Adjunct Therapies for Depression: More Treatment Options

Mental health disorders, including depression and anxiety, continue to be leading causes of health-related burdens worldwide.¹ According to the World Health Organization, an estimated 5% of adults worldwide experience depression.² While depression is most acutely seen in females and young adults (aged 18-34),³ the prevalence among children and adolescents has significantly increased in recent years.⁴

Depression is a multifactorial condition that may have several different antecedents and triggers unique to each individual; as such, a singular focus on antidepressant medication therapy may not be the optimal approach. In fact, a major study published in 2018 found that only about a third of patients diagnosed with depression actually start treatment.⁵ Nonadherence to antidepressants is also common among different populations.⁶ A 2017 study found that 68% of the females surveyed did not follow their prescribed antidepressant therapy.⁷ Forgetfulness was the main reason for missing doses. A 2019 observational study of 278 older veterans with depression found that nearly a third were nonadherent to their antidepressant medication.⁸ Nonadherence was significantly associated with veterans who were Black, those who were unmarried, and those with greater medical comorbidity, level of functional impairment, and self-reported side effects.⁸

For those who adhere to antidepressant therapies, treatment of the acute phase of major depressive disorder (MDD) leads to a greater number of adverse events in patients 65 and over, according to a 2019 systematic review.⁹ Antidepressants included in the study were selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), bupropion, mirtazapine, trazodone, vilazodone, and vortioxetine. 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.⁹

Many factors can impact the efficacy of a given treatment, but with lower rates of patient engagement to medication therapy, it may not be as effective as standalone treatment. When the cycle of depression continues for your patients and they still do not find relief, the clinical encounter can seem as hopeless as the patient feels. How can you get to the root cause for an individual patient, and what adjunct therapeutic interventions may improve outcomes?

The Path Forward: Complementary Therapies

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, Patrick Hanaway, MD, IFM educator and senior advisor to IFM’s CEO, talks about how a clinician might unravel the root cause of depression by looking at several factors, including levels of vitamin D and other vitamins, amino acids, and minerals—as well as the gut microbiome.

(Video Time: 4 minutes) Dr. Hanaway is a board-certified family physician who teaches on the clinical application of nutritional biochemistry, with an emphasis on digestion, immunology, mitochondrial function, and wellness. He is also the former medical director of the Center for Functional Medicine at the Cleveland Clinic.

Clearly, variable reports on the efficacy and acceptability of antidepressants,^10,11 combined with the high prevalence of depression,^12,13 have left many clinicians challenged about how to help patients. Research continues to point to the effectiveness of non-pharmacological approaches as adjunctive treatments for depression.

DIET AND NUTRIENTS

For patients who have tried several different antidepressants to no avail, other therapeutic interventions such as diet may yield better results. Although epidemiological studies do not establish causality, some have suggested an association between diet and mental health.¹⁴ A recent study found that long-term adherence to a healthy diet may offer protection against recurrent depressive symptoms.¹⁵ 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.¹⁵

Evidence suggests that if appropriate for an individual patient, the dietary or supplemented intake of other nutrients, such as those listed below, may be protective against depression development risk or reduce depressive symptoms:

• Vitamin K¹⁶
• Zinc (postpartum depression)¹⁷
• Magnesium^18,19
• B vitamins²⁰
• Vitamin D²¹

PHYSICAL ACTIVITY AND MOVEMENT ROUTINES

Exercise and movement are also not to be overlooked. Research suggests that physical activity improves mental health and lowers the risk of depression²² and is an effective approach to treating mild to moderate depression symptoms among different patient populations.^23-26 A 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.²⁷

Accumulating evidence also suggests that tai chi and yoga can significantly regulate emotion and relieve the symptoms of depressive disorders.^28,29 A 2021 systematic review (n=19 randomized controlled trials; 1,080 total participants) and meta-analysis found that among adults with a diagnosed mental disorder, yoga interventions were associated with a greater reduction in depressive symptoms compared to controls.³⁰ Researchers noted that a higher frequency in yoga sessions per week resulted in greater reductions in symptoms.³⁰

Depression is a common and complex mood disorder that can severely affect a patient’s quality of life and even their family dynamic. The source 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 navigate a path to recovery.

Gain new tools to more effectively evaluate and personalize treatments for depression and other disorders at the Bioenergetics Advanced Practice Module (APM).