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


Omega-3 polyunsaturated fatty acids (PUFAs) were associated with significantly reduced rate of progression from subthreshold psychosis to psychotic disorder, compared with placebo, when administered to a high risk population. Due to their lack of clinically relevant side effects, omega-3 PUFAs may be useful in preventing psychosis in young high-risk populations.


  • N=81, ages 13-25, with subthreshold psychosis (ultra-high risk of psychotic disorder), defined as meeting one of three groups of inclusion criteria:
    • Attenuated Psychotic Symptoms: Positive and Negative Syndrome Scale (PANSS) scores of 3 for delusions, 2-3 for hallucinations, 3-4 for suspiciousness, or 3-4 for conceptual disorganization. Frequency: ≥ twice/week for ≥ 1 week, but no longer than 5 years, occurring in last year.
    • Transient Psychosis: PANSS score ≥4 for hallucinations, ≥4 for delusions, or ≥5 for conceptual disorganization. Symptom duration: less than one week, resolved without antipsychotic medication, occurring in last year.
    • Trait Plus State Risk Factors: schizotypal personality disorder or 1st-degree relative with psychotic disorder, and 30% decrease in Global Assessment of Functioning Scale, for at least 1 month in the past year.
  • Participants randomized to receive 12 weeks of:
    • 1.2 grams/day of long-chain omega-3 polyunsaturated fatty acids (n=41)
    • Placebo pill (n=40)
  • Setting: psychosis detection unit at large public hospital in Vienna, Austria, 2004-2007.
  • Primary outcome: Transition to psychotic disorder, defined as PANSS score ≥4 on hallucinations, ≥4 on delusions, or ≥5 on conceptual disorganization, sustained for at least one week.
  • Secondary outcome: symptomatic and functional changes, based on PANSS, Montgomery Asberg Depression Rating Scale (MADRS), and Global Assessment of Functioning.
  • Follow up for 12 months.


  • At 12 months, transition to psychotic disorder had occurred in significantly fewer participants in the omega-3 arm (P=0.007):
    • 4.9% (2/41) in omega-3 group
    • 27.5% (11/40) in placebo group
  • Number needed to treat with omega-3 PUFA to prevent 1 progression to psychosis during a 12-month period was 4 (95% CI: 3-14).
  • Omega-3 PUFAs, compared with placebo, were associated with significantly improved functioning (P=0.002) and significantly reduced:
    • Positive symptoms (P=0.01)
    • Negative symptoms (P=0.02)
    • General symptoms (P=0.002)


Amminger GP, Schäfer MR, Papageorgiou K, et al. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2010;67(2):146-154. doi:10.1001/archgenpsychiatry.2009.192.

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