S-FLUOXETINE IN THE PROPHYLAXIS OF MIGRAINE - A PHASE-II DOUBLE-BLINDRANDOMIZED PLACEBO-CONTROLLED STUDY

S-fluoxetine is the long-acting enantiomer of the racemic antidepressa nt serotonin reuptake inhibitor. Sixty-five patients needing migraine prophylaxis were recruited into a phase II,double-blind, placebo-contr olled trial. After a 1-month placebo run-in, 53 patients met entry cri teria with regard to attack frequency and were randomized, 27 to S-flu oxetine and 26 to matching placebo. Three failed to start treatment an d there were 17 early discontinuations, 9 from S-fluoxetine, 8 from pl acebo, at similar times and for similar reasons. The primary efficacy variable was attack frequency and analysis compared decline-from-basel ine in the two groups. This was earlier and greater (1.7 attacks/28 da ys, or 52%) on active therapy than on placebo (1.1 attacks/28 days, or 27%), and statistically significant in month 2 (F=4.93; p=0.033) and month 4 (F=4.55; p = 0.041). As secondary measures of efficacy, migrai ne-days per month and Patient's Global Impression of Disease Severity coherently reflected the changes in attack frequency. Mean attack seve rity and acute medication use (doses per attack) were unaltered by eit her treatment. There were no serious adverse events. Withdrawals for a dverse events were four from each group but none was considered causal ly related. The finding of greater efficacy of S-fluoxetine than of pl acebo should be interpreted conservatively, Since the analysis in the final month was made on only half of the entered patients. It supports progression to phase III evaluation, which was the purpose of the stu dy.