Meta-analyses on the effect of omega-3 used as a supplement at different stages of schizophrenia suggest that the supplement is efficacious at reducing symptoms in the earlier stages of schizophrenia but results are mixed for chronic schizophrenia patients [179,180]. Indeed, some studies on chronic schizophrenia patients find that omega-3 supplementation improves symptomatology and prevents some of the antipsychotic side effects [50,181,182], while others find no efficacy of omega-3 supplementation in the stable or acute phases of the disorder [183,184]. In FEP, a clinical trial found that the efficacy of the supplementation was dependent on the dose and the length of the supplementation, with higher doses and longer periods of supplementation being associated with better clinical outcomes [185,186]. In UHR patients, omega-3 supplementation has been shown to reduce the risk of psychotic transition (27.5% vs. 4.9%; p = 0.007)  with a long-lasting effect (seven years follow-up) , although a more recent multi-center study shows a lack of effect of omega-3 supplementation . However, this multi-center cohort presented lower rates of psychotic transition, which may have been attributed to several biases related to compliance with the treatment … Indeed, almost 60% of participants had not taken the omega-3 supplement as required, and a secondary analysis that compared compliant versus non-compliant participants showed that the cumulative psychotic conversion rate within one year was significantly higher in the non-compliant group compared to the compliant group (14.8% vs. 4.7%)
This review is a contribution to our understanding of the role played by omega-3 fatty acids in different biological pathways that are involved in schizophrenia. Exploring the biological pathways omega-3 is involved in improves our knowledge about the mechanisms underlying the pathophysiology of schizophrenia. We show that omega-3 supplementation is involved in mechanisms and has biological actions similar to antipsychotics. However, omega-3 does not present the cumbersome side effects that antipsychotics do. Further, omega-3 appears to be efficient as soon as the first symptoms of schizophrenia emerge, in UHR patients, a phase in which antipsychotics are the least effective. Thus, omega-3 supplementation has been proposed as an alternative to antipsychotics in this very early stage. In FEP patients, omega-3 appears to improve recovery and could be prescribed as add-on to their current medication. The low cost associated with omega-3 supplementation makes it a realistic and relatively easy treatment to implement. While omega-3 supplementation appears to be a promising therapeutic strategy, it is possible that only a subgroup of the individuals would benefit from this treatment. Further research is needed to determine the biological factors justifying this supplementation, paving the way to a more personalised medicine.