Pilot Trial of Adjunctive Curcumin for Treatment-Resistant Bipolar Depression in Youth: Focus on Inflammation and Oxidative Stress

Introduction: While youth with bipolar disorder (BD) spend the majority of the time experiencing symptoms of depression, there are fewer evidence-based options for the pharmacological treatment of bipolar depression versus mania. Given evidence of increased inflammation and oxidative stress in BD, engaging these treatment targets may address underlying pathophysiological mechanisms. We conducted a pilot trial of curcumin, a widely available, safe nutraceutical with anti-inflammatory and antioxidative properties, for the treatment of bipolar depression in youth. Methods: Six participants with bipolar depression were enrolled and received 8 weeks of open-label curcumin. The starting dose was 500 mg daily, then increased to 500 mg twice daily at week 2, then increased to 1000 mg twice daily at weeks 3–8. Symptoms were evaluated with the Children’s Depression Rating Scale–Revised (CDRS-R), Kiddie Schedule for Affective Disorders and Schizophrenia Depression Rating Scale (DRS), and Clinical Global Impression Scale. Treatment response was defined as greater than or equal to 50% reduction in CDRS-R score. Blood biomarkers of inflammation (interferon‐gamma, interleukin-10 [IL-10], IL-8, tumor necrosis factor alpha) and oxidative stress (8-iso-prostaglandin F2alpha [8-ISO], lipid peroxidation [LPO]) were evaluated at baseline, 4 weeks, and 8 weeks. Analyses examined changes in depressive symptoms in relation to changes in biomarkers over time. Results: There were significant reductions in clinical global impression of depression severity [χ 2 (4) = 10.97, p = 0.03, W = 0.46] and overall illness severity [χ 2 (4) = 10.25, p = 0.04, W = 0.43] from baseline to 8 weeks. The most common side effects were related to the central nervous system and gastrointestinal system. From baseline to 4 weeks, greater reduction in CDRS-R scores was associated with greater reduction in 8-ISO ( r = 0.89, p = 0.02), and a greater reduction in DRS scores was associated with a greater reduction in LPO ( r = 0.82, p = 0.05). Conclusions: This trial provides preliminary evidence that the antidepressant effects of curcumin may be associated with its antioxidative properties. However, larger controlled trials are needed to evaluate the efficacy of curcumin for bipolar depression, and to examine oxidative stress markers as predictors and/or mediators of antidepressant effects.