Vitamin D and Depression: A Critical Appraisal of the Evidence and Future Directions

Growing evidence points to the role of vitamin D in the pathobiology and treatment of depression. However, the evidence is inconsistent in many aspects. The objectives of this narrative review were to evaluate the state of the evidence, synthesize the knowledge gaps, and formulate recommendations for more enhanced research in this growing area.

Electronic searches of MEDLINE via PubMed, Cochrane Library, and Google Scholar databases were carried out from inception till February 2019 to identify relevant English language peer-reviewed articles. Abstracts generated were systematically screened for eligibility. Included articles were grouped under three broad themes: The association between vitamin D and depression, its biological underpinnings, and trials evaluating the efficacy of vitamin D supplementation in depression. Relevant data were extracted as per a structured proforma.

A total of 61 articles were included in the present review. Overall findings were that there is a relationship between vitamin D and depression, though the directionality of this association remains unclear. The association appears to be driven by the homeostatic, trophic, and immunomodulatory effects of vitamin D. Evidence from supplementation trials suggest a more robust therapeutic effect on subjects with major depression and concurrent vitamin D deficiency.

Serum vitamin D levels inversely correlate with clinical depression, but the evidence is not strong enough to recommend universal supplementation in depression. Enriching depression treatment trials with subjects having concurrent vitamin D deficiency appears to be a potential step forward in identifying subgroups who may maximally benefit from this approach.