A single parenteral administration of high-dose vitamin D at the start of antidepressant therapy was associated with significant improvements in depression over 12 weeks in patients with major depression and vitamin D deficiency, according to a study published in the Journal of Psychiatric Research.

Patients with major depression and concurrent vitamin D deficiency (mean age, 35.9±11.6 years) who attended a walk-in clinic in India were included in this double-blind study. Testing of 25-hydroxyvitamin D status was performed on venous blood samples, and major depression was identified using DSM-5 criteria.

The clinical severity of depression was assessed using the Hamilton Depression rating scale-17 (HDRS-17), quality of life was assessed with the 16-item Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (QLES), and global improvement or change in disease severity was assessed using the 3-item Clinical Global Impression (CGI) severity of illness (CGI-S) observer-rated scale.

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Following these assessments, patients started standard treatment that included the use of antidepressants and psychotherapy. Patients were then randomly assigned to either standard treatment alone (n=23) or standard treatment plus a single parenteral dose of 300,000 IU of vitamin D (n=23). Vitamin D was administered once at baseline. Patients underwent testing again with the HDRS-17, QLES, and CGI-S at 12 weeks.

At the end of the 12 weeks, baseline treatment with vitamin D plus standard care was associated with significant improvement in depression scores in the intention-to-treat (ITT) population (P =.001) as well as in those who completed the trial (P =.001). In addition, adjunctive use of high-dose vitamin D was associated with improvements in QLES scores by 12 weeks in the ITT population (P <.001) and those who completed the study (P <.001).

Parental vitamin D given at the start of antidepressant therapy was also associated with improvements in the clinical severity of depression at 12 weeks in the ITT (P <.001) and complete (P <.001) analyses.

Limitations of this study included its single-center design as well as the lack of post-trial vitamin D status assessment in vitamin D-treated patients. Additionally, the durability of the observed therapeutic benefits remains unclear as the trial was for a relatively short duration.

The investigators wrote that a single dose of parental vitamin D at the start of depression treatment “may be a viable step-up strategy to enhance treatment gains in major depression with concurrent vitamin D deficiency” and could help “minimize issues with compliance” that are typically associated with regular vitamin D supplementation.


Vellekkatt F, Menon V, Rajappa M, Sahoo J. Effect of adjunctive single dose parenteral Vitamin D supplementation in major depressive disorder with concurrent vitamin D deficiency: A double-blind randomized placebo-controlled trial. J Psychiatr Res. 2020;129:250-256. doi:10.1016/j.jpsychires.2020.07.037