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

•This meta-analysis of 18 placebo-controlled, randomized controlled trials in depressed patients found significant efficacy of vitamin D in improving depressive symptoms.•Vitamin D supplements for depression was safe among depressed patients.•Depressed adults may respond to vitamin D supplements better than depressed children and adolescents.•Vitamin D administered as bolus doses (oral intermittent high doses or intramuscular single high dose) appeared to be more effective than the oral daily route.•Patients with more severe depression had a tendency to respond better than those with less severe depression. 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. 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. 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). Heterogeneous data suggested that vitamin D supplements are effective and safe for depressed patients.