Dietary & Supplement Intervention for Perinatal Depression & Anxiety

Recruiting in Palo Alto (17 mi)

Overseen by Neda Ebrahimi, PhD

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: The Canadian College of Naturopathic Medicine

Disqualifiers: Bipolar, Psychosis, Schizophrenia, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Perinatal depression and anxiety (PDA) are the leading causes of maternal mortality in developed countries. Women with a history of depression have a 20 fold higher risk of PDA at subsequent pregnancies. The adverse outcomes extend beyond maternal well-being to long-term deficits in children and families. The gut-brain axis is a newly recognized key player in mental health disorders. Specifically, the microbial composition of the gut along with their metabolites are directly involved in disease onset and course. Recent clinical studies have identified diet as the most powerful environmental factor in manipulating gut microbiome. Given vulnerability and resistance of pregnant women to pharmacotherapy, particularly in those with a predisposition to mood disorders, as well as pregnant women's high motivation and commitment to improving gestational diet, a dietary/supplemental intervention to 'optimize' gut microbiome, is a favored approach in disease management. The study investigators aim to exploit microbial responsiveness to diet together with this maternal motivation, to alter the risk and severity of a universal public health concern that has dire and long-term consequences for new moms and their children. The investigators of this trial, will first study the challenges in pursuing a study aimed at changing the microbiome of pregnant women with a history of mood disorders. Pregnant women in their second trimester will be recruited. Each will be assigned or randomized to one of four groups that will use a combination of diet, supplementation with probiotics, fish oil or no intervention. Each participant will meet with the study team virtually every 3 months until 1 year after delivery. At each study visit participants will be required to complete some questionnaires about their food intake, mood, and other health related measures and will provide a stool sample using the stool collection kits provided. The findings from this study will help strategize for a larger study that will allow for comparison of the effects of diet, and/or supplementation with Omega-3 Fatty Acids (O3FA) and probiotics on the microbiome and the onset and severity of PDA.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it focuses on dietary and supplement interventions, so it's best to discuss your current medications with the study team.

What data supports the effectiveness of the treatment for perinatal depression and anxiety?

Research shows that omega-3 fatty acids, particularly those with a higher ratio of EPA to DHA, significantly improve depressive symptoms in perinatal women and are well-tolerated. These fatty acids have been effective in treating major depressive disorder and have anti-inflammatory and neuroplastic effects, which may contribute to their benefits in perinatal depression. ^{1 2 3 4 5}

Is it safe to use omega-3 fatty acids for perinatal depression?

Omega-3 fatty acids, often found in fish oil, appear to be safe for use during pregnancy and after childbirth, with common mild side effects like bad breath and stomach issues, but no serious adverse events reported. ^{1 5 6 7 8}

How is the treatment for perinatal depression and anxiety using diet quality, fish oil, and probiotics different from other treatments?

This treatment is unique because it combines dietary changes with supplements like omega-3 fatty acids (found in fish oil) and probiotics, which are beneficial bacteria for gut health. Unlike traditional medications, this approach focuses on improving diet and gut microbiota, which may help reduce inflammation and support brain health, offering a potentially safer option for mothers and infants. ^{1 2 3 4 9}

Eligibility Criteria

This trial is for English-speaking women aged 18-43, in their second trimester of pregnancy, who have a history of depression or anxiety but are currently well. They must be non-smokers and not use alcohol or drugs, and should be financially stable. Women with high BMI, other major mental health disorders, severe medical conditions, allergies to fish oils/supplements ingredients, or those needing chronic antibiotics are excluded.

Inclusion Criteria

I have been diagnosed with depression/anxiety in the past but am currently well.

English speaking

12-35 weeks of gestation

Exclusion Criteria

My BMI is 30 or higher.

I am unwilling to change my current medication for the study's.

I struggle to afford basic daily needs like shelter and food.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dietary modification, fish oil, and probiotics or placebo from enrollment until 1 year postpartum, with virtual visits every 3 months and weekly follow-ups for dietary adherence.

12 months postpartum

6 visits (virtual), weekly follow-ups

Follow-up

Participants are monitored for safety and effectiveness after treatment, with final visit expected between 9-12 months after delivery.

3 months

1 visit (virtual)

Treatment Details

Interventions

• Diet Quality (Other)
• Fish oil (Dietary Supplement)
• Probiotics (Dietary Supplement)

Trial Overview The study tests if improving diet quality and adding supplements like prebiotics, probiotics, and fish oil can positively change the gut microbiome to reduce the risk and severity of perinatal depression and anxiety (PDA). Participants will be randomly assigned to one of four groups with different combinations of dietary changes and supplementation.

Participant Groups

Group I: Gutopia Experimental Treatment 3 Interventions

Women in this arm will receive dietary modification, fish oil and probiotics from the time of enrollment till completion of last study visit (12 months postpartum). The dietary modification will be conducted by a dietician that will provide feedback on the participants diet at enrollment, ways to improve diet quality to meet pregnancy needs, and increase prebiotic foods. Weekly follow-ups will be conducted by the research team to ensure dietary target is met and to help address challenges in doing so. The initial dietary consult will be 30-45 minutes long with 10-15 minute for each subsequent follow-up.

Group II: Gutless Experimental Treatment 1 Intervention

Women in this arm will receive fish oil and placebo probiotic from the time enrollment till 1 year postpartum .

Group III: Gutboost Experimental Treatment 2 Interventions

Women in this arm will receive a daily probiotic and fish oil supplement from the time of enrollment till 1 year postpartum.

Group IV: Gutnone Active Control 1 Intervention

Women in this arm will only be receiving standard care by their obstetrician, and a one time, 30 minutes consult on how to improve baseline diet quality to meet pregnancy needs will be provided by a dietician at the time of enrollment.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Sunnybrook Health Science Center Toronto, Canada

Who Is Running the Clinical Trial?

The Canadian College of Naturopathic Medicine Lead Sponsor

Lotte & John Hecht Memorial Foundation Collaborator

Sunnybrook Health Sciences Centre Collaborator

References

1. United States pubmed.ncbi.nlm.nih.gov

The efficacy and safety of omega-3 fatty acids on depressive symptoms in perinatal women: a meta-analysis of randomized placebo-controlled trials. [2023] Omega-3 fatty acids (FA), as a nutrient, has been proven effective in major depressive disorder (MDD), however, the results of monotherapy in perinatal depression (PND) remain unclear. To examine the efficacy and safety of omega-3 fatty acids (FA) monotherapy for perinatal depression (PND) compared with placebo. PubMed, Embase, PsycINFO, MEDLINE, Cochrane Library, and CINAHL were searched from inception up to November 2019. The reference lists of relevant review articles and included studies were also reviewed. Randomized placebo-controlled trials examining the efficacy and safety of omega-3 FA monotherapy in perinatal women with depressive symptoms were included. Pooled standard mean differences (SMD) were calculated and random-effects models were adopted for all analyses. Subgroups analyses and meta-regression were performed to quantify characteristics of the subjects and trials influencing the omega-3 response. In addition, meta-regression was conducted to identify the source of heterogeneity. The study protocol was registered at PROSPERO, CRD42020159542. Eight eligible randomized placebo-controlled trials were included involving 638 participants. There was a significant effect of omega-3 FA on perinatal depression. Omega-3 with higher ratio of EPA/DHA (≥1.5) had significant efficacy both in mild-to-moderate pregnant and postpartum depression with low incidence of side effects. Among the included trials reporting adverse effects, there was no significant difference in incidence of gastrointestinal and neurologic events between the omega-3 and placebo groups. There was no evidence of publication bias. Our findings suggested that omega-3 FA significantly improved depressive symptoms in perinatal women regardless of pregnant or postpartum and well-tolerated. Furthermore, the omega-3 response was linked to higher EPA proportion in omega-3 formula and mild- to-moderate depression.

2. England pubmed.ncbi.nlm.nih.gov

Role of omega-3 fatty acids as a treatment for depression in the perinatal period. [2017] To consider the possible rationale and utility of omega-3 fatty acids as a treatment for depression in the perinatal period.

3. United States pubmed.ncbi.nlm.nih.gov

Polyunsaturated Fatty Acids in Perinatal Depression: A Systematic Review and Meta-analysis. [2018] Omega-3 (or n-3) polyunsaturated fatty acids (PUFAs) are promising antidepressant treatments for perinatal depression (PND) because of supporting evidence from clinical trials, the advantage in safety, and their anti-inflammatory and neuroplastic effects. Although several observational studies have shown n-3 PUFA deficits in women with PND, the results of individual PUFAs from different studies were inconsistent.

4. Netherlands pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acids and supportive psychotherapy for perinatal depression: a randomized placebo-controlled study. [2022] Perinatal major depressive disorder (MDD), including antenatal and postpartum depression, is common and has serious consequences. This study was designed to investigate the feasibility, safety, and efficacy of omega-3 fatty acids for perinatal depression in addition to supportive psychotherapy.

5. United States pubmed.ncbi.nlm.nih.gov

The Mothers, Omega-3, and Mental Health Study: a double-blind, randomized controlled trial. [2022] Maternal deficiency of the omega-3 fatty acid, docosahexaenoic acid (DHA), has been associated with perinatal depression, but there is evidence that supplementation with eicosapentaenoic acid (EPA) may be more effective than DHA in treating depressive symptoms. This trial tested the relative effects of EPA- and DHA-rich fish oils on prevention of depressive symptoms among pregnant women at an increased risk of depression.

6. United States pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acids influence mood in healthy and depressed individuals. [2019] Depression is one of the most prevalent disorders in the United States, and rates of depression are higher for women than men. Despite their widespread use, drugs used in the treatment of depression are only moderately more effective than placebo in treating the disorder. Effective treatment of perinatal depression is of particular concern as treatment can influence both the mother and the developing child. Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation may reduce symptoms of major depressive disorder and perinatal depression. The aim of the present review was to evaluate epidemiological studies examining PUFA intake and depressive symptoms in the general population, as well as double-blind, placebo-controlled trials assessing the influence of n-3 PUFA in healthy individuals and those with depression; specific consideration was given to perinatal depression and potential gender differences in the relationship. Although there is some evidence to suggest that n-3 PUFA intake is associated with reduced depressive symptoms, particularly in females, these results are generally limited to epidemiological studies, whereas results from randomized controlled trials are mixed.

7. United States pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acids for the prevention of postpartum depression: negative data from a preliminary, open-label pilot study. [2014] Based on the putative relationship between depleted omega-3 fatty acids and postpartum depression, we initiated an open-label pilot study of omega-3 fatty acid supplementation with the aim of preventing postpartum depression. Euthymic pregnant females with a past history of depression in the postpartum period were started on 2960 mg of fish oil (1.4:1 eicosapentaenoic acid:docosahexaenoic acid) per day between the 34th to 36th week of pregnancy and assessed through 12 weeks postpartum. Four of seven participants had a depressive episode during the study period. No participants withdrew from the study due to adverse events. This preliminary, small, open-label pilot study failed to show promising results for the use of omega-3 fatty acid monotherapy beginning at 34 to 36 weeks gestation for the prevention of postpartum depression in patients with a prior postpartum depression history. Controlled studies are lacking.

8. United States pubmed.ncbi.nlm.nih.gov

Role of omega-3 Fatty acids for prevention or treatment of perinatal depression. [2022] Perinatal depression is a complex mental health disorder that can manifest during pregnancy or after childbirth. Women with perinatal depression may not receive proper medical treatment because of concerns over teratogenic effects related to drug therapy. Evidence suggests that low levels of omega-3 fatty acids are correlated with depressive symptoms during pregnancy and after delivery. Omega-3 fatty acids may produce antidepressant effects due to their role in serotonin functioning. A literature search identified seven clinical trials of omega-3 fatty acids for the prevention or treatment of perinatal depression. Depression rating scale scores used in the studies improved, but results were statistically significant in only three trials. Four studies were randomized and placebo controlled, and three were open label. One study evaluating the prevention of postpartum depression in women with a history of depression was discontinued early due to relapse of depressive symptoms. In the trials we evaluated, the most common adverse effects were foul breath and/or unpleasant taste, and gastrointestinal complaints; no serious adverse events were reported. The seven studies were limited by small sample sizes and variable dosing and study durations. In the studies that demonstrated statistical significance, improvement in depression rating scale scores for omega-3 fatty acids was comparable to placebo. Overall, results have been inconclusive, but further investigation of omega-3 fatty acids is warranted because they did improve depression scores and appeared to be safe during pregnancy.

9. England pubmed.ncbi.nlm.nih.gov

Dietary supplements for preventing postnatal depression. [2023] Postnatal depression is a medical condition that affects many women and the development of their infants. There is a lack of evidence for treatment and prevention strategies that are safe for mothers and infants. Certain dietary deficiencies in a pregnant or postnatal woman's diet may cause postnatal depression. By correcting these deficiencies postnatal depression could be prevented in some women. Specific examples of dietary supplements aimed at preventing postnatal depression include: omega-3 fatty acids, iron, folate, s-adenosyl-L-methionine, cobalamin, pyridoxine, riboflavin, vitamin D and calcium.