Multi-country RCT finds limited effects of omega-3 on high psychosis risk
Researchers in Australia, Austria, Germany, Switzerland, Hong Kong, the Netherlands, Denmark, Singapore and the UK conducted a randomised, double-blind, placebo-controlled trial on omega-3 in patients at ultra high-risk (UHR) for psychosis, with a medium-term follow-up.
The trial's primary outcomes of interest entailed any transition to psychosis, as well as symptomatic and functional outcomes. The researchers also aimed to investigate clinical predictors the medium-term outcome of such a trial.
Improvement…but only post-intervention?
They recruited 304 UHR patients from across 10 specialised early psychosis services in Australia, Asia and Europe, giving them each either 1.4g of omega-3 fatty acids or a placebo every day, as well as up to two sessions of cognitive-behavioural case management over a six-month study period.
The participants also received additional sessions as needed after that, for up to another six months.
The mean follow-up time was 3.4 years, after which the researchers reported a "modest increase" in transitions between 12-month and medium-term follow-up (11% to 13%).
They observed "substantial improvement" in symptoms and functioning from baseline to follow-up. However, there were no differences between the treatment and control groups.
Instead, it was more likely that the improvement had occurred when 55% of the participants had been given mental health treatment between the end of the intervention and the follow-up period.
The researchers wrote: "Omega-3 PUFAs did not provide additional benefits to good quality psychosocial intervention over the medium term. Although most improvement had been achieved by end of intervention, the substantial rates of post-intervention mental health service use indicate longer-term clinical needs in UHR patients."
They added that it was either the longer-term effect of cognitive-behavioural case management or the post-intervention treatment, or a combination of the two, that contributed to maintaining any improvement that had occurred during the intervention itself, and prevented considerable mental health deterioration post-intervention.
Previous studies have also reported contradictory findings regarding omega-3's impact on cognitive function, behaviour and mental health.
A recent Japanese study found insufficient evidence to support omega-3's anti-depression properties, attributing only very minor effects to omega-3 consumption.
On the other hand, an earlier Taiwanese study had linked low omega-3 levels to the prevalence of prenatal depression.
Additionally, a study published in the journal Psychiatry reported that omega-3 consumption effectively helped to reduce aggression in adults aged 18 to 45.
The researchers behind the current study said the results of the trial warranted further investigation into whether omega-3 fatty acids might play a part in treating this patient population, adding that other trials on the topic were in progress.
Furthermore, they did not test omega-3's efficacy on sub-groups of patients — such as those with aberrant inflammatory markers — and despite an 89% follow-up rate for the main outcome (transition to psychosis), the follow-up rate was significantly lower for other outcomes.
These factors could have skewed the results, especially considering that previous studies had reported difficulty following up with adolescent and young adult psychiatric patients, which was linked to greater disorder during follow-up.
The researchers concluded: "This medium-term follow-up indicated substantial improvement in symptoms and functioning in a UHR cohort over a mean 3.4-year follow-up period, with no difference between the omega-3 and placebo-treated groups.
"Most of this improvement had been achieved by the end of the intervention period (12 months), although high rates of post-intervention mental health service use indicate ongoing clinical need after this time.
"This post-intervention phase intervention or the longer-term effect of CBCM, or a combination of the two, may have contributed to maintaining the gains achieved during the intervention phase and prevented significant deterioration after this time."
Source: Nature Partner Journals
"NEURAPRO: a multi-centre RCT of omega-3 polyunsaturated fatty acids versus placebo in young people at ultra-high risk of psychotic disorders—medium-term follow-up and clinical course"
Authors: B. Nelson, et al.