Clinical Application of Vitamin D in Depression

Vitamin D, a neuroactive steroid with widespread receptors in brain tissue, has garnered increasing attention as a potential therapeutic agent for major depressive disorder (MDD). This article reviews the current evidence on the efficacy, mechanisms of action, and clinical implications of vitamin D supplementation in MDD treatment. The antidepressant effects of vitamin D are thought to be mediated through multiple mechanisms, including modulation of the hypothalamic-pituitary-adrenal axis, enhancement of neuroplasticity, and anti-inflammatory effects. Current evidence provides mixed support for the use of vitamin D primarily as an adjunctive therapy to standard antidepressants, with limited data on its efficacy as monotherapy. Dosages ranging from 1,500 to 5,000 IU/day for 8 to 20 weeks have shown mixed efficacy in improving depressive symptoms. While generally well tolerated, monitoring is advisable to prevent potential toxicity with long-term use of high doses. The efficacy of vitamin D supplementation may be limited in certain populations such as older adults, while evidence remains inconclusive for perinatal depression. Given its favorable safety profile and potential benefits, vitamin D supplementation warrants consideration as part of a comprehensive treatment approach for MDD, particularly in patients with concurrent vitamin D deficiency. Further research is needed to establish optimal dosing regimens, treatment duration and to explore its efficacy as monotherapy. This review synthesizes the current understanding of the role of vitamin D in MDD treatment and highlights areas for future investigation. [ Psychiatr Ann . 2025;55(2):e40–e45.]