Magnesium for the treatment of nocturnal leg cramps - A crossover randomized trial

BACKGROUND. Nocturnal leg cramps are a common health problem in the ambulat ory setting. Our objective was to evaluate the efficacy of magnesium in the treatment of nocturnal leg cramps. METHODS. Our study was a crossover randomized double-blind placebo-controll ed trial. We included patients from a large university-based ambulatory cli nic in Buenos Aires, Argentina, with at least 6 cramps during the previous month. A total of 93 subjects took part in a 4-week washout period with pla cebo. Those who were still eligible (n = 45) were randomized to receive eit her (1) an oral dose of 900 mg magnesium citrate twice daily for 1 month, f ollowed by a matching placebo for 1 month, or (2) the placebo first, follow ed by magnesium. Both groups had a 4-week washout period with placebo betwe en each treatment month. Forty-two patients completed the 4-month study. Th e main outcome was the number of nocturnal leg cramps, and the secondary ou tcomes were duration, severity, and sleep disorders caused by those cramps. RESULTS. There were no significant differences between magnesium and placeb o in any of the evaluated outcomes. The mean number of cramps was 11.1 (sta ndard deviation [SD] +/- 7.3) for placebo versus 11.8 (SD +/- 7.6) for magn esium (P = .59). We observed a significant period-effect bias: All patients improved over time regardless of the treatment sequence they received. CONCLUSIONS. Magnesium was not effective for the treatment of nocturnal leg cramps. The period-effect bias probably occurred because of a combination of the natural history of this condition, a regression to the mean, and a t rue placebo effect.