By Erin Hawkes, MSc

Omega-3 is a fatty acid critical in normal brain development (both biochemically and structurally). It maintains cell walls, but also affects receptors in those walls for various neurotransmitters (“messenger” molecules between brain cells; these same “messengers” are affected in schizophrenia). There different types of omega-3, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Overall, they are polyunsaturated fatty acids (PUFAs). They are neuroprotective: they are anti-oxidants and can prevent cell death. PUFA treatment may be best used in schizophrenia prevention in high-risk populations. Omega-3s have minimal side effects, public acceptance, low cost, and benefits for health.

Likely Effectiveness: Reasonably likely to be effective as a preventative measure, with exposure before a psychotic break. Unlikely to improve symptoms of chronic schizophrenia, although it may help with side effects (e.g., extrapyramidal symptoms).

Effective Dosage:  1 to 4 grams per day (with food if taking supplements). Nuts, seeds (e.g., flaxseed), salmon, and seafood are examples of high-PUFA foods. (Note: Both eating little to no fish, or too much (>5 times per week) are associated with psychosis, while those who eat medium amounts show fewer signs of psychosis.)

Research: Excellent: randomized, double-blind, placebo-controlled experiments; meta-analysis; review. Very current.

Risks:  No side effects at therapeutic doses.

Selected references

1) Amminger GP, Schäfer MR, Papageorgiou et al. K  Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2010; 67:146-154.

This reputable (“randomized, double-blind, placebo-controlled”) study included 81 adolescents and young adults (ages 13 to 25) who were at significantly higher risk of developing schizophrenia than the general population. They were administered either 1.2 g/day of omega-3 fatty acid or placebo for 12 weeks, then monitored for 40 more weeks. The omega-3 group showed moderate to large effects: only two omega-3-treated subjects became psychotic (compared to 11 in the placebo group). In contrast to antipsychotics, the effects of omega-3s persisted beyond treatment and are considered safer than antipsychotics, particularly for adolescents and children.

2) Mossaheb N, Schloegelhofer M, Schaefer MR, et al. Polyunsaturated fatty acids in emerging psychosis. Curr Pharm Des. 2010; 18: 576-591.

This lengthy review examined multiple studies regarding the use of PUFAs in treating psychosis. While PUFAs are well tolerated, they do little to alleviate symptoms of schizophrenia. Perhaps the ratio of omega-3s to omega-6s may be more important than absolute values. They conclude that while they are generally not effective in treating established schizophrenia, PUFAs may be preventative to those susceptible to schizophrenia. Reports of using PUFAs to treat tardive dyskinesia or extra-pyramidal symptoms are inconclusive.

3) Fusar-Poli P, and Berger G. Eicosapentaenoic acid interventions in schizophrenia: meta-analysis of randomized, placebo-controlled studies. J Clin Psych. 2012; 32: 179-185.

Focusing on EPA, this meta-analysis (statistical review of several studies together; here, seven, including 167 patients treated with EPA and 168 who received placebo) found no benefit in EPA supplementation for people with established schizophrenia. EPA, however, is not the only omega-3 fatty acid, and treatment of schizophrenia may require others (e.g., DHA). Dosing was only 2 g per day, for 12 to 16 weeks; these measures may simply be insufficient. EPA supplementation may be preventative for pre-psychotic populations and also may alleviate extrapyramidal and metabolic side effects of antipsychotics.