Vitamin D supplementation did not improve effects of antidepressant medication – 12-week RCT

By Tingmin Koe

- Last updated on GMT

Supplementation with vitamin D does not improve the effects of antidepressant medication, according to a study conducted in India. © Getty Images
Supplementation with vitamin D does not improve the effects of antidepressant medication, according to a study conducted in India. © Getty Images

Related tags Vitamin d Depression India

Supplementation with vitamin D does not improve the effects of antidepressant medication, specifically escitalopram, according to a 12-week RCT conducted in India.

Findings of the clinical trial were recently published in the Journal of Affective Disorders.

Vitamin D was of interest in this study as it has been suggested to modulate the association between depression and the inflammatory response through its effect on the immune system.

It is also said to play a neuroprotective role in the brain by downregulating the proinflammatory cytokines associated with depression.  

However, the pooled results of vitamin D’s supplementation on major depression have been inconclusive.

According to the researchers, so far, there are only two studies assessing the effects of vitamin D supplementation in patients with major depression in India. Both showed beneficial effects of the vitamin D supplementation.  

Study design

The current trial took place in 2020 in the psychiatry outpatient clinic of IQRAA International Hospital and Research Center in Kerela, India.

Fifty-nine adults diagnosed with major depressive disorder and were vitamin D deficient – with a serum 25(OH)D of less than 20ng/ml were recruited.

They were then randomised into the placebo and the intervention group which took 60,000 IU of vitamin D every five days for 12 weeks. 

At the same time, all subjects were prescribed escitalopram, a medicine to treat symptoms of depression, at flexible doses of 10 to 20mg per day.  


No significant correlations were observed between vitamin D serum levels and depression ratings.  

Depression ratings were measured using the Hamilton Depression Scale, the Beck Depression Inventory, and the Montgomery Asberg Depression Rating Scale. 

With the Hamilton Depression Scale as an example, the depression rating had dropped for both groups.

For the intervention group, the score dropped progressively from 25.7 at baseline to 15.7 at week four, to 7.8 at week eight, and 5.7 by the end of the study for the intervention group.

Similarly, for the placebo group, it also dropped from the baseline of 25.8 to 14.6 at week four, 6.2 at week eight, and 5 at week 12. 

Apparently, the subjects did not follow the vitamin D intervention protocol strictly, however, the researchers noted that this would not affect their assessment of vitamin D serum levels and its association with depression ratings.

“We expected that, with the vitamin D treatment protocol that we followed, 25(OH)D levels would increase by at least 10ng/mL in the vitamin D group and by less than this value in the placebo group.

“To our surprise, at treatment endpoint, we found that 7 of 28 placebo group completers exceeded this threshold and 10 of 31 vitamin D group completers did not reach this threshold.

“This suggests that some of the placebo group patients may have taken vitamin D supplements out of protocol, and that some of the vitamin D group patients may not have taken their prescribed capsules.

“Because the patterns of rise in vitamin D levels in the placebo and vitamin D groups were contrary to our expectations based on the treatment protocol, one may expect that it would have influenced the change in primary outcome measure. In this context, our cross-sectional examination of the correlation between 25(OH)D levels and depression ratings assumes importance.”

Aside from the Hamilton Depression Scale, the researchers did not find significant relationship between serum vitamin D levels and depression ratings using the Beck Depression Inventory and the Montgomery Asberg Depression Rating Scale.

“We found that, on all clinical outcome measures, and at all assessment points in this 12-week study, vitamin D augmentation did not outperform placebo augmentation with regard to either speed or magnitude of improvement.

“We additionally found that 25(OH)D levels did not correlate with subjective and objective depression ratings at any point during the course of the study.”

Vitamin D deficient and medication

On the other hand, the researchers found that subjects who remained vitamin D deficient had to take a higher dose of the antidepressant escitalopram.

This suggested that patients who are vitamin D deficient, will need to receive a higher dose of the antidepressant medication. 

“We did find that patients whose vitamin D deficiency was left uncorrected (because they received placebo) received significantly higher doses of escitalopram, by a mean of about 4mg/day.

“These findings suggest that the correction of vitamin D deficiency is not essential for clinical recovery in antidepressant-treated MDD and that, as a novel finding in the research literature, patients with vitamin D deficiency can recover, provided that they receive adequate (higher) doses of antidepressant medication; in our study, escitalopram.”


Source: Journal of Affective Disorders

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

Authors: P.N. Suresh Kumar et al

Related news

Related products

show more

Krill oil supports six key areas of healthy aging

Krill oil supports six key areas of healthy aging

Content provided by Aker BioMarine | 26-Feb-2024 | White Paper

The global population is getting older—according to WHO by 2050 the world’s population over 60 years will double and the population above 80 years will...

Nootropics Report 2.0: Brain Health Insights

Nootropics Report 2.0: Brain Health Insights

Content provided by dsm-firmenich | 22-Feb-2024 | Insight Guide

The brain health market is constantly growing and evolving, with more consumers looking for innovative ways to support total mind and body wellness.

Revolutionizing Brain Health with BioKesum®

Revolutionizing Brain Health with BioKesum®

Content provided by Biotropics Malaysia | 20-Feb-2024 | Data Sheet

Revitalize the nootropic industry with new clinically proven herbal extract from Kesum leaves shown to improve executive memory, mood and brain markers...

Follow us


View more


Nutra Champions Podcast

Nutra Champions Podcast