Propranolol for migraine prophylaxis

Klaus Linde, Karin Rossnagel

Propranolol is one of the most commonly prescribed drugs for migraine prophylaxis. We aimed to determine whether there is evidence that propranolol is more effective than placebo and as effective as other drugs for the interval (prophylactic) treatment of patients with migraine. Potentially eligible studies were identified by searching MEDLINE/PubMed (1966 to May 2003) and the Cochrane Central Register of Controlled Trials (Issue 2, 2003), and by screening bibliographies of reviews and identified articles. We included randomised and quasi-randomised clinical trials of at least 4 weeks duration comparing clinical effects of propranolol with placebo or another drug in adult migraine sufferers. Two reviewers extracted information on patients, methods, interventions, outcomes measured, and results using a pre-tested form. Study quality was assessed using two checklists (Jadad scale and Delphi list). Due to the heterogeneity of outcome measures and insufficient reporting of the data, only selective quantitative meta-analyses were performed. As far as possible, effect size estimates were calculated for single trials. In addition, results were summarised descriptively and by a vote count among the reviewers. A total of 58 trials with 5072 participants met the inclusion criteria. The 58 selected trials included 26 comparisons with placebo and 47 comparisons with other drugs. The methodological quality of the majority of trials was unsatisfactory. The principal shortcomings were high dropout rates and insufficient reporting and handling of this problem in the analysis. Overall, the 26 placebo-controlled trials showed clear short-term effects of propranolol over placebo. Due to the lack of studies with long-term follow up, it is unclear whether these effects are stable after stopping propranolol. The 47 comparisons with calcium antagonists, other beta-blockers, and a variety of other drugs did not yield any clear-cut differences. Sample size was, however, insufficient in most trials to establish equivalence. Although many trials have relevant methodological shortcomings, there is clear evidence that propranolol is more effective than placebo in the short-term interval treatment of migraine. Evidence on long-term effects is lacking. Propranolol seems to be as effective and safe as a variety of other drugs used for migraine prophylaxis.