Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial.
BACKGROUND
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.


METHODS
Randomized, double-blind, placebo-controlled trial conducted between 2004 and 2007.


METHODS
Psychosis detection unit of a large public hospital in Vienna, Austria.


METHODS
Eighty-one individuals at ultra-high risk of psychotic disorder.


METHODS
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.


METHODS
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.
Amminger
G Paul
GP
Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria. gpamminger@gmail.com
Schäfer
Miriam R
MR
Papageorgiou
Konstantinos
K
Klier
Claudia M
CM
Cotton
Sue M
SM
Harrigan
Susan M
SM
Mackinnon
Andrew
A
McGorry
Patrick D
PD
Berger
Gregor E
GE
D000293:Adolescent; D000328:Adult; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006304:Health Status; D006801:Humans; D008297:Male; D010342:Patient Acceptance of Health Care / Q000706:statistics & numerical data; D011618:Psychotic Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D012307:Risk Factors; D012569:Schizotypal Personality Disorder / Q000453:epidemiology; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
D015525:Fatty Acids, Omega-3