a 25-point difference between twin pairs.
Dopaminergic System
The vast majority of RLS patients respond to treatment with dopaminergic agents, although the efficacy is not always maintained on a long-term basis. Conversely, the use of dopamine receptor antagonists that the cross the blood-brain barrier exacerbates the symptoms RLS. However, results of imaging studies, including SPECT and PET, that have attempted to identify abnormalities in the dopamine system have been equivocal. Furthermore, these results may reflect the fact that none of these studies were performed during the night, when RLS symptoms are typically most severe.
None of the 123I β-CIT SPECT studies that have been published to date have shown a difference in the dopamine transporter in patients with RLS, as compared with control subjects.181-184 One 123I-IBZM SPECT study181 has shown a difference in D2-receptor binding between normal control subjects and those with RLS,183-186 and one SPECT study has shown a decrease in D2-receptor binding in patients with nocturnal myoclonus (ie, periodic limb movement disorder187) as compared with controls.188 A single study addressing the issue of regional cerebral blood flow in patients with painful RLS found an increase in anterior cingulate regional cerebral blood flow as pain increased; this pain was secondary to increasing length of immobility.189
PET studies in patients with RLS, as compared with those in control subjects, have shown decreased 18F-DOPA uptake in both the caudate and putamen190 and in only the putamen 191; a decrease in D2-receptor binding in the caudate and putamen191; and, using 18FDG and 18F-DOPA, no difference between the groups.192 The recently published results of research that used 11C-diprenorphine in PET studies to assess the role of the endogenous opioid system in RLS showed that, although there was no difference between patients with RLS and control subjects with regard to opioid-receptor binding, RLS severity and ligand binding were negatively correlated in the medial thalamus, amygdala, caudate, anterior cingulate gyrus insular cortex, and orbitofrontal cortex—areas involved in the medial pain system.193
fMRI studies performed in 1996 did not elicit any structural abnormalities in the brainstem or spinal pathways of patients with idiopathic RLS but did reveal increased activity in the cerebellum, thalamus and pons during RLS symptoms. 194
Iron
The preponderance of recent research dedicated to ascertaining the pathophysiology of RLS, outside that seeking to identify the genetic underpinnings, has been related to iron. As the rate-regulating enzyme in the biosynthesis of dopamine, tyrosine hydroxylase requires iron stores to be present. Serum ferritin levels most accurately reflect stores of iron in the periphery.
Nordlander first proposed the connection between iron deficiency and RLS and the use of intravenous infusions of iron for the treatment of RLS in the 1950s.195 Subsequently, Ekbom noted the prevalence of iron deficiency among his patients with RLS—one in four was found to be iron deficient196—as well as an increase in RLS among blood donors197 and as an early finding in patients with cancer.198 The iron-RLS connection lapsed into obscurity until resurrected by O'Keeffe in Ireland56 and researchers at Johns Hopkins University55 in the 1990s. Both of these groups identified an inverse relationship between symptom severity and levels of ferritin in the serum (< 45 ng/dL in the elderly and < 50 ng/dL in general in patients with RLS, respectively) and a decrease in ferritin levels and an increase in transferrin levels in the cerebrospinal fluid of patients with RLS, as compared with that of controls.199 One caveat worth noting is that serum ferritin levels are elevated in response to both chronic and acute inflammation, a common occurrence in patients with secondary forms of RLS, particularly ESRD200 or infection201; therefore, serum ferritin levels as high as 70 ng/dL may be more reflective of iron stores and may correspond more favorably with RLS symptomatology in patients with inflammatory or infectious states.202
The Hopkins researchers have also performed MRI studies to measure regional brain iron concentration.203 Their use of R'2 as a marker of regional brain iron revealed that iron content is much lower in the substantia nigra of patients with RLS, as compared with that of normal control subjects. The Hopkins group, in collaboration with Connor et al., have clearly established the role of iron deficiency in the brain in the pathogenesis of RLS. Their research from postmortem studies has shown that tissue from RLS patients, as compared with tissue from controls, has reductions in the substantia nigra in heavy-chain or H-ferritin (an indication of high iron utilization and low iron storage), an abnormal distribution of light-chain or L-ferritin within the cells (L-ferritin promotes cerebral iron storage), and decreased transferrin-receptor staining on and increased transferrin staining in cells that contain neuromelanin.204 A second postmortem study has shown a decrease in ferritin, divalent metal transporter 1, ferroportin, and transferrin receptor, with a concomitant increase in transferrin expression in neuromelanin cells; the study also found a decrease in the activity of total iron-regulatory proteins (IRP) and IRP-1, a decrease in the levels of IRP-1, but no changes in IRP-2 activity or levels, indicating an overall iron-deficient state at the cellular level of neuromelanin and a potential defect in IRP-1.205 Most recently, their postmortem studies of RLS patients have revealed a more than 50% decrease in Thy-1, a glycoprotein that is profusely present on the surface of mature neurons and is also present at synaptic vesicles.206 The role of Thy-1 is in regulating vesicular release of neurotransmitters, stabilizing synapses, and suppressing dendritic outgrowth, with coordination of the dopaminergic innervation during development. Expression of Thy-1 is negatively affected by iron deficiency, particularly during early development.
Further support for the iron-RLS connection comes from the efficacy of therapeutic trials of intravenously administered iron45,195,207 and erythropoietin166 and orally administered iron in patients with evidence of low ferritin levels.56 The results of two studies have been recently published: one was an open-label trial of a single 1000-mg infusion of iron dextran in 10 patients with RLS who did not use RLS-related medications in the 5 days prior to the study,207 and the other, a randomized, double-blind, placebo-controlled trial of the same treatment in 30 patients with ESRD and no biochemical evidence of iron deficiency, who continued their concurrent RLS-related therapy.45 Both studies assessed change from baseline, using subjective rating scales, while the open-label study also used actigraphy as an objective measure of periodic limb movements. Six of the 10 patients in the open-label trial were deemed responders to therapy two weeks after treatment, having a dramatic reduction in the global rating scale, a decrease in the PLMS index, and improvement in hours per day without RLS symptoms but no change in total sleep time. The placebo-controlled trial found that baseline symptom severity correlated with serum ferritin levels and iron saturation, which increased with treatment in the control group. Subjective improvement in symptoms was greater in the treated versus the placebo group at one week and two weeks after treatment but not at four weeks; 82% of patients responded to treatment.
Finally, a recent study of children with a PLMS index above 5 per hour showed that 28 of the 39 children had low ferritin levels (below 50 ng/dL); however, serum iron, but not ferritin, correlated significantly with the PLMS index.208,209 Nonetheless, 19 of the children with low ferritin levels had a reduction in the PLMS index and an increase in serum ferritin levels 3 months after treatment with orally administered iron (3 mg/kg per day of ferrous sulfate).
Neurophysiologic Testing
Although traditional studies of electromyography and nerve conduction velocity and evoked potentials are typically normal in patients with RLS,194,210 research evidence from studies seeking to identify the generator of the periodic movements and sensations of RLS have been mixed, showing both cerebral211 as well as spinal sites.212-214 In addition, case reports and prevalence ascertainment studies of RLS in populations with impairments in the spinal cord have found either an increased prevalence in this population or symptom resolution with pharmacologic intervention.187,215-224
The finding of Trenkwalder et al. of a normal Bereitschaftspotential in patients with primary RLS and RLS related to ESRD led the authors to conclude that a subcortical or spinal site generates the involuntary movements of RLS.225 A subcortical site was also posited as the result of abnormal blink reflexes found in a study of 19 patients with PLMS.226 A video-polysomnography-based study of 10 medication-free patients with primary RLS found no regular recruitment pattern preceding PLMS, implying multiple unsynchronized generating sites, most likely due to abnormal hyperexcitability of the spinal cord.227
Transcranial magnetic stimulation studies in patients with RLS, as compared with those in normal control subjects, have shown variable results, ranging from normal motor threshold, duration of silent period, and motor evoked potential recruitment and reduced cortical inhibition after stimulation of foot and ankle muscles,228 and a decreased duration of the cortical silent period,229 to completely normal findings.230 In the most recent study, Scalise et al.231 showed reduced cortical inhibition in six patients with primary RLS, manifest by a lack of increase in the amplitude of the motor evoked potentials and delay of facilitation after rest following a bilateral two-finger tapping task in single transcranial magnetic stimulation.
Two recent studies have identified abnormalities in central somatosensory processing in patients with RLS.232,233 In the first, 16 patients with secondary RLS (72.5%) and 11 with primary RLS (55%) had pathologic changes in temperature sensitivity, with sensory deficits likely linked to small-fiber neuropathy in secondary RLS and a central process in primary RLS.232 Stiasny-Kolster et al.233 examined pain sensitivity at baseline and after long-term treatment with levodopa in 11 patients with primary RLS; they found that mechanical pain was increased in the arms (by a factor of 5.3) and legs (by a factor of 6.4) in RLS subjects, as compared with controls, and that long-term dopaminergic therapy modulated this static mechanical hyperalgesia, highlighting for the first time, the impression that RLS may be a disorder of pain modulation as well as of motor control.
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Epidemiology
The establishment of diagnostic criteria for RLS has provided the framework upon which to build the prevalence estimates of RLS. These efforts have been further enhanced by the development of three proposed questions specifically related to epidemiologic studies as part of the 2002 National Institutes of Health workshop (Table 4).87 By slightly changing the wording of the three questions, it is possible to establish a point prevalence rather than a lifetime history of RLS. A fourth question—How often do these feelings occur?—serves as a surrogate for symptom severity.
Table 4
Proposed Questions for the Epidemiologic Study of Restless Legs Syndrome
Do you have unpleasant sensations in your legs combined with an urge or need to move your legs?
Do these feelings occur mainly or only at rest and do they improve with movement?
Are these feelings worse in the evening or night than in the morning?
Modified from Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4(2):101-119.87
Although epidemiologic studies show a wide variation in the prevalence of RLS—dependent upon the population studied, the degree of scrutiny exercised, and the criteria used to diagnose the condition—RLS appears, in general, to affect approximately 7% to 12% of people of European extraction, with lower numbers identified in people of African and Asian descent. Specific populations, including the elderly, patients with ESRD, and pregnant women, have RLS at an increased rate compared with the general population, even in those ethnic populations in which RLS is virtually nonexistent. In most studies, women appear to be affected more often than men.
General Population
Ekbom proposed a 5% prevalence rate of RLS among adults in Sweden,2 and Lavigne and Montplaisir found a prevalence of 8% overall and a higher rate in Roman Catholic French-speaking as compared with Protestant English-speaking Canadians subjects, perhaps indicating a founder effect.234 Over the past 8 years, the National Sleep Foundation has found that 13% to 15% of the respondents to their random-dial telephone surveys acknowledge having "unpleasant feelings in their legs (such as creepy, crawly or tingly feelings) at least a few nights a week"; 3% of respondents have been told by their physician that they have RLS.235-240 The single question regarding symptoms of RLS on the 1996 Kentucky Behavior Risk Factor Surveillance identified 19.4% of 1456 respondents as ever having such symptoms, with 5.9% having them more than 15 times per month.241
Ohayon and Roth242 ascertained the prevalence of RLS in 5 European countries via telephone interviews and identified 5.5% of the population as having RLS, with only 11.9% of these individuals having had consulted a physician about their symptoms.242 The Study of Health in Pomerania165 found the prevalence of RLS in women to be 13.4% overall, with a low of 4.9% among those aged 20 to 29 years and a high of 19.4% among women aged 50 to 59 years; in men, the overall prevalence was 7.6%, with prevalences of 3.0% among the youngest men and 13.2% of men aged 60 to 69 years. Of postal workers in Switzerland (532 men and 136 women), 2% admit that they often have symptoms of RLS.243 A population of Italian shift workers had an 8.5% prevalence of RLS; the rate was 4.2% among those who worked the day shift.244 The point prevalence of primary RLS was 3.19% in an epidemiologic study in Turkey,245 which specifically excluded secondary RLS. Of those people who were found to have RLS in this study, 30% had told their physicians of their symptoms, but only one person had a previous diagnosis of RLS. In two studies in Sweden, 5.8% of men246 and 11.6% of women247 were found to have RLS, with rates highest in those aged 55 to 64 years (10.5%). Ulfberg and Nyström248 also surveyed 946 blood donors in Sweden and found that 14.7% of the men and 24.7% of the women had symptoms that were diagnostic for RLS according to the International RLS Study Group criteria.
Although not directly tied to the rates of RLS in the general population, ascertaining prevalence among primary-care patients does likely reflect the overall prevalence of the disorder. In Singapore, researchers found only 1 person whose symptoms met the diagnostic criteria for RLS in a total patient population of 1000.249 In Ireland, O'Keeffe et al.250 found an overall prevalence of RLS of 10.3% among their primary care patients, with higher rates in woman than in men (12.4% versus 6.5%, respectively). Among 2009 patients seen at a single, rural, primary care clinic, Nichols et al251,252 identified 504 (24%) as having RLS, including those with only mild, occasional, or setting-specific symptoms; when weekly symptoms that were at least mildly distressing were required, the prevalence was 13.7%.
The largest epidemiologic study of RLS to date, which included data from more than 23,000 patients attending primary care clinics in 5 countries, including France (n, 4808), Germany (n, 6723), Spain (n, 5752), the United Kingdom (n, 2114), and the United States (n, 3655), found a prevalence of 9.6%.253 This study also found wide discrepancies between patients' and physicians' perceptions of the symptoms of RLS: most of the 551 patients whose symptoms met the diagnostic criteria, occurred at least twice a week, and had at least a mild negative impact on quality of life, reported that they had contacted their physician about their symptoms in the previous year; half of these patients received any diagnosis, and only 49 had a correct diagnosis of RLS.
Special Populations
Elderly
Epidemiologic studies in six countries have focused specifically on symptoms of RLS in older adults. In their 1981 review of polysomnographic records from 83 elderly patients seen the Stanford sleep clinic over a two-year period, Coleman et al.254 identified 18% as having what the researchers termed periodic movements-restless legs syndrome. The 2003 National Sleep Foundation Sleep in America Poll survey of adults aged 55 to 75 years old who were living in their homes identified 17% of people as having symptoms of RLS, with 6% of them having been told by their physician that they have RLS and 3% being treated for the disorder.255
At a geriatric outpatient center in Ireland, 5% of 307 consecutive patients were found to meet the diagnostic criteria for RLS and have bilateral leg involvement.256 In the first large-scale epidemiologic study of RLS using the 1995 criteria, Rothdach et al.170 found a prevalence of RLS of 9.76% in Germans over the age of 65 years, with women having a higher rate, as compared with men. A recent study of RLS prevalence among those aged 50 years and older in the Netherlands elicited a prevalence rate of 7.1%, with higher rates among women and those who were older.171
In Singapore, only 1 of 157 adults aged 55 years or older who were examined met the criteria for RLS (0.6%).249 Sukegawa et al.257 quantified the association between sleep disturbances and depression among 2023 Japanese adults (aged 65 years or older) and found that more people in the depression group (5.8%) had symptoms of RLS, as compared with those in a control group (2.4%). The highest prevalence was found in men younger than 75 years of age (8.4%).
End-Stage Renal Disease
The increased prevalence of RLS in patients with ESRD has been well established, although the percentage of affected individuals varies dependent upon the ethnic makeup of the population, as well as the criteria and degree of scrutiny used in making the determination. Indeed, the presence of RLS symptoms has been correlated with premature discontinuation of dialysis,37 decreased quality of life,24,30,38,166,258,259 and lower 1- and 2-year survival rates.37 Winkelman et al.37 found that 20% of patients with ESRD reported moderate to severe symptoms of RLS, as opposed to 6% in a control group.
Walker et al.38 established an RLS prevalence of 57.4% among 54 patients being treated at a dialysis center in Canada. The study of Collado-Seidel et al.36 at 2 centers in Germany found that 23% of the 136 patients who had been on stable dialysis for the previous 2 years had RLS, with intact parathyroid hormone levels correlating with the presence of RLS. In two studies at dialysis clinics in Hong Kong, Hui et al.32,260 established the prevalence of RLS as 62% of 201 and 70% of 43 ethnic Chinese patients, respectively. In Chile, Miranda and colleagues261 found that 26% of 166 patients with ESRD and 13% of a control group (comprising patients' relatives) had RLS. Studies among patients at dialysis clinics in Italy,262 India,31 and Japan258 have found prevalence rates of RLS of 37%, 6.6%, and 25.3%, respectively. In the study conducted in India, no RLS was found in a control population. Another recent study at a dialysis clinic in Italy263 found a prevalence of 21.5%, with 37.5% of patients with polyneuropathy having a positive diagnosis of RLS.
Kutner and her coworkers29 at Emory University in Atlanta, Georgia, looked at the racial differences in a statewide study of elderly people (60 years and older) who were receiving dialysis treatment for ESRD: 68% of Caucasians and 48% of African Americans had symptoms of RLS. A study in Brazil27 also looked at the racial differences in 176 patients with ESRD; they found that 11.4% of non-Caucasian patients compared with 17.5% of Caucasian patients had RLS (overall prevalence of 14.8%).
Pregnancy
Women with preexisting RLS often experience an increase in symptom severity, particularly in the third trimester, and those without previous symptoms often experience RLS for the first time during pregnancy. Goodman et al.8 determined that approximately 19% of 500 women during their third trimester of a singleton pregnancy experienced symptoms of RLS—16 had symptoms that predated their pregnancies. By the fourth week postpartum, symptoms had resolved in all but 3 women.
Ekbom identified a prevalence rate of approximately 11% in 788 pregnant women.264,265 Botez et al.,9 found that 9% of their pregnant patients who were taking folate supplements had RLS; 80% of those who did not supplement their folate intake experienced RLS symptoms.
Recent studies in Italy,266 Japan,20 Finland,10 and the United States,267 which employed a variety of diagnostic criteria, confirmed rates of RLS in pregnant women as 27%, 19.9%, 37.7%, and 23%, respectively. Even though other epidemiologic studies in Japan (including in general and elderly populations) have found relatively low rates of RLS, the study by Suzuki and colleagues20 of more than 16,000 pregnant women found rates varying from 19% to 26%, depending upon maternal age.
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Diagnosis
The diagnosis of RLS is based upon the history obtained from the patient and physical examination, with history confirming the four required diagnostic criteria. The differential includes a variety of neurologic, vascular, and other sensory conditions (Table 5).
Table 5
Conditions in the Differential Diagnosis of RLS
Akathisia
Burning feet syndrome
Fibromyalgia
Intermittent claudication
Meralgia paresthetica
Nocturnal leg cramps
Pathophysiologic insomnia
Polyneuropathy
Positional discomfort
Radiculopathy
Tardive dyskinesia
Tourette syndrome
Vascular insufficiency
Elicitation of the history should focus on factors related to family history, gross or microscopic blood loss (eg, recent operation or injury, frequent blood donation, hypermenorrhea, aspirin use, vitamin K deficiency, and infection with Helicobacter pylori or other causes of gastrointestinal bleeding), and the use of or exposure to medications or substances that are known to be associated with an increase in RLS symptomatology (Table 6). Antidepressant medications have been clinically reported to exacerbate RLS, thereby worsening sleep problems. Paradoxically, some patients report benefit from the use of these medications. While no studies have clearly addressed these issues, the treating physician should be aware of the potential of tricyclic antidepressants and serotonin reuptake inhibitors, such as mianserin, fluoxetine (Prozac®), and sertraline (Zoloft®) to worsen the symptoms of RLS.
Table 6
Medications and Substances Related to Increased RLS Symptoms
Medications Substances
Dopamine receptor antagonists60 Caffeine268,269
Metoclopramide59 Nicotine165,241,242,270,271
Antipsychotics Alcohol242
Droperidol57,58
Prochlorperazine
Antidepressants, particularly those causing sedation
Selective serotonin reuptake inhibitors62-69
Tricyclics70,71
Antihistamines, particularly first-generation H1-receptor antagonists61
As mentioned in the section on associated features, the examination is typically normal in patients with primary RLS. Findings on physical examination in patients with secondary RLS are most often those related to the associated condition and guide the clinician in obtaining additional testing. Although no standardized tests reveal the diagnosis of RLS, laboratory measures of anemia status, iron stores (e.g., ferritin, total iron-binding capacity, and percentage of transferrin saturation) and serum glucose levels may be warranted. Nerve conduction studies and electromyography may be appropriate for patients with evidence on physical examination of neuropathy. In patients who have symptoms of a sleep disorder other than RLS, polysomnography may be necessary, and results may help to clarify clinical challenges.272
A recently validated telephone interview, based on the 1995 International RLS Study Group criteria, is useful for the diagnosis of RLS for research purposes.273 Reliability of the diagnosis among the three raters was strong, with good sensitivity (97%) and specificity (92%). The diagnosis was most easily established in patients with severe symptoms of RLS and most difficult to ascertain in control subjects. Elucidating differences between symptoms of RLS and those of nocturnal leg cramps proved to be the greatest challenge.
Rating Scales
Rating scales have recently been developed and validated to quantify the severity of RLS symptoms for research purposes and to measure treatment efficacy. The scale of the International RLS Study Group includes patient-rated subjective responses to 10 questions, with responses ranging from 0 to 4.274 This scale, validated at 20 centers in six countries, discriminated the 196 patients with RLS from the 209 control subjects. A single factor—general severity—explained 59% of the variance in the pooled items, and repeat testing in patients and subjects showed good internal consistency. A subsequent factor analysis of this scale identified two subscales—the symptom severity subscale, which includes the impact of sleep disturbance, and the symptom impact subscale, which measures impact on quality of life.275
The Johns Hopkins RLS Rating Scale assesses a single factor, timing of symptom severity, to identify RLS severity.276 In a validation study, based upon patient response (0-4) to the 2 questions, clinician-determined diagnoses, and results of polysomnography, results of this scale correlated well with sleep efficiency and PLMS index, with good interrater reliability.
A recently developed instrument has been shown to be valid164 in measuring the profoundly negative impact of RLS symptoms on quality of life.24,38,127,163,165-171 The Restless Legs Syndrome Quality of Life Instrument comprises 17 questions (6-point responses) that have good internal consistency and test-retest stability. Four factors—daily function, social function, sleep quality, and emotional well-being—account for 73.3% of variance in the questions. A subsequent study, aimed at modeling the relationship between symptoms and impact on quality of life, revealed that the decrease in functional alertness and the emotional distress in patients with RLS is caused by the impact of RLS symptoms on sleep.168
continued next post
Nowadays, there are various websites devoted to RLS.
For example
http://www.ninds.nih.gov/disorders/restless_legs/restless_legs.htm#What_is
What is Restless Legs Syndrome?
Restless legs syndrome (RLS) is a common neurological disorder characterized by unpleasant sensations of the legs and an urge to move them for relief. Individuals affected with the disorder describe the sensations as pulling, drawing, crawling, wormy, boring, tingling, pins and needles, prickly, and sometimes painful sensations that are usually accompanied by an overwhelming urge to move the legs. Movement provides temporary relief from the discomfort.
Is there any treatment?
Massage and application of cold compresses may provide temporary relief. Medications such as temazepam, levodopa/carbidopa, bromocriptine, pergolide mesylate, oxycodone, propoxyphene, and codeine are effective in relieving the symptoms. Current research suggests that correction of iron deficiency may improve symptoms for some patients.
What is the prognosis?
RLS is a life-long condition for which there is no cure. Symptoms may gradually worsen with age. Because symptoms are intensified by inactivity and lying down, RLS patients often have difficulty falling asleep and staying asleep. Left untreated, RLS causes exhaustion and fatigue, which can affect occupational performance, social activities, and family life.
What research is being done?
The National Institute of Neurological Disorders and Stroke (NINDS) and other institutes of the National Institutes of Health (NIH) conduct RLS research in laboratories at the NIH and also support research through grants to major medical institutions across the country. NINDS-supported research is aimed at discovering the mechanisms responsible for motor disorders such as RLS, especially those associated with sleep changes. The goal of this research is to discover ways to prevent, diagnose, treat, and ultimately find cures for motor disorders including RLS.
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Also
http://www.wemove.org/rls/rls.html
What are the symptoms of restless legs syndrome?
In 1995, the International Restless Legs Syndrome Study Group, then comprising 28 investigators from seven countries, defined the four primary features of RLS.
The desire to move the legs in association with unusual or uncomfortable sensations (paresthesias/dysesthesias) deep within the legs, usually in the calves; in some cases, the arms may also be affected. These sensations are described as creeping, burning, tingling, cramping, aching, itching, pulling, crawling, or "water flowing" deep within the affected extremities. Patients with mild or moderate RLS characterize these sensations as uncomfortable; for the most part, they are not perceived as painful. In rare cases, unusual sensations occur in the feet. In even rarer cases, these sensations may also be present in the trunk or genital area. These feelings may move from one part of the body to another or may affect only one side of the body (asymmetric). For example, one leg may have unusual sensations whereas the other does not.
Motor restlessness in response to or in an effort to relieve unusual sensations or discomfort. To the extent that a patient feels a compelling urge to move, these movements may be termed involuntary; however, in so far as a patient chooses which type of movement to perform, these movements are voluntary. Such movements are often repetitive and may include pacing, rocking, shaking, tossing and turning in bed, stretching, bending, marching in place, or engaging in certain repetitive exercises, such as riding an exercise bike or walking on a treadmill. Many individuals develop their own routine of stereotypical movements and tend to repeat these same movements in response to uncomfortable sensations.
Symptoms become obvious or worse while at rest (during periods of inactivity or relaxation) and may be temporarily diminished by voluntary movements of the affected limb(s). This restlessness is sometimes mistaken as "fidgetiness" or "nervousness." The unusual sensations and motor restlessness associated with RLS may also be provoked by prolonged periods of inactivity such as occurs during travel in a plane, train, or car.
Symptoms occur most frequently during the evening or the early part of the night (e.g., between 6 p.m. and 4 a.m.). Individuals with even the most severe RLS symptoms typically obtain some measure of relief during the early morning hours. Worsening of symptoms while at rest and at nighttime may be a very distinctive pattern that is unique to restless legs syndrome.
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And from http://www.mdvu.org/library/disease/rls/ this :
Restless Legs Syndrome
This... ailment... occurs most often when the legs get warm in bed, and prevents going to sleep... A curious unlocalized restlessness is felt in one or both legs. It is not quite a pain, but is distinctly unpleasant. A combination of voluntary movement and involuntary jerks of the affected limb fails to find rest. In ten minutes to an hour the "jitters" depart and sleep comes... The disagreeable sensation stops at once on chewing 1/100 grain of nitroglycerine, suggesting that the cause is vascular.1
Introduction
Known in the common vernacular as the heebie jeebies, Elvis legs, the fidgets, and simply the leg thing, restless legs syndrome (RLS)—a term coined by Swedish neurologist Karl-Axel Ekbom2—is a sensory and movement disorder with a profound impact on sleep. The pulling, tugging, creepy-crawly, electric shock-like, bubbling, or jittery and not infrequently painful sensations are often difficult for patients to describe, leading to reports of sometimes bizarre-sounding symptoms such as Coca-Cola in the veins, insects crawling deep in the tissue, and itching bones. Relief with movement of the affected limb—typically the legs and, not uncommonly, the arms—is one of the distinguishing features. Because of the exacerbation in symptoms with quiescence and the circadian properties of the condition, when people with RLS do seek medical attention, it is often because of their difficulty initiating and maintaining sleep. It is common for people with RLS—after enduring the symptoms for many years—to hear about the disorder in the media and recognize for the first time that their odd sensations indeed constitute a real and treatable condition.
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Primary and Secondary RLS
Primary RLS has been identified as having a more insidious onset of symptoms, which occur at an earlier age (usually before 40 years); patients with primary RLS are more likely to have affected family members than are people in the general population or even those patients with the secondary form of RLS.3-6 In secondary RLS, the onset is usually more precipitous and typically occurs after age 40 years.3-5,7 In this case, RLS occurs in relationship to other conditions, such as pregnancy,8-20 end-stage renal disease (ESRD),21-42 and iron deficiency (with or without anemia)43-56 or with the use of medications, such as dopamine receptor antagonists,57-60 histamine-receptor antagonists,61 selective serotonin reuptake inhibitors,62-70 and other antidepressant drugs.71 Any drugs that cause sedation may prove to be problematic for patients with RLS, particularly if the drugs are taken during the daytime.72
Patients with a late age of onset of symptoms are also less likely to have decreased serum ferritin levels, as compared with patients with early-onset RLS.7 Children and adults with RLS often exhibit symptoms of attention-deficit hyperactivity disorder (ADHD). Whether this occurs because of the impact of RLS on sleep or an overlapping dopaminergic dysfunction is not known.73-80 In children, symptoms of RLS are frequently mislabeled as growing pains.4,6,73,79,81-85
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Diagnostic Criteria
Essential Criteria
Conforming with Ekbom's original description of RLS, the International RLS Study Group developed and published four essential diagnostic criteria for RLS in adults 50 years after Ekbom's original 1945 dissertation86; members of the Study Group and other interested parties revised these criteria in 2002 at a workshop held at the National Institutes of Health (Table 1).87 To support a diagnosis of RLS, all four of these criteria—the sensations and urge to move, relief with movement, exacerbation during quiescence, and worsening of symptoms in the evening and at night—must have been met at some time throughout the course of the patient's condition.
Table 1
Essential Diagnostic Criteria
An urge to move the legs is present, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs.
Sometimes the urge to move is present without the uncomfortable sensations, and sometimes the arms or other body parts are involved in addition to the legs.
The urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity such as lying or sitting.
The urge to move or unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues.
The urge to move or unpleasant sensations are worse in the evening or night than during the day or only occur in the evening or night.
When symptoms are severe, the worsening at night may not be noticeable but must have been previously present.
Modified from Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4(2):101-119.87
The first criterion requires that the patient has an urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs. Some patients, however, are unable to delineate a specific sensation and only relate an overwhelming urge to move the limbs. Typically, these sensations occur in the legs; however, they may also occur in the arms6,88-91 and, very rarely, the trunk or face.92
Criterion two relates to the role of quiescence in increasing the sensations and urge to move. This criterion is supported by the recent work of Michaud et al.,93 who, through the use of the Suggested Immobilization Test (SIT), have verified that patients with RLS, as compared with matched controls, experience more discomfort and have more periodic limb movements during a one-hour testing period.
Criterion three requires that the urge to move or unpleasant sensations be partially or totally relieved by movement. Patients employ a variety of techniques to relieve the sensations and urge to move. These techniques range from simply stretching or rubbing the leg, to pounding the leg and performing deep knee bends, to executing convoluted contortions. The critical factor in this criterion is that the relief is experienced almost as soon as the patient begins the movement and persists as long as the patient continues performing the sensation-relieving movement.
Intrinsic circadian factors define criterion four, with a worsening of symptoms during the evening and night relative to daytime levels94; however, patients with severe RLS may not exhibit a diurnal variation in symptoms. Evidence supports the finding of increased symptoms, both sensory and limb movement, occurring on the falling phase of core body temperature95-98; however, both differences99 and no differences100,101 have been found between daytime and nighttime excretion of melatonin or pulses of prolactin, growth hormone, and cortisol. Recent studies following nighttime treatment with levodopa, as compared with baseline levels before treatment, have shown changes in prolactin release and secretion of growth hormone102 and in the dim-light melatonin onset in patients with RLS but not controls.103
Supportive Clinical Features
In situations with diagnostic uncertainty, the supportive clinical features (Table 2) may assist the clinician in delineating cases of RLS. These features are not required for the diagnosis of RLS, but their presence does lend reinforcement to the diagnosis.
Table 2
Supportive Clinical Features of Restless Legs Syndrome
More than 50% of patients with primary RLS have affected family members.
A positive response to dopaminergic therapy is almost universal.
As many as 85% of people with RLS have periodic limb movements during wakefulness or sleep.
Modified from Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4(2):101-119.87
A variety of research studies have verified the clinical impression that approximately 50% of patients with RLS have a family history of the disorder.3,5,7,104-111 A person with RLS is three to six times more likely to have another family member with RLS than is someone without RLS.7,104
Another clinical feature of both primary and secondary RLS is the almost universal response to dopaminergic therapy.43,103,112-160 The vast majority of people with RLS will have an initial positive response to treatment with either levodopa or a dopamine receptor agonist. If the patient's symptoms do not respond to dopaminergic therapy, the diagnosis may need to be reevaluated.
More than 85% of people with RLS have periodic limb movements during sleep (PLMS), during wakefulness, or during both sleep and wakefulness.161 (Thanks to the popular television program Seinfeld, this condition is also known as jimmy legs162 George Constanza's mother has a derivation known as jimmy arms). Montplaisir and his colleagues have studied the prevalence of both arm and leg movements during sleep, using polysomnography (which in a typical clinical scenario does not include the assessment of arm movements), and during wakefulness, using the SIT.88 During the SIT, patients remain in bed in a semirecumbent position for one hour before their typical sleep time; they are instructed to keep their limbs still. During this test, objective electromyography of leg movements is recorded, as are subjective patient reports of the sensory component.
Associated Features
Associated features of RLS include that those are frequently found in affected individuals but are not specific to the diagnosis of RLS (Table 3).
Table 3
Associated Features of Restless Legs Syndrome
The natural clinical course varies between primary and secondary forms.
Sleep onset and sleep maintenance may be impacted, resulting in severe sleep loss.
Normal findings are present on physical examination in primary RLS; abnormal findings of associated conditions in secondary RLS may be present and may impact the presentation of RLS.
Modified from Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4(2):101-119.87
The natural clinical course of RLS is dependent upon whether the RLS is a primary or a secondary form of the disorder. As mentioned previously, in primary RLS, the onset of symptoms typically occurs at a younger age, is insidious and slowly progressive, and is not related to any secondary etiology. The onset of symptoms in secondary RLS typically begins after age 40 years. The course is one of more-rapid onset and escalation of symptoms coinciding with the causative factor, i.e., ESRD, pregnancy, neuropathy, and iron deficiency—with or without anemia.
The second associated feature of RLS—the disturbance of sleep onset and maintenance of sleep—reflects both the circadian and quiescegenic features of RLS. As the primary precipitating event leading patients to seek treatment, the negative impact of RLS on sleep is at least partially responsible for the reduced quality of life in patients with RLS.24,38,127,163-171
Finally, unless the RLS is related to a secondary condition, the findings on physical examination are typically normal. Identifying and treating relevant secondary causes of RLS will assist in guiding treatment and lead to improved outcome.
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Pathophysiology
Although the underlying cause of RLS has not been determined with certainty, multiple etiologies likely impact the dopaminergic, opioidergic, or both the dopaminergic and opioidergic systems, leading to the symptoms of RLS.
Genetics
The increase of RLS among first-degree relatives, as compared with the prevalence among the general population,104,106,111 has led researchers to investigate the genetic basis of RLS. In 2001, Desautels and his colleagues in Montreal identified a major susceptibility locus on a 14.71-cM region between D12S1044 and D12S78 on chromosome 12q in their large population of French-speaking Canadians.172 Study of a three-generation Italian family subsequently identified another locus—the 14q13-21 region173; this locus was further confirmed by Desautels' group in one of their kindred.174 With the assumption that the RLS in their 15-family, multigenerational pedigrees was inherited in an autosomal-dominant fashion, Chen et al.175 performed a genomewide scan and found evidence suggestive of linkage at 9p24-22 in two families.
Desautels and his colleagues have also examined candidate genes, including those for neurotensin176 and tyrosine hydroxylase, dopamine transporter, dopamine receptors D1 to D5, and dopamine β-hydroxylase177; they found no evidence of genetic linkage to support the role of the dopamine system in the etiology of RLS symptoms. Li et al178 also did not find evidence of linkage when they examined genes responsible for dopamine and iron metabolism in a Chinese Han population with RLS.178 Using complex segregation analysis, Winkelmann et al.108 found evidence supporting the role of a single gene transmitted in an autosomal-dominant pattern in their patients with early-onset RLS; no evidence was found for a major gene in those patients with late-onset RLS.
In studying almost 2000 twin pairs—933 of whom were monozygotic—Desai et al.179 found that 54% of RLS and 60% of PLMS cases were due to heritability. Ondo and his colleagues,180 when examining 12 monozygotic twin pairs with RLS, found a concordance rate of 83%; all of the 10 concordant pairs had at least one affected parent, as did one of the discordant pairs. The age of onset varied by as much as 42 years between the members of the pairs; the severity of symptoms, according to the International RLS Rating Scale, ranged from a low of a two-point difference to a high of a 25-point difference between twin pairs.
Dopaminergic System
The vast majority of RLS patients respond to treatment with dopaminergic agents, although the efficacy is not always maintained on a long-term basis. Conversely, the use of dopamine receptor antagonists that the cross the blood-brain barrier exacerbates the symptoms RLS. However, results of imaging studies, including SPECT and PET, that have attempted to identify abnormalities in the dopamine system have been equivocal. Furthermore, these results may reflect the fact that none of these studies were performed during the night, when RLS symptoms are typically most severe.
None of the 123I β-CIT SPECT studies that have been published to date have shown a difference in the dopamine transporter in patients with RLS, as compared with control subjects.181-184 One 123I-IBZM SPECT study181 has shown a difference in D2-receptor binding between normal control subjects and those with RLS,183-186 and one SPECT study has shown a decrease in D2-receptor binding in patients with nocturnal myoclonus (ie, periodic limb movement disorder187) as compared with controls.188 A single study addressing the issue of regional cerebral blood flow in patients with painful RLS found an increase in anterior cingulate regional cerebral blood flow as pain increased; this pain was secondary to increasing length of immobility.189
PET studies in patients with RLS, as compared with those in control subjects, have shown decreased 18F-DOPA uptake in both the caudate and putamen190 and in only the putamen 191; a decrease in D2-receptor binding in the caudate and putamen191; and, using 18FDG and 18F-DOPA, no difference between the groups.192 The recently published results of research that used 11C-diprenorphine in PET studies to assess the role of the endogenous opioid system in RLS showed that, although there was no difference between patients with RLS and control subjects with regard to opioid-receptor binding, RLS severity and ligand binding were negatively correlated in the medial thalamus, amygdala, caudate, anterior cingulate gyrus insular cortex, and orbitofrontal cortex—areas involved in the medial pain system.193
fMRI studies performed in 1996 did not elicit any structural abnormalities in the brainstem or spinal pathways of patients with idiopathic RLS but did reveal increased activity in the cerebellum, thalamus and pons during RLS symptoms. 194
Iron
The preponderance of recent research dedicated to ascertaining the pathophysiology of RLS, outside that seeking to identify the genetic underpinnings, has been related to iron. As the rate-regulating enzyme in the biosynthesis of dopamine, tyrosine hydroxylase requires iron stores to be present. Serum ferritin levels most accurately reflect stores of iron in the periphery.
Nordlander first proposed the connection between iron deficiency and RLS and the use of intravenous infusions of iron for the treatment of RLS in the 1950s.195 Subsequently, Ekbom noted the prevalence of iron deficiency among his patients with RLS—one in four was found to be iron deficient196—as well as an increase in RLS among blood donors197 and as an early finding in patients with cancer.198 The iron-RLS connection lapsed into obscurity until resurrected by O'Keeffe in Ireland56 and researchers at Johns Hopkins University55 in the 1990s. Both of these groups identified an inverse relationship between symptom severity and levels of ferritin in the serum (< 45 ng/dL in the elderly and < 50 ng/dL in general in patients with RLS, respectively) and a decrease in ferritin levels and an increase in transferrin levels in the cerebrospinal fluid of patients with RLS, as compared with that of controls.199 One caveat worth noting is that serum ferritin levels are elevated in response to both chronic and acute inflammation, a common occurrence in patients with secondary forms of RLS, particularly ESRD200 or infection201; therefore, serum ferritin levels as high as 70 ng/dL may be more reflective of iron stores and may correspond more favorably with RLS symptomatology in patients with inflammatory or infectious states.202
The Hopkins researchers have also performed MRI studies to measure regional brain iron concentration.203 Their use of R'2 as a marker of regional brain iron revealed that iron content is much lower in the substantia nigra of patients with RLS, as compared with that of normal control subjects. The Hopkins group, in collaboration with Connor et al., have clearly established the role of iron deficiency in the brain in the pathogenesis of RLS. Their research from postmortem studies has shown that tissue from RLS patients, as compared with tissue from controls, has reductions in the substantia nigra in heavy-chain or H-ferritin (an indication of high iron utilization and low iron storage), an abnormal distribution of light-chain or L-ferritin within the cells (L-ferritin promotes cerebral iron storage), and decreased transferrin-receptor staining on and increased transferrin staining in cells that contain neuromelanin.204 A second postmortem study has shown a decrease in ferritin, divalent metal transporter 1, ferroportin, and transferrin receptor, with a concomitant increase in transferrin expression in neuromelanin cells; the study also found a decrease in the activity of total iron-regulatory proteins (IRP) and IRP-1, a decrease in the levels of IRP-1, but no changes in IRP-2 activity or levels, indicating an overall iron-deficient state at the cellular level of neuromelanin and a potential defect in IRP-1.205 Most recently, their postmortem studies of RLS patients have revealed a more than 50% decrease in Thy-1, a glycoprotein that is profusely present on the surface of mature neurons and is also present at synaptic vesicles.206 The role of Thy-1 is in regulating vesicular release of neurotransmitters, stabilizing synapses, and suppressing dendritic outgrowth, with coordination of the dopaminergic innervation during development. Expression of Thy-1 is negatively affected by iron deficiency, particularly during early development.
Further support for the iron-RLS connection comes from the efficacy of therapeutic trials of intravenously administered iron45,195,207 and erythropoietin166 and orally administered iron in patients with evidence of low ferritin levels.56 The results of two studies have been recently published: one was an open-label trial of a single 1000-mg infusion of iron dextran in 10 patients with RLS who did not use RLS-related medications in the 5 days prior to the study,207 and the other, a randomized, double-blind, placebo-controlled trial of the same treatment in 30 patients with ESRD and no biochemical evidence of iron deficiency, who continued their concurrent RLS-related therapy.45 Both studies assessed change from baseline, using subjective rating scales, while the open-label study also used actigraphy as an objective measure of periodic limb movements. Six of the 10 patients in the open-label trial were deemed responders to therapy two weeks after treatment, having a dramatic reduction in the global rating scale, a decrease in the PLMS index, and improvement in hours per day without RLS symptoms but no change in total sleep time. The placebo-controlled trial found that baseline symptom severity correlated with serum ferritin levels and iron saturation, which increased with treatment in the control group. Subjective improvement in symptoms was greater in the treated versus the placebo group at one week and two weeks after treatment but not at four weeks; 82% of patients responded to treatment.
Finally, a recent study of children with a PLMS index above 5 per hour showed that 28 of the 39 children had low ferritin levels (below 50 ng/dL); however, serum iron, but not ferritin, correlated significantly with the PLMS index.208,209 Nonetheless, 19 of the children with low ferritin levels had a reduction in the PLMS index and an increase in serum ferritin levels 3 months after treatment with orally administered iron (3 mg/kg per day of ferrous sulfate).
Neurophysiologic Testing
Although traditional studies of electromyography and nerve conduction velocity and evoked potentials are typically normal in patients with RLS,194,210 research evidence from studies seeking to identify the generator of the periodic movements and sensations of RLS have been mixed, showing both cerebral211 as well as spinal sites.212-214 In addition, case reports and prevalence ascertainment studies of RLS in populations with impairments in the spinal cord have found either an increased prevalence in this population or symptom resolution with pharmacologic intervention.187,215-224
The finding of Trenkwalder et al. of a normal Bereitschaftspotential in patients with primary RLS and RLS related to ESRD led the authors to conclude that a subcortical or spinal site generates the involuntary movements of RLS.225 A subcortical site was also posited as the result of abnormal blink reflexes found in a study of 19 patients with PLMS.226 A video-polysomnography-based study of 10 medication-free patients with primary RLS found no regular recruitment pattern preceding PLMS, implying multiple unsynchronized generating sites, most likely due to abnormal hyperexcitability of the spinal cord.227
Transcranial magnetic stimulation studies in patients with RLS, as compared with those in normal control subjects, have shown variable results, ranging from normal motor threshold, duration of silent period, and motor evoked potential recruitment and reduced cortical inhibition after stimulation of foot and ankle muscles,228 and a decreased duration of the cortical silent period,229 to completely normal findings.230 In the most recent study, Scalise et al.231 showed reduced cortical inhibition in six patients with primary RLS, manifest by a lack of increase in the amplitude of the motor evoked potentials and delay of facilitation after rest following a bilateral two-finger tapping task in single transcranial magnetic stimulation.
Two recent studies have identified abnormalities in central somatosensory processing in patients with RLS.232,233 In the first, 16 patients with secondary RLS (72.5%) and 11 with primary RLS (55%) had pathologic changes in temperature sensitivity, with sensory deficits likely linked to small-fiber neuropathy in secondary RLS and a central process in primary RLS.232 Stiasny-Kolster et al.233 examined pain sensitivity at baseline and after long-term treatment with levodopa in 11 patients with primary RLS; they found that mechanical pain was increased in the arms (by a factor of 5.3) and legs (by a factor of 6.4) in RLS subjects, as compared with controls, and that long-term dopaminergic therapy modulated this static mechanical hyperalgesia, highlighting for the first time, the impression that RLS may be a disorder of pain modulation as well as of motor control.
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Epidemiology
The establishment of diagnostic criteria for RLS has provided the framework upon which to build the prevalence estimates of RLS. These efforts have been further enhanced by the development of three proposed questions specifically related to epidemiologic studies as part of the 2002 National Institutes of Health workshop (Table 4).87 By slightly changing the wording of the three questions, it is possible to establish a point prevalence rather than a lifetime history of RLS. A fourth question—How often do these feelings occur?—serves as a surrogate for symptom severity.
Table 4
Proposed Questions for the Epidemiologic Study of Restless Legs Syndrome
Do you have unpleasant sensations in your legs combined with an urge or need to move your legs?
Do these feelings occur mainly or only at rest and do they improve with movement?
Are these feelings worse in the evening or night than in the morning?
Modified from Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4(2):101-119.87
Although epidemiologic studies show a wide variation in the prevalence of RLS—dependent upon the population studied, the degree of scrutiny exercised, and the criteria used to diagnose the condition—RLS appears, in general, to affect approximately 7% to 12% of people of European extraction, with lower numbers identified in people of African and Asian descent. Specific populations, including the elderly, patients with ESRD, and pregnant women, have RLS at an increased rate compared with the general population, even in those ethnic populations in which RLS is virtually nonexistent. In most studies, women appear to be affected more often than men.
General Population
Ekbom proposed a 5% prevalence rate of RLS among adults in Sweden,2 and Lavigne and Montplaisir found a prevalence of 8% overall and a higher rate in Roman Catholic French-speaking as compared with Protestant English-speaking Canadians subjects, perhaps indicating a founder effect.234 Over the past 8 years, the National Sleep Foundation has found that 13% to 15% of the respondents to their random-dial telephone surveys acknowledge having "unpleasant feelings in their legs (such as creepy, crawly or tingly feelings) at least a few nights a week"; 3% of respondents have been told by their physician that they have RLS.235-240 The single question regarding symptoms of RLS on the 1996 Kentucky Behavior Risk Factor Surveillance identified 19.4% of 1456 respondents as ever having such symptoms, with 5.9% having them more than 15 times per month.241
Ohayon and Roth242 ascertained the prevalence of RLS in 5 European countries via telephone interviews and identified 5.5% of the population as having RLS, with only 11.9% of these individuals having had consulted a physician about their symptoms.242 The Study of Health in Pomerania165 found the prevalence of RLS in women to be 13.4% overall, with a low of 4.9% among those aged 20 to 29 years and a high of 19.4% among women aged 50 to 59 years; in men, the overall prevalence was 7.6%, with prevalences of 3.0% among the youngest men and 13.2% of men aged 60 to 69 years. Of postal workers in Switzerland (532 men and 136 women), 2% admit that they often have symptoms of RLS.243 A population of Italian shift workers had an 8.5% prevalence of RLS; the rate was 4.2% among those who worked the day shift.244 The point prevalence of primary RLS was 3.19% in an epidemiologic study in Turkey,245 which specifically excluded secondary RLS. Of those people who were found to have RLS in this study, 30% had told their physicians of their symptoms, but only one person had a previous diagnosis of RLS. In two studies in Sweden, 5.8% of men246 and 11.6% of women247 were found to have RLS, with rates highest in those aged 55 to 64 years (10.5%). Ulfberg and Nyström248 also surveyed 946 blood donors in Sweden and found that 14.7% of the men and 24.7% of the women had symptoms that were diagnostic for RLS according to the International RLS Study Group criteria.
Although not directly tied to the rates of RLS in the general population, ascertaining prevalence among primary-care patients does likely reflect the overall prevalence of the disorder. In Singapore, researchers found only 1 person whose symptoms met the diagnostic criteria for RLS in a total patient population of 1000.249 In Ireland, O'Keeffe et al.250 found an overall prevalence of RLS of 10.3% among their primary care patients, with higher rates in woman than in men (12.4% versus 6.5%, respectively). Among 2009 patients seen at a single, rural, primary care clinic, Nichols et al251,252 identified 504 (24%) as having RLS, including those with only mild, occasional, or setting-specific symptoms; when weekly symptoms that were at least mildly distressing were required, the prevalence was 13.7%.
The largest epidemiologic study of RLS to date, which included data from more than 23,000 patients attending primary care clinics in 5 countries, including France (n, 4808), Germany (n, 6723), Spain (n, 5752), the United Kingdom (n, 2114), and the United States (n, 3655), found a prevalence of 9.6%.253 This study also found wide discrepancies between patients' and physicians' perceptions of the symptoms of RLS: most of the 551 patients whose symptoms met the diagnostic criteria, occurred at least twice a week, and had at least a mild negative impact on quality of life, reported that they had contacted their physician about their symptoms in the previous year; half of these patients received any diagnosis, and only 49 had a correct diagnosis of RLS.
Special Populations
Elderly
Epidemiologic studies in six countries have focused specifically on symptoms of RLS in older adults. In their 1981 review of polysomnographic records from 83 elderly patients seen the Stanford sleep clinic over a two-year period, Coleman et al.254 identified 18% as having what the researchers termed periodic movements-restless legs syndrome. The 2003 National Sleep Foundation Sleep in America Poll survey of adults aged 55 to 75 years old who were living in their homes identified 17% of people as having symptoms of RLS, with 6% of them having been told by their physician that they have RLS and 3% being treated for the disorder.255
At a geriatric outpatient center in Ireland, 5% of 307 consecutive patients were found to meet the diagnostic criteria for RLS and have bilateral leg involvement.256 In the first large-scale epidemiologic study of RLS using the 1995 criteria, Rothdach et al.170 found a prevalence of RLS of 9.76% in Germans over the age of 65 years, with women having a higher rate, as compared with men. A recent study of RLS prevalence among those aged 50 years and older in the Netherlands elicited a prevalence rate of 7.1%, with higher rates among women and those who were older.171
In Singapore, only 1 of 157 adults aged 55 years or older who were examined met the criteria for RLS (0.6%).249 Sukegawa et al.257 quantified the association between sleep disturbances and depression among 2023 Japanese adults (aged 65 years or older) and found that more people in the depression group (5.8%) had symptoms of RLS, as compared with those in a control group (2.4%). The highest prevalence was found in men younger than 75 years of age (8.4%).
End-Stage Renal Disease
The increased prevalence of RLS in patients with ESRD has been well established, although the percentage of affected individuals varies dependent upon the ethnic makeup of the population, as well as the criteria and degree of scrutiny used in making the determination. Indeed, the presence of RLS symptoms has been correlated with premature discontinuation of dialysis,37 decreased quality of life,24,30,38,166,258,259 and lower 1- and 2-year survival rates.37 Winkelman et al.37 found that 20% of patients with ESRD reported moderate to severe symptoms of RLS, as opposed to 6% in a control group.
Walker et al.38 established an RLS prevalence of 57.4% among 54 patients being treated at a dialysis center in Canada. The study of Collado-Seidel et al.36 at 2 centers in Germany found that 23% of the 136 patients who had been on stable dialysis for the previous 2 years had RLS, with intact parathyroid hormone levels correlating with the presence of RLS. In two studies at dialysis clinics in Hong Kong, Hui et al.32,260 established the prevalence of RLS as 62% of 201 and 70% of 43 ethnic Chinese patients, respectively. In Chile, Miranda and colleagues261 found that 26% of 166 patients with ESRD and 13% of a control group (comprising patients' relatives) had RLS. Studies among patients at dialysis clinics in Italy,262 India,31 and Japan258 have found prevalence rates of RLS of 37%, 6.6%, and 25.3%, respectively. In the study conducted in India, no RLS was found in a control population. Another recent study at a dialysis clinic in Italy263 found a prevalence of 21.5%, with 37.5% of patients with polyneuropathy having a positive diagnosis of RLS.
Kutner and her coworkers29 at Emory University in Atlanta, Georgia, looked at the racial differences in a statewide study of elderly people (60 years and older) who were receiving dialysis treatment for ESRD: 68% of Caucasians and 48% of African Americans had symptoms of RLS. A study in Brazil27 also looked at the racial differences in 176 patients with ESRD; they found that 11.4% of non-Caucasian patients compared with 17.5% of Caucasian patients had RLS (overall prevalence of 14.8%).
Pregnancy
Women with preexisting RLS often experience an increase in symptom severity, particularly in the third trimester, and those without previous symptoms often experience RLS for the first time during pregnancy. Goodman et al.8 determined that approximately 19% of 500 women during their third trimester of a singleton pregnancy experienced symptoms of RLS—16 had symptoms that predated their pregnancies. By the fourth week postpartum, symptoms had resolved in all but 3 women.
Ekbom identified a prevalence rate of approximately 11% in 788 pregnant women.264,265 Botez et al.,9 found that 9% of their pregnant patients who were taking folate supplements had RLS; 80% of those who did not supplement their folate intake experienced RLS symptoms.
Recent studies in Italy,266 Japan,20 Finland,10 and the United States,267 which employed a variety of diagnostic criteria, confirmed rates of RLS in pregnant women as 27%, 19.9%, 37.7%, and 23%, respectively. Even though other epidemiologic studies in Japan (including in general and elderly populations) have found relatively low rates of RLS, the study by Suzuki and colleagues20 of more than 16,000 pregnant women found rates varying from 19% to 26%, depending upon maternal age.
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Diagnosis
The diagnosis of RLS is based upon the history obtained from the patient and physical examination, with history confirming the four required diagnostic criteria. The differential includes a variety of neurologic, vascular, and other sensory conditions (Table 5).
Table 5
Conditions in the Differential Diagnosis of RLS
Akathisia
Burning feet syndrome
Fibromyalgia
Intermittent claudication
Meralgia paresthetica
Nocturnal leg cramps
Pathophysiologic insomnia
Polyneuropathy
Positional discomfort
Radiculopathy
Tardive dyskinesia
Tourette syndrome
Vascular insufficiency
Elicitation of the history should focus on factors related to family history, gross or microscopic blood loss (eg, recent operation or injury, frequent blood donation, hypermenorrhea, aspirin use, vitamin K deficiency, and infection with Helicobacter pylori or other causes of gastrointestinal bleeding), and the use of or exposure to medications or substances that are known to be associated with an increase in RLS symptomatology (Table 6). Antidepressant medications have been clinically reported to exacerbate RLS, thereby worsening sleep problems. Paradoxically, some patients report benefit from the use of these medications. While no studies have clearly addressed these issues, the treating physician should be aware of the potential of tricyclic antidepressants and serotonin reuptake inhibitors, such as mianserin, fluoxetine (Prozac®), and sertraline (Zoloft®) to worsen the symptoms of RLS.
Table 6
Medications and Substances Related to Increased RLS Symptoms
Medications Substances
Dopamine receptor antagonists60 Caffeine268,269
Metoclopramide59 Nicotine165,241,242,270,271
Antipsychotics Alcohol242
Droperidol57,58
Prochlorperazine
Antidepressants, particularly those causing sedation
Selective serotonin reuptake inhibitors62-69
Tricyclics70,71
Antihistamines, particularly first-generation H1-receptor antagonists61
As mentioned in the section on associated features, the examination is typically normal in patients with primary RLS. Findings on physical examination in patients with secondary RLS are most often those related to the associated condition and guide the clinician in obtaining additional testing. Although no standardized tests reveal the diagnosis of RLS, laboratory measures of anemia status, iron stores (e.g., ferritin, total iron-binding capacity, and percentage of transferrin saturation) and serum glucose levels may be warranted. Nerve conduction studies and electromyography may be appropriate for patients with evidence on physical examination of neuropathy. In patients who have symptoms of a sleep disorder other than RLS, polysomnography may be necessary, and results may help to clarify clinical challenges.272
A recently validated telephone interview, based on the 1995 International RLS Study Group criteria, is useful for the diagnosis of RLS for research purposes.273 Reliability of the diagnosis among the three raters was strong, with good sensitivity (97%) and specificity (92%). The diagnosis was most easily established in patients with severe symptoms of RLS and most difficult to ascertain in control subjects. Elucidating differences between symptoms of RLS and those of nocturnal leg cramps proved to be the greatest challenge.
Rating Scales
Rating scales have recently been developed and validated to quantify the severity of RLS symptoms for research purposes and to measure treatment efficacy. The scale of the International RLS Study Group includes patient-rated subjective responses to 10 questions, with responses ranging from 0 to 4.274 This scale, validated at 20 centers in six countries, discriminated the 196 patients with RLS from the 209 control subjects. A single factor—general severity—explained 59% of the variance in the pooled items, and repeat testing in patients and subjects showed good internal consistency. A subsequent factor analysis of this scale identified two subscales—the symptom severity subscale, which includes the impact of sleep disturbance, and the symptom impact subscale, which measures impact on quality of life.275
The Johns Hopkins RLS Rating Scale assesses a single factor, timing of symptom severity, to identify RLS severity.276 In a validation study, based upon patient response (0-4) to the 2 questions, clinician-determined diagnoses, and results of polysomnography, results of this scale correlated well with sleep efficiency and PLMS index, with good interrater reliability.
A recently developed instrument has been shown to be valid164 in measuring the profoundly negative impact of RLS symptoms on quality of life.24,38,127,163,165-171 The Restless Legs Syndrome Quality of Life Instrument comprises 17 questions (6-point responses) that have good internal consistency and test-retest stability. Four factors—daily function, social function, sleep quality, and emotional well-being—account for 73.3% of variance in the questions. A subsequent study, aimed at modeling the relationship between symptoms and impact on quality of life, revealed that the decrease in functional alertness and the emotional distress in patients with RLS is caused by the impact of RLS symptoms on sleep.168
continued next post
posted by bakerchiropractic at 8:16 PM
links to this post
Cost Effectiveness of Chiropractic in Work Comp in Texas
State of Texas Workers' Compensation Study ~ 2003
In 2002, the Texas Chiropractic Association (TCA) commissioned an independent study to determine the use and effectiveness of chiropractic with regard to workers' compensation, the results of which were published in February. According to the report, Chiropractic Treatment of Workers' Compensation Claimants in the State of Texas, chiropractic care was associated with significantly lower costs and more rapid recovery in treating workers with low-back injuries. They found: Lower back and neck injuries accounted for 38 percent of all claims costs. Chiropractors treated about 30 percent of workers with lower back injuries, but were responsible for only 17.5 percent of the medical costs and 9.1 percent of the total costs. These findings were even more intertesting: The average claim for a worker with a low-back injury was $15,884. However, if a worker received at least 75 percent of his or her care from a chiropractor, the total cost per claimant decreased by nearly one-fourth to $12,202. If the chiropractor provided at least 90 percent of the care, the average cost declined by more than 50 percent, to $7,632
In 2002, the Texas Chiropractic Association (TCA) commissioned an independent study to determine the use and effectiveness of chiropractic with regard to workers' compensation, the results of which were published in February. According to the report, Chiropractic Treatment of Workers' Compensation Claimants in the State of Texas, chiropractic care was associated with significantly lower costs and more rapid recovery in treating workers with low-back injuries. They found: Lower back and neck injuries accounted for 38 percent of all claims costs. Chiropractors treated about 30 percent of workers with lower back injuries, but were responsible for only 17.5 percent of the medical costs and 9.1 percent of the total costs. These findings were even more intertesting: The average claim for a worker with a low-back injury was $15,884. However, if a worker received at least 75 percent of his or her care from a chiropractor, the total cost per claimant decreased by nearly one-fourth to $12,202. If the chiropractor provided at least 90 percent of the care, the average cost declined by more than 50 percent, to $7,632
posted by bakerchiropractic at 9:26 AM
links to this post
The Cost-Effectiveness of Chiropractic
Effects of a Managed Chiropractic Benefit on the Use of Specific Diagnostic and Therapeutic Procedures in the Treatment of Low Back and Neck Pain
J Manipulative Physiol Ther 2005 (Oct); 28 (8): 564–569
For the treatment of low back and neck pain, the inclusion of a chiropractic benefit resulted in a reduction in the rates of surgery, advanced imaging, inpatient care, and plain-film radiographs. This effect was greater on a per-episode basis than on a per-patient basis.
Cost-effectiveness of Medical and Chiropractic Care for Acute and Chronic Low Back Pain
J Manipulative Physiol Ther 2005 (Oct); 28 (8): 555–563
Acute and chronic chiropractic patients experienced better outcomes in pain, functional disability, and patient satisfaction. Chiropractic care appeared relatively cost-effective for the treatment of chronic LBP. Chiropractic and medical care performed comparably for acute patients. Practice-based clinical outcomes were consistent with systematic reviews of spinal manipulation efficacy: manipulation-based therapy is at least as good as and, in some cases, better than other therapeusis. This evidence can guide physicians, payers, and policy makers in evaluating chiropractic as a treatment option for low back pain. There are more articles like this in the Low Back Pain Page.
Comparative Analysis of Individuals With and Without Chiropractic Coverage: Patient Characteristics, Utilization, and Costs
Arch Intern Med 2004 (Oct 11); 164 (18): 1985–1892
A 4-year retrospective claims data analysis comparing more than 700,000 health plan members within a managed care environment found that members had lower annual total health care expenditures, utilized x-rays and MRIs less, had less back surgeries, and for patients with chiropractic coverage, compared with those without coverage, also had lower average back pain episode-related costs ($289 vs $399, P<.001). The authors concluded: "Access to managed chiropractic care may reduce overall health care expenditures through several effects, including (1) positive risk selection; (2) substitution of chiropractic for traditional medical care, particularly for spine conditions; (3) more conservative, less invasive treatment profiles; and (4) lower health service costs associated with managed chiropractic care." You will also enjoy this recent press release.
The medical "debate" has been going on for years...is spinal adjusting (a.k.a manipulation) effective for Low Back Pain? The original Meade study (British Medical Journal 1990) demonstrated that chiropractic was much more effective for LBP than conventional medical care. Medicine was horrified when the Agency for Health Care Policy and Research (AHCPR) confirmed in 1994 that most of what medicine did for LBP was useless, and that only chiropractic care could both reduce pain AND improve function. Then Meade did the follow-up study in British Medical Journal 1995, which once again demonstrated that those treated by chiropractic derive more benefit and long term satisfaction than those treated by hospitals, especially for chronic (long-term) LBP!
A recent study in SPINE Journal revealed that health care expenditures for back pain sufferers were a staggering $90.7 billion in 1998 and that prescription drugs accounted for more than 15% of that figure. Considering that muscle relaxants are associated with slower recovery, and that steroid injections offer minimal relief, one has to ask why drug use costs continue to climb?
A recent 4-year retrospective study of 700,000 health plan members revealed that offering chiropractic services within a managed-care environment could save insurers 27% in back pain episode-related costs! The Cost-effectiveness Page documents many other studies with similar findings.
In December 2004, the British Medical Research Council published 2 papers in the British Medical Journal demonstrating both the efficacy and cost-effectiveness of chiropractic compared with medical management. I believe this concludes the debate portion of our presentation!
An Evaluation of Medical and Chiropractic Provider Utilization and Costs: Treating Injured Workers in North Carolina
J Manipulative Physiol Ther 2004 (Sep); 27 (7): 442–448
Average cost of treatment, hospitalization, and compensation payments were higher for patients treated by MDs than for patients treated by DCs. Average number of lost workdays for patients treated by MDs was higher than for those treated by DCs. Combined care patients generated higher costs than patients treated by MDs or DCs alone.
Clinical and Cost Outcomes of an Integrative Medicine IPA
J Manipulative Physiol Ther 2004 (Jun) ; 27 (5): 336–347
Analysis of clinical and cost outcomes on 21,743 member months over a 4-year period demonstrated decreases of 43.0% in hospital admissions per 1000, 58.4% hospital days per 1000, 43.2% outpatient surgeries and procedures per 1000, and 51.8% pharmaceutical cost reductions when compared with normative conventional medicine IPA performance for the same HMO product in the same geography over the same time frame.
Effects of Inclusion of a Chiropractic Benefit on the Utilization of Health Care Resources in Managed Health Care Plan
Craig F Nelson, D.C., MS
A four-year longitudinal study using administrative claims data compared 700,000 health plan members with chiropractic coverage to 1 million health plan members without chiropractic coverage. This study demonstrates that the inclusion of a chiropractic benefit in a managed health care plan results in a reduction in the overall utilization of health care resources, and thereby, cost savings. There are four mechanism that produce this cost reduction: 1. A favorable selection process; 2. A substitution effect of chiropractic care for medical care; 3. Lower rates of use of high cost procedures; 4. Lower cost management of care episodes by chiropractors. You might also enjoy this sidebar article on this topic.
Chiropractic Care: Is It Substitution Care or Add-on Care in Corporate Medical Plans?
J Occup Environ Med 2004 (Aug); 46 (8): 847-855
An analysis of claims data from a managed care health plan was performed to evaluate whether patients use chiropractic care as a substitution for medical care or in addition to medical care. For the 4-year study period, there were 3,129,752 insured member years in the groups with chiropractic coverage and 5,197,686 insured member years in the groups without chiropractic coverage. These results (of this file review) indicate that patients use chiropractic care as a direct substitution for medical care.
Preliminary Findings of Analysis of Chiropractic Utilization and Cost in the Workers' Compensation System of New South Wales, Australia
J Manipulative Physiol Ther 1995 (Oct); 18 (8): 503–511
The methodology used was found to be able to provide a basis for comparison of costs for care apportioned to chiropractic and other interventions. An analysis of 20 randomly selected cases from the WCA suggested that chiropractic intervention for certain conditions may be more cost-effective than other forms of intervention.
A Comparison of Health Care Costs for Chiropractic and Medical Patients
J Manipulative Physiol Ther 1993 (Jun); 16 (5): 291–299
Nearly one-fourth of patients were treated by chiropractors. Patients receiving chiropractic care experienced significantly lower health care costs as represented by third party payments in the fee-for-service sector. Total cost differences on the order of $1,000 over the 2-yr period were found in the total sample of patients as well as in subsamples of patients with specific disorders. The lower costs are attributable mainly to lower inpatient utilization. The cost differences remain statistically significant after controlling for patient demographics and insurance plan characteristics.
Further Analysis of Health Care Costs for Chiropractic and Medical Patients
J Manipulative Physiol Ther 1994 (Sep); 17 (7): 442–446
The analysis of well-insured patients in plans that do not restrict the chiropractic benefit strengthens results previously reported. In this study, therefore, the favorable cost patterns for chiropractic patients cannot be attributed to insurance restrictions limiting reimbursement for chiropractic services relative to other services. Because adjustments for patient characteristics systematically reduce the cost advantages of chiropractic patients as compared to mean differences derived from unadjusted data, the results also demonstrate that adjusted values should be used for meaningful comparisons between the two groups of patients.
Economic Case for the Integration of Chiropractic Services into the Health Care System
J Manipulative Physiol Ther 2000 (Feb); 23 (2): 118-122
For much of its history, chiropractic care has been both an alternative therapeutic paradigm and separate from or marginal to the mainstream health care system. Over the past decade, the situation has changed somewhat in that chiropractic care is gradually being integrated within a variety of health care delivery organizations. According to Triano et al,1 by the application of evidence-based health care and good business, there is a surge in cooperation and integration among chiropractors, allopathic physicians, allied health care providers, ancillary therapists, and respective support staff. There is, however, no quantification of the level of integration. Integration may also be more true of the United States than elsewhere. The overall position of chiropractic care as alternative and separate still predominates. This situation does not serve the interests of the chiropractic profession nor the public well. There is a persuasive economic case for a radical shift in the role of chiropractic care to one that may succinctly be described as alternative and mainstream. The chiropractic profession must preserve its identity and its unique therapeutic paradigm and continue to be seen as an alternative to other health care professions, especially medical doctors. However, it should also become mainstream and thus widely available and accessible to the public by being integrated into the wide variety of health care delivery organizations that collectively constitute the health care system.
In the treatment of musculoskeletal disorders, despite the fact that most studies have not properly factored in such patient characteristics as severity and chronicity and lack the complete assessment of all direct costs and most indirect costs, the bulk of articles reviewed demonstrate lower costs for chiropractic. 9 This pattern is consistently observed from the perspectives of workers' compensation studies, 10-15 databases from insurers, 16-18 or the analysis of a health economist employed by the provincial government of Ontario. 19-20 Other studies have suggested the opposite [that chiropractic services are more expensive than medical], 5,21,22 but these contain significant flaws 21 which have been refuted. 23
The cost advantages for chiropractic for matched conditions appear to be so dramatic that Pran Manga, the aforementioned Canadian health economist, has concluded that doubling the utilization of chiropractic services from 10% to 20% may realize savings as much as $770 million in direct costs and $3.8 billion in indirect costs. 20 When iatrogenic effects [yet to be discussed] are factored in, the cost advantages of spinal manipulation as a treatment alternative become even more prominent. In one study, for instance, it was shown that for managing disc herniations, the cost of treatment failures following a medical course of treatment [chymopapain injections] averaged 300 British pounds per patient, while there were no such costs following spinal manipulation. 24 Imagine how failed back surgery might compare. Finally, in no cost studies to date have legal burdens been calculated, which one would expect should be heavily advantageous for chiropractic health management.
From: Testimony to the Department of Veterans Affairs' Chiropractic Advisory Committee
George B. McClelland, D.C., Foundation for Chiropractic Education and Research
March 25, 2003
9 Cost Comparison of Chiropractic and Medical Treatment of Common Musculoskeletal Disorders: A Review of the Literature After 1980
Topics in Clinical Chiropractic 1999; 6 (2): 57–68
A total of 5 prospective and 19 retrospective studies was identified. Twelve of the 24 studies were published since 1994. Sixteen of the 24 studies' average total costs favored chiropractic treatment.
10 Cost Per Case Comparison of Back Injury Claims of Chiropractic Versus Medical Management for Conditions With Identical Diagnostic Codes
J Occup Med 1991 (Aug); 33 (8): 847–852
This workers’ compensation study conducted in Utah compared the cost of chiropractic care to the costs of medical care for conditions with identical diagnostic codes. The study indicated that costs were significantly higher for medical claims than for chiropractic claims. The sample consisted of 3062 claims or 40.6% of the 7551 estimated back injury claims from the 1986 Workers' Compensation Fund of Utah. For the total data set, cost for care was significantly more for medical claims, and compensation costs were 10-fold less for chiropractic claims.
11 Disabling Low Back Oregon Workers' Compensation Claims. Part I: Methodology and Clinical Categorization of Chiropractic and Medical Cases
J Manipulative Physiol Ther 1991 (Mar-Apr); 14 (3): 177–184
The two provider groups differed in the proportion of claimants who had physical factors contributing to low back compromise. DC claimants were less likely than MD claimants to have sought initial treatment in the emergency room, more likely to have a history of chronic, recurrent low back pain and more likely to have suffered exacerbation episodes. These differences suggest a greater level of chronicity among chiropractic claimants.
12 Disabling Low Back Oregon Workers' Compensation Claims. Part II: Time Loss
J Manipulative Physiol Ther 1991 (May); 14 (4): 231–239
for claimants with a history of chronic low back problems, the median time loss days for MD cases was 34.5 days, compared to 9 days for DC cases. It is suggested that chiropractors are better able to manage injured workers with a history of chronic low back problems and to return them more quickly to productive employment.
14 A Comparison of Chiropractic, Medical and Osteopathic Care for Work-related Sprains and Strains
J Manipulative Physiol Ther 1989 (Oct); 12 (5): 335–344
For those who received care from DCs (n = 266), the mean number of compensated days lost from work was at least 2.3 days less than for those who were treated by MDs (n = 494; p less than 0.025) and at least 3.8 days less than for those who were treated by DOs (n = 102; p less than 0.025). Consequently, much less money in employment compensation was paid, on the average, to those who saw DCs.
15 An Analysis of Florida Workers' Compensation Medical Claims for Back-related Injuries
Journal of the American Chiro Association 1988; 25 (7): 50–59
This study of 10,652 Florida Workers’ Compensation cases was conducted by Steve Wolk, Ph.D. , and reported by the Foundation for Chiropractic Education and Research. It was concluded that “a claimant with a back-related injury, when initially treated by a chiropractor versus a medical doctor, is less likely to become temporarily disabled, or if disabled, remains disabled for a shorter period of time; and claimants treated by medical doctors were hospitalized at a much higher rate than claimants treated by chiropractors.” The analysis focused on the cost of treatment, frequency of compensable injuries (an injury which disables an individual for more than seven days, resulting in wage compensation benefits), and frequency of hospitalization for workers' compensation claim patient (end of reference).
16 A Comparison of the Cost of Chiropractors Versus Alternative Medical Practitioners
Richmond, VA: Virginia Chiropractic Association, 1992
A 1992 study conducted by L.G. Schifrin, Ph.D., provided an economic assessment of mandated health insurance coverage for chiropractic treatment within the Commonwealth of Virginia. As reported by the College of William and Mary, and the Medical College of Virginia, the study indicated that chiropractic provides therapeutic benefits at economical costs. The report also recommended that chiropractic be a widely available form of health care. This paper is unavailable through PubMed or the Mantis database.
17 Chiropractic and Medical Costs of Low Back Care
Med Care 1996 (Mar); 34 (3): 191–204
This study compares health insurance payments and patient utilization patterns for episodes of care for common lumbar and low back conditions treated by chiropractic and medical providers. Using 2 years of insurance claims data, this study examines 6,183 patients who had episodes with medical or chiropractic first-contact providers. Multiple regression analysis, to control for differences in patient, clinical, and insurance characteristics, indicates that total insurance payments were substantially greater for episodes with a medical first-contact provider.
18 Costs and Recurrences of Chiropractic and Medical Episodes of Low-back Care
J Manipulative Physiol Ther 1997 (Jan); 20 (1): 5–12
Total insurance payments within and across episodes were substantially greater for medically initiated episodes. Analysis of recurrent episodes as measures of patient outcomes indicated that chiropractic providers retain more patients for subsequent episodes, but that there is no significant difference in lapse time between episodes for chiropractic vs. medical providers. Chiropractic and medical patients were comparable on measures of severity; however, the chiropractic cohort included a greater proportion of chronic cases.
19 The Effectiveness and Cost-Effectiveness of Chiropractic Management of Low-Back Pain
Richmond Hill, Ontario: Kenilworth Publishing, 1993
A major study to assess the most appropriate use of available health care resources was reported in 1993. This was an outcomes study funded by the Ontario Ministry of Health. The study was conducted by three health economists led by University of Ottawa Professor Pran Manga, Ph.D. The report of the study is commonly called the Manga Report. The Manga Report overwhelmingly supported the efficacy, safety, scientific validity, and cost-effectiveness of chiropractic for low-back pain. Additionally, it found that higher patient satisfaction levels were associated with chiropractic care than with medical treatment alternatives. On the evidence, particularly the most scientifically valid clinical studies, spinal manipulation applied by chiropractors is shown to be more effective than alternative treatments for LBP. Many medical therapies are of questionable validity or are clearly inadequate.
20 Enhanced Chiropractic Coverage Under OHIP as a Means for Reducing Health Care Costs, Attaining Better Health Outcomes and Achieving Equitable Access to Health Services
Report to the Ontario Ministry of Health, 1998
Expenditure to improve access to chiropractic services, and the changed utilization patterns it produces, will lead to very substantial net savings in direct and indirect costs. Direct savings to Ontario's health care system may be as much as $770 million, will very likely be $548 million, and will be at least $380 million. The corresponding savings in indirect costs - made up of the short and long term costs of disability - are $3.775 billion, $1.849 billion and $1.255 billion.
21 Comparing the Costs Between Provider Types of Episodes of Back Pain Care
Spine 1995 (Jan 15); 20 (2): 221–227
There were 1020 episodes of back pain care made by 686 different persons and encompassing 8825 visits. Chiropractors and general practitioners were the primary providers for 40% and 26% of episodes, respectively. Chiropractors had a significantly greater mean number of visits per episode (10.4) than did other practitioners. Orthopedic physicians and "other" physicians were significantly more costly on a per visit basis. Orthopedists had the highest mean total cost per episode, and general practitioners the lowest.
23 [Letter to the editor regarding] Comparing the Costs Between Provider Types of Episodes of Back Pain Care
Spine 1995 (Dec); 20 (23): 2595–2596
Based on the proliferation of more recent studies that have selected (by means of provider codes) a patient population that is narrower, yet more homogeneous, I conclude that the burden of proof for the higher cost of chiropractic healthcare without hospital services remains on the authors of this article. There appears to be too many questions raised by this study that, if they remain unanswered, prevent it from becoming a major addition to the chiropractic literature.
24 Single-blind Randomised Controlled Trial of Chemonucleolysis and Manipulation in the Treatment of Symptomatic Lumbar Disc Herniation
Eur Spine J 2000 (Jun); 9 (3): 202–207
In this study it was shown that for managing disc herniations, the cost of treatment failures following a medical course of treatment [chymopapain injections] averaged 300 British pounds per patient, while there were no such costs following spinal manipulation.
Additional Cost-Effectiveness Studies
Thanks to the National Board of Chiropractic Examiners
for collecting some of these studies!
State of Texas Workers' Compensation Study ~ 2003
In 2002, the Texas Chiropractic Association (TCA) commissioned an independent study to determine the use and effectiveness of chiropractic with regard to workers' compensation, the results of which were published in February. According to the report, Chiropractic Treatment of Workers' Compensation Claimants in the State of Texas, chiropractic care was associated with significantly lower costs and more rapid recovery in treating workers with low-back injuries. They found: Lower back and neck injuries accounted for 38 percent of all claims costs. Chiropractors treated about 30 percent of workers with lower back injuries, but were responsible for only 17.5 percent of the medical costs and 9.1 percent of the total costs. These findings were even more intertesting: The average claim for a worker with a low-back injury was $15,884. However, if a worker received at least 75 percent of his or her care from a chiropractor, the total cost per claimant decreased by nearly one-fourth to $12,202. If the chiropractor provided at least 90 percent of the care, the average cost declined by more than 50 percent, to $7,632.
University of Saskatchewan Study ~ 1985
In 1985 the University of Saskatchewan conducted a study of 283 patients “who had not responded to previous conservative or operative treatment” and who were initially classified as totally disabled. The study revealed that “81% ... became symptom free or achieved a state of mild intermittent pain with no work restrictions” after daily spinal manipulations were administered.
American Health Policy Report ~ 1992
A 1992 review of data from over 2,000,000 users of chiropractic care in the U.S., reported in the Journal of American Health Policy, stated that “chiropractic users tend to have substantially lower total health care costs,” and “chiropractic care reduces the use of both physician and hospital care.”
British Medical Journal ~ 1990
A study conducted by T.W. Meade, a medical doctor, and reported in the June 2, 1990, British Medical Journal concluded after two years of patient monitoring, “for patients with low-back pain in whom manipulation is not contraindicated, chiropractic almost certainly confers worthwhile, long-term benefit in comparison with hospital outpatient management.” More importantly, this article contradicts other articles which maintained that spinal adjusting (manipulation) was only effective for "acute" low back pain. This article found: The benefit is seen mainly in those with chronic or severe pain. Introducing chiropractic into NHS practice should be considered.
British Medical Journal ~ 1995
In the follow-up study to the Meade 1990 BMJ article mentioned above, (August 5, 1995 , British Medical Journal) the author states: At three years the results confirm the findings of an earlier report that when chiropractic or hospital therapists treat patients with low back pain as they would in day to day practice those treated by chiropractic derive more benefit and long term satisfaction than those treated by hospitals.
Washington HMO Study
In 1989, a survey administered by Daniel C. Cherkin, Ph.D., and Frederick A. MacCornack, Ph.D., concluded that patients receiving care from health maintenance organizations (HMOs) within the state of Washington were three times as likely to report satisfaction with care from chiropractors as they were with care from other physicians. The patients were also more likely to believe that their chiropractor was concerned about them.
Patient Disability Comparison
A 1992 article in the Journal of Family Practice reported a study by DC Cherkin, Ph.D., which compared patients of family physicians and of chiropractors. The article stated “the number of days of disability for patients seen by family physicians was significantly higher (mean 39.7) than for patients managed by chiropractors (mean 10.8).” A related editorial in the same issue referred to risks of complications from lumbar manipulation as being “very low.”
Stano Cost Comparison Study
A study by Miron Stano, Ph.D., reported in the June 1993 Journal of Manipulative and Physiological Therapeutics involved 395,641 patients with neuromusculoskeletal conditions. Results over a two-year period showed that patients who received chiropractic care incurred significantly lower health care costs than did patients treated solely by medical or osteopathic physicians.
Gallup Poll ~ 1991
A 1991 demographic poll conducted by the Gallup Organization revealed that 90% of chiropractic patients felt their treatment was effective; more than 80% were satisfied with that treatment; and nearly 75% felt most of their expectations had been met during their chiropractic visits.
ACA's Cost Effectiveness Page
A broad collection of studies which find chiropractic to be cost-effective.
Other Studies Focusing on Chiropractic's Cost Effectiveness
This page reviews numerous oyhrt studies which find chiropractic to be cost-effective.
J Manipulative Physiol Ther 2005 (Oct); 28 (8): 564–569
For the treatment of low back and neck pain, the inclusion of a chiropractic benefit resulted in a reduction in the rates of surgery, advanced imaging, inpatient care, and plain-film radiographs. This effect was greater on a per-episode basis than on a per-patient basis.
Cost-effectiveness of Medical and Chiropractic Care for Acute and Chronic Low Back Pain
J Manipulative Physiol Ther 2005 (Oct); 28 (8): 555–563
Acute and chronic chiropractic patients experienced better outcomes in pain, functional disability, and patient satisfaction. Chiropractic care appeared relatively cost-effective for the treatment of chronic LBP. Chiropractic and medical care performed comparably for acute patients. Practice-based clinical outcomes were consistent with systematic reviews of spinal manipulation efficacy: manipulation-based therapy is at least as good as and, in some cases, better than other therapeusis. This evidence can guide physicians, payers, and policy makers in evaluating chiropractic as a treatment option for low back pain. There are more articles like this in the Low Back Pain Page.
Comparative Analysis of Individuals With and Without Chiropractic Coverage: Patient Characteristics, Utilization, and Costs
Arch Intern Med 2004 (Oct 11); 164 (18): 1985–1892
A 4-year retrospective claims data analysis comparing more than 700,000 health plan members within a managed care environment found that members had lower annual total health care expenditures, utilized x-rays and MRIs less, had less back surgeries, and for patients with chiropractic coverage, compared with those without coverage, also had lower average back pain episode-related costs ($289 vs $399, P<.001). The authors concluded: "Access to managed chiropractic care may reduce overall health care expenditures through several effects, including (1) positive risk selection; (2) substitution of chiropractic for traditional medical care, particularly for spine conditions; (3) more conservative, less invasive treatment profiles; and (4) lower health service costs associated with managed chiropractic care." You will also enjoy this recent press release.
The medical "debate" has been going on for years...is spinal adjusting (a.k.a manipulation) effective for Low Back Pain? The original Meade study (British Medical Journal 1990) demonstrated that chiropractic was much more effective for LBP than conventional medical care. Medicine was horrified when the Agency for Health Care Policy and Research (AHCPR) confirmed in 1994 that most of what medicine did for LBP was useless, and that only chiropractic care could both reduce pain AND improve function. Then Meade did the follow-up study in British Medical Journal 1995, which once again demonstrated that those treated by chiropractic derive more benefit and long term satisfaction than those treated by hospitals, especially for chronic (long-term) LBP!
A recent study in SPINE Journal revealed that health care expenditures for back pain sufferers were a staggering $90.7 billion in 1998 and that prescription drugs accounted for more than 15% of that figure. Considering that muscle relaxants are associated with slower recovery, and that steroid injections offer minimal relief, one has to ask why drug use costs continue to climb?
A recent 4-year retrospective study of 700,000 health plan members revealed that offering chiropractic services within a managed-care environment could save insurers 27% in back pain episode-related costs! The Cost-effectiveness Page documents many other studies with similar findings.
In December 2004, the British Medical Research Council published 2 papers in the British Medical Journal demonstrating both the efficacy and cost-effectiveness of chiropractic compared with medical management. I believe this concludes the debate portion of our presentation!
An Evaluation of Medical and Chiropractic Provider Utilization and Costs: Treating Injured Workers in North Carolina
J Manipulative Physiol Ther 2004 (Sep); 27 (7): 442–448
Average cost of treatment, hospitalization, and compensation payments were higher for patients treated by MDs than for patients treated by DCs. Average number of lost workdays for patients treated by MDs was higher than for those treated by DCs. Combined care patients generated higher costs than patients treated by MDs or DCs alone.
Clinical and Cost Outcomes of an Integrative Medicine IPA
J Manipulative Physiol Ther 2004 (Jun) ; 27 (5): 336–347
Analysis of clinical and cost outcomes on 21,743 member months over a 4-year period demonstrated decreases of 43.0% in hospital admissions per 1000, 58.4% hospital days per 1000, 43.2% outpatient surgeries and procedures per 1000, and 51.8% pharmaceutical cost reductions when compared with normative conventional medicine IPA performance for the same HMO product in the same geography over the same time frame.
Effects of Inclusion of a Chiropractic Benefit on the Utilization of Health Care Resources in Managed Health Care Plan
Craig F Nelson, D.C., MS
A four-year longitudinal study using administrative claims data compared 700,000 health plan members with chiropractic coverage to 1 million health plan members without chiropractic coverage. This study demonstrates that the inclusion of a chiropractic benefit in a managed health care plan results in a reduction in the overall utilization of health care resources, and thereby, cost savings. There are four mechanism that produce this cost reduction: 1. A favorable selection process; 2. A substitution effect of chiropractic care for medical care; 3. Lower rates of use of high cost procedures; 4. Lower cost management of care episodes by chiropractors. You might also enjoy this sidebar article on this topic.
Chiropractic Care: Is It Substitution Care or Add-on Care in Corporate Medical Plans?
J Occup Environ Med 2004 (Aug); 46 (8): 847-855
An analysis of claims data from a managed care health plan was performed to evaluate whether patients use chiropractic care as a substitution for medical care or in addition to medical care. For the 4-year study period, there were 3,129,752 insured member years in the groups with chiropractic coverage and 5,197,686 insured member years in the groups without chiropractic coverage. These results (of this file review) indicate that patients use chiropractic care as a direct substitution for medical care.
Preliminary Findings of Analysis of Chiropractic Utilization and Cost in the Workers' Compensation System of New South Wales, Australia
J Manipulative Physiol Ther 1995 (Oct); 18 (8): 503–511
The methodology used was found to be able to provide a basis for comparison of costs for care apportioned to chiropractic and other interventions. An analysis of 20 randomly selected cases from the WCA suggested that chiropractic intervention for certain conditions may be more cost-effective than other forms of intervention.
A Comparison of Health Care Costs for Chiropractic and Medical Patients
J Manipulative Physiol Ther 1993 (Jun); 16 (5): 291–299
Nearly one-fourth of patients were treated by chiropractors. Patients receiving chiropractic care experienced significantly lower health care costs as represented by third party payments in the fee-for-service sector. Total cost differences on the order of $1,000 over the 2-yr period were found in the total sample of patients as well as in subsamples of patients with specific disorders. The lower costs are attributable mainly to lower inpatient utilization. The cost differences remain statistically significant after controlling for patient demographics and insurance plan characteristics.
Further Analysis of Health Care Costs for Chiropractic and Medical Patients
J Manipulative Physiol Ther 1994 (Sep); 17 (7): 442–446
The analysis of well-insured patients in plans that do not restrict the chiropractic benefit strengthens results previously reported. In this study, therefore, the favorable cost patterns for chiropractic patients cannot be attributed to insurance restrictions limiting reimbursement for chiropractic services relative to other services. Because adjustments for patient characteristics systematically reduce the cost advantages of chiropractic patients as compared to mean differences derived from unadjusted data, the results also demonstrate that adjusted values should be used for meaningful comparisons between the two groups of patients.
Economic Case for the Integration of Chiropractic Services into the Health Care System
J Manipulative Physiol Ther 2000 (Feb); 23 (2): 118-122
For much of its history, chiropractic care has been both an alternative therapeutic paradigm and separate from or marginal to the mainstream health care system. Over the past decade, the situation has changed somewhat in that chiropractic care is gradually being integrated within a variety of health care delivery organizations. According to Triano et al,1 by the application of evidence-based health care and good business, there is a surge in cooperation and integration among chiropractors, allopathic physicians, allied health care providers, ancillary therapists, and respective support staff. There is, however, no quantification of the level of integration. Integration may also be more true of the United States than elsewhere. The overall position of chiropractic care as alternative and separate still predominates. This situation does not serve the interests of the chiropractic profession nor the public well. There is a persuasive economic case for a radical shift in the role of chiropractic care to one that may succinctly be described as alternative and mainstream. The chiropractic profession must preserve its identity and its unique therapeutic paradigm and continue to be seen as an alternative to other health care professions, especially medical doctors. However, it should also become mainstream and thus widely available and accessible to the public by being integrated into the wide variety of health care delivery organizations that collectively constitute the health care system.
In the treatment of musculoskeletal disorders, despite the fact that most studies have not properly factored in such patient characteristics as severity and chronicity and lack the complete assessment of all direct costs and most indirect costs, the bulk of articles reviewed demonstrate lower costs for chiropractic. 9 This pattern is consistently observed from the perspectives of workers' compensation studies, 10-15 databases from insurers, 16-18 or the analysis of a health economist employed by the provincial government of Ontario. 19-20 Other studies have suggested the opposite [that chiropractic services are more expensive than medical], 5,21,22 but these contain significant flaws 21 which have been refuted. 23
The cost advantages for chiropractic for matched conditions appear to be so dramatic that Pran Manga, the aforementioned Canadian health economist, has concluded that doubling the utilization of chiropractic services from 10% to 20% may realize savings as much as $770 million in direct costs and $3.8 billion in indirect costs. 20 When iatrogenic effects [yet to be discussed] are factored in, the cost advantages of spinal manipulation as a treatment alternative become even more prominent. In one study, for instance, it was shown that for managing disc herniations, the cost of treatment failures following a medical course of treatment [chymopapain injections] averaged 300 British pounds per patient, while there were no such costs following spinal manipulation. 24 Imagine how failed back surgery might compare. Finally, in no cost studies to date have legal burdens been calculated, which one would expect should be heavily advantageous for chiropractic health management.
From: Testimony to the Department of Veterans Affairs' Chiropractic Advisory Committee
George B. McClelland, D.C., Foundation for Chiropractic Education and Research
March 25, 2003
9 Cost Comparison of Chiropractic and Medical Treatment of Common Musculoskeletal Disorders: A Review of the Literature After 1980
Topics in Clinical Chiropractic 1999; 6 (2): 57–68
A total of 5 prospective and 19 retrospective studies was identified. Twelve of the 24 studies were published since 1994. Sixteen of the 24 studies' average total costs favored chiropractic treatment.
10 Cost Per Case Comparison of Back Injury Claims of Chiropractic Versus Medical Management for Conditions With Identical Diagnostic Codes
J Occup Med 1991 (Aug); 33 (8): 847–852
This workers’ compensation study conducted in Utah compared the cost of chiropractic care to the costs of medical care for conditions with identical diagnostic codes. The study indicated that costs were significantly higher for medical claims than for chiropractic claims. The sample consisted of 3062 claims or 40.6% of the 7551 estimated back injury claims from the 1986 Workers' Compensation Fund of Utah. For the total data set, cost for care was significantly more for medical claims, and compensation costs were 10-fold less for chiropractic claims.
11 Disabling Low Back Oregon Workers' Compensation Claims. Part I: Methodology and Clinical Categorization of Chiropractic and Medical Cases
J Manipulative Physiol Ther 1991 (Mar-Apr); 14 (3): 177–184
The two provider groups differed in the proportion of claimants who had physical factors contributing to low back compromise. DC claimants were less likely than MD claimants to have sought initial treatment in the emergency room, more likely to have a history of chronic, recurrent low back pain and more likely to have suffered exacerbation episodes. These differences suggest a greater level of chronicity among chiropractic claimants.
12 Disabling Low Back Oregon Workers' Compensation Claims. Part II: Time Loss
J Manipulative Physiol Ther 1991 (May); 14 (4): 231–239
for claimants with a history of chronic low back problems, the median time loss days for MD cases was 34.5 days, compared to 9 days for DC cases. It is suggested that chiropractors are better able to manage injured workers with a history of chronic low back problems and to return them more quickly to productive employment.
14 A Comparison of Chiropractic, Medical and Osteopathic Care for Work-related Sprains and Strains
J Manipulative Physiol Ther 1989 (Oct); 12 (5): 335–344
For those who received care from DCs (n = 266), the mean number of compensated days lost from work was at least 2.3 days less than for those who were treated by MDs (n = 494; p less than 0.025) and at least 3.8 days less than for those who were treated by DOs (n = 102; p less than 0.025). Consequently, much less money in employment compensation was paid, on the average, to those who saw DCs.
15 An Analysis of Florida Workers' Compensation Medical Claims for Back-related Injuries
Journal of the American Chiro Association 1988; 25 (7): 50–59
This study of 10,652 Florida Workers’ Compensation cases was conducted by Steve Wolk, Ph.D. , and reported by the Foundation for Chiropractic Education and Research. It was concluded that “a claimant with a back-related injury, when initially treated by a chiropractor versus a medical doctor, is less likely to become temporarily disabled, or if disabled, remains disabled for a shorter period of time; and claimants treated by medical doctors were hospitalized at a much higher rate than claimants treated by chiropractors.” The analysis focused on the cost of treatment, frequency of compensable injuries (an injury which disables an individual for more than seven days, resulting in wage compensation benefits), and frequency of hospitalization for workers' compensation claim patient (end of reference).
16 A Comparison of the Cost of Chiropractors Versus Alternative Medical Practitioners
Richmond, VA: Virginia Chiropractic Association, 1992
A 1992 study conducted by L.G. Schifrin, Ph.D., provided an economic assessment of mandated health insurance coverage for chiropractic treatment within the Commonwealth of Virginia. As reported by the College of William and Mary, and the Medical College of Virginia, the study indicated that chiropractic provides therapeutic benefits at economical costs. The report also recommended that chiropractic be a widely available form of health care. This paper is unavailable through PubMed or the Mantis database.
17 Chiropractic and Medical Costs of Low Back Care
Med Care 1996 (Mar); 34 (3): 191–204
This study compares health insurance payments and patient utilization patterns for episodes of care for common lumbar and low back conditions treated by chiropractic and medical providers. Using 2 years of insurance claims data, this study examines 6,183 patients who had episodes with medical or chiropractic first-contact providers. Multiple regression analysis, to control for differences in patient, clinical, and insurance characteristics, indicates that total insurance payments were substantially greater for episodes with a medical first-contact provider.
18 Costs and Recurrences of Chiropractic and Medical Episodes of Low-back Care
J Manipulative Physiol Ther 1997 (Jan); 20 (1): 5–12
Total insurance payments within and across episodes were substantially greater for medically initiated episodes. Analysis of recurrent episodes as measures of patient outcomes indicated that chiropractic providers retain more patients for subsequent episodes, but that there is no significant difference in lapse time between episodes for chiropractic vs. medical providers. Chiropractic and medical patients were comparable on measures of severity; however, the chiropractic cohort included a greater proportion of chronic cases.
19 The Effectiveness and Cost-Effectiveness of Chiropractic Management of Low-Back Pain
Richmond Hill, Ontario: Kenilworth Publishing, 1993
A major study to assess the most appropriate use of available health care resources was reported in 1993. This was an outcomes study funded by the Ontario Ministry of Health. The study was conducted by three health economists led by University of Ottawa Professor Pran Manga, Ph.D. The report of the study is commonly called the Manga Report. The Manga Report overwhelmingly supported the efficacy, safety, scientific validity, and cost-effectiveness of chiropractic for low-back pain. Additionally, it found that higher patient satisfaction levels were associated with chiropractic care than with medical treatment alternatives. On the evidence, particularly the most scientifically valid clinical studies, spinal manipulation applied by chiropractors is shown to be more effective than alternative treatments for LBP. Many medical therapies are of questionable validity or are clearly inadequate.
20 Enhanced Chiropractic Coverage Under OHIP as a Means for Reducing Health Care Costs, Attaining Better Health Outcomes and Achieving Equitable Access to Health Services
Report to the Ontario Ministry of Health, 1998
Expenditure to improve access to chiropractic services, and the changed utilization patterns it produces, will lead to very substantial net savings in direct and indirect costs. Direct savings to Ontario's health care system may be as much as $770 million, will very likely be $548 million, and will be at least $380 million. The corresponding savings in indirect costs - made up of the short and long term costs of disability - are $3.775 billion, $1.849 billion and $1.255 billion.
21 Comparing the Costs Between Provider Types of Episodes of Back Pain Care
Spine 1995 (Jan 15); 20 (2): 221–227
There were 1020 episodes of back pain care made by 686 different persons and encompassing 8825 visits. Chiropractors and general practitioners were the primary providers for 40% and 26% of episodes, respectively. Chiropractors had a significantly greater mean number of visits per episode (10.4) than did other practitioners. Orthopedic physicians and "other" physicians were significantly more costly on a per visit basis. Orthopedists had the highest mean total cost per episode, and general practitioners the lowest.
23 [Letter to the editor regarding] Comparing the Costs Between Provider Types of Episodes of Back Pain Care
Spine 1995 (Dec); 20 (23): 2595–2596
Based on the proliferation of more recent studies that have selected (by means of provider codes) a patient population that is narrower, yet more homogeneous, I conclude that the burden of proof for the higher cost of chiropractic healthcare without hospital services remains on the authors of this article. There appears to be too many questions raised by this study that, if they remain unanswered, prevent it from becoming a major addition to the chiropractic literature.
24 Single-blind Randomised Controlled Trial of Chemonucleolysis and Manipulation in the Treatment of Symptomatic Lumbar Disc Herniation
Eur Spine J 2000 (Jun); 9 (3): 202–207
In this study it was shown that for managing disc herniations, the cost of treatment failures following a medical course of treatment [chymopapain injections] averaged 300 British pounds per patient, while there were no such costs following spinal manipulation.
Additional Cost-Effectiveness Studies
Thanks to the National Board of Chiropractic Examiners
for collecting some of these studies!
State of Texas Workers' Compensation Study ~ 2003
In 2002, the Texas Chiropractic Association (TCA) commissioned an independent study to determine the use and effectiveness of chiropractic with regard to workers' compensation, the results of which were published in February. According to the report, Chiropractic Treatment of Workers' Compensation Claimants in the State of Texas, chiropractic care was associated with significantly lower costs and more rapid recovery in treating workers with low-back injuries. They found: Lower back and neck injuries accounted for 38 percent of all claims costs. Chiropractors treated about 30 percent of workers with lower back injuries, but were responsible for only 17.5 percent of the medical costs and 9.1 percent of the total costs. These findings were even more intertesting: The average claim for a worker with a low-back injury was $15,884. However, if a worker received at least 75 percent of his or her care from a chiropractor, the total cost per claimant decreased by nearly one-fourth to $12,202. If the chiropractor provided at least 90 percent of the care, the average cost declined by more than 50 percent, to $7,632.
University of Saskatchewan Study ~ 1985
In 1985 the University of Saskatchewan conducted a study of 283 patients “who had not responded to previous conservative or operative treatment” and who were initially classified as totally disabled. The study revealed that “81% ... became symptom free or achieved a state of mild intermittent pain with no work restrictions” after daily spinal manipulations were administered.
American Health Policy Report ~ 1992
A 1992 review of data from over 2,000,000 users of chiropractic care in the U.S., reported in the Journal of American Health Policy, stated that “chiropractic users tend to have substantially lower total health care costs,” and “chiropractic care reduces the use of both physician and hospital care.”
British Medical Journal ~ 1990
A study conducted by T.W. Meade, a medical doctor, and reported in the June 2, 1990, British Medical Journal concluded after two years of patient monitoring, “for patients with low-back pain in whom manipulation is not contraindicated, chiropractic almost certainly confers worthwhile, long-term benefit in comparison with hospital outpatient management.” More importantly, this article contradicts other articles which maintained that spinal adjusting (manipulation) was only effective for "acute" low back pain. This article found: The benefit is seen mainly in those with chronic or severe pain. Introducing chiropractic into NHS practice should be considered.
British Medical Journal ~ 1995
In the follow-up study to the Meade 1990 BMJ article mentioned above, (August 5, 1995 , British Medical Journal) the author states: At three years the results confirm the findings of an earlier report that when chiropractic or hospital therapists treat patients with low back pain as they would in day to day practice those treated by chiropractic derive more benefit and long term satisfaction than those treated by hospitals.
Washington HMO Study
In 1989, a survey administered by Daniel C. Cherkin, Ph.D., and Frederick A. MacCornack, Ph.D., concluded that patients receiving care from health maintenance organizations (HMOs) within the state of Washington were three times as likely to report satisfaction with care from chiropractors as they were with care from other physicians. The patients were also more likely to believe that their chiropractor was concerned about them.
Patient Disability Comparison
A 1992 article in the Journal of Family Practice reported a study by DC Cherkin, Ph.D., which compared patients of family physicians and of chiropractors. The article stated “the number of days of disability for patients seen by family physicians was significantly higher (mean 39.7) than for patients managed by chiropractors (mean 10.8).” A related editorial in the same issue referred to risks of complications from lumbar manipulation as being “very low.”
Stano Cost Comparison Study
A study by Miron Stano, Ph.D., reported in the June 1993 Journal of Manipulative and Physiological Therapeutics involved 395,641 patients with neuromusculoskeletal conditions. Results over a two-year period showed that patients who received chiropractic care incurred significantly lower health care costs than did patients treated solely by medical or osteopathic physicians.
Gallup Poll ~ 1991
A 1991 demographic poll conducted by the Gallup Organization revealed that 90% of chiropractic patients felt their treatment was effective; more than 80% were satisfied with that treatment; and nearly 75% felt most of their expectations had been met during their chiropractic visits.
ACA's Cost Effectiveness Page
A broad collection of studies which find chiropractic to be cost-effective.
Other Studies Focusing on Chiropractic's Cost Effectiveness
This page reviews numerous oyhrt studies which find chiropractic to be cost-effective.
posted by bakerchiropractic at 9:25 AM
links to this post
About Chiropractic -from the National Institutes of Health - US Government
About Chiropractic and Its Use in Treating Low-Back Pain
On this page
Key Points
What is chiropractic?
What is the history of the discovery and use of chiropractic?
Who uses chiropractic and for what health problems?
What kind of training do chiropractors receive?
What do chiropractors do in treating patients?
Have side effects or problems been reported from using chiropractic to treat back pain?
Does the government regulate chiropractic?
Do health insurance plans pay for chiropractic treatment?
What has scientific research found out about whether chiropractic works for low-back pain?
Are there scientific controversies associated with chiropractic?
Is NCCAM funding research on chiropractic?
For More Information
Definitions
References
Appendix I
Appendix II
Chiropractic ("kye-roh-PRAC-tic") is a form of health care that focuses on the relationship between the body's structure, primarily of the spine, and function. Doctors of chiropractic, who are also called chiropractors or chiropractic physicians, use a type of hands-on therapy called manipulation (or adjustment) as their core clinical procedure. While there are some differences in beliefs and approaches within the chiropractic profession, this Research Report will give you a general overview of chiropractic, discuss scientific research findings on chiropractic treatment for low-back pain, and suggest other sources of information. Terms that are linked are defined in the "Definitions" section of this report.
Key Points
Chiropractic is most often used to treat musculoskeletal conditions--problems with the muscles, joints, bones, and connective tissue such as cartilage, ligaments, and tendons.
Research studies of chiropractic treatment for low-back pain have been of uneven quality and insufficient to allow firm conclusions. Nonetheless, the overall sense of the data is that for low-back pain, chiropractic treatment and conventional medical treatments are about equally helpful. It is harder to draw conclusions about the relative value of chiropractic for other clinical conditions.
The risk of experiencing complications from chiropractic adjustment of the low back appears to be very low. However, the risk appears to be higher for adjustment of the neck.
It is important to inform all of your health care providers about any treatment that you are using or considering, including chiropractic. This will help each provider make sure that all aspects of your health care are working together.
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1. What is chiropractic?
The word "chiropractic" combines the Greek words cheir (hand) and praxis (action) and means "done by hand." Chiropractic is an alternative medical system and takes a different approach from conventional medicine (see box) in diagnosing, classifying, and treating medical problems.
What is conventional medicine?
Conventional medicine is medicine as practiced by holders of M.D. (Doctor of Medicine) or D.O. (Doctor of Osteopathic Medicine) degrees and by their allied health professionals, such as physical therapists, psychologists, and registered nurses. Other terms for conventional medicine include allopathy; Western, mainstream, orthodox, and regular medicine; and biomedicine.
What is complementary and alternative medicine (CAM)?
Health care practices and products that are not presently considered to be part of conventional medicine are called CAM. Complementary medicine is used together with conventional medicine. Alternative medicine is used in place of conventional medicine.
For more information on conventional medicine and CAM, see the NCCAM fact sheet "What Is Complementary and Alternative Medicine (CAM)?"
The basic concepts of chiropractic can be described as follows:
The body has a powerful self-healing ability.
The body's structure (primarily that of the spine) and its function are closely related, and this relationship affects health.
Chiropractic therapy is given with the goals of normalizing this relationship between structure and function and assisting the body as it heals.
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2. What is the history of the discovery and use of chiropractic?
Chiropractic is a form of spinal manipulation, which is one of the oldest healing practices. Spinal manipulation was described by Hippocrates in ancient Greece.1-3 In 1895, Daniel David Palmer founded the modern profession of chiropractic in Davenport, Iowa. Palmer was a self-taught healer and a student of healing philosophies of the day. He observed that the body has a natural healing ability that he believed was controlled by the nervous system. He also believed that subluxations, or misalignments of the spine (a concept that had already existed in the bonesetter and osteopathic traditions), interrupt or interfere with this "nerve flow." Palmer suggested that if an organ does not receive its normal supply of impulses from the nerves, it can become diseased. This line of thinking led him to develop a procedure to "adjust" the vertebrae, the bones of the spinal column, with the goal of correcting subluxations.
Some chiropractors continue to view subluxation as central to chiropractic health care.2 However, other chiropractors no longer view the subluxation theory as a unifying theme in health and illness or as a basis for their practice. Other theories as to how chiropractic might work have been developed.
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3. Who uses chiropractic and for what health problems?
In 1997, it was estimated that Americans made nearly 192 million visits a year to chiropractors.4 Over 88 million of those visits were to treat back or neck pain.5 In one recent survey, more than 40 percent of patients receiving chiropractic care were being treated for back or low-back problems.6 More than half of those surveyed said that their symptoms were chronic. Conditions commonly treated by chiropractors include back pain, neck pain, headaches, sports injuries, and repetitive strains. Patients also seek treatment of pain associated with other conditions, such as arthritis.7
Low-back pain is a common medical problem, occurring in up to one-quarter of the population each year. Most people experience significant back pain at least once during their lifetime.8 Several recent reviews on low-back pain have noted that in most cases acute low-back pain gets better in several weeks, no matter what treatment is used.8-10 Often, the cause of back pain is unknown, and it varies greatly in terms of how people experience it and how professionals diagnose it.11 This makes back pain challenging to study.
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4. What kind of training do chiropractors receive?
Chiropractic training is a 4-year academic program consisting of both classroom and clinical instruction (see box). At least 3 years of preparatory college work are required for admission to chiropractic schools.12,13 Students who graduate receive the degree of Doctor of Chiropractic (D.C.) and are eligible to take state licensure board examinations in order to practice. Some schools also offer postgraduate courses, including 2- to 3-year residency programs in specialized fields.14
Chiropractic Training
Chiropractic training typically includes12:
Coursework in anatomy, physiology, microbiology, biochemistry, pathology, nutrition, public health, and many other subjects
The principles and practice of chiropractic
Research methods and procedures
Direct experience in caring for patients
The Council on Chiropractic Education, an agency certified by the U.S. Department of Education, is the accrediting body for chiropractic colleges in the United States.14
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5. What do chiropractors do in treating patients?
If you become a chiropractic patient, during your initial visit the chiropractor will take your health history. He will perform a physical examination, with special emphasis on the spine, and possibly other examinations or tests such as x-rays.15 If he determines that you are an appropriate candidate for chiropractic therapy, he will develop a treatment plan.
When the chiropractor treats you, he may perform one or more adjustments. An adjustment (also called a manipulation treatment) is a manual therapy, or therapy delivered by the hands. Given mainly to the spine, chiropractic adjustments involve applying a controlled, sudden force to a joint. They are done to increase the range and quality of motion in the area being treated. Other health care professionals--including physical therapists, sports medicine doctors, orthopedists, physical medicine specialists, doctors of osteopathic medicine, doctors of naturopathic medicine, and massage therapists--perform various types of manipulation. In the United States, chiropractors perform over 90 percent of manipulative treatments.16
Most chiropractors use other treatments in addition to adjustment, such as mobilization, massage, and nonmanual treatments (see examples in the box).1
Examples of Nonmanual Chiropractic Treatments1
Heat and ice
Ultrasound
Electrical stimulation
Rehabilitative exercise
Magnetic therapy
Counseling about diet, weight loss, and other lifestyle factors
Dietary supplements
Homeopathy
Acupuncture
To find out more about magnetic therapy, homeopathy, acupuncture, and other CAM therapies, contact the NCCAM Clearinghouse (see "For More Information").
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6. Have side effects or problems been reported from using chiropractic to treat back pain?
Patients may or may not experience side effects from chiropractic treatment. Effects may include temporary discomfort in parts of the body that were treated, headache, or tiredness. These effects tend to be minor and to resolve within 1 to 2 days.7,17
The rate of serious complications from chiropractic has been debated. There have been no organized prospective studies on the number of serious complications. From what is now known, the risk appears to be very low.14,16,17 It appears to be higher for cervical-spine, or neck, manipulation (e.g., cases of stroke have been reported18,19). The rare complication of concern from low-back adjustment is cauda equina syndrome, estimated to occur once per millions of treatments (the number of millions varies; one study placed it at 100 million16).1,20,a
For your safety, it is important to inform all of your health care providers about any care or treatments that you are using or considering, including chiropractic. This is to help ensure a coordinated course of care (to find out more, see the NCCAM fact sheet "Selecting a Complementary and Alternative Medicine Practitioner").
aMore information on the topic of complications can be found in references 1-3, 14, 21, and 22, and in scientific databases such as CAM on PubMed (see "For More Information").
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7. Does the government regulate chiropractic?
Chiropractic practice is regulated individually by each state and the District of Columbia. Most states require chiropractors to earn continuing education credits to maintain their licenses.1,13 Chiropractors' scope of practice varies by state--including with regard to laboratory tests or diagnostic procedures, the dispensing or selling of dietary supplements, and the use of other CAM therapies such as acupuncture or homeopathy.13,14,23 Chiropractors are not licensed in any state to perform major surgery or prescribe drugs.b
bIn Oregon, chiropractors can become certified to perform minor surgery (such as stitching cuts) and to deliver children by natural childbirth.14,23,24
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8. Do health insurance plans pay for chiropractic treatment?
Compared with CAM therapies as a whole (few of which are reimbursed), coverage of chiropractic by insurance plans is extensive. As of 2002, more than 50 percent of health maintenance organizations (HMOs), more than 75 percent of private health care plans, and all state workers' compensation systems covered chiropractic treatment.1 Chiropractors can bill Medicare, and over two dozen states cover chiropractic treatment under Medicaid.23
If you have health insurance, check whether chiropractic care is covered before you seek treatment. Your plan may require care to be approved in advance, limit the number of visits covered, and/or require that you use chiropractors within its network (read more in the NCCAM fact sheet "Consumer Financial Issues in Complementary and Alternative Medicine").
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9. What has scientific research found out about whether chiropractic works for low-back pain?
For this report, the results of individual clinical trials and reviews of groups of clinical trials were examined. Sources were drawn from the National Library of Medicine's PubMed database; were published in English; and studied chiropractic techniques that were identified as such (e.g., "chiropractic manipulation") rather than some other forms of "manipulation" or "spinal manipulation therapy"--which, as noted above, may be delivered by certain other health care providers.c
Clinical Trials
A clinical trial is a research study in which a treatment or therapy is tested in people to see whether it is safe and effective. Clinical trials are a key part of the process in finding out which treatments work, which do not, and why. Clinical trial results also contribute new knowledge about diseases and medical conditions. To find out more, see NCCAM's fact sheet "About Clinical Trials and Complementary and Alternative Medicine."
So far, the scientific research on chiropractic and low-back pain has focused on if, and how well, chiropractic care helps in relieving pain and other symptoms that people have with low-back pain. This research often compares chiropractic to other treatments.
Research studies
Appendix I gives detailed findings from seven controlled clinical trials and one prospective observational study of chiropractic treatment for low-back pain published between January 1994 and June 2003.
Summary of the research findings
The studies all found at least some benefit to the participants from chiropractic treatment. However, in six of the eight studies, chiropractic and conventional treatments were found to be similar in effectiveness.22,25-29 One trial found greater improvement in the chiropractic group than in groups receiving either sham manipulation or back school.30. Another trial found treatment at a chiropractic clinic to be more effective than outpatient hospital treatment.31
General reviews, systematic reviews, and meta-analyses
Appendix II lists three reviews of clinical trials on chiropractic treatment for back pain, published between October 1996 and June 2003.
Summary of the research findings
Overall, the evidence was seen as weak and less than convincing for the effectiveness of chiropractic for back pain. Specifically, the 1996 systematic review reported that there were major quality problems in the studies analyzed; for example, statistics could not be effectively combined because of missing and poor-quality data. The review concludes that the data "did not provide convincing evidence for the effectiveness of chiropractic."32 The 2003 general review states that since the 1996 systematic review, emerging trial data "have not tended to be encouraging…. The effectiveness of chiropractic spinal manipulation for back pain is thus at best uncertain."33 The 2003 meta-analysis found spinal manipulation to be more effective than sham therapy but no more or no less effective than other treatments.10
Several other points are helpful to keep in mind about the research findings. Many clinical trials of chiropractic analyze the effects of chiropractic manipulation alone, but chiropractic practice includes more than manipulation (see Question 5).34 Results of a trial performed in one setting (such as a managed care organization or a chiropractic college) may not completely apply in other settings.29,35 And, researchers have observed that the placebo effect may be at work in chiropractic care,34 as in other forms of health care.
cThis fact sheet often uses the term "adjustment" to refer to chiropractic manipulation. In Question 9 and Appendices I and II, "manipulation" is used where it is used in the source(s) on chiropractic being discussed.
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10. Are there scientific controversies associated with chiropractic?
Yes, there are scientific controversies about chiropractic, both inside and outside the profession. For example, within the profession, there have been disagreements about the use of physical therapy techniques, which techniques are most appropriate for certain conditions, and the concept of subluxations. Outside views have questioned the effectiveness of chiropractic treatments, their scientific basis, and the potential risks in subsets of patients (for example, the risks of certain types of adjustments to patients with osteoporosis or risk factors for osteoporosis, compared to patients with healthier bone structures33,36).
Research studies on chiropractic are ongoing. The results are expected to expand scientific understanding of chiropractic. A key area of research is the basic science of what happens in the body (including its cells and nerves) when specific chiropractic treatments are given.
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11. Is NCCAM funding research on chiropractic?
Yes. For example, recent projects supported by NCCAM include:
Comparing conventional medical care for acute back pain with an "expanded benefits" package (consisting of conventional care plus a choice of chiropractic, massage, or acupuncture)
Finding out what happens (through measurement) in the lumbar portion of the spine after chiropractic positioning and adjustment
Evaluating the effects of the speed of spinal adjustment on muscles and nerves
Studying the effectiveness of chiropractic adjustment for a variety of conditions, including neck pain, chronic pelvic pain, and temporomandibular disorders (TMD) in the jaw
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For More Information
NCCAM Clearinghouse
Toll-free in the U.S.: 1-888-644-6226
International: 301-519-3153
TTY (for deaf and hard-of-hearing callers): 1-866-464-3615
E-mail: info@nccam.nih.gov
NCCAM Web site: nccam.nih.gov
Address: NCCAM Clearinghouse, P.O. Box 7923, Gaithersburg, MD 20898-7923
Fax: 1-866-464-3616
Fax-on-Demand service: 1-888-644-6226
The NCCAM Clearinghouse provides information on CAM and on NCCAM. Services include fact sheets, other publications, and searches of Federal databases of scientific and medical literature. The Clearinghouse does not provide medical advice, treatment recommendations, or referrals to practitioners.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Web site: www.niams.nih.gov
Toll-free in the U.S.: 1-877-22-NIAMS (or 301-495-4484)
NIAMS supports research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; training of scientists; and information based on research. Publications are available.
Agency for Healthcare Research and Quality (AHRQ)
Web site: www.ahrq.gov
Telephone: 301-427-1364
AHRQ is the health services research arm of the Department of Health and Human Services. Publications that may be of interest include Chiropractic in the United States: Training, Practice, and Research (1998) and AHRQ's Clinical Practice Guideline No. 14: Acute Low-Back Problems in Adults (1994; however, this document has been archived by AHRQ and is not considered current clinical guidance).
CAM on PubMed
Web site: www.nlm.nih.gov/nccam/camonpubmed.html
CAM on PubMed, a database on the Internet developed jointly by NCCAM and the National Library of Medicine, offers citations to (and in most cases, brief summaries of) articles on CAM in scientifically based, peer-reviewed journals. CAM on PubMed also links to many publisher Web sites, which may offer the full text of articles.
ClinicalTrials.gov
Web site: www.clinicaltrials.gov
ClinicalTrials.gov is a database of information on clinical trials, primarily in the United States and Canada, for a wide range of diseases and conditions. It is sponsored by the National Institutes of Health and the U.S. Food and Drug Administration.
The Cochrane Library
Web site: www.cochrane.org/reviews/clibintro.htm
The Cochrane Library is a collection of science-based reviews from the Cochrane Collaboration, an international nonprofit organization that seeks to provide "up-to-date, accurate information about the effects of health care." Its authors analyze the results of rigorous clinical trials on a given topic and prepare systematic reviews. Abstracts (brief summaries) of these reviews can be read online without charge. You can search by treatment name or medical condition. Subscriptions to the full text are offered at a fee and are carried by some libraries.
Definitions
Acupuncture: A health care practice that originated in traditional Chinese medicine. Acupuncture involves inserting needles at specific points on the body, in the belief that this will help improve the flow of the body's energy (or qi, pronounced "chee") and thereby help the body achieve and maintain health.
Acute pain: Pain that has lasted a short time (e.g., less than 3 weeks) or is severe.
Alternative medical system: A medical system built upon a complete system of theory and practice; these systems have often evolved apart from and earlier than the conventional medical approach used in the United States. An example from a Western culture is naturopathic medicine; from a non-Western culture, traditional Chinese medicine.
Bonesetter: A health care practitioner (not necessarily a licensed physician) whose occupation is setting fractured or dislocated bones.
Cauda equina syndrome: A syndrome that occurs when the nerves of the cauda equina (a bundle of spinal nerves extending beyond the end of the spinal cord) are compressed and damaged. Symptoms include leg weakness; loss of bowel, bladder, and/or sexual functions; and changes in sensation around the rectum or genitalia.
Chronic pain: Pain that has lasted a long time (more than 3 months).
Clinical trial: A clinical trial is a research study in which a treatment or therapy is tested in people to see whether it is safe and effective. Clinical trials are a key part of the process in finding out which treatments work, which do not, and why. Clinical trial results also contribute new knowledge about diseases and medical conditions.
Complication: A secondary disease or condition that develops in the course of a primary disease or condition, or as the result of a treatment.
Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all.
General review: An analysis in which information from various studies is summarized and evaluated; conclusions are made based on this evidence.
Hippocrates: A Greek physician born in 460 B.C. who became known as the founder of Western medicine.
Homeopathy: Also known as homeopathic medicine. It is an alternative medical system that was invented in Germany. In homeopathic treatment, there is a belief that "like cures like," meaning that small, highly diluted quantities of medicinal substances are given to cure symptoms, when the same substances given at higher or more concentrated doses would actually cause those symptoms.
Manipulation: Passive joint movement beyond the normal range of motion. The term adjustment is preferred in chiropractic.
Massage: A therapy in which muscle and connective tissue are manipulated to enhance function of those tissues and promote relaxation and well-being.
Meta-analysis: A type of research review that uses statistical techniques to analyze results from a collection of individual studies.
Mobilization: A technique, used by chiropractors and other health care professionals, in which a joint is passively moved within its normal range of motion.
Myofascial therapy: A type of physical therapy that uses stretches and massage.
Naturopathic medicine: Also known as naturopathy. It is an alternative medical system in which practitioners work with natural healing forces within the body, with a goal of helping the body heal from disease and attain better health. Practices may include dietary modifications, massage, exercise, acupuncture, minor surgery, and various other interventions.
Observational study: A type of study in which individuals are observed or certain outcomes are measured. No attempt is made to affect the outcome (for example, no treatment is given).
Orthopedist: Doctor of Medicine (M.D.) who is a surgeon specializing in disorders of the musculoskeletal system.
Osteopathic medicine: Also known as osteopathy. It is a form of conventional medicine that, in part, emphasizes diseases arising in the musculoskeletal system. There is an underlying belief that all of the body's systems work together, and disturbances in one system may affect function elsewhere in the body. Most osteopathic physicians practice osteopathic manipulation, a full-body system of hands-on techniques to alleviate pain, restore function, and promote health and well-being.
Osteoporosis: A reduction in the amount of bone mass, which can lead to breaking a bone after a minor injury, such as a fall.
Placebo: Resembles a treatment being studied in a clinical trial, except that the placebo is inactive. One example is a sugar pill. By giving one group of participants a placebo and the other group the active treatment, the researchers can compare how the two groups respond and get a truer picture of the active treatment's effects. In recent years, the definition of placebo has been expanded to include other things that could affect the results of health care, such as how a patient feels about receiving the care and what she expects to happen from it.
Prospective study: A type of research study in which participants are followed over time for the effect(s) of a health care treatment.
Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.
Review: See general review, systematic review, or meta-analysis.
Sham: A treatment or device that is a type of placebo. An example would be positioning the patient's body and placing the chiropractor's hands in a way that mimics an actual treatment, but is not a treatment.
Subacute pain: Pain that has lasted somewhat longer than acute pain (for example, more than a few days or weeks) but is not yet chronic pain.
Systematic review: A type of research review in which data from a set of studies on a particular question or topic are collected, analyzed, and critically reviewed.
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References
Meeker WC, Haldeman S. Chiropractic: a profession at the crossroads of mainstream and alternative medicine. Annals of Internal Medicine. 2002;136(3):216-227.
Kaptchuk TJ, Eisenberg DM. Chiropractic: origins, controversies, and contributions. Archives of Internal Medicine. 1998;158(20):2215-2224.
Bronfort G. Spinal manipulation: current state of research and its indications. Neurologic Clinics. 1999;17(1):91-111.
Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. Journal of the American Medical Association. 1998;280(18):1569-1575.
Wolsko PM, Eisenberg DM, Davis RB, et al. Patterns and perceptions of care for treatment of back and neck pain: results of a national survey. Spine. 2003;28(3):292-297.
Coulter ID, Hurwitz EL, Adams AH, et al. Patients using chiropractors in North America: who are they, and why are they in chiropractic care? Spine. 2002;27(3):291-296.
Vickers A, Zollman C. ABC of complementary medicine. The manipulative therapies: osteopathy and chiropractic. BMJ. 1999;319(7218):1176-1179.
Atlas SJ, Nardin RA. Evaluation and treatment of low back pain: an evidence-based approach to clinical care. Muscle and Nerve. 2003;27(3):265-284.
Pengel HM, Maher CG, Refshauge KM. Systematic review of conservative interventions for subacute low back pain. Clinical Rehabilitation. 2002;16(8):811-820.
Assendelft WJ, Morton SC, Yu EI, et al. Spinal manipulative therapy for low back pain. Annals of Internal Medicine. 2003;138(11):871-881.
Complementary medicine: fact and fiction about chiropractic. Harvard Health Letter. 1999;24(3):1-3.
The Council on Chiropractic Education. Standards for Doctor of Chiropractic Programs and Requirements for Institutional Status January 2003. Council on Chiropractic Education Web site. Accessed at www.cce-usa.org on June 16, 2003.
Eisenberg DM, Cohen MH, Hrbek A, et al. Credentialing complementary and alternative medical providers. Annals of Internal Medicine. 2002;137(12):965-973.
Agency for Health Care Policy and Research. Chiropractic in the United States: Training, Practice, and Research. Rockville, MD: Agency for Health Care Policy and Research; 1998. AHCPR publication no. 98-N002.
Dagenais S, Haldeman S. Chiropractic. Primary Care. 2002;29(2):419-437.
Shekelle PG, Adams AH, Chassin MR, et al. Spinal manipulation for low-back pain. Annals of Internal Medicine. 1992;117(7):590-598.
Senstad O, Leboeuf-Yde C, Borchgrevink C. Frequency and characteristics of side effects of spinal manipulative therapy. Spine. 1997;22(4):435-440.
Hufnagel A, Hammers A, Schonle PW, et al. Stroke following chiropractic manipulation of the cervical spine. Journal of Neurology. 1999;246(8):683-688.
Jeret JS, Bluth M. Stroke following chiropractic manipulation: report of 3 cases and review of the literature. Cerebrovascular Diseases. 2002;13(3):210-213.
Haldeman S, Rubinstein SM. Cauda equina syndrome in patients undergoing manipulation of the lumbar spine. Spine. 1992;17(12):1469-1473.
Haldeman S, Rubinstein SM. Compression fractures in patients undergoing spinal manipulative therapy. Journal of Manipulative and Physiological Therapeutics. 1992;15(7):450-454.
Hurwitz EL, Morgenstern H, Harber P, et al. A randomized trial of medical care with and without physical therapy and chiropractic care with and without physical modalities for patients with low back pain: 6-month follow-up outcomes from the UCLA low back pain study. Spine. 2002;27(20):2193-2204.
Cooper RA, Henderson T, Dietrich CL. Roles of nonphysician clinicians as autonomous providers of patient care. Journal of the American Medical Association. 1998;280(9):795-802.
Chiropractic regulatory boards. Federation of Chiropractic Licensing Boards Web site. Accessed at www.fclb.org/boards.htm on June 16, 2003.
Hsieh CY, Adams AH, Tobis J, et al. Effectiveness of four conservative treatments for subacute low back pain: a randomized clinical trial. Spine. 2002;27(11):1142-1148.
Cherkin DC, Deyo RA, Battie M, et al. A comparison of physical therapy, chiropractic manipulation, and provision of an educational booklet for the treatment of patients with low back pain. New England Journal of Medicine. 1998;339(15):1021-1029.
Bronfort G, Goldsmith CH, Nelson CF, et al. Trunk exercise combined with spinal manipulative or NSAID therapy for chronic low back pain: a randomized, observer-blinded clinical trial. Journal of Manipulative and Physiological Therapeutics. 1996;19(9):570-582.
Carey TS, Garrett J, Jackman A, et al. The outcomes and costs of care for acute low back pain among patients seen by primary care practitioners, chiropractors, and orthopedic surgeons. The North Carolina Back Pain Project. New England Journal of Medicine. 1995;333(14):913-917.
Pope MH, Phillips RB, Haugh LD, et al. A prospective randomized three-week trial of spinal manipulation, transcutaneous muscle stimulation, massage and corset in the treatment of subacute low back pain. Spine. 1994;19(22):2571-2577.
Triano JJ, McGregor M, Hondras MA, et al. Manipulative therapy versus education programs in chronic low back pain. Spine. 1995;20(8):948-955.
Meade TW, Dyer S, Browne W, et al. Randomised comparison of chiropractic and hospital outpatient management for low back pain: results from extended follow up. BMJ. 1995;311(7001):349-351.
Assendelft WJ, Koes BW, van der Heijden GJ, et al. The effectiveness of chiropractic for treatment of low back pain: an update and attempt at statistical pooling. Journal of Manipulative and Physiological Therapeutics. 1996;19(8):499-507.
Ernst E. Chiropractic spinal manipulation for back pain. British Journal of Sports Medicine. 2003;37(3):195-196.
Ernst E. Chiropractic care: attempting a risk-benefit analysis. American Journal of Public Health. 2002;92(10):1603-1604.
Hurwitz EL, Morgenstern H, Harber P, et al. A randomized trial of chiropractic manipulation and mobilization for patients with neck pain: clinical outcomes from the UCLA neck-pain study. American Journal of Public Health. 2002;92(10):1634-1641.
Sran MM. Commentary on "Chiropractic spinal manipulation for back pain." British Journal of Sports Medicine. 2003;37:196.
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Appendix I
Research Studies of Chiropractic Treatment in Adults with Back Pain
Published from January 1994 through June 2003
Citation Description Findings
Hurwitz et al., 200222 Randomized clinical trial (RCT) of patients in a managed care organization compared chiropractic cared (with and without any of the following added: heat or cold therapy, ultrasound, electrical muscle stimulation) with conventional medical care (with and without physical therapy added). Participants (652) had acute, subacute, or chronic low-back pain with or without leg pain. Back-pain intensity and back-related disability were measured. After 6 months of followup, the conventional medical care and chiropractic regimens were found to be comparably effective.
Hsieh et al., 200225 RCT compared four treatments for subacute low-back pain (LBP): "joint manipulation" by a chiropractor, back school (program of counseling and exercises), myofascial therapy, and joint manipulation plus myofascial therapy. Participants (178) had LBP for either >3 weeks but <6 months in a current episode or >2 months within the preceding 8 months for recurrent LBP, and were evaluated 3 weeks and 6 months after treatment. No statistically significant differences were found between groups at 3 weeks or 6 months.
Cherkin et al., 199826 RCT in an HMO setting of 321 adults aged 20-64 with low-back pain. Patients received either chiropractic manipulation, physical therapy (PT), or a booklet on self-managing back pain. They were monitored for 2 years and evaluated for bothersomeness of symptoms and level of dysfunction. The outcomes for those who received manipulation or PT were better than those who received the booklet, but "only marginally better." There were no significant differences between the manipulation and PT groups. Authors note that manipulation and PT "may slightly reduce symptoms."
Bronfort et al., 199627 For chronic low-back pain, prospective RCT compared (1) chiropractic spinal manipulation therapy (SMT) plus trunk-strengthening exercises with (2) chiropractic SMT plus trunk-stretching exercises and (3) trunk-strengthening exercises combined with an NSAID (drug). Enrollees (174) were measured for low-back pain, disability, and functional health status at 5 and 11 weeks. Each of the 3 regimens yielded a "similar and clinically important improvement over time that was considered superior to the expected natural history of long-standing chronic low back pain."
Carey et al., 199528 Prospective observational study on the outcomes of care for acute low-back pain by chiropractors, primary care practitioners, and orthopedic surgeons, including how long it took to return to functional status. Participants (1,633) had acute pain of less than 10 weeks' duration. Time to recovery was "essentially the same," regardless of which provider provided the care.
Meade et al., 199531 RCT of 741 patients who came to chiropractic and hospital outpatient clinics in 11 centers, for low-back pain. Participants were randomized to receive either chiropractic or hospital-outpatient management. Outcomes were measured mainly with a pain disability questionnaire, at 6 weeks, 6 months, and 1, 2, and 3 years. Chiropractic was found to be more effective, especially for those with "short current episodes, a history of back pain, and initially high [pain scale] scores." Benefit was less evident at 2 and 3 years than earlier. Authors noted that further trials are needed, e.g., on specific components of chiropractic.
Triano et al., 199530 RCT comparing chiropractic spinal manipulation, sham manipulation, and a back education program. Participants (170) had low-back pain (lasting 7 weeks or longer or consisting of at least 6 episodes in 12 months) and were evaluated for pain and activity tolerance at enrollment, after 2 weeks of treatment, and after 2 weeks of no treatment. Greater improvement was found in the manipulation group than in other groups. Pain relief continued to end of evaluation period.
Pope et al., 199429 Prospective RCT compared chiropractic spinal manipulation for treatment of subacute low-back pain to massage, use of a corset, and TMS (electrical muscle stimulation). Patients (164) were treated for 3 weeks and evaluated through various standardized instruments and examinations. Various improvements were seen in all 4 groups. The manipulation group had the most improvement in flexion and pain. However, authors concluded overall that none of the changes in physical outcomes measured was significantly different between groups.
dHurwitz et al. define chiropractic care as "spinal manipulation or another spinal-adjusting technique."
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Appendix II
Reviews on Chiropractic Treatment for Back Pain in Adults
Published from October 1996 through June 2003
Citation Description Findings
Assendelft et al., 200310,e Meta-analysis of 39 randomized clinical trials of treatments for acute or chronic low-back pain in adults. The trials compared spinal manipulation (by chiropractors and other health care providers) with another treatment or control condition (including no treatment, conventional medical care, pain-relieving drugs, physical therapy, exercise, and back school). Spinal manipulation was more effective than sham therapy, but no more or no less effective than other treatments.
Authors found that the specific profession of the manipulators (including chiropractors) did not affect these results.
Ernst, 200333 General review of the scientific evidence for the effectiveness of chiropractic spinal manipulation for back pain (this review is not limited to low-back pain studies). Author noted there has been only one systematic review of chiropractic spinal manipulation exclusively (Assendelft et al., 1996, see below), and that, since that study, emerging trial data "have not tended to be encouraging…. The effectiveness of chiropractic spinal manipulation for back pain is thus at best uncertain."
Assendelft et al., 199632 Systematic review of 8 RCTs of chiropractic for acute or chronic low-back pain. Authors stated that all studies analyzed had serious flaws in design, execution, and reporting. Studies could not be pooled to reach statistical conclusions because of insufficient data and data quality problems. Authors summarized the available data narratively; concluded they "did not provide convincing evidence for the effectiveness of chiropractic for acute or chronic low back pain"; and noted that better-executed trials are needed in future.
eThis study on spinal manipulation is included because the authors were able to break down the findings according to the profession of the manipulator, including chiropractors.
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This publication is not copyrighted and is in the public domain. Duplication is encouraged.
NCCAM has provided this material for your information. It is not intended to substitute for the medical expertise and advice of your primary health care provider. We encourage you to discuss any decisions about treatment or care with your health care provider. The mention of any product, service, or therapy in this information is not an endorsement by NCCAM.
National Institutes of Health
U.S. Department of Health and Human Services
NCCAM Publication No. D196
November 2003
On this page
Key Points
What is chiropractic?
What is the history of the discovery and use of chiropractic?
Who uses chiropractic and for what health problems?
What kind of training do chiropractors receive?
What do chiropractors do in treating patients?
Have side effects or problems been reported from using chiropractic to treat back pain?
Does the government regulate chiropractic?
Do health insurance plans pay for chiropractic treatment?
What has scientific research found out about whether chiropractic works for low-back pain?
Are there scientific controversies associated with chiropractic?
Is NCCAM funding research on chiropractic?
For More Information
Definitions
References
Appendix I
Appendix II
Chiropractic ("kye-roh-PRAC-tic") is a form of health care that focuses on the relationship between the body's structure, primarily of the spine, and function. Doctors of chiropractic, who are also called chiropractors or chiropractic physicians, use a type of hands-on therapy called manipulation (or adjustment) as their core clinical procedure. While there are some differences in beliefs and approaches within the chiropractic profession, this Research Report will give you a general overview of chiropractic, discuss scientific research findings on chiropractic treatment for low-back pain, and suggest other sources of information. Terms that are linked are defined in the "Definitions" section of this report.
Key Points
Chiropractic is most often used to treat musculoskeletal conditions--problems with the muscles, joints, bones, and connective tissue such as cartilage, ligaments, and tendons.
Research studies of chiropractic treatment for low-back pain have been of uneven quality and insufficient to allow firm conclusions. Nonetheless, the overall sense of the data is that for low-back pain, chiropractic treatment and conventional medical treatments are about equally helpful. It is harder to draw conclusions about the relative value of chiropractic for other clinical conditions.
The risk of experiencing complications from chiropractic adjustment of the low back appears to be very low. However, the risk appears to be higher for adjustment of the neck.
It is important to inform all of your health care providers about any treatment that you are using or considering, including chiropractic. This will help each provider make sure that all aspects of your health care are working together.
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1. What is chiropractic?
The word "chiropractic" combines the Greek words cheir (hand) and praxis (action) and means "done by hand." Chiropractic is an alternative medical system and takes a different approach from conventional medicine (see box) in diagnosing, classifying, and treating medical problems.
What is conventional medicine?
Conventional medicine is medicine as practiced by holders of M.D. (Doctor of Medicine) or D.O. (Doctor of Osteopathic Medicine) degrees and by their allied health professionals, such as physical therapists, psychologists, and registered nurses. Other terms for conventional medicine include allopathy; Western, mainstream, orthodox, and regular medicine; and biomedicine.
What is complementary and alternative medicine (CAM)?
Health care practices and products that are not presently considered to be part of conventional medicine are called CAM. Complementary medicine is used together with conventional medicine. Alternative medicine is used in place of conventional medicine.
For more information on conventional medicine and CAM, see the NCCAM fact sheet "What Is Complementary and Alternative Medicine (CAM)?"
The basic concepts of chiropractic can be described as follows:
The body has a powerful self-healing ability.
The body's structure (primarily that of the spine) and its function are closely related, and this relationship affects health.
Chiropractic therapy is given with the goals of normalizing this relationship between structure and function and assisting the body as it heals.
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2. What is the history of the discovery and use of chiropractic?
Chiropractic is a form of spinal manipulation, which is one of the oldest healing practices. Spinal manipulation was described by Hippocrates in ancient Greece.1-3 In 1895, Daniel David Palmer founded the modern profession of chiropractic in Davenport, Iowa. Palmer was a self-taught healer and a student of healing philosophies of the day. He observed that the body has a natural healing ability that he believed was controlled by the nervous system. He also believed that subluxations, or misalignments of the spine (a concept that had already existed in the bonesetter and osteopathic traditions), interrupt or interfere with this "nerve flow." Palmer suggested that if an organ does not receive its normal supply of impulses from the nerves, it can become diseased. This line of thinking led him to develop a procedure to "adjust" the vertebrae, the bones of the spinal column, with the goal of correcting subluxations.
Some chiropractors continue to view subluxation as central to chiropractic health care.2 However, other chiropractors no longer view the subluxation theory as a unifying theme in health and illness or as a basis for their practice. Other theories as to how chiropractic might work have been developed.
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3. Who uses chiropractic and for what health problems?
In 1997, it was estimated that Americans made nearly 192 million visits a year to chiropractors.4 Over 88 million of those visits were to treat back or neck pain.5 In one recent survey, more than 40 percent of patients receiving chiropractic care were being treated for back or low-back problems.6 More than half of those surveyed said that their symptoms were chronic. Conditions commonly treated by chiropractors include back pain, neck pain, headaches, sports injuries, and repetitive strains. Patients also seek treatment of pain associated with other conditions, such as arthritis.7
Low-back pain is a common medical problem, occurring in up to one-quarter of the population each year. Most people experience significant back pain at least once during their lifetime.8 Several recent reviews on low-back pain have noted that in most cases acute low-back pain gets better in several weeks, no matter what treatment is used.8-10 Often, the cause of back pain is unknown, and it varies greatly in terms of how people experience it and how professionals diagnose it.11 This makes back pain challenging to study.
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4. What kind of training do chiropractors receive?
Chiropractic training is a 4-year academic program consisting of both classroom and clinical instruction (see box). At least 3 years of preparatory college work are required for admission to chiropractic schools.12,13 Students who graduate receive the degree of Doctor of Chiropractic (D.C.) and are eligible to take state licensure board examinations in order to practice. Some schools also offer postgraduate courses, including 2- to 3-year residency programs in specialized fields.14
Chiropractic Training
Chiropractic training typically includes12:
Coursework in anatomy, physiology, microbiology, biochemistry, pathology, nutrition, public health, and many other subjects
The principles and practice of chiropractic
Research methods and procedures
Direct experience in caring for patients
The Council on Chiropractic Education, an agency certified by the U.S. Department of Education, is the accrediting body for chiropractic colleges in the United States.14
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5. What do chiropractors do in treating patients?
If you become a chiropractic patient, during your initial visit the chiropractor will take your health history. He will perform a physical examination, with special emphasis on the spine, and possibly other examinations or tests such as x-rays.15 If he determines that you are an appropriate candidate for chiropractic therapy, he will develop a treatment plan.
When the chiropractor treats you, he may perform one or more adjustments. An adjustment (also called a manipulation treatment) is a manual therapy, or therapy delivered by the hands. Given mainly to the spine, chiropractic adjustments involve applying a controlled, sudden force to a joint. They are done to increase the range and quality of motion in the area being treated. Other health care professionals--including physical therapists, sports medicine doctors, orthopedists, physical medicine specialists, doctors of osteopathic medicine, doctors of naturopathic medicine, and massage therapists--perform various types of manipulation. In the United States, chiropractors perform over 90 percent of manipulative treatments.16
Most chiropractors use other treatments in addition to adjustment, such as mobilization, massage, and nonmanual treatments (see examples in the box).1
Examples of Nonmanual Chiropractic Treatments1
Heat and ice
Ultrasound
Electrical stimulation
Rehabilitative exercise
Magnetic therapy
Counseling about diet, weight loss, and other lifestyle factors
Dietary supplements
Homeopathy
Acupuncture
To find out more about magnetic therapy, homeopathy, acupuncture, and other CAM therapies, contact the NCCAM Clearinghouse (see "For More Information").
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6. Have side effects or problems been reported from using chiropractic to treat back pain?
Patients may or may not experience side effects from chiropractic treatment. Effects may include temporary discomfort in parts of the body that were treated, headache, or tiredness. These effects tend to be minor and to resolve within 1 to 2 days.7,17
The rate of serious complications from chiropractic has been debated. There have been no organized prospective studies on the number of serious complications. From what is now known, the risk appears to be very low.14,16,17 It appears to be higher for cervical-spine, or neck, manipulation (e.g., cases of stroke have been reported18,19). The rare complication of concern from low-back adjustment is cauda equina syndrome, estimated to occur once per millions of treatments (the number of millions varies; one study placed it at 100 million16).1,20,a
For your safety, it is important to inform all of your health care providers about any care or treatments that you are using or considering, including chiropractic. This is to help ensure a coordinated course of care (to find out more, see the NCCAM fact sheet "Selecting a Complementary and Alternative Medicine Practitioner").
aMore information on the topic of complications can be found in references 1-3, 14, 21, and 22, and in scientific databases such as CAM on PubMed (see "For More Information").
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7. Does the government regulate chiropractic?
Chiropractic practice is regulated individually by each state and the District of Columbia. Most states require chiropractors to earn continuing education credits to maintain their licenses.1,13 Chiropractors' scope of practice varies by state--including with regard to laboratory tests or diagnostic procedures, the dispensing or selling of dietary supplements, and the use of other CAM therapies such as acupuncture or homeopathy.13,14,23 Chiropractors are not licensed in any state to perform major surgery or prescribe drugs.b
bIn Oregon, chiropractors can become certified to perform minor surgery (such as stitching cuts) and to deliver children by natural childbirth.14,23,24
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8. Do health insurance plans pay for chiropractic treatment?
Compared with CAM therapies as a whole (few of which are reimbursed), coverage of chiropractic by insurance plans is extensive. As of 2002, more than 50 percent of health maintenance organizations (HMOs), more than 75 percent of private health care plans, and all state workers' compensation systems covered chiropractic treatment.1 Chiropractors can bill Medicare, and over two dozen states cover chiropractic treatment under Medicaid.23
If you have health insurance, check whether chiropractic care is covered before you seek treatment. Your plan may require care to be approved in advance, limit the number of visits covered, and/or require that you use chiropractors within its network (read more in the NCCAM fact sheet "Consumer Financial Issues in Complementary and Alternative Medicine").
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9. What has scientific research found out about whether chiropractic works for low-back pain?
For this report, the results of individual clinical trials and reviews of groups of clinical trials were examined. Sources were drawn from the National Library of Medicine's PubMed database; were published in English; and studied chiropractic techniques that were identified as such (e.g., "chiropractic manipulation") rather than some other forms of "manipulation" or "spinal manipulation therapy"--which, as noted above, may be delivered by certain other health care providers.c
Clinical Trials
A clinical trial is a research study in which a treatment or therapy is tested in people to see whether it is safe and effective. Clinical trials are a key part of the process in finding out which treatments work, which do not, and why. Clinical trial results also contribute new knowledge about diseases and medical conditions. To find out more, see NCCAM's fact sheet "About Clinical Trials and Complementary and Alternative Medicine."
So far, the scientific research on chiropractic and low-back pain has focused on if, and how well, chiropractic care helps in relieving pain and other symptoms that people have with low-back pain. This research often compares chiropractic to other treatments.
Research studies
Appendix I gives detailed findings from seven controlled clinical trials and one prospective observational study of chiropractic treatment for low-back pain published between January 1994 and June 2003.
Summary of the research findings
The studies all found at least some benefit to the participants from chiropractic treatment. However, in six of the eight studies, chiropractic and conventional treatments were found to be similar in effectiveness.22,25-29 One trial found greater improvement in the chiropractic group than in groups receiving either sham manipulation or back school.30. Another trial found treatment at a chiropractic clinic to be more effective than outpatient hospital treatment.31
General reviews, systematic reviews, and meta-analyses
Appendix II lists three reviews of clinical trials on chiropractic treatment for back pain, published between October 1996 and June 2003.
Summary of the research findings
Overall, the evidence was seen as weak and less than convincing for the effectiveness of chiropractic for back pain. Specifically, the 1996 systematic review reported that there were major quality problems in the studies analyzed; for example, statistics could not be effectively combined because of missing and poor-quality data. The review concludes that the data "did not provide convincing evidence for the effectiveness of chiropractic."32 The 2003 general review states that since the 1996 systematic review, emerging trial data "have not tended to be encouraging…. The effectiveness of chiropractic spinal manipulation for back pain is thus at best uncertain."33 The 2003 meta-analysis found spinal manipulation to be more effective than sham therapy but no more or no less effective than other treatments.10
Several other points are helpful to keep in mind about the research findings. Many clinical trials of chiropractic analyze the effects of chiropractic manipulation alone, but chiropractic practice includes more than manipulation (see Question 5).34 Results of a trial performed in one setting (such as a managed care organization or a chiropractic college) may not completely apply in other settings.29,35 And, researchers have observed that the placebo effect may be at work in chiropractic care,34 as in other forms of health care.
cThis fact sheet often uses the term "adjustment" to refer to chiropractic manipulation. In Question 9 and Appendices I and II, "manipulation" is used where it is used in the source(s) on chiropractic being discussed.
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10. Are there scientific controversies associated with chiropractic?
Yes, there are scientific controversies about chiropractic, both inside and outside the profession. For example, within the profession, there have been disagreements about the use of physical therapy techniques, which techniques are most appropriate for certain conditions, and the concept of subluxations. Outside views have questioned the effectiveness of chiropractic treatments, their scientific basis, and the potential risks in subsets of patients (for example, the risks of certain types of adjustments to patients with osteoporosis or risk factors for osteoporosis, compared to patients with healthier bone structures33,36).
Research studies on chiropractic are ongoing. The results are expected to expand scientific understanding of chiropractic. A key area of research is the basic science of what happens in the body (including its cells and nerves) when specific chiropractic treatments are given.
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11. Is NCCAM funding research on chiropractic?
Yes. For example, recent projects supported by NCCAM include:
Comparing conventional medical care for acute back pain with an "expanded benefits" package (consisting of conventional care plus a choice of chiropractic, massage, or acupuncture)
Finding out what happens (through measurement) in the lumbar portion of the spine after chiropractic positioning and adjustment
Evaluating the effects of the speed of spinal adjustment on muscles and nerves
Studying the effectiveness of chiropractic adjustment for a variety of conditions, including neck pain, chronic pelvic pain, and temporomandibular disorders (TMD) in the jaw
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For More Information
NCCAM Clearinghouse
Toll-free in the U.S.: 1-888-644-6226
International: 301-519-3153
TTY (for deaf and hard-of-hearing callers): 1-866-464-3615
E-mail: info@nccam.nih.gov
NCCAM Web site: nccam.nih.gov
Address: NCCAM Clearinghouse, P.O. Box 7923, Gaithersburg, MD 20898-7923
Fax: 1-866-464-3616
Fax-on-Demand service: 1-888-644-6226
The NCCAM Clearinghouse provides information on CAM and on NCCAM. Services include fact sheets, other publications, and searches of Federal databases of scientific and medical literature. The Clearinghouse does not provide medical advice, treatment recommendations, or referrals to practitioners.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Web site: www.niams.nih.gov
Toll-free in the U.S.: 1-877-22-NIAMS (or 301-495-4484)
NIAMS supports research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; training of scientists; and information based on research. Publications are available.
Agency for Healthcare Research and Quality (AHRQ)
Web site: www.ahrq.gov
Telephone: 301-427-1364
AHRQ is the health services research arm of the Department of Health and Human Services. Publications that may be of interest include Chiropractic in the United States: Training, Practice, and Research (1998) and AHRQ's Clinical Practice Guideline No. 14: Acute Low-Back Problems in Adults (1994; however, this document has been archived by AHRQ and is not considered current clinical guidance).
CAM on PubMed
Web site: www.nlm.nih.gov/nccam/camonpubmed.html
CAM on PubMed, a database on the Internet developed jointly by NCCAM and the National Library of Medicine, offers citations to (and in most cases, brief summaries of) articles on CAM in scientifically based, peer-reviewed journals. CAM on PubMed also links to many publisher Web sites, which may offer the full text of articles.
ClinicalTrials.gov
Web site: www.clinicaltrials.gov
ClinicalTrials.gov is a database of information on clinical trials, primarily in the United States and Canada, for a wide range of diseases and conditions. It is sponsored by the National Institutes of Health and the U.S. Food and Drug Administration.
The Cochrane Library
Web site: www.cochrane.org/reviews/clibintro.htm
The Cochrane Library is a collection of science-based reviews from the Cochrane Collaboration, an international nonprofit organization that seeks to provide "up-to-date, accurate information about the effects of health care." Its authors analyze the results of rigorous clinical trials on a given topic and prepare systematic reviews. Abstracts (brief summaries) of these reviews can be read online without charge. You can search by treatment name or medical condition. Subscriptions to the full text are offered at a fee and are carried by some libraries.
Definitions
Acupuncture: A health care practice that originated in traditional Chinese medicine. Acupuncture involves inserting needles at specific points on the body, in the belief that this will help improve the flow of the body's energy (or qi, pronounced "chee") and thereby help the body achieve and maintain health.
Acute pain: Pain that has lasted a short time (e.g., less than 3 weeks) or is severe.
Alternative medical system: A medical system built upon a complete system of theory and practice; these systems have often evolved apart from and earlier than the conventional medical approach used in the United States. An example from a Western culture is naturopathic medicine; from a non-Western culture, traditional Chinese medicine.
Bonesetter: A health care practitioner (not necessarily a licensed physician) whose occupation is setting fractured or dislocated bones.
Cauda equina syndrome: A syndrome that occurs when the nerves of the cauda equina (a bundle of spinal nerves extending beyond the end of the spinal cord) are compressed and damaged. Symptoms include leg weakness; loss of bowel, bladder, and/or sexual functions; and changes in sensation around the rectum or genitalia.
Chronic pain: Pain that has lasted a long time (more than 3 months).
Clinical trial: A clinical trial is a research study in which a treatment or therapy is tested in people to see whether it is safe and effective. Clinical trials are a key part of the process in finding out which treatments work, which do not, and why. Clinical trial results also contribute new knowledge about diseases and medical conditions.
Complication: A secondary disease or condition that develops in the course of a primary disease or condition, or as the result of a treatment.
Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all.
General review: An analysis in which information from various studies is summarized and evaluated; conclusions are made based on this evidence.
Hippocrates: A Greek physician born in 460 B.C. who became known as the founder of Western medicine.
Homeopathy: Also known as homeopathic medicine. It is an alternative medical system that was invented in Germany. In homeopathic treatment, there is a belief that "like cures like," meaning that small, highly diluted quantities of medicinal substances are given to cure symptoms, when the same substances given at higher or more concentrated doses would actually cause those symptoms.
Manipulation: Passive joint movement beyond the normal range of motion. The term adjustment is preferred in chiropractic.
Massage: A therapy in which muscle and connective tissue are manipulated to enhance function of those tissues and promote relaxation and well-being.
Meta-analysis: A type of research review that uses statistical techniques to analyze results from a collection of individual studies.
Mobilization: A technique, used by chiropractors and other health care professionals, in which a joint is passively moved within its normal range of motion.
Myofascial therapy: A type of physical therapy that uses stretches and massage.
Naturopathic medicine: Also known as naturopathy. It is an alternative medical system in which practitioners work with natural healing forces within the body, with a goal of helping the body heal from disease and attain better health. Practices may include dietary modifications, massage, exercise, acupuncture, minor surgery, and various other interventions.
Observational study: A type of study in which individuals are observed or certain outcomes are measured. No attempt is made to affect the outcome (for example, no treatment is given).
Orthopedist: Doctor of Medicine (M.D.) who is a surgeon specializing in disorders of the musculoskeletal system.
Osteopathic medicine: Also known as osteopathy. It is a form of conventional medicine that, in part, emphasizes diseases arising in the musculoskeletal system. There is an underlying belief that all of the body's systems work together, and disturbances in one system may affect function elsewhere in the body. Most osteopathic physicians practice osteopathic manipulation, a full-body system of hands-on techniques to alleviate pain, restore function, and promote health and well-being.
Osteoporosis: A reduction in the amount of bone mass, which can lead to breaking a bone after a minor injury, such as a fall.
Placebo: Resembles a treatment being studied in a clinical trial, except that the placebo is inactive. One example is a sugar pill. By giving one group of participants a placebo and the other group the active treatment, the researchers can compare how the two groups respond and get a truer picture of the active treatment's effects. In recent years, the definition of placebo has been expanded to include other things that could affect the results of health care, such as how a patient feels about receiving the care and what she expects to happen from it.
Prospective study: A type of research study in which participants are followed over time for the effect(s) of a health care treatment.
Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.
Review: See general review, systematic review, or meta-analysis.
Sham: A treatment or device that is a type of placebo. An example would be positioning the patient's body and placing the chiropractor's hands in a way that mimics an actual treatment, but is not a treatment.
Subacute pain: Pain that has lasted somewhat longer than acute pain (for example, more than a few days or weeks) but is not yet chronic pain.
Systematic review: A type of research review in which data from a set of studies on a particular question or topic are collected, analyzed, and critically reviewed.
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References
Meeker WC, Haldeman S. Chiropractic: a profession at the crossroads of mainstream and alternative medicine. Annals of Internal Medicine. 2002;136(3):216-227.
Kaptchuk TJ, Eisenberg DM. Chiropractic: origins, controversies, and contributions. Archives of Internal Medicine. 1998;158(20):2215-2224.
Bronfort G. Spinal manipulation: current state of research and its indications. Neurologic Clinics. 1999;17(1):91-111.
Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. Journal of the American Medical Association. 1998;280(18):1569-1575.
Wolsko PM, Eisenberg DM, Davis RB, et al. Patterns and perceptions of care for treatment of back and neck pain: results of a national survey. Spine. 2003;28(3):292-297.
Coulter ID, Hurwitz EL, Adams AH, et al. Patients using chiropractors in North America: who are they, and why are they in chiropractic care? Spine. 2002;27(3):291-296.
Vickers A, Zollman C. ABC of complementary medicine. The manipulative therapies: osteopathy and chiropractic. BMJ. 1999;319(7218):1176-1179.
Atlas SJ, Nardin RA. Evaluation and treatment of low back pain: an evidence-based approach to clinical care. Muscle and Nerve. 2003;27(3):265-284.
Pengel HM, Maher CG, Refshauge KM. Systematic review of conservative interventions for subacute low back pain. Clinical Rehabilitation. 2002;16(8):811-820.
Assendelft WJ, Morton SC, Yu EI, et al. Spinal manipulative therapy for low back pain. Annals of Internal Medicine. 2003;138(11):871-881.
Complementary medicine: fact and fiction about chiropractic. Harvard Health Letter. 1999;24(3):1-3.
The Council on Chiropractic Education. Standards for Doctor of Chiropractic Programs and Requirements for Institutional Status January 2003. Council on Chiropractic Education Web site. Accessed at www.cce-usa.org on June 16, 2003.
Eisenberg DM, Cohen MH, Hrbek A, et al. Credentialing complementary and alternative medical providers. Annals of Internal Medicine. 2002;137(12):965-973.
Agency for Health Care Policy and Research. Chiropractic in the United States: Training, Practice, and Research. Rockville, MD: Agency for Health Care Policy and Research; 1998. AHCPR publication no. 98-N002.
Dagenais S, Haldeman S. Chiropractic. Primary Care. 2002;29(2):419-437.
Shekelle PG, Adams AH, Chassin MR, et al. Spinal manipulation for low-back pain. Annals of Internal Medicine. 1992;117(7):590-598.
Senstad O, Leboeuf-Yde C, Borchgrevink C. Frequency and characteristics of side effects of spinal manipulative therapy. Spine. 1997;22(4):435-440.
Hufnagel A, Hammers A, Schonle PW, et al. Stroke following chiropractic manipulation of the cervical spine. Journal of Neurology. 1999;246(8):683-688.
Jeret JS, Bluth M. Stroke following chiropractic manipulation: report of 3 cases and review of the literature. Cerebrovascular Diseases. 2002;13(3):210-213.
Haldeman S, Rubinstein SM. Cauda equina syndrome in patients undergoing manipulation of the lumbar spine. Spine. 1992;17(12):1469-1473.
Haldeman S, Rubinstein SM. Compression fractures in patients undergoing spinal manipulative therapy. Journal of Manipulative and Physiological Therapeutics. 1992;15(7):450-454.
Hurwitz EL, Morgenstern H, Harber P, et al. A randomized trial of medical care with and without physical therapy and chiropractic care with and without physical modalities for patients with low back pain: 6-month follow-up outcomes from the UCLA low back pain study. Spine. 2002;27(20):2193-2204.
Cooper RA, Henderson T, Dietrich CL. Roles of nonphysician clinicians as autonomous providers of patient care. Journal of the American Medical Association. 1998;280(9):795-802.
Chiropractic regulatory boards. Federation of Chiropractic Licensing Boards Web site. Accessed at www.fclb.org/boards.htm on June 16, 2003.
Hsieh CY, Adams AH, Tobis J, et al. Effectiveness of four conservative treatments for subacute low back pain: a randomized clinical trial. Spine. 2002;27(11):1142-1148.
Cherkin DC, Deyo RA, Battie M, et al. A comparison of physical therapy, chiropractic manipulation, and provision of an educational booklet for the treatment of patients with low back pain. New England Journal of Medicine. 1998;339(15):1021-1029.
Bronfort G, Goldsmith CH, Nelson CF, et al. Trunk exercise combined with spinal manipulative or NSAID therapy for chronic low back pain: a randomized, observer-blinded clinical trial. Journal of Manipulative and Physiological Therapeutics. 1996;19(9):570-582.
Carey TS, Garrett J, Jackman A, et al. The outcomes and costs of care for acute low back pain among patients seen by primary care practitioners, chiropractors, and orthopedic surgeons. The North Carolina Back Pain Project. New England Journal of Medicine. 1995;333(14):913-917.
Pope MH, Phillips RB, Haugh LD, et al. A prospective randomized three-week trial of spinal manipulation, transcutaneous muscle stimulation, massage and corset in the treatment of subacute low back pain. Spine. 1994;19(22):2571-2577.
Triano JJ, McGregor M, Hondras MA, et al. Manipulative therapy versus education programs in chronic low back pain. Spine. 1995;20(8):948-955.
Meade TW, Dyer S, Browne W, et al. Randomised comparison of chiropractic and hospital outpatient management for low back pain: results from extended follow up. BMJ. 1995;311(7001):349-351.
Assendelft WJ, Koes BW, van der Heijden GJ, et al. The effectiveness of chiropractic for treatment of low back pain: an update and attempt at statistical pooling. Journal of Manipulative and Physiological Therapeutics. 1996;19(8):499-507.
Ernst E. Chiropractic spinal manipulation for back pain. British Journal of Sports Medicine. 2003;37(3):195-196.
Ernst E. Chiropractic care: attempting a risk-benefit analysis. American Journal of Public Health. 2002;92(10):1603-1604.
Hurwitz EL, Morgenstern H, Harber P, et al. A randomized trial of chiropractic manipulation and mobilization for patients with neck pain: clinical outcomes from the UCLA neck-pain study. American Journal of Public Health. 2002;92(10):1634-1641.
Sran MM. Commentary on "Chiropractic spinal manipulation for back pain." British Journal of Sports Medicine. 2003;37:196.
Top
Appendix I
Research Studies of Chiropractic Treatment in Adults with Back Pain
Published from January 1994 through June 2003
Citation Description Findings
Hurwitz et al., 200222 Randomized clinical trial (RCT) of patients in a managed care organization compared chiropractic cared (with and without any of the following added: heat or cold therapy, ultrasound, electrical muscle stimulation) with conventional medical care (with and without physical therapy added). Participants (652) had acute, subacute, or chronic low-back pain with or without leg pain. Back-pain intensity and back-related disability were measured. After 6 months of followup, the conventional medical care and chiropractic regimens were found to be comparably effective.
Hsieh et al., 200225 RCT compared four treatments for subacute low-back pain (LBP): "joint manipulation" by a chiropractor, back school (program of counseling and exercises), myofascial therapy, and joint manipulation plus myofascial therapy. Participants (178) had LBP for either >3 weeks but <6 months in a current episode or >2 months within the preceding 8 months for recurrent LBP, and were evaluated 3 weeks and 6 months after treatment. No statistically significant differences were found between groups at 3 weeks or 6 months.
Cherkin et al., 199826 RCT in an HMO setting of 321 adults aged 20-64 with low-back pain. Patients received either chiropractic manipulation, physical therapy (PT), or a booklet on self-managing back pain. They were monitored for 2 years and evaluated for bothersomeness of symptoms and level of dysfunction. The outcomes for those who received manipulation or PT were better than those who received the booklet, but "only marginally better." There were no significant differences between the manipulation and PT groups. Authors note that manipulation and PT "may slightly reduce symptoms."
Bronfort et al., 199627 For chronic low-back pain, prospective RCT compared (1) chiropractic spinal manipulation therapy (SMT) plus trunk-strengthening exercises with (2) chiropractic SMT plus trunk-stretching exercises and (3) trunk-strengthening exercises combined with an NSAID (drug). Enrollees (174) were measured for low-back pain, disability, and functional health status at 5 and 11 weeks. Each of the 3 regimens yielded a "similar and clinically important improvement over time that was considered superior to the expected natural history of long-standing chronic low back pain."
Carey et al., 199528 Prospective observational study on the outcomes of care for acute low-back pain by chiropractors, primary care practitioners, and orthopedic surgeons, including how long it took to return to functional status. Participants (1,633) had acute pain of less than 10 weeks' duration. Time to recovery was "essentially the same," regardless of which provider provided the care.
Meade et al., 199531 RCT of 741 patients who came to chiropractic and hospital outpatient clinics in 11 centers, for low-back pain. Participants were randomized to receive either chiropractic or hospital-outpatient management. Outcomes were measured mainly with a pain disability questionnaire, at 6 weeks, 6 months, and 1, 2, and 3 years. Chiropractic was found to be more effective, especially for those with "short current episodes, a history of back pain, and initially high [pain scale] scores." Benefit was less evident at 2 and 3 years than earlier. Authors noted that further trials are needed, e.g., on specific components of chiropractic.
Triano et al., 199530 RCT comparing chiropractic spinal manipulation, sham manipulation, and a back education program. Participants (170) had low-back pain (lasting 7 weeks or longer or consisting of at least 6 episodes in 12 months) and were evaluated for pain and activity tolerance at enrollment, after 2 weeks of treatment, and after 2 weeks of no treatment. Greater improvement was found in the manipulation group than in other groups. Pain relief continued to end of evaluation period.
Pope et al., 199429 Prospective RCT compared chiropractic spinal manipulation for treatment of subacute low-back pain to massage, use of a corset, and TMS (electrical muscle stimulation). Patients (164) were treated for 3 weeks and evaluated through various standardized instruments and examinations. Various improvements were seen in all 4 groups. The manipulation group had the most improvement in flexion and pain. However, authors concluded overall that none of the changes in physical outcomes measured was significantly different between groups.
dHurwitz et al. define chiropractic care as "spinal manipulation or another spinal-adjusting technique."
Top
Appendix II
Reviews on Chiropractic Treatment for Back Pain in Adults
Published from October 1996 through June 2003
Citation Description Findings
Assendelft et al., 200310,e Meta-analysis of 39 randomized clinical trials of treatments for acute or chronic low-back pain in adults. The trials compared spinal manipulation (by chiropractors and other health care providers) with another treatment or control condition (including no treatment, conventional medical care, pain-relieving drugs, physical therapy, exercise, and back school). Spinal manipulation was more effective than sham therapy, but no more or no less effective than other treatments.
Authors found that the specific profession of the manipulators (including chiropractors) did not affect these results.
Ernst, 200333 General review of the scientific evidence for the effectiveness of chiropractic spinal manipulation for back pain (this review is not limited to low-back pain studies). Author noted there has been only one systematic review of chiropractic spinal manipulation exclusively (Assendelft et al., 1996, see below), and that, since that study, emerging trial data "have not tended to be encouraging…. The effectiveness of chiropractic spinal manipulation for back pain is thus at best uncertain."
Assendelft et al., 199632 Systematic review of 8 RCTs of chiropractic for acute or chronic low-back pain. Authors stated that all studies analyzed had serious flaws in design, execution, and reporting. Studies could not be pooled to reach statistical conclusions because of insufficient data and data quality problems. Authors summarized the available data narratively; concluded they "did not provide convincing evidence for the effectiveness of chiropractic for acute or chronic low back pain"; and noted that better-executed trials are needed in future.
eThis study on spinal manipulation is included because the authors were able to break down the findings according to the profession of the manipulator, including chiropractors.
Top
This publication is not copyrighted and is in the public domain. Duplication is encouraged.
NCCAM has provided this material for your information. It is not intended to substitute for the medical expertise and advice of your primary health care provider. We encourage you to discuss any decisions about treatment or care with your health care provider. The mention of any product, service, or therapy in this information is not an endorsement by NCCAM.
National Institutes of Health
U.S. Department of Health and Human Services
NCCAM Publication No. D196
November 2003
posted by bakerchiropractic at 9:23 AM
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Chiropractic More Effective Than Outpatient Hospital Care for Lower Back Pain
The British Medical Journal reports that a three-year study proves what most chiropractic patients already know. Chiropractic care is more effective with higher patient satisfaction than outpatient medical care for these types of problems. The study reported involved 741 men and women with low back pain. A 3 year follow up showed that there was 29% higher improvement in those receiving chiropractic care over those receiving out-patient medical care. In addition more of the patients rated chiropractic more helpful than the hospital management. The conclusion of the study was that those seen by chiropractors derive more benefits and long-term satisfaction than those treated by hospitals.
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British Researchers Show Chiropractic More Effective
--------------------------------------------------------------------------------
"Patients suffering from back pain gain greater benefit from chiropractors than from conventional treatment in National Health Service hospitals, an independent study of the two methods says today." -- David Fletcher, Health Services Correspondent, Daily Telegraph
"The Medical Research Council yesterday urged Mr. Kenneth Clarke, Secretary of State for Health, to ease the distress of Britain's back pain sufferers by making an alternative treatment (chiropractic) available on the National Health Service." -- The London Times
"Patients with back pain who go to a chiropractor do better than those treated in hospital, says a report. They suffer less pain and need fewer days off work. Wider use of the treatment could save the country millions of pounds in lost output and social security payments, it is claimed." -- Clare Dover, Medical Reporter, Daily Express
Not fiction or fantasy, these are headlines in three major British newspapers announcing the results of an independent study reported in the British Medical Journal, June 2, 1990, entitled, "Low Back Pain of Mechanical Origin: Randomized Comparison of Chiropractic and Hospital Outpatient Treatment." This study is filled with information that is very positive for the chiropractic profession.
In this study made by the Medical Research Council, chiropractic treatment was shown to be more effective than hospital outpatient management. The results were especially significant for patients with chronic or severe back pain. The benefits of chiropractic care became more evident throughout the two year follow-up period. According to the study's results, even the secondary outcome measures showed chiropractic to be more beneficial. This is one of the only studies that demonstrates the effectiveness of chiropractic care on a long-term basis. As the abstract states: "Conclusions -- For patients with low back pain in whom manipulation is not contraindicated, chiropractic almost certainly confers worthwhile, long-term benefit in comparison with hospital outpatient management. The benefit is seen mainly in those with chronic or severe pain. Introducing chiropractic into National Health Services should be considered." -- Meade, et. al.
In the past few years, chiropractic research has become more and more important in the establishment of chiropractic as a scientifically supported discipline. There are some in the chiropractic profession who have questioned the need for "scientific proof" and who have criticized both the researchers themselves as well as the amounts of money spent on research. This study alone, clearly demonstrates the need for and benefits of chiropractic research.
This particular study has made a very strong case for the inclusion of chiropractic care in the National Health Service of Great Britain. This is a tremendously important statement in light of the fact that the United States is considering a national health plan. This research illustrates the cost effectiveness of the inclusion of chiropractic treatment in national health care as well supporting the effectiveness of chiropractic treatment.
(pls change "L" to pounds symbol)
Though the average cost of chiropractic investigation and treatment was L165 in 1988-89 compared to L111 for hospital treatment, the overall cost was dramatically less in terms of frequency and duration of absence from work. This study showed significant reduction of work days lost when patients received chiropractic treatment in comparison with those patients treated as hospital outpatients. According to Meade et. al., there could be a reduction in sickness absence of some 290,000 days over a two year period. This would lead to a savings of "about L13 million in out-put and L2.9 million in social security payments," (These payments correspond to our workers' compensation payments.) according to the study's results.
To quote: "The economic, resource, and policy implications of our results are extensive... There is, therefore, economic support for use of chiropractic in low back pain, though the obvious clinical improvement in pain and disability attributable to chiropractic treatment is in itself an adequate reason for considering the use of chiropractic."
It should be noted that chiropractors participating in these trials were limited to a maximum of ten treatments, intended to be concentrated in the first three months but which could be spread out over a year's time if necessary. This fact may prove significant in later studies. It should also be considered by those practitioners who have a tendency to schedule their patients for 30 visits or more upon the initial examination.
Another point of great interest to chiropractors is the statement that the effects of chiropractic treatment seem to be long-term, as the study showed no return to pre-treatment pain levels during the two years of follow-up. This is in comparison to hospital treatment where patients began to deteriorate after six months to a year. "This pragmatic comparison of two types of treatment used in day to day practice shows that patients treated by chiropractors were not only no worse off than those treated in hospital but almost certainly fared considerably better and that they maintained their improvement for at least two years." -- Meade et. al.
The benefits of this research have not been limited to exposure in medical and scientific circles. The public image of the chiropractic profession in Great Britain has been considerably strengthened by the results of this study and the widespread publicity of these results in the press. Three major British papers, including the front page of the Daily Telegraph reported these incredibly positive research results to the general public. Again, research-based support of chiropractic treatment provided the means to inform the public about the benefits of chiropractic. The chiropractic profession could not ask for any better PR than this.
It is time for chiropractic in the United States, as national health care looms on the horizon, to look to chiropractic research as the means to ensuring chiropractic's place in the nation's health care systems. We have the opportunity and the obligation to support chiropractic research now so that chiropractic care and treatment will be assured worldwide in the future. This study by Meade et. al. concluded with a call for further research. Trials are needed which will identify the specific component(s) responsible for the effectiveness of chiropractic.
Also
http://www.chiroweb.com/archives/08/14/06.html
Other MPAmedia
Alternative Health
Site Links
Chiropractic
ChiroExpo
ChiroFind
ChiroMall
ChiropracticResearch
Review
Acupuncture
AcupunctureToday
Massage Therapy
MassageToday
SpaTherapy
Nutrition
NutritionalWellness
Naturopathy
NaturopathyDigest
British Researchers Show Chiropractic More Effective
--------------------------------------------------------------------------------
"Patients suffering from back pain gain greater benefit from chiropractors than from conventional treatment in National Health Service hospitals, an independent study of the two methods says today." -- David Fletcher, Health Services Correspondent, Daily Telegraph
"The Medical Research Council yesterday urged Mr. Kenneth Clarke, Secretary of State for Health, to ease the distress of Britain's back pain sufferers by making an alternative treatment (chiropractic) available on the National Health Service." -- The London Times
"Patients with back pain who go to a chiropractor do better than those treated in hospital, says a report. They suffer less pain and need fewer days off work. Wider use of the treatment could save the country millions of pounds in lost output and social security payments, it is claimed." -- Clare Dover, Medical Reporter, Daily Express
Not fiction or fantasy, these are headlines in three major British newspapers announcing the results of an independent study reported in the British Medical Journal, June 2, 1990, entitled, "Low Back Pain of Mechanical Origin: Randomized Comparison of Chiropractic and Hospital Outpatient Treatment." This study is filled with information that is very positive for the chiropractic profession.
In this study made by the Medical Research Council, chiropractic treatment was shown to be more effective than hospital outpatient management. The results were especially significant for patients with chronic or severe back pain. The benefits of chiropractic care became more evident throughout the two year follow-up period. According to the study's results, even the secondary outcome measures showed chiropractic to be more beneficial. This is one of the only studies that demonstrates the effectiveness of chiropractic care on a long-term basis. As the abstract states: "Conclusions -- For patients with low back pain in whom manipulation is not contraindicated, chiropractic almost certainly confers worthwhile, long-term benefit in comparison with hospital outpatient management. The benefit is seen mainly in those with chronic or severe pain. Introducing chiropractic into National Health Services should be considered." -- Meade, et. al.
In the past few years, chiropractic research has become more and more important in the establishment of chiropractic as a scientifically supported discipline. There are some in the chiropractic profession who have questioned the need for "scientific proof" and who have criticized both the researchers themselves as well as the amounts of money spent on research. This study alone, clearly demonstrates the need for and benefits of chiropractic research.
This particular study has made a very strong case for the inclusion of chiropractic care in the National Health Service of Great Britain. This is a tremendously important statement in light of the fact that the United States is considering a national health plan. This research illustrates the cost effectiveness of the inclusion of chiropractic treatment in national health care as well supporting the effectiveness of chiropractic treatment.
(pls change "L" to pounds symbol)
Though the average cost of chiropractic investigation and treatment was L165 in 1988-89 compared to L111 for hospital treatment, the overall cost was dramatically less in terms of frequency and duration of absence from work. This study showed significant reduction of work days lost when patients received chiropractic treatment in comparison with those patients treated as hospital outpatients. According to Meade et. al., there could be a reduction in sickness absence of some 290,000 days over a two year period. This would lead to a savings of "about L13 million in out-put and L2.9 million in social security payments," (These payments correspond to our workers' compensation payments.) according to the study's results.
To quote: "The economic, resource, and policy implications of our results are extensive... There is, therefore, economic support for use of chiropractic in low back pain, though the obvious clinical improvement in pain and disability attributable to chiropractic treatment is in itself an adequate reason for considering the use of chiropractic."
It should be noted that chiropractors participating in these trials were limited to a maximum of ten treatments, intended to be concentrated in the first three months but which could be spread out over a year's time if necessary. This fact may prove significant in later studies. It should also be considered by those practitioners who have a tendency to schedule their patients for 30 visits or more upon the initial examination.
Another point of great interest to chiropractors is the statement that the effects of chiropractic treatment seem to be long-term, as the study showed no return to pre-treatment pain levels during the two years of follow-up. This is in comparison to hospital treatment where patients began to deteriorate after six months to a year. "This pragmatic comparison of two types of treatment used in day to day practice shows that patients treated by chiropractors were not only no worse off than those treated in hospital but almost certainly fared considerably better and that they maintained their improvement for at least two years." -- Meade et. al.
The benefits of this research have not been limited to exposure in medical and scientific circles. The public image of the chiropractic profession in Great Britain has been considerably strengthened by the results of this study and the widespread publicity of these results in the press. Three major British papers, including the front page of the Daily Telegraph reported these incredibly positive research results to the general public. Again, research-based support of chiropractic treatment provided the means to inform the public about the benefits of chiropractic. The chiropractic profession could not ask for any better PR than this.
It is time for chiropractic in the United States, as national health care looms on the horizon, to look to chiropractic research as the means to ensuring chiropractic's place in the nation's health care systems. We have the opportunity and the obligation to support chiropractic research now so that chiropractic care and treatment will be assured worldwide in the future. This study by Meade et. al. concluded with a call for further research. Trials are needed which will identify the specific component(s) responsible for the effectiveness of chiropractic.
posted by bakerchiropractic at 9:20 AM
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Medicare project expands chiropractic services
"REGIONAL (Dec 2, 2005): From time to time, Medicare announces changes to its coverage plan. These may go unnoticed until actually needed. If you live in Maine and use chiropractic services, you may be interested in the following information which was shared with me recently by another Windham senior citizen. Please read carefully.
The Centers of Medicare and Medicaid Services (CMS) is conducting a two-year demonstration project that expands coverage for chiropractic services for Medicare beneficiaries.
If you are a Medicare beneficiary who previously received such services from a chiropractor, you would have had to pay out of pocket. You will now be able to receive certain services from a chiropractor subject to the regular Medicare co-insurance and deductibles.
The demonstration will be conducted throughout the state.
Medicare currently helps pay for manual manipulation of the spine by chiropractors. But Medicare will now cover additional medical, diagnostic and therapy services that chiropractors are legally allowed to provide. These include: physical therapy, x-rays, lab tests, and extraspinal manipulation, which is a manipulation of a body part other than the spine. Chiropractors will also be able to order magnetic resonance imaging (MRIs) and CT scans, and refer patients to physical therapists for therapy services if they do not provide therapy services.
The project started Apr. 1, 2005 and ends Mar. 31, 2007. Medicare will not pay chiropractors for these expanded services after Mar. 31, 2007.
Confirm that your chiropractor is participating in the demonstration; if he or she is not participating, then your chiropractor may bill you for the full costs of these expanded services.
To be eligible, you must have Medicare Part B insurance and your chiropractor must practice in Maine. You must be enrolled in original Medicare and not in a Medicare Advantage plan.
Talk with your chiropractor to review the complete list of eligible services under the demonstration. Discuss what Medicare will cover.
If you receive the newly covered Medicare services from a chiropractor, you will simply pay your customary unmet deductibles and applicable co-insurance. If you have Medigap, the customary co-insurance and deductible usually covered for Medicare services should be covered. If you have employer coverage you will need to find out if they cover the co-insurance and/or deductible."
If you have any questions that cannot be answered by your chiropractic doctor, please call 1-800-MEDICARE or email: MMA_Section_651@cms.hhs.gov.
The Centers of Medicare and Medicaid Services (CMS) is conducting a two-year demonstration project that expands coverage for chiropractic services for Medicare beneficiaries.
If you are a Medicare beneficiary who previously received such services from a chiropractor, you would have had to pay out of pocket. You will now be able to receive certain services from a chiropractor subject to the regular Medicare co-insurance and deductibles.
The demonstration will be conducted throughout the state.
Medicare currently helps pay for manual manipulation of the spine by chiropractors. But Medicare will now cover additional medical, diagnostic and therapy services that chiropractors are legally allowed to provide. These include: physical therapy, x-rays, lab tests, and extraspinal manipulation, which is a manipulation of a body part other than the spine. Chiropractors will also be able to order magnetic resonance imaging (MRIs) and CT scans, and refer patients to physical therapists for therapy services if they do not provide therapy services.
The project started Apr. 1, 2005 and ends Mar. 31, 2007. Medicare will not pay chiropractors for these expanded services after Mar. 31, 2007.
Confirm that your chiropractor is participating in the demonstration; if he or she is not participating, then your chiropractor may bill you for the full costs of these expanded services.
To be eligible, you must have Medicare Part B insurance and your chiropractor must practice in Maine. You must be enrolled in original Medicare and not in a Medicare Advantage plan.
Talk with your chiropractor to review the complete list of eligible services under the demonstration. Discuss what Medicare will cover.
If you receive the newly covered Medicare services from a chiropractor, you will simply pay your customary unmet deductibles and applicable co-insurance. If you have Medigap, the customary co-insurance and deductible usually covered for Medicare services should be covered. If you have employer coverage you will need to find out if they cover the co-insurance and/or deductible."
If you have any questions that cannot be answered by your chiropractic doctor, please call 1-800-MEDICARE or email: MMA_Section_651@cms.hhs.gov.
posted by bakerchiropractic at 5:22 AM
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PILLOW OF YOUTH AT THE MALL
Pillow of Youth,Inc. and Marshmellow Pillows will be out at the Longview Mall this weekend with us (Dec. 2,3,and 4) and there will be samples of these great pillows on display. Crystal Anderson will be there to answer question and take orders for these excellent pillows.
posted by bakerchiropractic at 4:42 AM
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LONGVIEW MALL THIS WEEKEND - We are there
We will be at Longview Mall in front of Dillards (the Men's DILLARDS) meeting folks and passing out information. We hope to see you there, and wish everyone "HAPPY HOLIDAYS!"
~Dr. John Baker,DC
~Dr. John Baker,DC
posted by bakerchiropractic at 4:40 AM
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