Polyunsaturated fatty acid (fish or evening primrose oil) for schizophrenia

Limited evidence gives support to an hypothesis suggesting that the symptoms of schizophrenia may result from altered neuronal membrane structure and metabolism. The latter are dependent on blood plasma levels of certain essential fatty acids (EFAs) and their metabolites. Several studies have shown those with schizophrenia often have low levels of the particular EFAs necessary for normal nerve cell membrane metabolism.

To review the effects of supplementing standard antipsychotic treatment with polyunsaturated fatty acids, whether essential (EFAs) or non-essential, for those with schizophrenia and, in recent updates to also evaluate the effects of EFA's as a sole antipsychotic treatment. To evaluate the relative efficacy of different types of fatty acid supplementation.

Relevant randomised trials were identified by searching the following electronic databases: Biological Abstracts (1985-1998), CINAHL (1982-1998), Cochrane Library (Issue 4, 1999), Cochrane Schizophrenia Group's Register (February 2000), EMBASE (1980-1998), MEDLINE (1966-1998) and PsycLIT (1974-1998). In addition, reviewers searched references of included and excluded studies and contacted authors to identify further studies.

All randomised clinical trials of polyunsaturated fatty acid supplementation to standard treatment or as primary intervention for schizophrenia (however defined) versus standard care.

Reviewers evaluated data independently and analysed on an intention-to-treat basis. They assumed that people who left the study early or were lost to follow-up had no improvement. Where possible and appropriate relative risk (RR) and their 95% confidence intervals (CI) were calculated. The number needed to treat (NNT) was estimated. For continuous data weighted mean differences (WMD) and their 95% confidence intervals were calculated. Data were inspected for heterogeneity and publication biases.

Four relatively small trials (total n=204) showed low levels of loss to follow up and adverse effects for those taking essential fatty acids. Early results from a few trials suggest a positive effect of eicosapentaenoic acid (EPA) over placebo for scale-derived mental state outcomes. The data, however, is limited making these results difficult to analyse and interpret with confidence. A single small study (n=30) investigated the value of using EPA as sole treatment for people hospitalised for relapse. Results suggest that EPA may help one third of people avoid instigation of standard antipsychotic drugs for 12 weeks (RR 0.6, CI 0.4-0.91). There were no clear effects of primrose oil (omega-6) EFA supplementation.

All data are preliminary, but results look encouraging for fish oil. EPA does not seem harmful, may be acceptable to people with schizophrenia and have moderately positive effect. A further trial is soon to be reported from the USA and more are underway or planned in the South Africa and Norway. Considering that EPA may be an acceptable intervention, large, long simple studies reporting clincially meaningful data should be anticipated.