Fish oil may ease psychosis

“Taking a daily fish oil capsule can stave off mental illness in those at highest risk,” BBC News has reported.

The news comes from a study that enrolled 81 people at high risk of psychosis, and randomly assigned them to take either fish oil capsules or a dummy pill for three months. After a year, those in the fish oils group were about a quarter less likely to have developed a psychotic illness such as schizophrenia.

This small study does seem to suggest that, at least in the short term, fish oil supplementation could prevent young people at high risk from progressing to psychotic illness. However, while the study was robust in its design it was too short to say whether the illnesses were prevented completely or just delayed.

Psychotic illnesses are serious conditions and if fish oils can be confirmed to prevent or delay their development in susceptible individuals this would be a very important finding. However, it will require larger, long-term studies to know if this is the case.

Where did the story come from?

This research was conducted by Dr G Paul Amminger and colleagues from the Medical University of Vienna, Austria, as well as research centres in Australia and Switzerland. The study was funded by the Stanley Medical Research Institute and published in the peer-reviewed medical journal, Archives of General Psychiatry.

The BBC News website provides a reasonably accurate account of this study. Its suggestion early in the report, that fish oil “appeared to be as effective as drugs”, may suggest that fish oil was directly compared with drug treatment, but this was not the case. The report does clarify that fish oil was compared to a dummy pill later on.

What kind of research was this?

This was a double-blind placebo-controlled, randomised-controlled trial (RCT) looking at whether taking omega-3 supplements affected the risk of developing a psychotic illness such as schizophrenia in people at very high risk of these disorders.

The researchers report that previous studies have found low levels of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) in people with schizophrenia, and that some scientists have suggested that problems with fatty acid metabolism could play a role in the development of the disorder. However, studies looking at the effects of omega-3 PUFA supplementation in people with schizophrenia have so far been inconclusive. Types of omega-3 fatty acids are found in oily fish, certain vegetable oils and in fish oil capsules.

This study was a placebo-controlled RCT, the best study design for determining whether a treatment has an effect on an outcome of interest. The participants of an RCT are randomly allocated into groups, meaning the groups should be balanced for characteristics that could affect the results. Using balanced groups in a trial means any differences between the groups’ results should be due to the treatments they received.

The study also gave some of the participants a placebo treatment instead of fish oil, blinding the study participants and assessors to which treatment the participants were receiving. This means their beliefs about whether or not the supplements worked could not affect how they rated their outcomes.

What did the research involve?

The researchers recruited 81 adolescents and young adults aged 13 to 25 years old who had characteristics that put them at high risk of developing psychotic disorders such as schizophrenia. They randomly assigned the participants to take either daily fish oil capsules (containing about 1.2g omega-3 PUFAs) or placebo capsules for three months. The researchers then followed them up for a year to identify any participants who developed a psychotic disorder and to monitor the level of any psychotic symptoms seen.

The researchers enrolled participants who had at least one of the following risk factors for psychosis:

low levels of psychotic symptoms (delusions, hallucinations, suspiciousness, or conceptual disorganisation measured on a standard scale),
transient psychosis, i.e. lasted less than a week and resolved without antipsychotic medication, or
having either a schizotypal personality disorder or a first-degree relative (such as a mother, father, sister or brother) who had psychosis, plus the participant experienced a significant reduction in ability to function in the last year.

These people may have a high risk of developing psychosis within the following year. Participants were considered as having developed a psychotic disorder if they reached a pre-specified level of psychotic symptoms that lasted for at least a week, with all diagnoses being confirmed by a psychiatrist.

Researchers monitored how much of their supplements the participants took by monitoring the number of pills they had left and by taking blood samples. The placebo pill contained coconut oil (which does not contain PUFAs) and an equivalent amount of vitamin E to the fish oil capsules, plus 1% fish oil to make the taste of the capsules similar.

The researchers carried out statistical analyses to look for differences between the groups in terms of:

the proportion developing a first episode of psychotic illness,
how long it took before these illnesses developed, and
the participants’ levels of symptoms over time.

They also looked at whether the groups differed in their use of psychological and psychosocial treatments or in their use of medication.

What were the basic results?

During the year of follow up, 3 people out of 41 in the fish oil group (7.3%) and 2 out of 40 in the placebo group (5.0%) stopped taking their supplements, leaving 93.8% of participants for analysis.

Two people in the fish oil group (4.9%) and 11 in the placebo group (27.5%) developed psychotic illness (mostly schizophrenia) during the study. This represented a 22.6% lower risk of developing psychosis in the fish oil group. This difference was statistically significant. Theoretically this means that four people at high risk of psychosis would have to take fish oil for three months in order to prevent one of them from developing psychosis over the course of a year. This figure (in this case four people) is referred to as the “number needed to treat” or NNT.

The fish oil group had lower levels of psychotic symptoms and better overall functioning (psychological, social, and occupational) than the placebo group at the end of the study. There were no differences between the groups in terms of depressive symptoms or the risk of adverse effects.

How did the researchers interpret the results?

The researchers concluded that, “a 12-week intervention with omega-3 significantly reduced the transition rate to psychosis” and led to “significant symptomatic and functional improvements during the entire follow-up period (12 months)”. They also say that their study “strongly suggests that omega-3 PUFAs may offer a viable prevention and treatment strategy with minimal associated risk in young people at ultra-high risk of psychosis”. The researchers suggest that the potential of the supplements as a preventive intervention should be explored further.

Conclusion

This trial used a robust study design. It suggests that fish oil supplementation may reduce the risk of transition to psychotic illness in people at very high risk of these disorders. However, there are some points to consider, which the researchers themselves raise:

The study was relatively small (81 people). In smaller studies, randomising participants may be less effective at balancing groups. Although the researchers did show that the groups were balanced for a number of factors, there may have been others that were not balanced and could affect results. The small size of this study may also limit its ability to detect differences in the results from each group.
The people in this study were adolescents and young adults at very high risk of psychotic illness. They were referred to a specialised psychosis detection clinic and agreed to participate in the trial. The results may not apply to older adults, people who are at lower levels of risk, or those whose characteristics differ in other ways from those of the participants in this trial. For example, those who agreed to participate may have had different levels or types of symptoms to the people who would not agree to participate in a trial.
The study was only a year long and it is possible that the fish oil may delay, rather than prevented, transition to psychosis. A longer follow-up period would be needed to determine if this is the case.
The authors report that four very high-risk individuals would need to be treated with fish oil to prevent one transition to psychotic illness over a year (the NNT). They say this is similar to the NNT values obtained in two other studies looking at the effects of atypical antipsychotic drugs as preventive treatments. However, this comparison should be treated with caution, as the participants or measured outcomes in these different studies may have differed in important ways. Randomised-controlled trials directly comparing fish oils and antipsychotic drugs would be needed in order to draw firm conclusions about their comparative benefits.

Overall, this study provides promising results that suggest that fish oils warrant further investigation as a preventive treatment in young people at high risk of psychosis. Future studies should include a larger number of participants and follow them up for a longer period of time.