Root-Cause Treatment for Depression


José is on his third antidepressant, with no relief. He asks you what else he can try. How do you work with patients like José?

Variable reports on the efficacy of antidepressants compared to placebo,1,2 combined with the high prevalence of depression,3,4 has left many clinicians challenged about how to help patients with depression. According to one report, 42% of doctors had a hard time differentiating between unhappiness and clinical depression.5 What’s more, clinicians differ greatly in how they diagnose depression—from using checklists to using “gut sense.”6 Perhaps due to lack of time or the inherent difficulties of diagnosing it, some clinicians are not inquiring much or at all about depression.7

When several prescriptions fail, the clinical encounter can seem as hopeless as the patient feels. Depression is a multi-factorial condition with a large number of potential antecedents and triggers. Given the wide range of potential causes and factors that influence depression, how can you get to the root cause for an individual patient? At IFM’s Energy Advanced Practice Module (APM), one lecture delves into the considerations and labs you can use to pinpoint the causes of depression for each individual and treat it at its roots.

For patients like José, who have tried several antidepressants to no avail, other methods may yield better results. Testing his fatty acids may indicate that he is deficient and would respond well to EPA treatment (like many others8-10). If José was a woman who experienced depression after giving birth, zinc could be playing a role in postnatal depression.11 Oral magnesium supplementation may be helpful, as those who ingest more magnesium have a lower incidence of depression.12,13 Exercise and movement are also not to be overlooked. Research shows that physical activity alone can treat mild to moderate depression symptoms.14-16

Functional Medicine emphasizes treating the root cause for each individual patient. Learn more about this approach in our free, interactive, online course, Introduction to Functional Medicine.



  1. Barbui C, Cipriani A, Patel V, Ayuso-Mateos JL, van Ommeren M. Efficacy of antidepressants and benzodiazepines in minor depression: systematic review and meta-analysis. British J Psychiatry. 2011;198(1):11-16. doi:1192/bjp.bp.109.076448.
  2. Jakobsen JC, Katakam KK, Schou A, et al. Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis. BMC Psychiatry. 2017;17(1):58. doi:1186/s12888-016-1173-2.
  3. Lara Muñoz Mdel C, Jacobs EA, Escamilla MA, Mendenhall E. Depression among diabetic women in urban centers in Mexico and the United States of America: a comparative study. Rev Panam Salud Publica. 2014;36(4):225-231.
  4. Inglis AJ, Hippman CL, Carrion PB, Honer WG, Austin JC. Mania and depression in the perinatal period among women with a history of major depressive disorders. Arch Womens Ment Health. 2014;17(2):137-143. doi:1007/s00737-013-0408-1.
  5. Botega NJ, Silveira GM. General practitioners attitudes towards depression: a study in primary care setting in Brazil. Int J Soc Psychiatry. 1996;42(3):230-237. doi:1177/002076409604200307.
  6. Thomas-MacLean R, Stoppard J, Miedema BB, Tatemichi S. Diagnosing depression: there is no blood test. Can Fam Physician. 2005;51:1102-1103.
  7. Keeley RD, West DR, Tutt B, Nutting PA. A qualitative comparison of primary care clinicians’ and their patients’ perspectives on achieving depression care: implications for improving outcomes. BMC Fam Pract. 2014;15:13. doi:1186/1471-2296-15-13.
  8. Sublette ME, Ellis SP, Geant AL, Mann JJ. Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry. 2011;72(12):1577-1584. doi:4088/JCP.10m06634.
  9. Mozaffari-Khosravi H, Yassini-Ardakani M, Karamati M, Shariati-Bafghi SE. Eicosapentaenoic acid versus docosahexaenoic acid in mild-to-moderate depression: a randomized, double-blind, placebo-controlled trial. Eur Neuropsychopharmacol. 2013;23(7):636-644. doi:1016/j.euroneuro.2012.08.003.
  10. Carney RM, Steinmeyer BC, Freedland KE, Rubin EH, Rich MW, Harris WS. Baseline blood levels of omega-3 and depression remission: a secondary analysis of data from a placebo-controlled trial of omega-3 supplements. J Clin Psychiatry. 2016;77(2):e138-143. doi:4088/JCP.14m09660.
  11. Roomruangwong C, Kanchanatawan B, Sirivichayakul S, Mahieu B, Nowak G, Maes M. Lower serum zinc and higher CRP strongly predict prenatal depression and physio-somatic symptoms, which all together predict postnatal depressive symptoms. Mol Neurobiol. 2017;54(2):1500-1512. doi:1007/s12035-016-9741-5.
  12. Derom ML, Sayón-Orea C, Martínez-Ortega JM, Martínez-González MA. Magnesium and depression: a systematic review. Nutr Neurosci. 2013;16(5):191-206. doi:1179/1476830512Y.0000000044.
  13. Yary T, Aazami S, Soleimannejad K. Dietary intake of magnesium may modulate depression. Biol Trace Elem Res. 2013;151(3):324-329. doi:1007/s12011-012-9568-5.
  14. Hallgren M, Kraepelien M, Öjehagen A, et al. Physical exercise and internet-based cognitive-behavioural therapy in the treatment of depression: randomised controlled trial. Br J Psychiatry.2015;207(3):227-234. doi:1192/bjp.bp.114.160101.
  15. McCurdy AP, Boulé NG, Sivak A, Davenport MH. Effects of exercise on mild-to-moderate depressive symptoms in the postpartum period: a meta-analysis. Obstet Gynecol. 2017;129(6):1087-1097. doi:1097/AOG.0000000000002053.
  16. Josefsson T, Lindwall M, Archer T. Physical exercise intervention in depressive disorders: meta-analysis and systematic review. Scand J Med Sci Sports. 2014;24(2):259-272. doi:1111/sms.12050.

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