Clinical Edge

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Vitamin D Supplementation Improves MDD Symptoms

Key clinical point: Vitamin D supplementation improves symptoms of major depressive disorder (MDD), especially in female patients, through a serotonin-dependent mechanism.

Major finding: The Beck depression inventory (BDI) scores improved significantly after vitamin D supplementation in female patients with moderate, severe, and extreme depression (P less than .05), whereas BDI scores improved only in male patients with severe depression (P less than .05). Supplementation increased serum serotonin levels significantly in both sexes.

Study details: Randomized study of patients treated with oral vitamin D plus standard of care (n=49) vs. standard of care alone (n=13) for three months.

Disclosures: The study was supported by the deanship of scientific research–King Abdulaziz University, Saudi Arabia. The authors declared no conflicts of interest.


Alghamadi et al’s randomized control trial examines the important question of whether vitamin D3 (50000 iu) supplementation augmentation over three months improves standard care of major depression. Sixty two men and women who received standard care (psychological support with antidepressant medication) were randomized into receiving vitamin D3 supplementation (49 patients) or standard care alone (13 patients). In comparison to the group who received standard care, some subgroups of the vitamin D3 treatment cohort improved: BDI scores in women with moderate, severe, and extreme depression improved (P less than .05), whereas BDI scores improved only in male patients with severe depression (P less than .05). Multiple comparisons of subgroups based on gender and depression severity) were made. Without a Bonferroni correction for multiple comparisons, a type II error cannot be ruled out: The results are preliminary and may not be valid.

Systematic reviews in the past five years have examined whether vitamin D supplementation alone, or as augmentation to depression treatment, improves depression. These reviews, including the most recent (Parker et al, 20171) found the evidence inconclusive so far. Alghamadi et al’s study findings, though interesting, do not clarify whether vitamin D3 supplementation augments standard depression treatment. High quality future studies are still needed.

Gita Ramamurthy, MD, FRCP (C)

Director - Psychiatric Consultation-Liaison Service

SUNY Upstate Medical University

  1. Parker GB, Brotchie H, Graham RK. Vitamin D and depression. J Affect Disord. 2017;208:56-61.


Alghamdi S et al. J Mol Neurosci. 2019 Dec 13. doi: 10.1007/s12031-019-01461-2.