No Difference Between Omega-3 & Placebo in Patients at Ultrahigh Risk for Psychosis

A study found that depression increases the risk for ADHD.
A study found that depression increases the risk for ADHD.
PUFA supplementation offers little additional aid to psychosis when good psychosocial care is already sought.

In the last couple of decades, the concept of an ultrahigh risk (UHR) state for psychosis has been the subject of a growing body of research. According to  a multicenter randomized clinical trial (RCT) reported in JAMA Psychiatry, researchers at numerous international universities aimed to replicate the results of a 2010 single-center RCT linking long-chain ω-3 polyunsaturated fatty acid (PUFA) supplementation with reduced risk of progression to psychosis.1  

In the current study, 304 adults presenting to 10 early psychosis treatment centers with UHR received up to 20 sessions of a psychosocial intervention called cognitive behavioral case management (CBCM) over the 6-month study period. , One group also received 1.4 g of ω-3 PUFAs per day, while the other group received the same daily dose of paraffin oil as the placebo. Selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines were permitted for the treatment of depression and anxiety, respectively.

Participants were assessed 3 times: at baseline, at the end of the study period, and again 6 months later. The main outcome was transition to psychosis at the 6-month mark.

The results were as follows:

  • At 6 months, the Kaplan-Meier–estimated transition rates were 5.1% [95% confidence interval (CI), 1.3%-8.7%) among controls and 6.7% (95% CI, 2.3%-10.8%) in the treatment group.
  • The 12-month transition rates were 11.2% (95% CI, 5.5%-16.7%) among controls and 11.5% (95%CI, 5.8%-16.9%) in the treatment group.
  • No significant difference in transition rates was found between groups (hazard ratio, 1.1; 95% CI, 0.55-2.23; P = .76).

“The fact that the other treatments — CBCM and SSRIs — offered to patients in both the placebo and treatment groups were much more intensive and widely taken up in the current study than the original one meant that the outcomes were much better in both groups,” explained Patrick McGorry, MD, PhD, a professor of youth mental health at the University of Melbourne and executive director of Orygen, The National Centre of Excellence in Youth Mental Health in Australia. This could have resulted in a ceiling effect in which any additional benefit of the ω-3 PUFAs could not be detected.

“We can say that when patients are offered good psychosocial care and depression is actively treated then omega-3 is of no additional benefit,” Dr McGorry, who is also president of the Schizophrenia International Research Society, told Psychiatry Advisor. It is still possible that other trials without such background care may be able to replicate the original findings.

Next steps in this area should include “further studies in this and other diagnostic groups looking for subgroups with a particular ‘biosignature’ in terms of biomarkers like inflammation and lipid profiles,” Dr McGorry added.

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  1. McGorry PD, Nelson B, Markulev C, et al. Effect of ω-3 polyunsaturated fatty acids in young people at ultrahigh risk for psychotic disorders: the NEURAPRO randomized clinical trial. JAMA Psychiatry. 2016; doi:10.1001/jamapsychiatry.2016.2902
  2. 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.