Open Trial Determining Antidepressant Effects of Omega-3 Supplementation During Pregnancy
Open Trial Determining Antidepressant Effects of Omega-3 Supplementation During Pregnancy
The purpose of this study is to determine if omega-3 polyunsaturated fatty acids as a
 monotherapy have antidepressant effects during pregnancy. It will also provide pilot data
 pertaining to relationships between apparent response to omega-3 monotherapy and both plasma
 cytokine and erythrocyte essential fatty acid concentrations.
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.
Inclusion Criteria:

 1. Women with uncomplicated pregnancy within the 1st or 2nd trimester of pregnancy

 2. Score of 10 or greater on the nine item Patient Health Questionnaire (PHQ-9) for
 depression

 Exclusion Criteria:

 1. antidepressant use in preceding month

 2. use in previous 4 weeks of psychotropic medications other than hypnotics or
 benzodiazepines in diazepam dose-equivalents greater than or equal to 2mg/day for
 insomnia

 3. Fish allergy

 4. initiation of regularly scheduled course of psychotherapy within previous 2 months