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Teen depression and suicide rates have risen despite conventional treatments. This article reviews adjunctive interventions that may improve outcomes. A search of the National Library of Medicine database used tailored searches with combinations of specific terms. Modern lifestyle is associated with increased inflammation and pro-inflammatory cytokines leading to, for instance, hyperactivation of the hypothalamic-pituitary-adrenal axis, which promotes depression. Inflammation also increases oxidative stress, leading to mitochondrial dysfunction, also associated with depression. Diets with less probiotic-containing fermented foods change the microbiome and decrease the bio-availability of mood-regulating B vitamins crucial to neurotransmitter production. Vitamin D deficiency allows increased pro-inflammatory cytokines and disrupts mitochondrial function and monoamine production. Deficiencies/insufficiencies of magnesium, Vitamin D, and B vitamins correlate with depression severity. Deficiencies of the folate and methylation cycles may lead to treatment-resistant depression. Imbalance of omega-6 and omega-3 fatty acid intake allows more pro-inflammatory eicosanoids (prostaglandins, thromboxanes, leukotrienes) from omega-6 than anti-inflammatory eicosanoids from omega-3. Refractory youth depression may be linked to abnormalities in functional biological systems, with excessive inflammation, oxidative stress, and gut-brain issues. Mediterranean diet, vitamins/minerals, omega-3 fatty acids, methyl donors, meditation, and exercise are worth considering as adjunctive treatments. More research is needed.

The Roles of Inflammation, Oxidative Stress and the Gut-Brain Axis in Treatment Refractory Depression in Youth: Complementary and Integrative Medicine Interventions