QUININE FOR NOCTURNAL LEG CRAMPS - A METAANALYSIS INCLUDING UNPUBLISHED DATA

OBJECTIVE: With respect to the use of quinine for the treatment of noc turnal leg cramps, to determine whether the findings of a previously p erformed meta-analysis of published data are altered with the addition of unpublished data, and whether publication bias is present in this area. DESIGN:A meta-analysis of eight (four published and four unpubli shed) randomized, double-blind, placebo-controlled trials, seven of wh ich had a crossover design. SETTING: Randomized trials that were avail able as of July 1997. SUBJECTS: Ambulatory patients (659) who suffered from regular nocturnal leg cramps. MAIN RESULTS: When individual pati ent data from all crossover studies were pooled, persons had 3.60 (95% confidence interval [CI] 2.15, 5.05) fewer cramps in a 4-week period when taking quinine compared with placebo. This compared with an estim ate of 8.83 fewer cramps (95% CI 4.16, 13.49) from pooling published s tudies alone. The corresponding relative risk reductions were 21% (95% CI 12%, 30%) and 43% (95% CI 21%, 65%), respectively. Compared with p lacebo, the use of quinine was associated with an increased incidence of side effects, particularly tinnitus. Publication bias is present in the reporting of the efficacy of quinine for this indication, as almo st all published studies reported larger estimates of its efficacy tha n did unpublished studies. CONCLUSIONS: This study confirms that quini ne is efficacious in the prevention of nocturnal leg cramps. However, its benefit may not be as large as reported from the pooling of publis hed studies alone. Given the side effect profile of quinine, nonpharma cologic therapy (e.g., regular passive stretching of the affected musc le) is the best first-line treatment. For persons who find this ineffe ctive and whose quality of life is significantly affected, a trial of quinine is warranted. Prescribing physicians must closely monitor the risks and benefits in individual patients. Publication bias is present in this area even though there is controversy about the role of quini ne in the treatment of leg champs. To minimize the possibility of this bias, persons performing medication-related meta-analyses should seek high-quality unpublished data from drug regulatory agencies and pharm aceutical companies.