A randomized, controlled trial of omega-3 fatty acids plus an antioxidant for relapse prevention after antipsychotic discontinuation in first-episode schizophrenia

Background: While antipsychotics are effective in the maintenance treatment of schizophrenia they have safety and tolerability risks. We investigated whether a combination of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) and a metabolic antioxidant, alpha-lipoic acid (alpha-LA), is effective in preventing relapse after antipsychotic discontinuation in subjects who were successfully treated for 2-3 years after a first-episode of schizophrenia, schizo-affective or schizophreniform disorder. Methods: In this randomized, double-blind, placebo controlled study antipsychotic treatment was tapered and discontinued and participants received either omega-3 PUFAs (eicosapentaenoic acid 2 g/day and docosahexaenoic acid 1 g/day) + alpha-LA 300 mg/day or placebo. Subjects were followed up for two years, or until relapse. Results: Recruitment was terminated prematurely due to the high relapse rates in both treatment groups as well as the severity of some of the relapse episodes. Of the 33 participants, 19/21(90%) randomized to omega-3 PUFAs+alpha-LA relapsed and one (5%) completed two years without relapse (p = 0.6); and 9/12 (75%) randomized to placebo relapsed and none completed two years without relapse. Mean times to relapse were 39.8 +/- 25.4 and 38.3 +/- 26.6 weeks for the omega-3 PUFAs + alpha-LA and placebo groups, respectively (p = 0.9). There were no significant differences between the groups in relapse symptom severity. Conclusions: We found no evidence that omega-3 PUFAs + alpha-LA could be a suitable alternative to maintenance antipsychotic treatment in relapse prevention, in this small study. Antipsychotic discontinuation after a single episode of schizophrenia carries a very high risk of relapse, and treatment guidelines endorsing this practice should be revised. (C) 2014 Elsevier B. V. All rights reserved.