Long-Chain ω-3 Fatty Acids for Indicated Prevention of Psychotic Disorders: A Randomized, Placebo-Controlled Trial
Open accessAbstract
CONTEXT: The use of antipsychotic medication for the prevention of psychotic disorders is controversial. Long-chain omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) may be beneficial in a range of psychiatric conditions, including schizophrenia. Given that omega-3 PUFAs are generally beneficial to health and without clinically relevant adverse effects, their preventive use in psychosis merits investigation. OBJECTIVE: To determine whether omega-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, placebo-controlled 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 omega-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 omega-6 to omega-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 omega-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 full-threshold psychosis was 22.6% (95% confidence interval, 4.8-40.4). omega-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 omega-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.
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Only two included studies had an overall low risk of bias; five had unclear risk and nine had high risk.
“Only two studies had an overall low risk of bias 33,79 ; five had unclear risk [72][73][74][75][76] , and nine had high risk 30,31,36,37,39,41,77,78,81 .”
From Lack of evidence to favor specific preventive interventions in psychosis: a network meta‐analysis (2018) · cites this paper as [33]
Earlier studies that dominated the conclusions of some previous meta-analyses, such as the omega-3 trial, were probably false positives.
“Earlier studies that dominated the conclusions of some previous meta-analyses (e.g., the omega-3 trial 33 ) were likely false positives.”
From Lack of evidence to favor specific preventive interventions in psychosis: a network meta‐analysis (2018) · cites this paper as [33]
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- Authors
- Amminger, G. P., Schäfer, M. R., Papageorgiou, K., Klier, C. M., Cotton, S. M., Harrigan, S. M., Mackinnon, A., McGorry, P. D., & Berger, G. E.
- Affiliations
- Medical University of Vienna (AT)
- The University of Melbourne (AU)
- Clienia AG (CH)
- ORCID
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2010-02-01
- Volume
- 67
- Issue
- 2
- Pages
- 146
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2130372506
- Cited by
- 896
- References
- 45
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 29 · 2023: 22 · 2022: 20 · 2021: 51 · 2020: 42 · 2019: 59 · 2018: 33 · 2017: 52 · 2016: 69 · 2015: 82 · 2014: 95 · 2013: 85 · 2012: 98
- FWCI
- 92.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Stanley Medical Research Institute (03T-315)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- omega-3 polyunsaturated fatty acids, clinical high risk for psychosis, schizophrenia, adolescents and young adults, n-6/n-3 ratio, erythrocyte fatty acids, positive symptoms, negative symptoms, functional outcome, dietary supplementation, psychosis prevention, omega-3 deficiency
- MeSH terms
- Adolescent, Adult, Dose-Response Relationship, Drug, Double-Blind Method, Female, Health Status, Humans, Male, Patient Acceptance of Health Care, Psychotic Disorders, Risk Factors, Schizotypal Personality Disorder, Severity of Illness Index, Fatty Acids, Omega-3, Treatment Outcome, Diagnostic and Statistical Manual of Mental Disorders, Young Adult
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