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Preventing Psychotic Disorders in High-Risk Patients


Am Fam Physician. 2010 Nov 1;82(9):1141-1142.

Background: Dysfunctional fatty acid metabolism may contribute to the development of psychosis. Omega-3 polyunsaturated fatty acids (PUFAs) are known to interact with the dopaminergic and serotoninergic systems, and reduced levels of these acids have been reported in patients with schizophrenia. Therefore, omega-3 PUFA supplementation might be useful in preventing the transition to a psychotic state. Amminger and colleagues conducted a randomized, double-blind, placebo-controlled trial to determine if use of omega-3 PUFAs could prevent a first episode of psychosis.

The Study: The authors randomized 81 participants at high risk of developing a psychotic disorder to receive 1.2 g per day of omega-3 PUFAs (i.e., marine fish oil, including 700 mg of eicosapentaenoic acid [EPA] and 480 mg of docosahexaenoic acid [DHA]) or a placebo. Participants were 13 to 25 years of age and were classified as high-risk based on the presence of one or more of several criteria: attenuated positive psychotic symptoms (i.e., moderate to high levels of delusions, hallucinations, suspiciousness, or conceptual disorganization), spontaneously resolving transient psychosis (lasting less than one week), or having schizotypal personality disorder or a first-degree relative with a psychotic disorder. Patients were excluded if they had a history of psychosis or mania, neurologic disorders (e.g., epilepsy), substance dependence, previous use of an antipsychotic or mood stabilizer, or an IQ of less than 70. Participants received the treatment drug or placebo for 12 weeks and were followed for one year, with a primary end point of conversion to psychotic disorder.

Results: The risk of developing psychosis was significantly reduced for patients taking omega-3 PUFAs (4.9 versus 27.5 percent for placebo, respectively). The PUFA group also had significantly greater reductions in positive and negative psychotic symptoms, and a greater improvement in overall functioning (final mean Global Assessment of Functioning scores of 78.7 versus 67.2 for placebo, from respective baselines of 61.0 and 60.0). The groups also had similar adherence rates, antidepressant and benzodiazepine use, and need for interval psychological and psychosocial interventions.

Conclusion: The authors conclude that use of omega-3 PUFA supplementation for 12 weeks significantly reduces the likelihood that a high-risk patient will transition to a psychotic disorder, and improves symptoms and functioning for 12 months after treatment is initiated. The authors caution that their results were based on a small number of patients, and the effectiveness of omega-3 PUFAs beyond 12 months is unknown. However, they state that even delaying the onset of psychosis is a worthwhile achievement.


Amminger GP, et al. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry. February 2010;67(2):146–154.

editor's note: Although omega-3 fatty acids are most touted for cardiovascular health, their contribution to neuronal synaptic transmission has generated interest in their potential role in psychiatric disorders. For instance, close adherence to a Mediterranean-type diet (which is high in omega-3 PUFAs and monounsaturated fatty acids) has been associated with a greater than 30 percent reduction in unipolar depression.1

A 2006 review and meta-analysis by the Omega-3 Fatty Acids Subcommittee of the American Psychiatric Association concluded that omega-3 fatty acids (especially EPA and DHA) have a protective effect in patients with unipolar and bipolar depression, and that they may be useful as adjunctive therapy for schizophrenia and attention-deficit/hyperactivity disorder. They recommended that patients with mood, impulse control, or psychotic disorders consume 1 g total of EPA plus DHA daily. Those with mood disorders may also benefit from omega-3 supplementation (approximately 1 to 9 g per day). Although generally well-tolerated, high doses of omega-3 fatty acids can increase bleeding risk (especially if anticoagulants are also being used), and consuming more than 3 g per day of EPA plus DHA should be monitored by a physician for potential complications.2k.t.m.


1. Sánchez-Villegas A, Delgado-Rodríguez M, Alonso A, et al. Association of the Mediterranean dietary pattern with the incidence of depression: the Seguimiento Universidad de Navarra/University of Navarra follow-up (SUN) cohort. Arch Gen Psychiatry. 2009;66(10):1090–1098.

2. Freeman MP, Hibbeln JR, Wisner KL, et al. Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry [published correction appears in J Clin Psychiatry. 2007;68(2):338]. J Clin Psychiatry. 2006;67(12):1954–1967.



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