Longer-term outcome in the prevention of psychotic disorders by the Vienna omega-3 study

Abstract

Long-chain omega-3 polyunsaturated fatty acids (PUFAs) are essential for neural development and function. As key components of brain tissue, omega-3 PUFAs play critical roles in brain development and function, and a lack of these fatty acids has been implicated in a number of mental health conditions over the lifespan, including schizophrenia. We have previously shown that a 12-week intervention with omega-3 PUFAs reduced the risk of progression to psychotic disorder in young people with subthreshold psychotic states for a 12-month period compared with placebo. We have now completed a longer-term follow-up of this randomized, double-blind, placebo-controlled trial, at a median of 6.7 years. Here we show that brief intervention with omega-3 PUFAs reduced both the risk of progression to psychotic disorder and psychiatric morbidity in general in this study. The majority of the individuals from the omega-3 group did not show severe functional impairment and no longer experienced attenuated psychotic symptoms at follow-up.

Figure 1. Enrolment and outcomes flowchart.

We assessed 256 individuals for eligibility. Of those, 150 were excluded because they did not meet inclusion criteria or met exclusion criteria, while 25 refused participation. Eighty-one treatment-seeking individuals were enrolled in the trial, of which 41 were randomly assigned to omega-3 PUFAs and 40 to placebo. In each group, 38 individuals completed the intervention. Longer-term follow-up data on the primary outcome (that is, progression to psychotic disorder) were collected in 35 individuals from the omega-3 PUFA group and 36 individuals from the placebo group. Secondary outcome data on psychosocial functioning were collected in 34 and 35 individuals from the omega-3 and the placebo groups, respectively. Secondary outcome data on psychiatric symptoms, including positive symptoms, negative symptoms, general symptoms and depressive symptoms, were collected in 28 and 29 individuals from the omega-3 and the placebo group, respectively. All individuals enrolled in the trial were included in the data analysis.

Figure 2. Kaplan–Meier estimates of the risk of progression from the at-risk state to psychotic disorder in participants assigned to omega-3 PUFAs or placebo.

Four of 41 individuals from the omega-3 PUFA group and 16 of 40 individuals from the placebo group developed a psychotic disorder during the entire follow-up period. The difference between the groups in the cumulative risk of progression to psychosis was 30.2% (95% confidence interval, 10.1–50.4, with continuity correction). Kaplan–Meier survival analysis indicated the survival times were significantly different between the treatment groups, with a more rapid conversion time for the placebo group compared to the omega-3 PUFA group. χ²=9.84, P=0.002, log-rank test.