Summary
Duloxetine 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8 registered trials linking Duloxetine Hydrochloride to Major Depressive Disorder: 6 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 3 (NCT00321490). The largest enrolment is 976 participants (NCT01369095). Registration activity spans 2003 to 2020. The literature layer holds 4 publications for this pair: 2 meta-analyses and 2 clinical trial publications. Publication years run from 2002 to 2011. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
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 | 59.0 (trials 27.0, literature 12.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 0 recruiting, 0 active / not yet recruiting, 6 completed, 2 other |
| Linked publications | 4 (2 meta-analyses, 2 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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT00062673 | Study of Duloxetine in Elderly Patients With Major Depressive Disorder 2003 | completed | Phase 3 | 311 |
| 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 |
| NCT00321490 | Safety & Efficacy Study of Quetiapine Fumarate (SEROQUEL®) vs. Placebo and Active Control in Major Depressive Disorder 2006 | completed | Phase 3 | 600 |
| NCT00849693 | A Study in the Treatment of Children and Adolescents With Major Depressive Disorder 2009 | completed | Phase 3 | 463 |
| NCT00331799 | Pilot Study of Duloxetine in Psychological Resilience 2007 | completed | Phase 2 | 18 |
| NCT01369095 | Efficacy and Safety of Fixed Doses of BMS 820836 in the Treatment of Patients With Treatment Resistant Major Depression 2011 | completed | Phase 2 | 976 |
| NCT04347577 | Intestinal Flora and Major Depressive Disorders 2020 | status unknown | Not applicable | 40 |
| NCT01369290 | Electroencephalography (EEG) Signal Processing 2009 | status unknown | Not applicable | 150 |
Published literature
- Clinical trial publication Trajectories of depression severity in clinical trials of duloxetine: insights into antidepressant and placebo responsesGueorguieva R, Mallinckrodt C, Krystal JH · Archives of general psychiatry · 2011 · PMID 22147842
- Meta-analysis Comparative pain and mood effects in patients with comorbid fibromyalgia and major depressive disorder: secondary analyses of four pooled randomized controlled trials of duloxetineMarangell LB, Clauw DJ, Choy E et al. · Pain · 2011 · PMID 20598442
- Meta-analysis The relationship between antidepressant and analgesic responses: findings from six placebo-controlled trials assessing the efficacy of duloxetine in patients with major depressive disorderFishbain DA, Detke MJ, Wernicke J et al. · Current medical research and opinion · 2008 · PMID 18828958
- Clinical trial publication Duloxetine in the treatment of major depressive disorder: a double-blind clinical trialGoldstein DJ, Mallinckrodt C, Lu Y et al. · The Journal of clinical psychiatry · 2002 · PMID 11926722
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 Duloxetine Hydrochloride approved for Major Depressive Disorder?
Duloxetine 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 Duloxetine Hydrochloride in clinical trials for Major Depressive Disorder?
ClinicalTrials.gov lists 8 registered trials linking Duloxetine Hydrochloride to Major Depressive Disorder: 6 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 3 (NCT00321490). The largest enrolment is 976 participants (NCT01369095). Registration activity spans 2003 to 2020.
What does the evidence show for Duloxetine Hydrochloride in Major Depressive Disorder?
Duloxetine Hydrochloride has both completed registered trials and synthesis-level publications linked to Major Depressive Disorder. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. 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.