Depression is a common psychiatric disease that particularly affects older adults, at 15-20% of the US population.1 Yet despite this, a groundbreaking study in 2018 found that only a small fraction of patients diagnosed with depression actually start treatment—approximately one-third.2
Only 1/3 of patients diagnosed with depression start treatment.
For those who do adhere to antidepressant therapies, treatment of the acute phase of major depressive disorder (MDD) led to a greater number of adverse events in patients 65 and over, according to a 2019 systematic review.1 Antidepressants included in the study were the following:
- Selective serotonin reuptake inhibitors (SSRIs)
- Serotonin norepinephrine reuptake inhibitors (SNRIs)
Specifically, the reports found that SSRIs and SNRIs led to a greater number of study withdrawals due to adverse events, and duloxetine increased the risk of falls.1
Non-adherence to antidepressants is also common.3 A 2017 survey found that 68% of the females were non-adherent to their prescribed antidepressant therapy.3 Forgetfulness was the main reason for missing doses. Another study showed that antidepressant non-adherence is common among veterans, with ineffectiveness and side effects as commonly reported reasons.4
When several different prescriptions fail or the patient does not adhere to the prescribed treatment, 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. How can you get to the root cause for an individual patient? What are some alternatives to antidepressant medications?
The Path Forward: Alternatives to Antidepressants
The Functional Medicine model emphasizes a multi-pronged approach to health and wellness, engaging patients in a therapeutic partnership that recognizes that the current conventional paradigm does not optimally address the needs of patients with depressive symptoms. In the following video, IFM educator Patrick Hanaway, MD, talks about how a clinician might unravel the root cause of depression by looking at several factors, including vitamin D and other vitamins, amino acids, and minerals—as well as the gut microbiome.
Clearly, variable reports on the efficacy of antidepressants,5,6 combined with the high prevalence of depression,7,8 have left many clinicians challenged about how to help patients. According to one report, 42% of doctors had a hard time differentiating between unhappiness and clinical depression.9 What’s more, clinicians differ greatly in how they diagnose depression—from using checklists to using “gut sense.”10 Perhaps due to lack of time or the inherent difficulties of diagnosis, some clinicians are not inquiring much or at all about depression.11 But there is a wealth of medical research on the topic, and studies continue to point to the effectiveness of non-pharmacological treatments for depression.
For patients who have tried several different antidepressants to no avail, other methods like diet may yield better results.
Epidemiological studies suggest there is an association between diet and mental health.12 A 2019 study found that long-term adherence to a healthy diet may offer protection against recurrent depressive symptoms.13 Analyses were conducted on a sample of 4,949 men and women, and diet scores were calculated using data collected from food frequency questionnaires repeated over 11 years of exposure. Higher scores on the Alternative Healthy Eating Index-2010, Dietary Approaches to Stop Hypertension, and transformed Mediterranean diet were associated with a lower risk of recurrent depressive symptoms.13
Evidence suggests that dietary or supplemented intake of other nutrients, such as those listed below, can be protective or reduce depressive symptoms:
- Vitamin K14
- Fatty acids15,16,17
- Zinc (postpartum depression)18
Exercise and movement are also not to be overlooked. Research suggests that physical activity alone can treat mild to moderate depression symptoms.21,22,23 A 2015 cross-sectional national data study found that higher physical activity levels were associated with fewer self-reported days of poor mental health.24 Another large cohort study found that regular leisure-time exercise is associated with reduced incidence of future depression; it was predicted that 12% of future cases of depression could have been prevented if all participants had engaged in at least one hour of physical activity each week.25 Accumulating evidence also suggests that tai chi can significantly regulate emotion and relieve the symptoms of depressive disorders.26
Depression is a common and complex mood disorder that can severely affect a patient’s quality of life and even their family dynamic. Sources of distress can be biological, psychological, and/or social, and in the Functional Medicine model, it is incumbent upon the clinician to unravel the root cause of depression in order to address it effectively. Functional Medicine tools like the timeline, as well as other resources, can help the patient cope, manage, and support a path to recovery.
- Sobieraj DM, Baker WL, Martinez BK, et al. Adverse Effects of Pharmacologic Treatments of Major Depression in Older Adults: Comparative Effectiveness, No. 215. Agency for Healthcare Research and Quality; 2019. doi:10.23970/AHRQEPCCER215
- Waitzfelder B, Stewart C, Coleman KJ, et al. Treatment initiation for new episodes of depression in primary care settings. J Gen Intern Med. 2018;33(8):1283-1291. doi:10.1007/s11606-017-4297-2
- Shrestha Manandhar J, Shrestha R, Basnet N, et al. Study of adherence pattern of antidepressants in patients with depression. Kathmandu Univ Med J. 2017;15(57):3-9.
- Zivin K. Antidepressant non-adherence is common among veterans, with ineffectiveness and side effects as commonly reported reasons. Evid Based Ment Health. 2011;14(4):91. doi:10.1136/ebmh.2011.100177
- 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. Br J Psychiatry. 2011;198(1):11-16. doi:10.1192/bjp.bp.109.076448
- 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:10.1186/s12888-016-1173-2
- 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.
- 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:10.1007/s00737-013-0408-1
- 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:10.1177/002076409604200307
- Thomas-MacLean R, Stoppard J, Miedema BB, Tatemichi S. Diagnosing depression: there is no blood test. Can Fam Physician. 2005;51:1102-1103.
- 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:10.1186/1471-2296-15-13
- Nakamura M, Miura A, Nagahata T, Shibata Y, Okada E, Ojima T. Low zinc, copper, and manganese intake is associated with depression and anxiety symptoms in the Japanese working population: findings from the Eating Habit and Well-Being study. Nutrients. 2019;11(4):E847. doi:10.3390/nu11040847
- Recchia D, Baghdadli A, Lassale C, et al. Associations between long-term adherence to healthy diet and recurrent depressive symptoms in Whitehall II Study. Eur J Nutr. Published online April 13, 2019. doi:10.1007/s00394-019-01964-z
- Bolzetta F, Veronese N, Stubbs B, et al. The relationship between dietary vitamin K and depressive symptoms in late adulthood: a cross-sectional analysis from a large cohort study. Nutrients. 2019;11(4):E787. doi:10.3390/nu11040787
- 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:10.4088/JCP.10m06634
- 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:10.1016/j.euroneuro.2012.08.003
- 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:10.4088/JCP.14m09660
- 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:10.1007/s12035-016-9741-5
- 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:10.1179/1476830512Y.0000000044
- Yary T, Aazami S, Soleimannejad K. Dietary intake of magnesium may modulate depression. Biol Trace Elem Res. 2013;151(3):324-329. doi:10.1007/s12011-012-9568-5
- Hallgren M, Kraepelien M, Öjehagen A, et al. Physical exercise and internet-based cognitive-behavioural therapy in the treatment of depression: randomized controlled trial. Br J Psychiatry. 2015;207(3):227-234. doi:10.1192/bjp.bp.114.160101
- 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:10.1097/AOG.0000000000002053
- 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:10.1111/sms.12050
- Fluetsch N, Levy C, Tallon L. The relationship of physical activity to mental health: a 2015 behavioral risk factor surveillance system data analysis. J Affect Disord. 2019;253:96-101. doi:10.1016/j.jad.2019.04.086
- Harvey SB, Øverland S, Hatch SL, Wessely S, Mykletun A, Hotopf M. Exercise and the prevention of depression: results of the HUNT Cohort Study. Am J Psychiatry. 2018;175(1):28-36. doi:10.1176/appi.ajp.2017.16111223
- Kong J, Wilson G, Park J, Pereira K, Walpole C, Yeung A. Treating depression with tai chi: state of the art and future perspectives. Front Psychiatry. 2019;10:237. doi:10.3389/fpsyt.2019.00237
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