Summary
Trazodone Hydrochloride 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 Trazodone Hydrochloride to Major Depressive Disorder: 2 are currently recruiting; 1 is active or not yet recruiting; 3 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT01764867). It plans or enrolled 1080 participants. Registration activity spans 2005 to 2025. The literature layer holds 1 publication for this pair: 1 clinical trial publication. The dated items are from 2009. 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 | 46.5 (trials 24.5, literature 2.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 2 recruiting, 1 active / not yet recruiting, 3 completed, 2 other |
| Linked publications | 1 (1 clinical trial publication) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | Not recorded |
| Data sources | Open Targets, ChEMBL |
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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT00704860 | Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism 2005 | completed | Phase 4 | 27 |
| NCT01764867 | Algorithm Guided Treatment Strategies for Major Depressive Disorder 2012 | status unknown | Phase 4 | 1,080 |
| NCT00775203 | A Randomized, Double-blind, Two-arm Study Comparing the Efficacy and Safety of Trazodone Contramid® OAD and Placebo in the Treatment of Unipolar Major Depressive Disorder. 2007 | completed | Phase 3 | 412 |
| NCT07210112 | Efficacy of Psilocybin and Trazodone Combination in Treatment-resistant Depression: a Randomized Controlled Proof-of-concept Study (PSILOTRAZ) 2025 | not yet recruiting | Phase 2 | 112 |
| NCT04295941 | Long-term Study With Trazodone Once-a-Day 2020 | completed | Not applicable | 200 |
| NCT07377682 | Real-world Clinical Response to Trazodone in Italy, Poland, and Romania 2025 | recruiting | Not applicable | 120 |
| NCT07328373 | Neurobiological and Genomic Predictors of Relapse in Depression 2025 | recruiting | Not applicable | 204 |
| NCT05889234 | Multimodal Magnetic Resonance Imaging-based Study of Electroconvulsive Efficacy Prediction in Adolescents With Depression: a Multicenter Prospective Cohort Study 2023 | status unknown | Not applicable | 180 |
Published literature
- Clinical trial publication The efficacy and tolerability of once-daily controlled-release trazodone for depressed mood, anxiety, insomnia, and suicidality in major depressive disorderSheehan DV, Rozova A, Gossen ER et al. · Psychopharmacology bulletin · 2009 · PMID 20581790
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. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Trazodone Hydrochloride approved for Major Depressive Disorder?
Trazodone Hydrochloride 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 Trazodone Hydrochloride in clinical trials for Major Depressive Disorder?
ClinicalTrials.gov lists 8 registered trials linking Trazodone Hydrochloride to Major Depressive Disorder: 2 are currently recruiting; 1 is active or not yet recruiting; 3 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT01764867). It plans or enrolled 1080 participants. Registration activity spans 2005 to 2025.
What does the evidence show for Trazodone Hydrochloride in Major Depressive Disorder?
Trazodone Hydrochloride has 3 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 A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL. 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.