Long-chain ω-3 fatty acids for indicated prevention of psychotic disorders: A randomized, placebo-controlled trial

G. Paul Amminger, Miriam R. Schäfer, Konstantinos Papageorgiou, Claudia M. Klier, Sue M. Cotton, Susan M. Harrigan M, Andrew Mackinnon, Patrick D. McGorry, Gregor E. Berger

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677 Citations (Scopus)


Context: The use of antipsychotic medication for the prevention of psychotic disorders is controversial. Longchain ω-3 (omega-3) polyunsaturated fatty acids (PUFAs) may be beneficial in a range of psychiatric conditions, including schizophrenia. Given that ω-3 PUFAs are generally beneficial to health and without clinically relevant adverse effects, their preventive use in psychosis merits investigation. Objective: To determine whether ω-3 PUFAs reduce the rate of progression to first-episode psychotic disorder in adolescents and young adults aged 13 to 25 years with subthreshold psychosis. Design: Randomized, double-blind, placebocontrolled trial conducted between 2004 and 2007. Setting: Psychosis detection unit of a large public hospital in Vienna, Austria. Participants: Eighty-one individuals at ultra-high risk of psychotic disorder. Interventions: A 12-week intervention period of 1.2-g/d ω-3 PUFA or placebo was followed by a 40-week monitoring period; the total study period was 12 months. Main Outcome Measures: The primary outcome measure was transition to psychotic disorder. Secondary outcomes included symptomatic and functional changes. The ratio of ω-6 to ω-3 fatty acids in erythrocytes was used to index pretreatment vs posttreatment fatty acid composition. Results: Seventy-six of 81 participants (93.8%) completed the intervention. By study's end (12 months), 2 of 41 individuals (4.9%) in the ω-3 group and 11 of 40 (27.5%) in the placebo group had transitioned to psychotic disorder (P=.007). The difference between the groups in the cumulative risk of progression to fullthreshold psychosis was 22.6% (95% confidence interval, 4.8-40.4). ω-3 Polyunsaturated fatty acids also significantly reduced positive symptoms (P=.01), negative symptoms (P=.02), and general symptoms (P=.01) and improved functioning (P=.002) compared with placebo. The incidence of adverse effects did not differ between the treatment groups. Conclusions: Long-chain ω-3 PUFAs reduce the risk of progression to psychotic disorder and may offer a safe and efficacious strategy for indicated prevention in young people with subthreshold psychotic states. Trial Registration: clinicaltrials.gov Identifier: NCT00396643.

Original languageEnglish
Pages (from-to)146-154
Number of pages9
JournalArchives of General Psychiatry
Issue number2
Publication statusPublished - Feb 2010
Externally publishedYes

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