Open Trial Determining Antidepressant Effects of Omega-3 Supplementation During Pregnancy

Pregnancy does not reduce the risk of recurrence among women who have previously experienced depressive illness and the advent of new episodes during pregnancy raises particular problems. Lingering concerns over the possible teratogenicity of medications in general leave many women reluctant to continue preexisting antidepressant prophylaxis or to accept new trials of conventional antidepressant treatment. There is also now accumulating evidence that the SSRIs have short-, and perhaps longer-term, adverse effects on the newborn.

The antidepressant effects of omega-3 polyunsaturated fatty acid (PUFA) supplementation may offer a particularly appropriate alternative to conventional therapy for depressive episodes that occur during pregnancy. The nutritional needs of the fetus increase the likelihood of omega-3 PUFA deficits in the mother but access to adequate omega-3 PUFAs through fish intake is limited due to concerns over mercury levels. Because polyunsaturated fatty acids are dietary components essential for both fetal development and maternal health, and because their use as supplementation carries a minimal to non-existent side effect burden, women may be more likely to accept omega-3 supplementation over that of conventional antidepressants to manage depressive illness if provided sufficient evidence for effectiveness.

Data supporting the antidepressant potential of omega-3 PUFA supplementation derive first from numerous case-control studies that have associated depressive illness with lower tissue concentrations of omega-3 PUFAs and with higher ratios of omega-6 to omega-3. These findings prompted antidepressant trials of omega-3 supplementation as augmentation or as mono-therapy and many reports described significant benefits over placebo, including one that targeted pregnant women and yielded a large effect size. A number of other trials, however, failed to show clear antidepressant effects. Meta-analyses have highlighted these inconsistencies in results but have found no explanations for them in differing sample demographics, baseline depressive severity levels, PUFA dosing, or trial durations. Other sources of study outcome differences undoubtedly exist and a clear possibility is that the studies with positive results involved subjects more likely to truly benefit from omega-3 supplementation. The characteristics of such individuals are entirely unknown. Though valid predictors of antidepressant response to omega-3 PUFA supplementation would provide powerful tools for personalizing treatment no study has sought to identify them.

One feature that might characterize an individual likely to respond to omega-3 PUFA supplementation is, of course, the presence of relatively low tissue concentrations of omega-3 PUFAs and/or high ratios of omega-6 to omega-3 concentrations. The likelihood that omega-3 PUFA supplementation exerts antidepressant effects via modulation of the inflammatory cascade, and the extensive evidence that high levels of pro-inflammatory markers characterize individuals with depressive disorders, indicate that these measures too may help to select those most likely to benefit from treatment with omega-3 PUFAs.

The identification of response predictors for a specific antidepressant strategy would not only have value for the selection of acute treatment for individuals with active depression but could also be used to choose preventative strategies for individuals who are not currently depressed but who are at high risk because of a recent history of a depressive episode. Prophylaxis against depressive illness in such individuals would have special importance during pregnancy. The adverse effects of depressive illness on both maternal and newborn well-being are widely appreciated but women who develop depressive disorders during pregnancy may, for a variety of reasons, fail to report symptoms to their health care provider or, if they do, treatment response may be delayed or even absent after one or more trials.