Food and Behaviour Research

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Omega-3 fatty acids to prevent psychosis: the importance of replication (NEURAPRO trial)

R Underwood (2017)    National Elf Service

Web URL: View the full article here


Psychotic illnesses, such as schizophrenia, develop gradually, beginning with subtle changes in perceptual experiences and thought processes. These changes evolve into a ‘prodromal’ phase characterised by subthreshold positive symptoms such as infrequent/less intense hallucinations and delusions (Yung, McGorry, et al., 2004). Individuals in the prodromal phase are termed Ultra-High Risk (UHR) (Yung & McGorry, 1996).

Observational studies have identified conversion rates from UHR to psychosis of:

  • 17.7% at 6 months,
  • 21.7% at 12 months,
  • and up to 31.5% over 3 years (Fusar-Poli et al., 2012).

Much research has been dedicated towards preventing the transition from UHR status to psychotic illness (Yung, Phillips, et al., 2004). Eleven trials have assessed the effectiveness of talking therapies and pharmacological interventions, alone or combined, in UHR groups (van der Gaag et al., 2013). From these trials, cognitive behavioural therapy (CBT) and long-chain Omega-3 fatty acids (PUFAs) emerged as effective first-line treatments.

PUFAs were found to be effective not only during the period of treatment (Amminger et al., 2010), but also up to 7 years later (Amminger et al., 2015). These are exciting findings as conventional antipsychotics carry undesirable side-effects and an increased risk of adverse events (Kane & Correll, 2017). In a newly published study (McGorry et al., 2017), the authors attempted to replicate these impressive findings.


This study shows the enormous value of replication. While it may be costly, time-consuming, and (currently) less attractive to high-ranking journals, it increases the credibility of the published scientific literature (Munafò et al., 2017).

The authors conclude:

This trial has failed to replicate the findings of a previous single-centre study. Other multi-centre trials, ongoing analysis of the data from the present study, and future research will help to ultimately determine whether ω-3 PUFAs have a role in the reduction of risk and early treatment of psychotic disorder.

Strengths and limitations

  • While not the first trial of PUFAs, it is the first to be randomized, placebo-controlled, multi-centred, and combined with a CBT-derived treatment.
  • The authors used inter-rater reliability testing, standardised interviewing, and case review to ensure that participants met criteria for transition.
  • ω-3 PUFAs supplements are commercially available, and it is not known whether participants took them outside of the study.
  • These supplements are potentially effective for use in depression with high levels of neuronal inflammation. The authors plan to address this by conducting subgroup analyses using baseline membrane fatty acid levels and inflammatory markers.
  • Some participants may not truly have been at risk of transitioning to psychosis, although transition rates in PUFAs group were similar to that observed in previous trials, making this unlikely.
  • There were relatively low adherence rate in both groups.
  • Data was collected at ten specialty clinics, which may not be representative of the care that most UHR individuals receive.
  • This study shows the value of replication, but it leaves us uncertain about the value of using PUFAs to prevent or treat psychosis.
  • This study shows the value of replication, but it leaves us uncertain about the value of using PUFAs to prevent or treat psychosis.

Primary papers

McGorry Et Al 2017 - Effect Of Omega-3 PUFA In Young People At Ultrahigh Risk For Psychotic Disorders: The NEURAPRO RCT

Kane & Correll 2017 - Omega-3 Polyunsaturated Fatty Acids To Prevent Psychosis - The Importance Of Replication Studies