 Mental
Neurological Health
Abstract:
Long-Chain Omega-3 Fatty Acids for Indicated Prevention
of Psychotic Disorders: A Randomized, Placebo-Controlled Trial
G. Paul Amminger, MD; Miriam R. Schäfer, MD; Konstantinos Papageorgiou, MD;
Claudia M. Klier, MD; Sue M. Cotton, PhD; Susan M. Harrigan, MSc;
Andrew Mackinnon, PhD;
Patrick D. McGorry, MD, PhD; Gregor E. Berger, MD
Context: The use of antipsychotic medication for the
prevention of psychotic disorders is controversial. Longchain
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 -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 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 -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). -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
Arch Gen Psychiatry. 2010;67(2):146-154
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