Disease × agent evidence record

Paroxetine for Major Depressive Disorder: evidence, trials and status

Paroxetine 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.

8 registered trials 0 recruiting 14 publications Evidence tier A · Strong Score 79.5
Research Tracker › Pairs › Major Depressive Disorder › Paroxetine
Research map, not treatment advice. This page aggregates registry and literature records. It does not evaluate efficacy, dosing or safety for any individual. Discuss any treatment decision with a qualified clinician.

Summary

Paroxetine 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lists 8 registered trials linking Paroxetine to Major Depressive Disorder: 6 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00519012). The largest enrolment is 1986 participants (NCT01838681). Registration activity spans 2002 to 2013. The literature layer holds 14 publications for this pair: 5 Cochrane reviews, 3 meta-analyses, 1 systematic review and 5 clinical trial publications. Publication years run from 2022 to 2026. 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.

Open in Repurposing ExplorerMajor Depressive Disorder hubMajor Depressive Disorder biomarkers & interventionsChEMBLOpen Targets

Evidence table

Evidence tierA · Strong
Evidence score79.5 (trials 29.5, literature 30.0, tier 15, approved bonus 5.0)
Registered trials8 total: 0 recruiting, 0 active / not yet recruiting, 6 completed, 2 other
Linked publications14 (5 Cochrane reviews, 5 clinical trial publications, 3 meta-analyses, 1 systematic review)
Agent typeDrug (Small molecule)
Development stage (any indication)Approved
Mechanism / classNot recorded
Data sourcesOpen 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 IDTitleStatusPhaseEnrolment
NCT00519012Benefits of Switching Antidepressants Following Early Nonresponse
2007
status unknownPhase 4200
NCT00385307Efficacy and Safety of SR58611A in Patients With Major Depressive Disorder (SIRIUS)
2006
completedPhase 3680
NCT00048607Treatment of Patients With Major Depressive Disorder With MK0869 (0869-062)(COMPLETED)
2002
completedPhase 3600
NCT01838876Long-term Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy in Patients With Major Depressive Disorder
2013
completedPhase 3442
NCT00825058Efficacy and Safety of SR58611 Compared to Placebo and Paroxetine
2003
completedPhase 3317
NCT01838681Brexpiprazole as Adjunctive Treatment in Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment
2013
completedPhase 31,986
NCT00206765Risperidone vs. Paroxetine for Panic Attacks
2003
terminatedPhase 290
NCT00457106A Single-Blind Trial of Risperidone vs. Paroxetine for Treatment of Panic Attacks
2002
completedNot applicable90

Search ClinicalTrials.gov for newer studies

Published literature

Run the live PubMed search

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 Paroxetine approved for Major Depressive Disorder?

Paroxetine 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 Paroxetine in clinical trials for Major Depressive Disorder?

ClinicalTrials.gov lists 8 registered trials linking Paroxetine to Major Depressive Disorder: 6 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00519012). The largest enrolment is 1986 participants (NCT01838681). Registration activity spans 2002 to 2013.

What does the evidence show for Paroxetine in Major Depressive Disorder?

Paroxetine 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

Open Source Medicine Foundation. Paroxetine for Major Depressive Disorder: evidence, trials and status. OSMF Research Tracker. Updated 2026-07-05. https://research.opensourcemed.info/pairs/major-depressive-disorder/paroxetine.html

Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.

Get OSMF research updates on Substack

This is a research map, not treatment advice. Evidence tiers and scores summarise what has been studied, not whether a treatment works or is safe for you.