Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Quinine is effective for preventing nocturnal leg cramps

ACP J Club. 1995 July-Aug;123:11. doi:10.7326/ACPJC-1995-123-1-011


Source Citation

Man-Son-Hing M, Wells G. Meta-analysis of efficacy of quinine for treatment of nocturnal leg cramps in elderly people. BMJ. Jan


Abstract

Objective

To determine the effectiveness of quinine for nocturnal leg cramps in ambulatory elderly persons.

Data Sources

Searches were done in MEDLINE (January 1966 to April 1994) and EMBASE (January 1975 to April 1994) using the terms quinine, muscle cramps, and legs; Current Contents was searched; relevant textbooks were consulted; references of identified studies were reviewed; and content experts were contacted.

Study Selection

Selected studies had to be randomized, double-blind, placebo-controlled, crossover studies of ambulatory patients. The methods sections of trials were assessed by 4 independent reviewers blinded to the rest of the article. For trials that did not include data about individual patients, authors were contacted and asked to supply this information. 6 of 11 studies identified met the inclusion criteria.

Data Extraction

2 independent reviewers recorded the number, sex, and age range of patients; criteria for eligibility; setting; quinine dose; treatment period; presence of a washout period; adverse effects; and outcome measures (number, severity, and duration of nocturnal leg cramps; and cramp index [duration × severity]).

Main Results

5 of the 6 studies (82 patients) reported change in the number of nocturnal leg cramps. Patients receiving quinine had a greater reduction in number of leg cramps over a 4-week period than did those receiving placebo (absolute reduction in number of cramps, 8.8; 95% CI, 4.16 to 13. 49). No difference was detected for severity or duration of leg cramps or for cramp index between patients receiving quinine and those receiving placebo. Of the 52 patients from 2 trials reporting change in number of nights with leg cramps, patients receiving quinine had a reduction of 27.5% (CI, 24.4% to 30.6%).

Conclusion

Quinine is effective in reducing the number of nocturnal leg cramps in ambulatory elderly persons but does not affect the severity or duration of leg cramps.

Source of funding: None.

For article reprint:Dr. M. Man-Son-Hing, Geriatric Assessment Unit, Ottawa Civic Hospital, Ottawa, Ontario K1Y 4E9. FAX 613-761-5334.


Commentary

General internists commonly face ambulatory patients not on dialysis who complain of nocturnal leg cramps. To date, available randomized controlled trials have been small and have yielded inconsistent results about whether quinine can decrease occurrence of the malady. Man-Son-Hing and Wells used meta-analytic techniques to combine the results from 6 placebo-controlled trials. The most common entry criterion was that participants had at least 2 cramps/wk. The authors' methodology is explicit, and they attempted to find all relevant published and unpublished evidence. Additionally, when they found significant heterogeneity among the studies, they did a sensitivity analysis. This still supported their conclusion that quinine decreased the number of leg cramps.

Application of these results to patient care must be tempered by several issues. First, no trials have assessed the long-term efficacy of quinine for reducing leg cramps. The best evidence, as summarized in this meta-analysis, reflects only 2- to 4-week interventions with quinine. The data, however, do show that dosing appears to be cumulative, because trials with treatment periods < 4 weeks were unable to show benefit from quinine. In addition, the title of this meta-analysis is misleading because the patients included in the trials were not all elderly. In fact, the mean age in 2 of the studies was < 60 years, and the youngest patients were 29 and 38 years old. These trials also do not clearly show whether older patients with a heavier burden of comorbidities and polypharmacy are more or less likely to benefit from quinine. Lastly, although it is somewhat reassuring that serious adverse effects occurred in only 1 of 107 patients, this does not clarify the effect of quinine on other important outcomes, such as possible drug interactions or the potential for reduced compliance with other established medical regimens.

This meta-analysis assists clinicians by showing that quinine at bedtime can modestly decrease the number of nocturnal leg cramps on a short-term basis. The authors wisely conclude that decision making for individual patients requires close monitoring during a therapeutic trial or even an n-of-1 trial.

Mark C. Wilson, MD, MPH
Bowman Gray School of Medicine Winston-Salem, North Carolina