Neurocognitive effects of an omega-3 fatty acid and vitamins E+C in schizophrenia: A randomised controlled trial

There is need for more efficient treatment of neurocognitive deficits in schizophrenia. In this 16 weeks randomised, placebo-controlled trial, we examined neurocognitive effects of adding ethyl-eicosapentaenoate 2g/day and/or vitamins E 364mg/day + C 1000mg/day to antipsychotics in 53 patients aged 18-39 years with acute schizophrenia. For the sake of validating neurocognitive tests, healthy subjects, not taking trial drugs, were also included in the study. Ethyl-EPA given alone to patients with low baseline RBC polyunsaturated fatty acids (PUFA), and Vitamins E+C given alone to high PUFA patients, impaired sustained attention (Continuous Performance Test, CPT-IP d prime score), standardised effect sizes d = 0.78 and d = 0.69, respectively. These adverse effects were paralleled by excessive increases in long-chain PUFA and serum alpha-tocopherol, respectively. They were counteracted by combining ethyl-EPA and vitamins, d = 0.80 and d = 0.74 in low and high PUFA patients, respectively. No other neurocognitive tests yielded significant results. Plausible mechanisms of harmful effects are oxidative stress and lipid raft disruption.