Abstract: Eight studies are now included in this review. 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, NNT 3 CI 2 to 29). There are no differences in the number of people leaving the study early (n=595, 6 RCTs, RR 0.86 CI 0.50 to 1.48). There are few data on the comparison of any dose omega-6 (GLA) with placebo. For movement disorder outcomes, the one small study we found does not show any difference for average short-term endpoint AIMS score (n=16, 1 RCT, WMD 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 significant 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 (1 g/day E-EPA vs placebo n=63, 1 RCT, RR 0.97 CI 0.60 to 1.56; 2 g/day E-EPA vs placebo n=63, 1 RCT, RR 0.67 CI 0.37 to 1.20; 4 g/day E-EPA vs placebo n=58, 1 RCT, RR 1.15 CI 0.72 to 1.82). Three updates of this review have resulted in more included studies and more people randomised but still 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.

Plain-language summary: The majority of the trials compared two different types of omega 3 fatty acids, EPA (usually as E-EPA) and DHA with placebo, in people with schizophrenia who are stable on antipsychotic medication. Some of these trials show some improvement in general functioning and in mental state but not to a statistically significant degree. In the longest trial there was no difference between the two groups at the end of the study.  One trial compared E-EPA with DHA and found a suggestion that E-EPA works better than DHA, but again it was not statistically significant.  Where EPA was compared to placebo as a first line treatment for schizophrenia (30 people), those taking EPA had a better overall outcome and improvement in mental state.  However, this was a short trial with few people. Finally, one trial compared a type of omega 6 with placebo in men who had the movement disorder tardive dykinesia (16 people). There was no improvement in the symptoms of movement adverse effects in either group at the end of six weeks. These trials were both small and short.  In addition most of the data they reported were not able to be used, and half of the trials were funded by the group supplying the trial medication. Therefore it is still not clear whether taking manufactured omega 3 or 6 improves overall functioning or mental state in people with schizophrenia. (Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org)