Effect of &ohgr;-3 Polyunsaturated Fatty Acids in Young People at Ultrahigh Risk for Psychotic Disorders: The NEURAPRO Randomized Clinical Trial

This was a multicenter randomized clinical trial conducted at 10 early psychosis services in Australia, Asia, and Europe. Participants were 13 to 40 years old and at ultrahigh risk for psychosis; 153 were assigned to the omega-3 PUFA arm and 151 to placebo, with both groups receiving cognitive behavioral case management.

The active intervention was oral omega-3 polyunsaturated fatty acids, delivered as 4 gelatin capsules daily for 6 months. The daily dose was approximately 1.4 g omega-3 PUFAs, including 840 mg eicosapentaenoic acid and 560 mg docosahexaenoic acid, compared with placebo paraffin oil capsules.

Omega-3 PUFA supplementation did not reduce transition to psychosis or improve overall symptoms and functioning when added to cognitive behavioral case management. The 6-month transition rate was 6.7% in the omega-3 group versus 5.1% in control, and the 12-month transition rate was 11.5% versus 11.2%; the hazard ratio was 1.1 (95% CI, 0.55-2.23; P = .76). Secondary outcomes were also largely null, with no significant differences at month 12 and a month 6 Global Functioning: Social and Role result favoring placebo (P = .02). These findings do not support benefit of omega-3 PUFAs under these treatment conditions.

Adherence was low in both groups, with 43.1% in the omega-3 arm and 41.1% in placebo classified as adherent. The event rate for transition to psychosis was relatively low, and all participants received concurrent cognitive behavioral case management, which may have limited the ability to detect an added supplement effect. The trial also did not replicate earlier single-center findings, raising questions about generalizability and consistency of benefit.