Dietary & Supplement Intervention for Perinatal Depression & Anxiety

Overseen By Sophie Grigoriadis, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2 & 3

Sponsor: The Canadian College of Naturopathic Medicine

Disqualifiers: Bipolar, Psychosis, Schizophrenia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 12 months postpartum

100 Participants Needed

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}

Research Team

Neda Ebrahimi, PhD

Principal Investigator

Canadian College of Naturopathic Medicine

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.

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
• Fish oil
• Probiotics

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.

Who Is Running the Clinical Trial?

The Canadian College of Naturopathic Medicine

Lead Sponsor

Trials

23

Recruited

2,600+

Lotte & John Hecht Memorial Foundation

Collaborator

Trials

18

Recruited

4,600+

Sunnybrook Health Sciences Centre

Collaborator

Trials

693

Recruited

1,569,000+

Findings from Research

Omega-3 fatty acids (FA) significantly improve depressive symptoms in perinatal women, based on a meta-analysis of 8 randomized placebo-controlled trials involving 638 participants.

Higher ratios of EPA to DHA (≥1.5) in omega-3 formulations were particularly effective for treating mild-to-moderate perinatal depression, with a low incidence of side effects compared to placebo.

NCBI (Pubmed)

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. Zhang, MM., Zou, Y., Li, SM., et al.[2023]

Epidemiological and laboratory studies suggest a link between low omega-3 fatty acid levels and increased rates of depression, particularly in women during the perinatal period, indicating that omega-3s may play a role in mood regulation.

Given the limited knowledge about the safety of traditional antidepressants for perinatal women, there is a strong need for further research into omega-3 fatty acids as a potential alternative treatment for depression during this critical time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of omega-3 fatty acids as a treatment for depression in the perinatal period. Rees, AM., Austin, MP., Parker, G.[2017]

Women with perinatal depression (PND) have significantly lower levels of total n-3 polyunsaturated fatty acids (PUFAs) and docosahexaenoic acid compared to healthy controls, indicating a potential nutritional deficiency linked to depression.

The increased n-6/n-3 ratio in PND patients suggests an imbalance in fatty acid levels, supporting the idea that omega-3 PUFAs could play a crucial role in treating and preventing PND, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polyunsaturated Fatty Acids in Perinatal Depression: A Systematic Review and Meta-analysis. Lin, PY., Chang, CH., Chong, MF., et al.[2018]

In a study of 59 perinatal women with major depressive disorder, omega-3 fatty acids (1.9g/day) were well tolerated but did not show significant efficacy over placebo when combined with supportive psychotherapy over 8 weeks.

Both groups experienced significant reductions in depression scores, indicating that supportive psychotherapy alone may be effective, and the low dietary intake of omega-3s among participants raises concerns about their overall nutritional status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acids and supportive psychotherapy for perinatal depression: a randomized placebo-controlled study. Freeman, MP., Davis, M., Sinha, P., et al.[2022]

In a study involving 126 pregnant women at risk for depression, supplementation with either EPA-rich or DHA-rich fish oil did not lead to significant differences in depressive symptoms compared to a placebo, as measured by the Beck Depression Inventory.

While both EPA and DHA supplementation increased their respective serum concentrations, the study found no evidence that these supplements could prevent depressive symptoms during pregnancy or postpartum.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Mothers, Omega-3, and Mental Health Study: a double-blind, randomized controlled trial. Mozurkewich, EL., Clinton, CM., Chilimigras, JL., et al.[2022]

Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation may help reduce symptoms of major depressive disorder and perinatal depression, especially in women, based on epidemiological studies.

However, randomized controlled trials show mixed results regarding the effectiveness of n-3 PUFA in treating depression, indicating that more research is needed to confirm its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acids influence mood in healthy and depressed individuals. Giles, GE., Mahoney, CR., Kanarek, RB.[2019]

In a small pilot study involving 7 pregnant women with a history of postpartum depression, omega-3 fatty acid supplementation did not effectively prevent depressive episodes, as 4 out of 7 participants experienced depression during the study.

Despite the lack of efficacy, the study reported no adverse events leading to participant withdrawal, suggesting that omega-3 supplementation may be safe for use during late pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acids for the prevention of postpartum depression: negative data from a preliminary, open-label pilot study. Marangell, LB., Martinez, JM., Zboyan, HA., et al.[2014]

Omega-3 fatty acids may help improve depression symptoms during pregnancy and after childbirth, with some studies showing statistically significant improvements in depression rating scores, although results were inconsistent across trials.

The trials indicated that omega-3 fatty acids are generally safe for use during pregnancy, with only mild side effects reported, such as foul breath and gastrointestinal issues, and no serious adverse events noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of omega-3 Fatty acids for prevention or treatment of perinatal depression. Borja-Hart, NL., Marino, J.[2022]

A systematic review of two randomized controlled trials involving 305 women found no significant evidence that dietary supplements like selenium, DHA, or EPA effectively prevent postnatal depression, indicating a need for further research in this area.

Despite some initial findings suggesting potential benefits, the studies faced high attrition rates and did not provide conclusive results, highlighting the challenges in establishing safe and effective dietary interventions for preventing postnatal depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary supplements for preventing postnatal depression. Miller, BJ., Murray, L., Beckmann, MM., et al.[2023]

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]

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

Role of omega-3 fatty acids as a treatment for depression in the perinatal period. [2017]

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

Polyunsaturated Fatty Acids in Perinatal Depression: A Systematic Review and Meta-analysis. [2018]

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

Omega-3 fatty acids and supportive psychotherapy for perinatal depression: a randomized placebo-controlled study. [2022]

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

The Mothers, Omega-3, and Mental Health Study: a double-blind, randomized controlled trial. [2022]

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

Omega-3 fatty acids influence mood in healthy and depressed individuals. [2019]

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]

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

Role of omega-3 Fatty acids for prevention or treatment of perinatal depression. [2022]

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

Dietary supplements for preventing postnatal depression. [2023]