Omega-3 capsules and placebo did not separate in a 135-person European trial of teenagers at risk of psychosis
- PURPOSE was a double-blind, placebo-controlled trial at 16 centres in 8 European countries and Israel. It randomized 135 people aged 13 to 20 at ultra-high risk of psychosis to six months of omega-3 fish oil (4 capsules of 0.6 g a day: 720 mg EPA, 480 mg DHA) or placebo (67 vs 68), with 18 months of follow-up afterwards. Published in Schizophrenia Bulletin, 2025;51(4):1082-1091, online 25 October 2024.
- Under the strict criterion, transition to psychosis over two years occurred in 5 of 67 (7.5%) on omega-3 and 3 of 68 (4.4%) on placebo (HR 1.67; 95% CI 0.40 to 6.98; P = 0.5).
- Under the extended criterion, which also counted exceeding a set antipsychotic dose, the figures were 16 (23.9%) vs 8 (11.8%) (HR 1.88; 95% CI 0.79 to 4.49; P = 0.2). Change in symptom severity over the six months of treatment did not differ between arms.
- 117 participants (87%) completed treatment and 92 (68%) completed follow-up. Dropout and serious adverse events were similar across arms. The trial ended early because recruitment was slow.
PURPOSE tested fish oil against matching placebo in young people who met ultra-high-risk criteria on the CAARMS, the structured interview used to define that state. It was run as a larger, multicentre check on an earlier single-centre trial that had reported fewer transitions on omega-3.
Who took part and what they received
The 135 analysed participants were help-seeking young people with a mean age of 15.8 years in the omega-3 arm and 15.5 in the placebo arm; 75 were female and 60 male. Treatment lasted six months and was followed by 18 months of assessment every six months for transition to psychosis.
Transition and symptoms
On the strict criterion, 5 of 67 on omega-3 (7.5%) and 3 of 68 on placebo (4.4%) made the transition. The extended criterion added anyone who exceeded a haloperidol-equivalent of 10 mg within two months; it gave 16 (23.9%) and 8 (11.8%). Neither comparison reached statistical significance, and symptom scores moved alike in both arms. The trial stopped before its planned 220 participants because enrolment was slow, mainly because of the COVID pandemic.
What to say when the family has already bought the capsules
Parents of a teenager at risk often arrive having started omega-3 on their own, as the one step that felt safe. In my view, the honest answer is narrow. In this trial, six months of the supplement did not change the rate of transition or the symptoms compared with placebo; that is a statement about this trial, not a verdict on every use of fish oil. Say so without alarm. Serious adverse events were similar in the two groups, but the trial is too small to settle the question of safety, so it gives no reason to ask the family to stop. Ask only that it not stand in for the things that can be checked: regular contact with the team, a named person to call if suspiciousness grows or sleep changes, and a plan agreed in advance.
In this trial, six months of omega-3 capsules did not change the rate of transition to psychosis or symptom severity compared with placebo in young people at ultra-high risk.
The authors note that daily dietary omega-3 intake was not measured and non-study supplements could not be excluded. The transition rate was lower than expected and the trial ended early, which left the sample underpowered. No method was used to enrich the sample for higher risk.