A negative trial of sodium valproate in cluster headache: methodological issues

We report the result of a double-blind placebo controlled study of sodium valproate (SV) (1000-2000 mg/day) in the prophylaxis of cluster headache CH. Episodic and chronic CH were defined according to the International Headache Society classification. Ninety-six patients were included, 50 in the SV group and 46 in the placebo group. After a 7-day run-in period, patients were treated for 2 weeks. The primary efficacy criterion was the percentage of patients successfully improved, i.e having an at least 50% reduction in the average number of attacks per week between the run-in period and the last week of treatment. Whatever the type of CH, there was no difference between the two groups: 50% of subjects in the SV group and 62% in the placebo group were successfully improved (P = 0.23). This high success rate observed in the placebo group, which is likely to be due to the spontaneous remission of the episode, does not allow us to draw any valid conclusion with regard to the true efficacy of SV in the prophylaxis of CH.