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

Schizophr Res. 2014 Sep;158(1-3):230-5. doi: 10.1016/j.schres.2014.06.004. Epub 2014 Jul 2.

Abstract

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 (ω-3 PUFAs) and a metabolic antioxidant, alpha-lipoic acid (α-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 ω-3 PUFAs (eicosapentaenoic acid 2g/day and docosahexaenoic acid 1g/day)+α-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 ω-3 PUFAs+α-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 ω-3 PUFAs+α-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 ω-3 PUFAs+α-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.

Keywords: Antioxidant; Omega-3; Placebo; Relapse-prevention; Schizophrenia.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antioxidants / therapeutic use*
  • Antipsychotic Agents / therapeutic use
  • Docosahexaenoic Acids / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Eicosapentaenoic Acid / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Psychiatric Status Rating Scales
  • Psychotropic Drugs / therapeutic use*
  • Schizophrenia / drug therapy*
  • Secondary Prevention
  • Thioctic Acid / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Antioxidants
  • Antipsychotic Agents
  • Psychotropic Drugs
  • Docosahexaenoic Acids
  • Thioctic Acid
  • Eicosapentaenoic Acid