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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how diet and supplements might aid depression and anxiety during and after pregnancy. Researchers are investigating how food and specific supplements, such as probiotics (beneficial bacteria) and fish oil (omega-3 fatty acids), can influence the gut, which may significantly impact mental health. Participants will be divided into groups to try different combinations of diet and supplements to determine the most effective approach. This trial could suit pregnant women in their second trimester who have experienced depression or anxiety in the past but are currently feeling well. As a Phase 2 and Phase 3 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group and is in the final step before FDA approval, offering a chance to contribute to significant advancements in maternal mental health.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Past studies have found dietary changes for depression and anxiety to be safe for many pregnant and new mothers. A balanced diet is believed to support mental health during and after pregnancy.

Research has shown that omega-3 fatty acids, found in fish oil, can reduce depression in pregnant and postpartum women. Most people can take them without major side effects.

Probiotics might also help with depression and anxiety. Studies suggest they can reduce these symptoms in new mothers who take them.

Overall, these treatments are often safe and well-tolerated, offering a hopeful option for managing depression and anxiety during and after pregnancy. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for perinatal depression and anxiety because they offer a natural and multifaceted approach. Unlike typical treatments such as antidepressants or therapy, these interventions focus on improving diet quality and gut health. The "Gutopia" arm is unique because it combines tailored dietary changes with fish oil and probiotics, aiming to enhance nutrition and support gut-brain health. The "Gutboost" arm emphasizes the potential benefits of probiotics and fish oil supplementation, which may influence mental health by altering gut microbiota composition. Lastly, the "Gutless" arm explores the impact of fish oil with a placebo probiotic, distinguishing the effects of fish oil alone. These approaches could pave the way for more holistic and accessible options for managing perinatal mental health, potentially reducing reliance on medications.

What evidence suggests that this trial's treatments could be effective for perinatal depression and anxiety?

Research has shown that dietary changes can significantly impact depression and anxiety during and after pregnancy. In this trial, participants in the "Gutopia" arm will receive dietary modification, fish oil, and probiotics. One study found that only 6% of women who took dietary supplements showed signs of major depression, compared to 15% who took a placebo, a harmless pill with no active ingredients. Participants in the "Gutboost" arm will receive a daily probiotic and fish oil supplement. Omega-3 fatty acids in fish oil have been proven to improve depression in pregnant and new mothers. Participants in the "Gutless" arm will receive fish oil and a placebo probiotic. Other studies suggest that probiotics, beneficial bacteria for the gut, can also help reduce anxiety and depression, supporting mental health during pregnancy. These treatments work by influencing the gut-brain connection, which links gut health to mood and mental well-being. ^{1 2 3 5 6}

Who Is on the Research Team?

Neda Ebrahimi, PhD

Principal Investigator

Canadian College of Naturopathic Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0002916523463150

Dietary interventions for perinatal depression and anxiety This systematic review and meta-analysis identified 36 RCTs that assessed the effectiveness of dietary interventions in the treatment of perinatal depression ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6865932/

The role of diet and nutritional supplementation in perinatal ... Results reported for one study site showed 6% of the supplementation group and 15% of the placebo group screened positive for major depressive disorder. This ...

3. ajcn.nutrition.org ajcn.nutrition.org/article/S0002-9165(23)46315-0/fulltext

Dietary interventions for perinatal depression and anxiety We performed a systematic review and meta-analysis to assess the effectiveness of dietary interventions for the treatment of perinatal depression and/or ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10463670/

A network analysis of nutritional markers and maternal ... This study aims to explore relationships between nutrition during pregnancy and perinatal maternal depression and anxiety symptoms using network analyses.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0165032725005117

Diet quality and depression risk: A systematic review ... This study aims to estimate the evidence for the prospective association between diet quality and depression.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8427431/

Association Between Dietary Quality and Postpartum ... This study aimed to examine the association between dietary quality and postpartum depression in Chinses lactating women.