Supplements for sadness: Safe or senseless?

Pediatric depression is increasingly recognized in the United States. The Centers for Disease Control and Prevention estimates that 1 in 20 children is diagnosed with anxiety or depression.¹ When discussing treatment options, patients or caregivers often express an interest in complementary and alternative medicine (CAM). Nutritional supplements are touted to the public as less toxic or more effective than conventional drugs because they are “natural” and their efficacy is based on knowledge gained over thousands of years.² Due to the black-box warnings on antidepressants issued by the US Food and Drug Administration (FDA) and recent negative media generated toward the scientific community, parents may shy away from evidence-based medications for their children.^3,4 Providers play an important role in explaining the risks and benefits associated with nutritional supplements as well as prescription medications.

Guideline recommendations

Only 2 drugs, fluoxetine and escitalopram, are approved by the FDA to treat childhood depression.^5,6 Nevertheless, consensus guidelines recommend fluoxetine, citalopram, and sertraline as first-line treatments for moderate to severe depression in pediatric patients. Venlafaxine, bupropion, mirtazapine, duloxetine, and lithium are alternatives for individuals with inadequate clinical response.⁷

Pediatric practice guidelines do not suggest herbal supplements as treatment options. However, the American Psychiatric Association’s (APA) depression guideline discusses CAM. The guideline states that folate is a reasonable, low-risk, adjunctive strategy but more data is necessary to establish a role for St. John’s wort, S-adenosyl methionine (SAMe), and omega-3 fatty acids (O3FA).⁸

Necessary precautions

Federal law does not require companies to prove safety or efficacy of dietary supplements prior to manufacturing.⁹ Because rigorous clinical testing is not mandated, dosing is often recommended upon small, poorly designed studies. Significant uncertainty surrounds the long-term consequences of exposure to some herbal remedies for which the toxicity profiles are incompletely characterized.²

There is also considerable risk of delaying therapy with an evidence-based medication, especially for suicidal patients. Additionally, drug-drug interactions may occur with herbal supplements and prescription medications, rendering pharmacotherapy ineffective or even dangerous. Finally, although supplements are readily available over-the-counter, they are typically not covered by insurance. Families may face significant financial burden when purchasing herbal products from a reputable source.

The Table reviews these over-the-counter supplements and the corroborating study data for each product.

Whereas there may be theoretical benefit or literature demonstrating positive outcomes in different populations, the following supplements were excluded from this review due to a lack of data in pediatric depression: acetyl-l-carnitine, B vitamins, dehydroepiandrosterone, folic acid, glutamine, 5-hydroxytryptophan, inositol, iron, phenylalanine, probiotics, saffron, turmeric, and tyrosine.

References:

1. Bitsko RH, Holbrook JR, Ghandour RM, et al. Epidemiology and impact of health care provider–diagnosed anxiety and depression among US children. J Dev Behav Pediatr. 2018;39(5):395-403.

2. Woolf AD. Herbal remedies and children: do they work? Are they harmful? Pediatrics. 2003;112(1 pt 2):240-246.

3. Friedman RA. Antidepressants’ black box warning--10 years later. N Engl J Med. 2014;371(18):1666-1668.

4. Tsipursky G. (Dis)trust in science. Scientific American. Available at: https://blogs.scientificamerican.com/observations/dis-trust-in-science/. Published July 5, 2018. Accessed February 14, 2019.

5. US National LIbrary of Medicine. Label: Prozac (fluoxetine hydrochloride capsule): drug label information. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c88f33ed-6dfb-4c5ebc01-d8e36dd97299. Accessed February 14, 2019.

6. US National LIbrary of Medicine. Label: Lexapro (escitalopram oxalate tablet): drug label information. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=23ff2d62-b5ff-4837-8b54-439a65609d90. Accessed February 14, 2019.

7. Hughes CW, Emslie GJ, Crismon ML, et al; Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder. Texas Children’s Medication Algorithm Project: update from Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder. J Am Acad Child Adolesc Psychiatry. 2007;46(6):667-686.

8. Gelenberg AJ, Freeman MP, Markowitz JC, et al. Practice guideline for the treatment of patients with major depressive disorder. 3rd ed. American Psychiatric Association. 2010;83-92.

9. US Food and Drug Administration. FDA 101: Dietary supplements. Available at: https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm050803.htm. Updated November 6. 2017. Accessed February 14, 2019.

10. Lopresti AL. A review of nutrient treatments for paediatric depression. J Affect Disord. 2015;181:24-32. 

11. Therapeutic Research Center. Natural Medicines. Available at: https://naturalmedicines.therapeuticresearch.com/. Accessed February 14, 2019.

12. Fristad MA, Vesco AT, Young AS, et al. Pilot randomized controlled trial of omega-3 and individual-family psychoeducational psychotherapy for children and adolescents with depression. J Clin Child Adolesc Psychol. 2016:1-14. Epub ahead of print.

13. Gabbay V, Freed RD, Alonso CM, et al. A double-blind placebo-controlled trial of omega-3 fatty acids as a monotherapy for adolescent depression. J Clin Psychiatry. 2018;79(4).

14. McNamara RK, Strimpfel J, Jandacek R, et al. Detection and treatment of long-chain omega-3 fatty acid deficiency in adolescents with SSRI-resistant major depressive disorder. Pharma Nutrition. 2014;2(2):38-46.

15. Nemets H, Nemets B, Apter A, Bracha Z, Belmaker RH. Omega-3 treatment of childhood depression: a controlled, double-blind pilot study. Am J Psychiatry. 2006;163(6):1098-1100.

16. Trebaticka J, Hradecna Z, Bohmer F, et al. Emulsified omega-3 fatty-acids modulate the symptoms of depressive disorder in children and adolescents: a pilot study. Child Adolesc Psychiatry Mental Health. 2017;11:30.

17. Schaller JL, Thomas J, Bazzan AJ. SAMe use in children and adolescents. Eur Child Adolesc Psychiatry. 2004;13(5):332-334.

18. Hubner WD, Kirste T. Experience with St John’s wort (Hypericum perforatum) in children under 12 years with symptoms of depression and psychovegetative disturbances. Phytother Research. 2001;15(4):367-370.

19. Findling RL, McNamara NK, O’Riordan MA, et al. An open-label pilot study of St. John’s wort in juvenile depression. J Am Acad Child Adolesc Psychiatry. 2003;42(8):908-914.

20. Simeon J, Nixon MK, Milin R, Jovanovic R, Walker S. Open-label pilot study of St. John’s wort in adolescent depression. J Child Adolesc Psychopharmacol. 2005;15(2):293-301.

21. Amr M, El-Mogy A, Shams T, Vieira K, Lakhan SE. Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. Nutr J. 2013;12:31. 

22. Bahrami A, Mazloum SR, Maghsoudi S, et al. High dose vitamin D supplementation is associated with a reduction in depression score among adolescent girls: a nine-week follow-up study. J Diet Suppl. 2018;15(2):173-182.

23. Hogberg G, Gustafsson SA, Hallstrom T, Gustafsson T, Klawitter B, Petersson M. Depressed adolescents in a case-series were low in vitamin D and depression was ameliorated by vitamin D supplementation. Acta Paediatrica. 2012;101(7):779-783.

24. DiGirolamo AM, Ramirez-Zea M, Wang M, et al. Randomized trial of the effect of zinc supplementation on the mental health of school-age children in Guatemala. Am J Clin Nutr. 2010;92(5):1241-1250.