A randomized, double-blind, placebo-controlled, 12-week trial of vitamin D augmentation in major depressive disorder associated with vitamin D deficiency

Background: Randomized controlled trials (RCTs) of vitamin D (VitD) supplementation for depression have yielded inconsistent results. We conducted the first RCT of VitD supplementation with multipoint serum 25(OH)D assessments in major depressive disorder (MDD) patients with concurrent severe VitD deficiency.

Methods: We randomized antidepressant-free depressed adults with mean baseline 25(OH)D of 11.5 ng/ml to VitD (60,000 IU every 5 days; n = 31) or placebo (n = 28) for 12 weeks. All patients also received escitalopram (10-20 mg/day). Patients were rated at baseline and at the end of weeks 4, 8, and 12. Serum 25(OH)D was estimated at baseline, week 8, and week 12.

Results: In an intent-to-treat analysis, mean Hamilton Depression Scale scores dropped from 25.7 to 5.7 and from 25.8 to 5.0 in VitD and placebo groups, respectively (primary outcome; P = 0.92). VitD and placebo groups did not differ on other objective and subjective ratings of depression, or on global ratings. Similar findings characterized completer analyses. No significant correlations were observed between 25(OH)D levels and depression ratings across the course of the study. Importantly, endpoint escitalopram doses were 4 mg/day higher in placebo than in VitD patients, and 4 mg/day higher in VitD deficient than in VitD sufficient patients.

Limitations: A ceiling effect with escitalopram may have prevented the discovery of benefits with VitD supplementation.

Conclusions: VitD supplementation does not improve antidepressant outcomes with flexibly dosed escitalopram. VitD deficient depressed patients may require higher antidepressant doses to experience benefits similar to those whose deficiency is corrected by VitD supplementation.