Omega-3 Fatty Acids for Depression: What the Data Show

Hi. I'm Dr Drew Ramsey, assistant clinical professor of psychiatry at Columbia University, reporting for Medscape Psychiatry.

For those of us in clinical practice, omega-3 fatty acids represent the Holy Grail in psychiatry because they're natural; palatable for patients; and work in a different way from our other medications, in the sense that they're influencing membrane physiology. Omega-3 fatty acids have a tremendous amount of data, but the data are confusing. They're very heterogeneous. There are lots of positive studies, but also a number of negative studies. I wanted to talk about these data, because we've seen a number of meta-analyses come out just in the past year.

Let's start with the first: a meta-analysis that was published just a couple of weeks ago in the American Journal of Psychiatry, with Jerome Sarris as the first author.^[1] This study was a meta-analysis looking at adjunctive treatment of antidepressants using omega-3 fatty acids, and they found that there was a strong to moderate effect for omega-3 fatty acids as adjunctive treatment.

This study follows up two larger meta-analyses that looked at omega-3 fatty acids as monotherapy for the treatment for depression.^[2,3] The first meta-analysis came out in November; it was a Cochrane review looking at a total of 25 studies.^[2] The majority of these studies compared omega-3 fatty acids with placebo. Appleton and colleagues^[2] found that although there was a possible clinically significant effect, it was very small, with a standardized mean difference of 0.32—which translated to about 2 points on the Hamilton Rating Scale for Depression (HAM-D).

Following that in March, Mocking and colleagues^[3] did another meta-analysis, because they had a few critiques in terms of what studies were selected and the replication of some data that had been included in other meta-analyses. They found a beneficial effect, with a standardized mean difference of 0.398—so this is clinically significant effect size for omega-3 fatty acids being used as a sole agent in the treatment of depression.

So, why are we seeing this heterogeneity? One reason is that we might not have been checking blood levels. We get a hint from our colleagues in cardiology with the Superko brothers and colleagues^[4] publishing a great review in 2013; I highly recommend you read it. This review looked at blood levels, and [the authors] reported that individuals who had higher omega-3 fatty acid blood levels had a more robust cardiac outcome—meaning that if omega-3 fatty acids were going to work for heart disease and for preventing such things as arrhythmia, individuals needed much higher blood levels. In cardiology, these doses are in the 2- to 4-g range, which is a little higher than we often use in psychiatry.

Another study that deserves mention is the Vienna Omega-3 Study.^[5] This was a prevention trial for individuals who were at high risk for psychosis and developed some prodromal symptoms. The trial found, very interestingly, that a high dose of omega-3 fatty acids for 12 weeks had an incredibly preventive effect. It was a very large trial, and [the authors] just shared their 7-year follow-up data and found that individuals who received high-dose omega-3 fatty acids in the small window during development of psychosis were protected from actually developing psychosis.^[6]

Of course, we need this to be replicated, but the findings are quite strong. And for any of you working with patients who are prodromal or for patients whom you're concerned about or have a high risk for psychosis, you should consider high-dose fish oil, because that now seems to be supported by at least one long-term trial.