Summary
Mecamylamine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Major Depressive Disorder would be drug repurposing rather than first-in-human development. This does not mean it is approved for Major Depressive Disorder. ClinicalTrials.gov lists 8 registered trials linking Mecamylamine to Major Depressive Disorder: 7 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 3 (NCT01153347). It plans or enrolled 2409 participants. Registration activity spans 2003 to 2011. The literature layer holds 3 publications for this pair: 3 clinical trial publications. Publication years run from 2002 to 2010. 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 | A · Strong |
|---|---|
| Evidence score | 56.0 (trials 30.0, literature 6.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 0 recruiting, 0 active / not yet recruiting, 7 completed, 1 other |
| Linked publications | 3 (3 clinical trial publications) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | Not recorded |
| Data sources | Open Targets, ChEMBL |
| Linked via biomarker / target | ADRA1A |
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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT01180400 | A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder 2010 | completed | Phase 3 | 295 |
| NCT01197508 | A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder. 2010 | completed | Phase 3 | 696 |
| NCT01152554 | A Study to Assess the Long- Term Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder 2010 | completed | Phase 3 | 813 |
| NCT01157078 | A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder (MDD) 2010 | completed | Phase 3 | 319 |
| NCT01153347 | A Study to Assess the Efficacy and Safety of TC-5214 as an Adjunct Therapy in Patients With Major Depressive Disorder 2010 | completed | Phase 3 | 2,409 |
| NCT00319319 | Nicotinic Receptor Augmentation of SSRI Antidepressants 2003 | completed | Phase 2 | 60 |
| NCT00692445 | TC-5214 as add-on the Treatment of Major Depressive Disorder 2008 | completed | Phase 2 | 574 |
| NCT01288079 | A Study to Assess the Safety and Effect of TC-5214 in Patients With Major Depressive Disorder. 2011 | terminated | Phase 2 | 145 |
Published literature
- Clinical trial publication (S)-(+)-mecamylamine (TC-5214): a neuronal nicotinic receptor modulator enters phase III trials as an adjunct treatment for Major Depressive Disorder (MDD)Lindsley CW · ACS chemical neuroscience · 2010 · PMID 22778844
- Clinical trial publication Nicotinic antagonist augmentation of selective serotonin reuptake inhibitor-refractory major depressive disorder: a preliminary studyGeorge TP, Sacco KA, Vessicchio JC et al. · Journal of clinical psychopharmacology · 2008 · PMID 18480694
- Clinical trial publication Neuronal nicotinic receptor inhibition for treating mood disorders: preliminary controlled evidence with mecamylamineShytle RD, Silver AA, Sheehan KH et al. · Depression and anxiety · 2002 · PMID 12415531
Mechanism and notes
No mechanism of action is recorded for this pair in the source databases.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL, in this case via the biomarker or target ADRA1A. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Mecamylamine approved for Major Depressive Disorder?
Mecamylamine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Major Depressive Disorder would be drug repurposing rather than first-in-human development. This does not mean it is approved for Major Depressive Disorder. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Mecamylamine in clinical trials for Major Depressive Disorder?
ClinicalTrials.gov lists 8 registered trials linking Mecamylamine to Major Depressive Disorder: 7 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 3 (NCT01153347). It plans or enrolled 2409 participants. Registration activity spans 2003 to 2011.
What does the evidence show for Mecamylamine in Major Depressive Disorder?
Mecamylamine has 7 completed trials and 3 linked publications 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 A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL, in this case via the biomarker or target ADRA1A. 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.