Summary
Vitamin D has reached Preclinical as its most advanced recorded development stage across any indication, and the database holds no approval for Major Depressive Disorder. ClinicalTrials.gov lists 7 registered trials linking Vitamin D to Major Depressive Disorder: 2 are currently recruiting; 3 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT01390662). It plans or enrolled 150 participants. Registration activity spans 2000 to 2026. The literature layer holds 11 publications for this pair: 2 Cochrane reviews, 2 meta-analyses, 2 systematic reviews and 5 clinical trial publications. Publication years run from 2019 to 2026. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
The RepurpOS disease-intelligence file for Major Depressive Disorder ranks 580 candidate therapeutics from Open Targets, ChEMBL, DGIdb and PubMed; only a minority carry direct clinical evidence, and this page covers one of those. Spontaneous remission context recorded for the condition: Relapse in 19-45% within 1 year of antidepressant discontinuation after remission; relapse risk ratio (off-medication vs on) falls from 3.69x at 2 months to 1.34x at 5 years.
Evidence table
| Evidence tier | C · Preliminary |
|---|---|
| Evidence score | 52.5 (trials 17.5, literature 30.0, tier 5, approved bonus 0.0) |
| Registered trials | 7 total: 2 recruiting, 0 active / not yet recruiting, 3 completed, 2 other |
| Linked publications | 11 (5 clinical trial publications, 2 Cochrane reviews, 2 meta-analyses, 2 systematic reviews) |
| Agent type | Supplement |
| Development stage (any indication) | Preclinical |
| Mechanism / class | Integrative interventions for improving outcomes in depression: a narrative review · Halma M, Plothe C, Marik PE · 2024 |
| Data sources | OSMF Chronic Disease Review |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT01390662 | Can Vitamin D3 Supplementation Affect Treatment Outcomes in Patients With Depression 2011 | status unknown | Phase 4 | 150 |
| NCT04898725 | Effects of Vitamin D Supplementation on Depression and Inflammatory Markers 2020 | completed | Not applicable | 142 |
| NCT01932931 | Vitamin D, SSRIs and the Musculoskeletal System 2013 | completed | Not applicable | 71 |
| NCT00005119 | Altered Calcium and Vitamin D in PMDD or Severe PMS 2000 | completed | Not applicable | — |
| NCT07579078 | Effect of Vitamin D Supplementation on Brain Waves in Female Major Depressive Disorder Patients With Hypovitaminosis D 2026 | enrolling by invitation | Not applicable | 34 |
| NCT05899660 | Impact of Omega 3 in Alcohol Use Disorder 2023 | recruiting | Not applicable | 100 |
| NCT03754712 | Effect of Vitamin D Administration Along With SSRIs in Patients With Major Depressive Disorder 2018 | status unknown | Not applicable | 90 |
Published literature
- Clinical trial publication Do probiotics modulate dietary intake? Pilot data from a randomized controlled sub-study of the ProBioHRV clinical trial in patients with depression and healthy controlsPutz JC, Wilding M, Lackner S et al. · PloS one · 2026 · PMID 42335165
- Clinical trial publication Effect of a six-month vitamin D supplementation on depressive symptoms in patients with major depressive episode (DepFuD): a double-blinded randomised controlled trialMikola T, Lehto SM, Tolmunen T et al. · Journal of affective disorders · 2026 · PMID 41933624
- Clinical trial publication Vitamin D supplementation and incidence of major depressive disorder - A randomized clinical trialAhl NM, Hantunen S, Tuomainen TP et al. · Clinical nutrition (Edinburgh, Scotland) · 2026 · PMID 41506003
- Clinical trial publication The protective effect of vitamin D supplementation as adjunctive therapy to antidepressants on brain structural and functional connectivity of patients with major depressive disorder: a randomized controlled trialZhao W, Zhu DM, Shen Y et al. · Psychological medicine · 2024 · PMID 38482853
- Clinical trial publication Effects of Vitamin D(3) and Marine Omega-3 Fatty Acids Supplementation on Indicated and Selective Prevention of Depression in Older Adults: Results From the Clinical Center Sub-Cohort of the VITamin D and OmegA-3 TriaL (VITAL)Vyas CM, Mischoulon D, Chang G et al. · The Journal of clinical psychiatry · 2023 · PMID 37378490
- Cochrane review Efficacy and acceptability of vitamin D supplements for depressed patients: A systematic review and meta-analysis of randomized controlled trialsSrifuengfung M, Srifuengfung S, Pummangura C et al. · Nutrition (Burbank, Los Angeles County, Calif.) · 2023 · PMID 36716601
- Systematic review Efficacy of B-vitamins and vitamin D therapy in improving depressive and anxiety disorders: a systematic review of randomized controlled trialsBorges-Vieira JG, Cardoso CKS · Nutritional neuroscience · 2023 · PMID 35156551
- Meta-analysis Genome-wide interaction study with major depression identifies novel variants associated with cognitive functionThalamuthu A, Mills NT, Berger K et al. · Molecular psychiatry · 2022 · PMID 34782712
- Systematic review Nutrient and genetic biomarkers of nutraceutical treatment response in mood and psychotic disorders: a systematic reviewvan der Burg KP, Cribb L, Firth J et al. · Nutritional neuroscience · 2021 · PMID 31397223
- Meta-analysis The effect of vitamin D supplement on negative emotions: A systematic review and meta-analysisCheng YC, Huang YC, Huang WL · Depression and anxiety · 2020 · PMID 32365423
- Cochrane review Efficacy of vitamin D supplementation in major depression: A meta-analysis of randomized controlled trialsVellekkatt F, Menon V · Journal of postgraduate medicine · 2019 · PMID 29943744
Mechanism and notes
Recorded mechanism or class: Integrative interventions for improving outcomes in depression: a narrative review · Halma M, Plothe C, Marik PE · 2024.
OSMF's existing evidence tier for this pair is C (Preliminary), derived from the strength of the disease association recorded in OSMF Chronic Disease Review. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Vitamin D approved for Major Depressive Disorder?
Vitamin D has reached Preclinical as its most advanced recorded development stage across any indication, and the database holds no approval for Major Depressive Disorder. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Vitamin D in clinical trials for Major Depressive Disorder?
ClinicalTrials.gov lists 7 registered trials linking Vitamin D to Major Depressive Disorder: 2 are currently recruiting; 3 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT01390662). It plans or enrolled 150 participants. Registration activity spans 2000 to 2026.
What does the evidence show for Vitamin D in Major Depressive Disorder?
Vitamin D has both completed registered trials and synthesis-level publications linked to Major Depressive Disorder. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. OSMF's existing evidence tier for this pair is C (Preliminary), derived from the strength of the disease association recorded in OSMF Chronic Disease Review. The tier describes how well the drug-disease link is documented, not how well the drug works.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.