Polyunsaturated fatty acid supplementation for schizophrenia.

The Cochrane database of systematic reviews

Jul 2006

DOI: 10.1002/14651858.CD001257.PUB2

Citations:155

Influential Citations:3

Systematic Reviews / Meta-Analyses

Enhanced Details

Methods

Randomized, double-blind, placebo-controlled parallel-group trials in adults with DSM-IV schizophrenia or related disorders; settings included inpatient and outpatient care; participants ranged from early to chronic illness; total across eight studies: 517 participants.

Intervention

Oral polyunsaturated fatty acid supplements (EPA or ethyl-EPA; sometimes DHA) given as capsules for 6–16 weeks; regimens included 1 g/day, 2 g/day, or 4 g/day; used as an adjunct to standard antipsychotic therapy, or as sole treatment in unmedicated participants in Peet 2001b; one small trial used omega-6 gamma-linolenic acid (GLA) 600 mg/day; formulations commonly involved EPA either alone or with DHA; some trials included vitamin E co-supplementation.

Results

Across trials, omega-3/omega-6 fatty acid supplementation showed no consistent, robust benefit for schizophrenia. In small short-term analyses, EPA/E-EPA vs placebo suggested: reduced need for neuroleptics in a unmedicated subsample (RR 0.73; 95% CI 0.54–1.00; n=30) and possible >25% PANSS improvement in unmedicated participants (RR 0.54; 95% CI 0.30–0.96; NNT 3; n=30). There were no differences in withdrawal due to adverse events (RR 0.86; 95% CI 0.50–1.48; n=595). Data on omega-6 (GLA) are limited and show no clear benefit for movement disorders. DHA vs EPA showed no clear difference in mental-state outcomes. Adverse events did not differ meaningfully by dosage. The review concludes omega-3/6 fatty acids for schizophrenia remain experimental; large, well-designed, long-duration trials are needed. If used, an omega-3 preparation may be acceptable within a rigorously designed trial.

Limitations

Small, short trials with heterogeneous populations and regimens; inconsistent outcome reporting and incomplete data; potential risk of bias and sponsor influence in several trials; lack of long-term and patient-centered outcomes; overall evidence is not sufficient to support routine use.

Abstract

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. show less