Summary
Magnesium 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 8 registered trials linking Magnesium to Major Depressive Disorder: 1 is currently recruiting; 2 are active or not yet recruiting; 4 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 2 (NCT01941043). It plans or enrolled 1357 participants. Registration activity spans 2009 to 2026. The literature layer holds 1 publication for this pair: 1 clinical trial publication. The dated items are from 2024. These are primary trial reports rather than syntheses, so results have not yet been pooled or graded independently.
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 | 30.0 (trials 23.0, literature 2.0, tier 5, approved bonus 0.0) |
| Registered trials | 8 total: 1 recruiting, 2 active / not yet recruiting, 4 completed, 1 other |
| Linked publications | 1 (1 clinical trial publication) |
| 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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT07458022 | MAGNESIUM & SSRI VS SSRI ALONE AMONG PATIENTS OF MAJOR DEPRESSIVE DISORDER 2025 | active, not recruiting | Phase 2 | 50 |
| NCT00797966 | Study of the Safety and Efficacy of OPC-34712 as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder 2009 | completed | Phase 2 | 850 |
| NCT01941043 | A Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Study of CERC-301 in the Adjunctive Treatment of Subjects With Severe Depression and Recent Active Suicidal Ideation Despite Antidepressant Treatment 2013 | completed | Phase 2 | 1,357 |
| NCT04880460 | Effect of Magnesium Supplementation in Selective Serotonin Reuptake Inhibitors Treated Major Depressive Disorder Patients 2021 | completed | Phase 2 | 90 |
| NCT07521358 | Magnesium Supplementation With Fluoxetine for Cognitive Function in Depression 2025 | completed | Not applicable | 40 |
| NCT07198477 | Sleep Disturbances and Their Association With Serum Magnesium Level in Patients With Major Depressive Disorder 2026 | not yet recruiting | Not applicable | 90 |
| NCT07633080 | Magnesium Bisglycinate in Major Depressive Disorder 2026 | recruiting | Not applicable | 84 |
| NCT03877393 | The Effect of Probiotic Supplementation on the Mental Status, Inflammation, and Intestinal Barrier in Major Depressive Disorder Patients Using Gluten-free or Gluten-containing Diet 2019 | status unknown | Not applicable | 120 |
Published literature
- Clinical trial publication Probiotics and magnesium orotate for the treatment of major depressive disorder: a randomised double blind controlled trialStrodl E, Bambling M, Parnam S et al. · Scientific reports · 2024 · PMID 39242786
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 Magnesium approved for Major Depressive Disorder?
Magnesium 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 Magnesium in clinical trials for Major Depressive Disorder?
ClinicalTrials.gov lists 8 registered trials linking Magnesium to Major Depressive Disorder: 1 is currently recruiting; 2 are active or not yet recruiting; 4 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 2 (NCT01941043). It plans or enrolled 1357 participants. Registration activity spans 2009 to 2026.
What does the evidence show for Magnesium in Major Depressive Disorder?
Magnesium has 4 completed trials and 1 linked publication for Major Depressive Disorder. Completed trials may or may not have posted results; follow the NCT links to check. 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.