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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 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]
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“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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Metadata
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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