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Abstract & Commentary
By Allan J. Wilke, MD, MA, Professor and Chair, Department of Integrative Medicine, Ross University (Bahamas) Limited, Freeport, Grand Bahama, The Bahamas. Dr. Wilke reports no financial relationship to this field of study.
Synopsis: While there are no easy remedies for idiopathic muscle cramps, physicians can consider vitamin B complex and diltiazem. Quinine should be avoided unless symptoms are severe and the patient has exhausted all other remedies.
Source: Katzberg HD, et al. Assessment: Symptomatic treatment for muscle cramps (an evidence-based review): Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2010;74:691-696.
Although muscle cramps are associated with a number of medical conditions (e.g., dehydration, neuropathies, hypomagnesemia, hypocalcemia, hypothyroidism, kidney disease, and pregnancy), they frequently occur without an identifiable underlying cause and are referred to as idiopathic muscle cramps. They are more frequent in the elderly. Although any muscle group can be affected, most commonly they occur at night in the lower limbs. In this systematic review of the literature, these authors set out to answer three questions: 1) "Are there effective nonpharmacologic treatments for muscle cramps?" 2) "Is quinine effective in the treatment of muscle cramps?" and 3) "Are there any other pharmacologic treatments effective for the treatment of muscle cramps?"
The working definition of a muscle cramp was "a sustained, generally painful, involuntary contraction of a muscle or muscle group." The authors searched MEDLINE and EMBASE for articles pertaining to "muscle cramp" and limited to treatment and prevention, and found 563 articles. Most of these articles were excluded from the systematic review, because they were reviews, meta-analyses, letters, or case reports, or addressed medical conditions associated with muscle cramps. In the end, 24 articles were reviewed.
The authors concluded: 1) The data were insufficient regarding whether any nonpharmacologic treatment (including hydration and calf stretching) is effective; 2) Quinine is modestly effective, but adverse (and occasionally serious) side effects limit its use to patients who have no other choice; and 3) Of the non-quinine pharmacologic treatments, naftidrofuryl (not available in the United States), vitamin B complex, and diltiazem (Cardizem® and others) are possibly effective and may be considered. Magnesium compounds and gabapentin (Neurontin®) are probably not effective.
Primary care physicians are often admonished for "treating the symptom and not the root cause," but, at the same time, we are charged "to cure sometimes, to relieve often, to comfort always" (attributed to Hippocrates, who also remarked "A physician without a knowledge of Astrology has no right to call himself a physician," so take the former with a grain of salt). Based on this review, the best approach to a patient with complaints of muscle cramps would be to rule out some common illnesses associated with cramps (see above), and then, after discussing with the patient the possible benefits and risks of vitamin B complex and diltiazem, perform a trial-of-one. If neither is effective, then, again after a serious discussion of risks and what symptoms to watch for, quinine could be considered, realizing that you would be prescribing off-label.
Muscle cramps are, at root, a neurological phenomenon, caused by repetitive nerve discharges. Use of medications, such as gabapentin, that inhibit these discharges has face validity, but as with much of what we find intuitively appealing, this is not the case. Why quinine? Quinine, derived from the bark of the cinchona tree in Peru, has muscle-relaxing properties related to a direct action on muscle fibers and the distribution of calcium within the cells and was originally used to reduce shivering. Coincidentally, it was discovered to have an antiprotozoal effect when it was used for the shivering that accompanies malaria. Its use for muscle cramps has been the subject of scientific study dating back to the 1930s and 1940s.1 On Aug. 22, 1994, the FDA published a rule banning the prescription of quinine for leg cramps, citing its toxicity and the lack of proof of efficacy, and then, on Dec. 11, 2006, ordered all unapproved quinine products from the U.S. market and cautioned consumers about the off-label use for leg cramps.2 Perhaps if the FDA had this review, it would have issued a different order.
I write this as I sip on a gin and tonic and wonder if I should heed the warnings about the consumption of tonic water.3,4 The label says it contains quinine, but doesn't say how much. Maybe it's time to switch to club soda.
1. Moss HK, Herrmann LG. Night cramps in human extremities; a clinical study of the physiologic action of quinine and prostigmine upon the spontaneous contractions of resting muscles. Am Heart J 1948;35:403-408.
2. Food and Drug Administration. FDA Advances Effort Against Marketed Unapproved Drugs. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108799. Accessed April 2, 2010.
3. Brasić JR. Risks of the consumption of beverages containing quinine. Psychol Rep 2003;93(3 Pt 2):1022-1024.
4. Muso Y, et al. Fixed eruption due to quinine: Report of two cases. J Dermatol 2007;34:385-386.