Efficacy of vitamin D supplementation in major depression: A meta-analysis of randomized controlled trials

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Authors: F. Vellekkatt and V. Menon
Date: April-June 2019
From: Journal of Postgraduate Medicine(Vol. 65, Issue 2)
Publisher: Medknow Publications and Media Pvt. Ltd.
Document Type: Report
Length: 4,118 words
Lexile Measure: 1620L

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Byline: F. Vellekkatt, V. Menon

Background: There is a need to develop and periodically evaluate new treatment strategies in major depression due to the high burden of nonresponse and inadequate response to antidepressants. Aim: We aimed to assess the effect of vitamin D supplementation on depression symptom scores among individuals with clinically diagnosed major depression. Materials and Methods: Electronic search of databases was carried out for published randomized controlled trials in English language, peer-reviewed journals from inception till August 2017. Outcome measure used for effect size calculation was depression symptom scores. Effect sizes for the trials were computed using standardized mean difference (Cohen's d), and I2 test was used to assess sample heterogeneity. Pooled mean effect sizes were derived using both fixed and random-effects model. Critical appraisal of studies was done using the Cochrane risk of bias assessment tool. Results: A total of four trials involving 948 participants were included in the study. In three trials, the intervention group received oral vitamin D supplementation whereas in one parenteral vitamin D was given. Pooled mean effect size for vitamin D supplementation on depressive symptom ratings in major depression was 0.58 (95% confidence interval, 0.45-0.72). The I2 value for heterogeneity was 0 suggesting low heterogeneity among studies. Egger plot intercept indicated minimal publication bias. Conclusion: Vitamin D supplementation favorably impacted depression ratings in major depression with a moderate effect size. These findings must be considered tentative owing to the limited number of trials available and inherent methodological bias noted in few of them.


Worldwide, it is estimated that more than 300 million people are affected by depression.[1] Unipolar depressive disorders were the third leading cause of disability-adjusted life years (DALY) lost based on the WHO report of 2004,[2] and were projected to rise to the second leading cause of DALY across all age group by 2020.[3] Despite burgeoning research on its neurobiological basis in the last decade, a significant gap exists in our understanding of the origins and progression of depressive disorders. Studies have suggested that depression may have multifactorial origins involving dysfunction of multiple brain areas and alteration in many biochemical functions such as gene expression and immune response.[4],[5] However, classical antidepressants mainly function by correction of monoamine imbalance. This may be a possible reason for the low rates of treatment-induced remission often noted in clinical trials on depressed patients.[6],[7] Therefore, there is a pressing need to look at other treatment targets that can optimize clinical management of depression.

A growing body of literature links vitamin D to the pathophysiology of depression.[8],[9],[10],[11] This has mainly come from three lines of evidence; first, lower serum vitamin D levels in depressed persons compared to controls;[8],[10],[12],[13] second, presence of vitamin D receptors in various parts of the brain limbic system, cerebellum, and cortex,[14],[15],[16] which controls emotions and behavior; and third, the important modulatory role that vitamin D plays in regulating immunoinflammatory pathways that have been found to be relevant to the pathophysiology of depression.[5],[17],[18] This evidence has spawned a series of trials that...

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Gale Document Number: GALE|A584164898