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

NCT ID: NCT03101527

Last Updated: 2017-04-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

EARLY_PHASE1

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-05-31

Study Completion Date

2012-02-29

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Major Depressive Disorder in Pregnancy

Keywords

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Major Depressive Disorder omega-3 polyunsaturated fatty acid PUFA Pregnancy eicosapentaenoic acid (EPA) supplementation

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

A single group model was used: pregnant women.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Supplementation

Subjects received Omega-3 PUFA supplementation

Group Type EXPERIMENTAL

Omega-3 PUFA supplementation

Intervention Type DRUG

Subjects received 2.2g of eicosapentaenoic acid (EPA) and 1.2g docosahexaenoic daily for the duration of the study

Interventions

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Omega-3 PUFA supplementation

Subjects received 2.2g of eicosapentaenoic acid (EPA) and 1.2g docosahexaenoic daily for the duration of the study

Intervention Type DRUG

Other Intervention Names

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eicosapentaenoic acid (EPA) docosahexaenoic acid (DHA)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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William Coryell

OTHER

Sponsor Role lead

Responsible Party

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William Coryell

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

References

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Hibbeln JR. Seafood consumption, the DHA content of mothers' milk and prevalence rates of postpartum depression: a cross-national, ecological analysis. J Affect Disord. 2002 May;69(1-3):15-29. doi: 10.1016/s0165-0327(01)00374-3.

Reference Type BACKGROUND
PMID: 12103448 (View on PubMed)

De Vriese SR, Christophe AB, Maes M. Lowered serum n-3 polyunsaturated fatty acid (PUFA) levels predict the occurrence of postpartum depression: further evidence that lowered n-PUFAs are related to major depression. Life Sci. 2003 Nov 7;73(25):3181-7. doi: 10.1016/j.lfs.2003.02.001.

Reference Type BACKGROUND
PMID: 14561523 (View on PubMed)

Peet M, Murphy B, Shay J, Horrobin D. Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients. Biol Psychiatry. 1998 Mar 1;43(5):315-9. doi: 10.1016/s0006-3223(97)00206-0.

Reference Type BACKGROUND
PMID: 9513745 (View on PubMed)

Rees AM, Austin MP, Owen C, Parker G. Omega-3 deficiency associated with perinatal depression: case control study. Psychiatry Res. 2009 Apr 30;166(2-3):254-9. doi: 10.1016/j.psychres.2007.12.011. Epub 2009 Mar 5.

Reference Type BACKGROUND
PMID: 19268372 (View on PubMed)

Other Identifiers

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201002781

Identifier Type: -

Identifier Source: org_study_id