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

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 x 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.