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Omega-3 fatty acids as a first line intervention for depression?

Posted by plosmedicine on 31 Mar 2009 at 00:22 GMT

Author: Lee E. Sieswerda
Position: Epidemiologist and Assistant Professor
Institution: Thunder Bay District Health Unit and Northern Ontario School of Medicine, Thunder Bay, Ontario, Canada
Additional Authors: Brian M. Ross, Northern Ontario School of Medicine, Thunder Bay, Ontario, Canada
Submitted Date: February 29, 2008
Published Date: March 3, 2008
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

We read with interest the article by Kirsch et al [1] because we recently published a meta-analysis of the effectiveness of supplementation with omega-3 fatty acids on improving depression scores.[2] All of the studies in our meta-analysis were randomized, placebo-controlled trials and varied in length from four weeks to four months, with most being three months or longer, and the participants mostly had mild to moderate depression. Our meta-analysis found omega-3 fatty acid supplementation improved HRSD scores by an average of 0.79 standard deviations better than placebo. This effect size is in the same range as what Kirsch et al found in this meta-analysis of antidepressant drugs.

Like this study, we also assessed the association between baseline scores and effect size, though we did so using meta-regression analysis. The average baseline HRSD scores among our trials varied from 11 to 26. We found that for trials with baseline HRSD scores less than 17 the average standardized mean difference (in standard deviations) was 0.48, compared to 1.01 in those trials with a mean baseline score greater than 17. Although the standardized mean difference was more than twice as great among those with higher baseline scores, the association was not statistically significant in our meta-analysis, perhaps because several of the trials did not include baseline information. Our conclusion from this analysis was somewhat different from the authors of this study, however. We concluded that the lower effect sizes at lower baseline severity scores represented a floor effect, whereby those with lower baseline scores would have less potential for improvement. Alternatively, you could describe this association between baseline severity score and effect size as regression-to-the-mean.

So what can we learn from these two meta-analyses? First, it is important to remember that meta-analysis does not really "prove" anything. No two trials are identical and there is heterogeneity among the trial results. However, one interesting hypothesis based on these data is that while antidepressant drugs are certainly effective, if we take into account cost, side effects, and relative effectiveness, patients with mild to moderate depression may be better off increasing their intake of omega-3 fatty acids (especially EPA) rather than taking antidepressant drugs. We state this as an hypothesis to be tested, not as a conclusion. As far as we are aware, there are no trials comparing omega-3 fatty acid supplementation directly to antidepressants, but such a trial would be interesting and potentially fruitful for patients. We may find that increasing dietary omega-3 fatty acids or taking a high-quality fish or flax oil supplement may be an effective first line intervention for patients with mild to moderate depression, and that many patients may never need to go on powerful anti-depressant drugs.


[1] Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, et al. (2008) Initial severity and antidepressant Benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med 5(2): e45.

[2] Ross BM, Seguin J, Sieswerda LE. (2007) Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid? Lipids in Health and Disease 6: 21. Open access at:

No competing interests declared.