title: A randomized, controlled trial of omega-3 fatty acids plus an antioxidant for relapse prevention after antipsychotic discontinuation in first-episode schizophrenia.
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.
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa. Electronic address: rae@sun.ac.za.
authors.forename: Robin
authors.initials: R
authors.lastname: Emsley
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa. Electronic address: bonga@sun.ac.za.
authors.forename: Bonginkosi
authors.initials: B
authors.lastname: Chiliza
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa. Electronic address: laila@su.ac.za.
authors.forename: Laila
authors.initials: L
authors.lastname: Asmal
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa. Electronic address: stefandup@sun.ac.za.
authors.forename: Stefan
authors.initials: S
authors.lastname: du Plessis
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa. Electronic address: lebogang@sun.ac.za.
authors.forename: Lebogang
authors.initials: L
authors.lastname: Phahladira
authors.affiliation: Division of Human Nutrition, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa. Electronic address: evettev@sun.ac.za.
authors.forename: Evette
authors.initials: E
authors.lastname: van Niekerk
authors.affiliation: Division of Chemical Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa. Electronic address: sjvr@sun.ac.za.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: van Rensburg
authors.affiliation: Center of Excellence for Pharmaceutical Sciences, School of Pharmacy, North West University, South Africa. Electronic address: Brian.Harvey@nwu.ac.za.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Harvey
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D011569:Psychiatric Status Rating Scales; D011619:Psychotropic Drugs / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D055502:Secondary Prevention; D008063:Thioctic Acid / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D014150:Antipsychotic Agents; D011619:Psychotropic Drugs; D004281:Docosahexaenoic Acids; D008063:Thioctic Acid; D015118:Eicosapentaenoic Acid
keywords: Antioxidant; Omega-3; Placebo; Relapse-prevention; Schizophrenia