Efficacy and acceptability of vitamin D supplements for depressed patients: A systematic review and meta-analysis of randomized controlled trials

Objectives: This systematic review and meta-analysis synthesized the evidence from randomized controlled trials comparing vitamin D and placebo in reducing depressive symptoms and contributing to all-cause dropout rates.

Methods: Inclusion criteria were randomized controlled trials comparing reduced depression between depressed patients receiving vitamin D and those receiving placebo. We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials through January 2022.

Results: Eighteen trials (1980 participants, median age 39 y) were included in the meta-analysis. Vitamin D supplements were significantly superior to placebo in reducing depression (standardized mean difference = -0.49; 95% confidence interval [CI], -0.75 to -0.23; I² = 81%). Depressed adults (standardized mean difference = -0.70; 95% CI, -1.09 to -0.31) responded to vitamin D significantly better than children and adolescents (standardized mean difference = 0.10; 95% CI -0.27 to 0.47). Vitamin D administered as bolus doses (oral intermittent high doses or intramuscular single high dose) appeared to be more effective than that taken daily by the oral route (P < 0.01). Patients with more severe depression tended to respond better than those with less severity (P = 0.053). We found no moderating effect of concurrent antidepressant use, presence of major depressive disorder diagnosis, physical comorbidity, sex, duration and doses of vitamin D supplement, serum 25-hydroxyvitamin D levels at baseline, and changes in serum 25-hydroxyvitamin D levels in the vitamin D group. Dropout rates were indifferent between the groups (17 trials; risk ratio = 0.84; 95% CI, 0.6-1.16; I² = 0).

Conclusions: Heterogeneous data suggested that vitamin D supplements are effective and safe for depressed patients.