Polyunsaturated fatty acid supplementation for schizophrenia.
BACKGROUND
Limited evidence supports a hypothesis suggesting that schizophrenic symptoms may be the result of altered neuronal membrane structure and metabolism. This structure and metabolism is dependent on blood plasma levels of certain essential fatty acids and their metabolites.


OBJECTIVE
To review the effects polyunsaturated fatty acids for people with schizophrenia.


METHODS
The initial search of 1998 was updated. We searched the Cochrane Schizophrenia Group's Register (July 2002), and authors of included studies and relevant pharmaceutical companies were contacted.


METHODS
All randomised clinical trials of polyunsaturated fatty acid treatment for schizophrenia.


METHODS
Reviewers, working independently, selected, quality assessed, and extracted relevant data. Analysis was on an intention-to-treat basis. Where possible and appropriate Relative Risk (RR) and their 95% confidence intervals (CI) were calculated and the number needed to treat (NNT) estimated. For continuous data, weighted mean differences (WMD) and their 95% confidence intervals were calculated. Data were inspected for heterogeneity.


RESULTS
Five short small studies (n=313) were included. One small study (n=30) suggested that an omega-3 EFA (ecisapentenoic acid (EPA) enriched oil) may have some antipsychotic properties when compared with placebo, even if not given as a supplement to standard drugs (RR not needing antipsychotic drugs 0.73 CI 0.54 to 1.00; RR less than 25% improvement in PANSS 0.54 CI 0.3 to 0.96, NNT 3 CI 2 to 29). Other studies comparing omega-3 EFA's with placebo as a supplement to antipsychotics were too small to be conclusive. There was a suggestion that people already on antipsychotics when given omega-3 EFA supplementation had greater improvement of mental state compared to those receiving a placebo supplementation but the result were not significant (n=29, 1 RCT, RR <25% improvement in PANSS 0.62 CI 0.37 to 1.05). However, the mental state of both medicated and un-medicated patients was significantly better for those receiving omega-3 EFA supplementation (n=59, 2 RCTs, RR <25% improved on PANSS 0.58 CI 0.39 to 0.85, NNT 3 CI 2-8). Medium term data, however, did not favour either group (n=87, 1 RCT, MD PANSS endpoint -1.0 CI -8.15 to 6.15). All studies had low attrition (<10% total, n=271, 4 RCTs, RR leaving the study early 0.91 CI 0.36 to 2.33). Another study (n=31) comparing two types of omega-3 EFA's, ecisapentenoic acid enriched oil and docosahexanoic acid oil, also found no differences between these two EFA's in measures of mental state. One small (n=16) study investigated the effects of an omega-6 EFA compared with placebo for tardive dyskinesia and found no clear effects. There is not a clear dose response to omega-3 supplementation. Adverse effects seem rare but diarrhoea may be a problem in the medium term.


CONCLUSIONS
The use of omega-3 polyunsaturated fatty acids for schizophrenia remains experimental and large well designed, conducted and reported studies are indicated and needed.
Joy
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Cochrane Schizophrenia Group, Academic Department of Psychiatry and Behavioural Sciences, Cochrane Schizophrenia Group, 15 Hyde Terrace, Leeds, West Yorkshire, UK, LS2 9LT. cjoy@cochrane.org or
Mumby-Croft
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Joy
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D014150:Antipsychotic Agents / Q000627:therapeutic use; D019587:Dietary Supplements; D004359:Drug Therapy, Combination; D005231:Fatty Acids, Unsaturated / Q000627:therapeutic use*; D005395:Fish Oils / Q000627:therapeutic use*; D006801:Humans; D010938:Plant Oils / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000178:diet therapy* / Q000188:drug therapy*
D014150:Antipsychotic Agents; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D010938:Plant Oils