Summary
Bupropion 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 Bupropion Hydrochloride to Major Depressive Disorder: 2 are currently recruiting; 5 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00590863). It plans or enrolled 665 participants. Registration activity spans 2004 to 2025. The literature layer holds 4 publications for this pair: 4 clinical trial publications. Publication years run from 2005 to 2019. 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 | 58.0 (trials 30.0, literature 8.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 2 recruiting, 0 active / not yet recruiting, 5 completed, 1 other |
| Linked publications | 4 (4 clinical trial publications) |
| 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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT00234195 | Wellbutrin XL, Major Depressive Disorder and Breast Cancer 2005 | completed | Phase 4 | 25 |
| NCT00590863 | Combining Medications to Enhance Depression Outcomes 2008 | completed | Phase 4 | 665 |
| NCT06417437 | Non-invasive BCI and Application Verification for Depressed People 2023 | recruiting | Phase 4 | 400 |
| NCT01838876 | Long-term Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy in Patients With Major Depressive Disorder 2013 | completed | Phase 3 | 442 |
| NCT00093288 | Major Depressive Disorder In The Elderly 2004 | completed | Phase 3 | 364 |
| NCT07523048 | Dextromethorphan-Bupropion on Striatal Activity in Adults With Major Depressive Disorder 2025 | recruiting | Phase 2 | 30 |
| NCT00289523 | EEG Biomarkers for Predicting Response to Antidepressant Therapy 2006 | completed | Not applicable | 375 |
| NCT01369290 | Electroencephalography (EEG) Signal Processing 2009 | status unknown | Not applicable | 150 |
Published literature
- Clinical trial publication Efficacy and safety of bupropion hydrochloride extended-release versus escitalopram oxalate in Chinese patients with major depressive disorder: Results from a randomized, double-blind, non-inferiority trialShen Y, Zhao Q, Yu Y et al. · Journal of affective disorders · 2019 · PMID 31301615
- Clinical trial publication An open-label, rater-blinded, 8-week trial of bupropion hydrochloride extended-release in patients with major depressive disorder with atypical featuresSeo HJ, Lee BC, Seok JH et al. · Pharmacopsychiatry · 2013 · PMID 23963965
- Clinical trial publication Selecting among second-step antidepressant medication monotherapies: predictive value of clinical, demographic, or first-step treatment featuresRush AJ, Wisniewski SR, Warden D et al. · Archives of general psychiatry · 2008 · PMID 18678792
- Clinical trial publication Cost-effectiveness of evidence-based pharmacotherapy or cognitive behavior therapy compared with community referral for major depression in predominantly low-income minority womenRevicki DA, Siddique J, Frank L et al. · Archives of general psychiatry · 2005 · PMID 16061764
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 Bupropion Hydrochloride approved for Major Depressive Disorder?
Bupropion 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 Bupropion Hydrochloride in clinical trials for Major Depressive Disorder?
ClinicalTrials.gov lists 8 registered trials linking Bupropion Hydrochloride to Major Depressive Disorder: 2 are currently recruiting; 5 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00590863). It plans or enrolled 665 participants. Registration activity spans 2004 to 2025.
What does the evidence show for Bupropion Hydrochloride in Major Depressive Disorder?
Bupropion Hydrochloride has 5 completed trials and 4 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. 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.