Both doses worked equally well — suggesting the real question isn’t how much, but whether
STUDY: Mikola T et al, Journal of Affective Disorders 2026;406:121709
STUDY TYPE: Randomized, double-blind, controlled trial
FUNDING: Finnish State Research Funding (VTR)
Background
Vitamin D deficiency is common in depression, but whether it treats depression is less clear. The trials — over 34 in all — are a confusing mix of positive and negative. This large trial asked a more granular question: does more vitamin D do more?
The Study
This Finnish double-blind RCT randomized 281 outpatients with mild-to-severe depression to either high-dose (4000 IU/day) or low-dose (400 IU/day) vitamin D as an add-on to their existing treatments for six months. The primary outcome was symptom change on the depression scale (MADRS). About 44% of participants were vitamin D deficient at baseline.
Both groups improved. High-dose supplementation corrected deficiency more thoroughly — only 1.7% remained deficient versus 17% in the low-dose group. But depression scores were nearly identical at six months: MADRS dropped from about 22 to about 15 in both arms. The effect size was trivial (Cohen’s d = −0.09).
Practice Implications
- The optimistic take: Meta-analyses usually come up positive for vitamin D. While this trial is large, it likely was too small to detect a difference between the two doses (it is easier to detect a difference between treatment and placebo).
- The pessimistic take: Many trials of vitamin D were negative in depression, suggesting the vitamin plays a limited role if any in treatment.
- The realistic take: Let’s wait for more data.
— Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
