Failure of omega-3 polyunsaturated fatty acids in prevention of migraine: a double-blind study versus placebo

Omega-3 polyunsaturated fatty acids (OPFA) have beneficial effects on infla mmatory reactions and production of cytokines. They decrease the release of 5HT by platelets and possess vasorelaxant activity. This led them to be tr ied in the prophylactic treatment of migraine. After 4 weeks of a single-bl ind placebo run-in period, patients were randomized and treated in double-b lind condition by placebo or OPFA 6 g a day for 16 weeks, followed by a 4-w eek placebo run-out period. The intention to treat population included 196 patients. Those who received all four treatment periods included 96 patient s taking OPFA and 87 taking placebo. The primary efficacy analysis was the number of migraine attacks during the last 4 weeks of treatment. During thi s period, the mean number of attacks was 1.20 +/-1.40 in the OPFA group and 1.26 +/-1.11 in the placebo group (NS). The total number of attacks during the 4-month period of the study was significantly different between groups : 7.05 in the placebo group, 5.95 in the OPFA group (P=0.036). Mean intensi ty, mean duration of the attacks and rescue medication use, were not signif icantly different between the two groups. Except for a significant differen ce against OPFA for eructations, the tolerance was satisfying. Despite a ru n-in placebo period of 1 month, a very strong placebo effect was observed i n this trial: 45% reduction of the attacks between run-in and 4-month treat ment period (55% in the OPFA group, P=0.058). Finally, this large study did not confirm two previous studies based on a small number of patients.