Omega-3 Treatment Shows Long-term Psychosis Prevention

Nancy A. Melville

August 20, 2015

Adolescents and young adults considered to be at high risk for psychosis show significant reductions in progression to psychotic disorder 7 years after a brief, 12-week intervention of omega-3 polyunsaturated fatty acids (PUFAs) compared with a group receiving placebo, a new study shows.

"This is the first study to show, to the best of our knowledge, that a 12-week intervention with omega-3 PUFAs prevented transition to full-threshold psychotic disorder and led to sustained symptomatic and functional improvements in young people with an at-risk mental state for [a median of] 7 years," the authors, led by G. Paul Amminger, MD, of the University of Melbourne, Australia, conclude.

The new research was published online August 11 in Nature Communications.

For the double-blind study, 81 patients (mean age, 16.5 years) who were considered to be at "ultra-high" risk for psychosis were treated for 12 weeks with daily supplementation of either fish oil capsules, providing omega-3 PUFAs of 700 mg of eicosapentaenoic acid (EPA) and 480 mg of docosahexaenoic acid (DHA) (n = 41), or placebo capsules matched in appearance and flavor with the active treatment (n = 40).

An earlier assessment of the patients at 12 months showed that those receiving the omega-3 intervention had a reduced risk for transition to psychotic disorder compared with those receiving placebo (P = .007).

In the new analysis, following up 71 of the original 81 patients at a median of 6.7 years from baseline, the cumulative conversion rate to psychosis was 9.8% in the omega-3 PUFA group, compared with 40% in the placebo group, with a more rapid conversion time in the placebo group among those who did develop psychosis (P < .0002).

Changes in scores on the Positive and Negative Syndrome Scale were significantly greater for the omega-3 PUFA group in the longer-term follow-up in terms of total scores (P = .003), positive and general scores (each P = .002), and, to a lesser degree, negative scores (P = .02).

Differences in the Montgomery-Åsberg Depression Rating Scale were not statistically significant (P = .117), and the omega-3 PUFA group had significantly higher functioning than the group receiving placebo, as reflected in Global Assessment of Functioning scores (P = .01).

The proportion of patients who reported being prescribed antipsychotic medication at the time of long-term follow-up was 29.4% in the omega-3 PUFA group, compared with 54.3% in the placebo group (P = .04).

Among those in the placebo group, 82.9% met the criteria for at least one DSM-IV Axis I disorder during the long-term follow-up period, compared with 52.9% in the omega-3 PUFA group (P = .008).

Even when ultra-high-risk patients do not convert to psychosis, research suggests their functioning outcomes can be poor. However, in looking at the patients with attenuated psychosis in the omega-3 PUFA group, only 6.7% had severe functional impairment, and as many as 70% were employed full-time, the authors note.

"The majority of the individuals from the omega-3 group did not show severe functional impairment, were employed full-time, and no longer experienced attenuated psychotic symptoms at follow- up," they note.

The authors speculate that the timing of the intervention may be critical ― during adolescence and before conversion to psychosis, when the neurodevelopment in brain regions relevant to schizophrenia occurs.

"Given the mean age of our sample and the fact that there is a well-established relationship between age and the onset of psychosis, we cannot assume with certainty that our preventive intervention would be effective in the same way in older individuals," Dr Amminger told Medscape Medical News.

Interest in the role of omega-3 PUFAs in preventing psychosis has been driven by their known role in reducing systemic inflammation, which has been linked to mental illness.

Furthermore, deficiencies in omega-3 PUFAs have been observed in schizophrenia, the authors note.

"Reductions in the cell membrane levels of the omega-3 and omega-6 PUFA series have been observed in patients with schizophrenia," they write.

Although the current study found no significant differences in the treatment and placebo groups in terms of depression, Dr Amminger said the study was not powered for the comparison. The authors are currently investigating that effect.

"We are currently conducting a randomized, controlled trial of omega-3s in young people with depression," Dr Amminger noted. In the meantime, the findings suggest a potentially beneficial therapy for psychosis with few side effects, he said.

"The study is not large enough to brand omega-3 as a miracle drug, but given there is still no 'gold standard' of care for patients with attenuated symptoms of psychosis, psychiatrists may well try a month or two of daily omega-3 supplements to see if there are any benefits," he suggested.

"Unlike antipsychotics, fish oil tablets have no side effects and aren't stigmatizing to patients."

Philip R. Muskin, MD, professor of psychiatry and chief of consultation psychiatry at New York-Presbyterian Hospital/Columbia University Medical Center, New York City, commented that the study offers some valuable insights into the role of omega-3 PUFAs in mental illness.

"This is very interesting and makes us pay attention to the role of nutrition in serious mental illness," he told Medscape Medical News.

He noted potential implications of a finding in the study showing the rate of cannabis abuse in the long-term follow-up was 0 in the omega-3 PUFA group and 11.4% (4 patients) in the placebo group.

"[Cannabis] use significantly impacts on psychotic symptom appearance, but [the study] never mentions this,” he said.

Noting that the difference could be statistically significant, "This would be more guiding with a large sample, controlling for substance use, particularly cannabis."

The authors and Dr Muskin have disclosed no relevant financial relationships.

Nat Commun. Published online August 11, 2015. Full text


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