Food and Behaviour Research

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A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms

Peet, M., Horrobin, D.F. (2002) Journal of Psychiatric Research 36(1) 7-18 

Web URL: View this and related abstracts via PubMed here


The objective was to test effects of ethyl eicosapentaenoate (E-E) on persistent ongoing symptoms in patients receiving different types of anti-schizophrenic drugs, typical antipsychotics, new atypical antipsychotics, and clozapine.

115 patients with DSM-IV-defined schizophrenia were studied, 31 on clozapine, 48 on new atypical drugs and 36 on typical antipsychotics. Placebo or 1, 2 or 4 g/day of E-E was given for 12 weeks in addition to the background medication. The main assessment was change from baseline to 12 weeks on the PANSS and its sub-scales.

There were no treatment-related side effects or adverse biochemical or haematological effects. Patients on 2 and 4 g/day E-E showed significant reductions in triglyceride levels which had been elevated by clozapine. In patients given 2 g/day E-E there were improvements on the PANSS and its sub-scales, but there was also a large placebo effect in patients on typical and new atypical antipsychotics and no difference between active treatment and placebo.

In patients on clozapine, in contrast, there was little placebo response, but a clinically important and statistically significant effect of E-E on all rating scales. This effect was greatest at 2 g/day. There was a positive relationship between improvement on rating scales and rise in red blood cell arachidonic acid concentration.


Previous studies have reported that dietary supplementation with the long-chain omega-3 fatty acid, EPA, may be of benefit in schizophrenia and related conditions; and low blood levels of the omega-3 fatty acids EPA and DHA (as well as omega-6 AA) have consistently been reported in at least a subset of schizophrenia patients.

In this randomised clinical trial, three different doses of pure ethyl-EPA (1g, 2g and 4g/day) were tested against placebo treatment in 115 patients with schizophrenia, who were also receiving standard treatment in the form of antipsychotic medications.

Treatment with 2g/day of EPA was significantly better than placebo in reducing schizophrenia symptoms, but less effect was found for the other doses, so the overall effect of EPA (across all dosage groups) vs placebo did not reach statistical significance.

Importantly, no adverse effects of EPA treatment were reported, and all doses were well tolerated.

This was the first dose-ranging study of EPA for schizophrenia, and indicates that 2g/day may be an optimal dose to use in further clinical trials.

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And for more information on this topic, please see the following list of research studies, which is regularly updated: