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Quinine for Treatment of Nocturnal Leg Cramps



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Am Fam Physician. 1999 Feb 1;59(3):656.

The use of quinine for the treatment of nocturnal leg cramps (painful, involuntary muscle contractions that commonly occur in elderly patients) is common. Quinine has been shown to prevent the occurrence of these cramps, although it has not seemed to affect the severity or duration of cramps. Man-Son-Hing and colleagues had previously conducted a meta-analysis of published research on this topic; the current study includes data from unpublished studies collected by the U.S. Food and Drug Administration (FDA).

A literature search using the key words “quinine,” “muscle cramps” and “legs” yielded three well-designed published trials. Queries to the FDA and other authorities in the field yielded four unpublished reports that also met the criteria for this meta-analysis. To be accepted, the trials had to include general ambulatory patients and be randomized, double-blind and placebo-controlled, in a crossover design. The outcomes studied were reduction in number, severity and duration of nocturnal leg cramps.

Published trials showed larger reductions in the number of nocturnal leg cramps than did unpublished trials. Although combining the results of the unpublished trials with the published data reduced the apparent efficacy of quinine, the reduction in the number of leg cramps remained statistically significant. The relative risk reduction in published studies was 43 percent; in the unpublished studies it was 21 percent. As the treatment period lengthened, the relative risk reduction improved. The severity of leg cramps was also found to decrease significantly in patients treated with quinine. No data were available to determine if the duration of leg cramps was improved in patients taking quinine. These patients experienced more side effects, with tinnitus occurring significantly more often in treated patients than in those taking placebo.

The authors acknowledge the difficulties inherent in including unpublished data in a meta-analysis and conclude that adding the unpublished reports to the published reports shows that treatment of nocturnal leg cramps with quinine has some benefit, but perhaps not as much as was originally thought. They recommend that nonpharmacologic management (such as regular passive stretching of the leg muscles) be used as first-line treatment for this condition. If the patient experiences no improvement, a trial of quinine therapy (lasting at least four weeks) may be useful.

Man-Son-Hing M, et al. Quinine for nocturnal leg cramps. A meta-analysis including unpublished data. J Gen Intern Med. September 1998;13:600–6.



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