Micronutrients as a Treatment for Antenatal Depression: Results from “NUTRIMUM”, an RCT using vitamins and minerals to treat depressive symptoms during pregnancy

Researchers from Te Puna Toiora (Mental Health and Nutrition Research Lab) have published a new study investigating whether broad-spectrum micronutrients (vitamins and minerals) can improve symptoms of depression during pregnancy.

0
64
AI generated illustration of pregnant woman surrounded by vtitamins and nutrition

Dr Hayley Bradley

 

Researchers from Te Puna Toiora (Mental Health and Nutrition Research Lab) have published a new study investigating whether broad-spectrum micronutrients (vitamins and minerals) can improve symptoms of depression during pregnancy.

Antenatal depression affects between 15-21% of pregnant women worldwide (1) and increases the risk pregnancy, birth, and neonatal complications as well as postnatal depression (2-4). It has also been associated with emotional, behavioural and developmental problems in the offspring (5).

Psychological therapy and antidepressant medication are recommended treatments for depression during pregnancy; however, barriers and risks associated with these treatments limit the number of women who access them (6-9). Alternative interventions that are accessible and safe are therefore needed.

Previous research has shown benefit of broad-spectrum micronutrients for the treatment of depression in non-pregnant populations (10-13,15) and other studies have found beneficial effects of micronutrients on mood and quality of life during pregnancy (14).

Until now, there have been no published randomised controlled trials (the gold standard method of assessing whether a treatment works) specifically designed to assess the efficacy and safety of broad-spectrum micronutrients on symptoms of antenatal depression and overall functioning.

The NUTRIMUM trial (16) recruited 88 women in their second trimester of pregnancy who reported depressive symptoms. They were randomly allocated to receive capsules of either broad-spectrum micronutrients or an active placebo containing iodine and riboflavin for a 12-week period.

The first key finding was that we found a treatment effect. This means that, overall, the group of people who were taking the micronutrients did better than the group who were taking the placebo when considering global improvement of change. This kind of measure considers all noted changes based on both self and clinician observations and can include sleep, mood regulation, coping, anxiety, and resilience. This is an important finding given the scepticism associated with taking micronutrients to treat mental health difficulties. Because no one knew whether they were taking the real thing or the placebo, this outcome is regarded highly in the scientific literature.

Interestingly, both groups improved on the self-report measure of mood, with over three quarters of participants no longer reported depressive symptoms at the end of the trial. Also, participants in the micronutrient group had significantly greater improvements in overall symptoms: 69% of participants taking the micronutrients rated themselves as “much” or “very much” improved as compared with 39% taking the placebo. Participants taking the micronutrients also experienced significantly greater improvements in sleep and overall day-to-day functioning compared to participants taking the placebo.

The second key finding was that there were no group differences in reported side effects or measures of safety. This means there were no adverse effects associated with taking the micronutrients. Common side effects reported in the trial were nausea, constipation, and difficulties with sleep; however, a similar number of participants in both the placebo group and micronutrient group reported these side effects. The one side effect that trended towards more reporting in the micronutrient group was nausea and stomach issues like diarrhoea, however, this was not significantly different to the placebo group. These findings suggest that any side effects reported were not specific to the micronutrients but may have more to do with taking the capsules, pregnancy or close monitoring of these types of symptoms over time. The lack of side effects is great news, as medications prescribed for depression often come with complications and can be the reason why many women do not want to take medications during pregnancy.

Micronutrients were particularly helpful for participants who have taken psychiatric medication in the past and/or who were more susceptible to mental health struggles due to their patterns of thinking, behaviour, emotions and relating to others. However, participants who did not demonstrate these same difficulties tended to do well regardless of whether they were taking the micronutrients or the active placebo which means that general care or time may be sufficiently beneficial for these women. This effect is illustrated in the figure below:

 

graph of results

 

Also of note, retention in the study was good (81%), compliance excellent (>90%), the blind well maintained and there were no group differences in the emergence of suicidal ideation. Outcomes were comparable to those obtained using psychotherapy but achieved with much less contact; response rates to psychotherapy range from 33-71% (17-19). However, these psychotherapy studies had typically smaller sample sizes, a higher number of dropouts and greater chance of bias, for example, the lack of blinding in psychotherapy trials. There are no medication RCTs to compare these results.

The findings of this study demonstrated that micronutrients may be a safe and helpful treatment option for women struggling with low mood during pregnancy, especially for those who are more susceptible to mental health difficulties or who have trialled psychiatric medication in the past. The researchers at Te Puna Toiora are hoping the trial will be replicated in the near future to confirm the study findings.

This work couldn’t have been completed without the time and commitment from our all our amazing participants and financial support from the University of Canterbury Research Funds, University of Canterbury Foundation, The Foundation for Excellence in Mental Health Care, The Nurture Foundation for Reproductive Research, St George’s Hospital (Christchurch, New Zealand) and The Waterloo Foundation. No funding was received from the manufacturer of the micronutrients.

We are also grateful to the companies that donated products for the gift hamper including Tui Balms, Noopi, Eco Store, Earthwise, Treasures, Nutrimetics, Sanitarium, Portrait Studio, and Pead PR.

References

  1. Yin X, Sun N, Jiang N, Xu X, Gan Y, Zhang J, et al. Prevalence and associated factors of antenatal depression: systematic reviews and meta-analyses. Clin Psychol Rev 2021; 83: 101932.
  2. Grote NK, Bridge JA, Gavin AR, Melville JL, Iyengar S and Katon WJ. A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch Gen Psychiatry 2010; 67: 1012-1024. DOI: doi:10.1001/archgenpsychiatry.2010.111
  3. Pampaka D, Papatheodorou SI, AlSeaidan M, Al Wotayan R, Wright RJ, Buring JE, et al. Postnatal depressive symptoms in women with and without antenatal depressive symptoms: results from a prospective cohort study. Archives of Women’s Mental Health 2019; 22: 93-103.
  4. Jahan N, Went TR, Sultan W, Sapkota A, Khurshid H, Qureshi IA, et al. Untreated Depression During Pregnancy and Its Effect on Pregnancy Outcomes: A Systematic Review. Cureus 2021; 13.
  5. Gentile S. Untreated depression during pregnancy: Short-and long-term effects in offspring. A systematic review. Neuroscience 2017; 342: 154-166.
  6. Malhi GS, Bell E, Bassett D, Boyce P, Bryant R, Hazell P, et al. The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust N Z J Psychiatry 2021; 55: 7-117.
  7. Goodman JH. Women’s attitudes, preferences, and perceived barriers to treatment for perinatal depression. Birth 2009; 36: 60-69. DOI: doi:10.1111/j.1523-536X.2008.00296.x.
  8. Kautzky A, Slamanig R, Unger A and Höflich A. Neonatal outcome and adaption after in utero exposure to antidepressants: A systematic review and meta‐analysis. Acta Psychiatr Scand 2022; 145: 6-28.
  9. Petersen I, McCrea RL, Lupattelli A and Nordeng H. Women’s perception of risks of adverse fetal pregnancy outcomes: a large-scale multinational survey. BMJ Open 2015; 5: e007390.
  10. Blampied M, Bell C, Gilbert C and Rucklidge JJ. Broad spectrum micronutrient formulas for the treatment of symptoms of depression, stress, and/or anxiety: a systematic review. Expert Rev Neurother 2020; 20: 351-371. DOI: 10.1080/14737175.2020.1740595.
  11. Rucklidge JJ, Johnstone JM and Kaplan BJ. Nutrition Provides the Essential Foundation for Optimizing Mental Health. Evidence-Based Practice in Child and Adolescent Mental Health 2021; 6: 131-154. DOI: 10.1080/23794925.2021.1875342.
  12. Rucklidge JJ, Frampton CM, Gorman B and Boggis A. Vitamin-mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial. Br J Psychiatry 2014; 204: 306-315. 2014/02/01. DOI: 10.1192/bjp.bp.113.132126.
  13. Blampied FM, Tylianakis JM, Bell C, Gilbert C and Rucklidge JJ. Efficacy and safety of a vitamin-mineral intervention for symptoms of anxiety and depression in adults: A randomised placebo-controlled trial “NoMAD”. J Affect Disord 2023 20230531. DOI: 10.1016/j.jad.2023.05.077.
  14. Smith Fawzi M, Kaaya S, Mbwambo J, Msamanga G, Antelman G, Wei R, et al. Multivitamin supplementation in HIV‐positive pregnant women: impact on depression and quality of life in a resource‐poor setting. HIV Med 2007; 8: 203-212
  15. Blampied M, Tylianakis JM, Bell C, Gilbert C, and Rucklidge, J J. Efficacy and safety of a vitamin-mineral intervention for symptoms of anxiety and depression in adults: A randomised placebo-controlled trial “NoMAD”. J Affective Disorders2023; 339: 954-964.
  16. Bradley HA, Moltchanova E, Mulder RT, Dixon L, Henderson J, Rucklidge JJ. Efficacy and safety of a mineral-vitamin treatment on symptoms of antenatal depression: a 12-week fully blinded randomised placebo-controlled trial (NUTRIMUM Trial). BJPsychOpen. 2024. https://doi.org/10.1192/bjo.2024.706
  17. Forsell E, Bendix M, Holländare F, von Schultz BS, Nasiell J, Blomdahl-Wetterholm M, et al. Internet delivered cognitive behavior therapy for antenatal depression: A randomised controlled trial. J Affect Disord 2017; 221: 56-64.
  18. Spinelli MG, Endicott J, Leon AC, Goetz RR, Kalish RB, Brustman LE, et al. A controlled clinical treatment trial of interpersonal psychotherapy for depressed pregnant women at 3 New York City sites. J Clin Psychiatry 2013; 74: 3725.
  19. Spinelli MG and Endicott J. Controlled clinical trial of interpersonal psychotherapy versus parenting education program for depressed pregnant women. Am J Psychiatry 2003; 160: 555-562.