Summary
SAMe (S-adenosylmethionine) 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 4 registered trials linking SAMe (S-adenosylmethionine) to Major Depressive Disorder: 3 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT04832178). The largest enrolment is 376 participants (NCT01912196). Registration activity spans 2005 to 2021. No published literature item is linked to SAMe (S-adenosylmethionine) and Major Depressive Disorder in the OSMF database yet, so the record rests on registry entries alone. Registry entries describe intent to study, not outcomes.
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 | 17.0 (trials 12.0, literature 0.0, tier 5, approved bonus 0.0) |
| Registered trials | 4 total: 0 recruiting, 0 active / not yet recruiting, 3 completed, 1 other |
| Linked publications | 0 |
| 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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT04832178 | Sumor as Adjuvant Therapy in Treatment-resistant Major Depression 2021 | status unknown | Phase 4 | 102 |
| NCT01912196 | Add-On Study of MSI-195 (S-Adenosyl-L-Methionine, SAMe) for Patients With Major Depressive Disorder (MDD) 2013 | completed | Phase 2 | 376 |
| NCT04623034 | Evaluation of the Safety and Pharmacokinetics of MSI-195 to a Commercial S-Adenosylmethionine 2013 | completed | Phase 1 | 34 |
| NCT00101452 | Safety and Effectiveness of S-adenosyl-l-methionine (SAMe) for the Treatment of Major Depression 2005 | completed | Not applicable | 199 |
Published literature
No publication is linked to this pair yet.
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 SAMe (S-adenosylmethionine) approved for Major Depressive Disorder?
SAMe (S-adenosylmethionine) 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 SAMe (S-adenosylmethionine) in clinical trials for Major Depressive Disorder?
ClinicalTrials.gov lists 4 registered trials linking SAMe (S-adenosylmethionine) to Major Depressive Disorder: 3 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT04832178). The largest enrolment is 376 participants (NCT01912196). Registration activity spans 2005 to 2021.
What does the evidence show for SAMe (S-adenosylmethionine) in Major Depressive Disorder?
SAMe (S-adenosylmethionine) has 3 completed registered trials for Major Depressive Disorder but no linked publication, which usually means results are unpublished, pending, or not yet matched to this record. 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.