Major Depressive Disorder in Pregnancy Clinical Trial
Official title:
Cytokines, PUFA Tissue Concentrations and Treatment Selection in Antenatal MDD
For a number of reasons women with major depressive disorder often discontinue conventional antidepressants when they become pregnant and prefer not to take them when depressive illness develops in the course of pregnancy. There is now considerable evidence that the administration of the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid (EPA), as monotherapy has antidepressant effects. If it could be clearly established as effective such an approach would offer a valuable alternative for woman who are at risk for, or who develop, depressive disorder during pregnancy. Strongly positive placebo-controlled trials of EPA supplementation, though, co-exist with entirely negative ones. No clear reasons for these discrepancies have emerged but one possibility is that the samples studied have differed in the proportion of individuals likely to benefit from EPA supplementation. As there has been no effort to identify such individuals we propose to explore two groups of measures, both relevant to EPA's likely mechanisms of action, as potential tools for identifying individuals likely to benefit this treatment. Hypothesis: Among women who experience major depressive episodes during their first two trimesters of pregnancy, baseline measures of cytokine activity and erythrocyte PUFA concentrations will be associated, in an additive or interactive fashion, with subsequent improvement in depressive symptoms among women taking omega-3 PUFA supplementation.
This is a project to determine whether certain measures of nutritional status and immune
functioning can be useful in the identification of women who would most benefit from omega-3
supplements as treatment for depression 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. 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 and there is accumulating evidence that the SSRIs
have short-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 but fish intake is limited due to concerns over
mercury levels. Antidepressant trials of omega-3 supplementation that have described
significant benefits over placebo include one that targeted pregnant women and yielded a
large effect size. Other trials, however, have failed to show clear antidepressant effects
and meta-analyses have yielded no explanations for these inconsistencies. A clear
possibility is that the studies with positive results involved subjects who more likely to
benefit from omega-3 supplementation but the characteristics of such individuals are
entirely unknown. Numerous case-control studies have associated depressive illness with
lower tissue concentration of omega-3 PUFAs and with higher ratios of omega-6 to omega-3.
Such measures may well identify individuals likely show antidepressant effects from
supplementation. The likelihood that omega-3 PUFAs exert antidepressant effects via
modulation of the inflammatory cascade, and the extensive evidence that high levels of
cytokines 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. A
group of 60 women who begin pregnancy in depressive episodes or who develop episodes in
their first two trimesters but who choose not to take conventional antidepressant therapy
would be used to test PUFA tissue concentration and inflammatory measures as predictors of
response to omega-3 supplementation monotherapy. Aim #1: To determine, among women with
first- or second-trimester major depressive episodes, relationships between subsequent
response to omega-3 PUFA supplementation and baseline measures of PUFA erythrocyte
concentrations and cytokine activity.
Hypothesis #1: Among women who experience major depressive episodes during their first two
trimesters of pregnancy, baseline measures of cytokine activity and erythrocyte PUFA
concentrations will be associated, in an additive or interactive fashion, with subsequent
improvement in depressive symptoms among women taking omega-3 PUFA supplementation. Aim #1
will test whether measures of PUFA tissue concentrations and cytokine activity have
potential value in treatment selection for women who experience depressive disorder during
pregnancy. The strength with which measures correlate with symptom outcome will be used to
select those for use in a definitive placebo-controlled trial that will target a sample
enriched for those likely to respond to EPA supplementation.The measures that emerge most
strongly as risk factors for new episodes would then be used to select subjects for
participation in a placebo-controlled trial of EPA supplementation as prophylaxis against
depressive disorder recurrence. The results would be integrated into the design of both
acute treatment and prophylaxis trials.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Terminated |
NCT03101527 -
Open Trial Determining Antidepressant Effects of Omega-3 Supplementation During Pregnancy
|
Early Phase 1 |