Major Depressive Disorder in Pregnancy Clinical Trial
Official title:
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.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Terminated |
NCT03101540 -
Cytokines, PUFA Tissue Concentrations and Treatment Selection in Antenatal MDD
|
Early Phase 1 |