A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia

Transl Psychiatry. 2013 Dec 17;3(12):e335. doi: 10.1038/tp.2013.110.


Membrane lipid metabolism and redox regulation may be disturbed in schizophrenia. We examined the clinical effect of adding an omega-3 fatty acid and/or vitamins E+C to antipsychotics. It was hypothesized that lower baseline levels of polyunsaturated fatty acids (PUFAs) would predict more benefit from the add-on treatment. The trial had a multicenter, randomized, double-blind, placebo-controlled 2 × 2 factorial design. Patients aged 18-39 years with schizophrenia or related psychoses were consecutively included at admission to psychiatric departments in Norway. They received active or placebo ethyl-eicosapentaenoate (EPA) 2 g day⁻¹ and active or placebo vitamin E 364 mg day⁻¹+vitamin C 1000 mg day⁻¹ (vitamins) for 16 weeks. The main outcome measures were Positive and Negative Syndrome Scale (PANSS) total and subscales scores, analyzed by linear mixed models. Ninety-nine patients were included. At baseline, erythrocyte PUFA were measured in 97 subjects. Given separately, EPA and vitamins increased drop-out rates, whereas when combined they did not differ from placebo. In low PUFA patients, EPA alone impaired the course of total PANSS (Cohen's d=0.29; P=0.03) and psychotic symptoms (d=0.40; P=0.003), especially persecutory delusions (d=0.48; P=0.0004). Vitamins alone impaired the course of psychotic symptoms (d= 0.37; P=0.005), especially persecutory delusions (d=0.47; P=0.0005). Adding vitamins to EPA neutralized the detrimental effect on psychosis (interaction d=0.31; P=0.02). In high PUFA patients, there were no significant effects of trial drugs on PANSS scales. In conclusion, given separately during an acute episode, EPA and vitamins E+C induce psychotic symptoms in patients with low levels of PUFA. Combined, these agents seem safe.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Ascorbic Acid / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Eicosapentaenoic Acid / analogs & derivatives*
  • Eicosapentaenoic Acid / therapeutic use
  • Fatty Acids, Omega-3 / therapeutic use*
  • Fatty Acids, Unsaturated / blood
  • Humans
  • Schizophrenia / blood
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology*
  • Treatment Outcome
  • Vitamin E / therapeutic use*
  • Vitamins / therapeutic use*
  • Young Adult


  • Antipsychotic Agents
  • Fatty Acids, Omega-3
  • Fatty Acids, Unsaturated
  • Vitamins
  • Vitamin E
  • eicosapentaenoic acid ethyl ester
  • Eicosapentaenoic Acid
  • Ascorbic Acid