Polyunsaturated fatty acid supplementation for schizophrenia

C B Joy, R Mumby-Croft, L A Joy
Cochrane Database of Systematic Reviews 2006, (3): CD001257

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

OBJECTIVES: To review the effects of polyunsaturated fatty acids for people with schizophrenia.

SEARCH STRATEGY: We have updated the initial searches of 1998 and 2002 (Cochrane Schizophrenia Group's Register, July 2005), and where necessary, we contacted authors and relevant pharmaceutical companies.

SELECTION CRITERIA: We included all randomised clinical trials of polyunsaturated fatty acid treatment for schizophrenia.

DATA COLLECTION AND ANALYSIS: Working independently, we selected studies for quality assessment and extracted relevant data. We analysed on an intention-to-treat basis. Where possible and appropriate we calculated the Relative Risk (RR) and their 95% confidence intervals (CI) and estimated the number needed to treat (NNT). For continuous data we calculated weighted mean differences (WMD) and their 95% confidence intervals. We also inspected the data for heterogeneity.

MAIN RESULTS: When any dose omega-3 (E-EPA or EPA) is compared with placebo, small short trials suggest that the need for neuroleptics appears to be reduced for people allocated omega-3 supplementation (n=30, 1 RCT, RR 0.73 CI 0.54 to 1.00) and mental state may improve (n=30, 1 RCT, RR not gaining 25% change in PANSS scores 0.54 CI 0.30 to 0.96, NNT3 CI 2-29). There are no differences in the number of people leaving the study early (n=271, 4 RCTs, RR 0.91 CI 0.36 to 2.33). There are few data on the comparison of any dose omega-6 (GLA) with placebo. For movement disorder outcomes, the only small study we found does not show any difference for average short-term endpoint AIMS score (n=16, 1 RCT, MD 1.30 CI -1.96 to 4.56). When any dose omega 3 (E-EPA or EPA) is compared with any dose omega-3 (DHA) there is no clear difference for mental state outcome of not gaining 25% change in PANSS scores (n=31, 1 RCT, RR 0.66 CI 0.39 to 1.11). When different doses of omega-3 (E-EPA) are compared with placebo there are no differences in measures of global and mental state between the studies. For the outcome of 'experiencing at least one adverse effect' no differences between groups are found for any dose (1g/day E-EPA vs placebo n=63 1 RCT, RR 0.97 CI 0.60 to 1.56; 2g/day E-EPA vs placebo n=63 1 RCT, RR 0.67 CI 0.37 to 1.20; 4g/day E-EPA vs placebo n=58, 1 RCT, RR 1.15 CI 0.72 to 1.82).

AUTHORS' CONCLUSIONS: Two updates of this review have resulted in more included studies but relatively little useful additional data. The results remain inconclusive. The new trials all compare the omega-3 polyunsaturated fatty acids, in particular eicosapentaenoic acid and its ester, ethyl-eicosapentaenoic acid. The use of omega-3 polyunsaturated fatty acids for schizophrenia still remains experimental and this review highlights the need for large well designed, conducted and reported studies.

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