Summary
Agomelatine 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lists 8 registered trials linking Agomelatine to Major Depressive Disorder: 7 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT04589143). The largest enrolment is 837 participants (NCT01156415). Registration activity spans 2006 to 2020. The literature layer holds 14 publications for this pair: 5 Cochrane reviews, 4 meta-analyses and 5 clinical trial publications. Publication years run from 2022 to 2025. 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 | 80.0 (trials 30.0, literature 30.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 0 recruiting, 0 active / not yet recruiting, 7 completed, 1 other |
| Linked publications | 14 (5 Cochrane reviews, 5 clinical trial publications, 4 meta-analyses) |
| 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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT04589143 | A Double-blind, Placebo-controlled Study of Antidepressant Augmentation With Agomelatine 2020 | completed | Phase 4 | 137 |
| NCT04181567 | Comparison of the Efficacy, Safety, and Relapse of ECT to ECT Plus Agomelatine for Depressed Patients 2014 | completed | Phase 4 | 97 |
| NCT01488071 | A Study of Vortioxetine (Lu AA21004) in Comparison to Agomelatine in Adults Suffering From Major Depression With Inadequate Response to Previous Medication 2012 | completed | Phase 3 | 495 |
| NCT01110889 | Efficacy, Safety and Tolerability of Agomelatine Sublingual Tablets in the Treatment of Major Depressive Disorder 2010 | completed | Phase 3 | 582 |
| NCT00411099 | Efficacy, Safety and Tolerability of Agomelatine in the Treatment of Major Depressive Disorder 2006 | completed | Phase 3 | 508 |
| NCT01156415 | Open-label Long Term (52 Weeks) Safety and Tolerability of Agomelatine Sublingual Tablets in Major Depressive Disorder (MDD) 2010 | terminated | Phase 3 | 837 |
| NCT01531309 | Pharmacokinetics of AGO178 in Participants With Liver Impairment 2011 | completed | Phase 1 | 32 |
| NCT01731899 | Agomelatine in Depressed Patients With Fibromyalgia 2010 | completed | Not applicable | 27 |
Published literature
- Clinical trial publication Agomelatine as adjunctive therapy with SSRIs or SNRIs for major depressive disorder: a multicentre, double-blind, randomized, placebo-controlled trialJu Y, Ou W, Chen H et al. · BMC medicine · 2025 · PMID 40038707
- Clinical trial publication Agomelatine in pediatric patients with moderate to severe major depressive disorder: an open-label extension studyArango C, Fegert JM, Picarel-Blanchot F et al. · European child & adolescent psychiatry · 2025 · PMID 39390266
- Cochrane review Side effect profile and comparative tolerability of newer generation antidepressants in the acute treatment of major depressive disorder in children and adolescents: protocol for a systematic review and network meta-analysisTürkmen C, Sacu S, Furukawa Y et al. · BMJ open · 2025 · PMID 41062142
- Cochrane review Comparative efficacy of antidepressant medication for adolescent depression: a network meta-analysis and systematic reviewWu T, Song F, Cao W et al. · BMC psychiatry · 2025 · PMID 40349006
- Meta-analysis Comparative gastrointestinal effects of antidepressants for the acute treatment of adults with major depressive disorder: a network and dose‒response meta-analysisWen S, Yan Y, Shao J et al. · Translational psychiatry · 2025 · PMID 41290573
- Meta-analysis Efficacy and Acceptability of Licensed and Off-Label Pharmacological Interventions for Insomnia in Patients With Severe Mental Illness: A Systematic Review and Meta-Analysis of Randomised TrialsFuglsang NFB, Madsen NM, Jacobsen SL et al. · Acta psychiatrica Scandinavica · 2025 · PMID 40898589
- Meta-analysis Effect of antidepressants on ejaculation dysfunction in patients with depression and anxiety: A systematic review and network meta-analysisWang Q, Xu Z, Chen X et al. · Andrology · 2025 · PMID 39344496
- Meta-analysis Efficacy and Safety of Agomelatine in Depressed Patients with Diabetes: A Systematic Review and Meta-AnalysisGędek A, Modrzejewski S, Materna M et al. · International journal of molecular sciences · 2024 · PMID 39684343
- Clinical trial publication Changes of Serum C-Reactive Protein Level in Patients With Depressive Disorders After Treatment With Agomelatine Combined With Aerobic Exercise and Its SignificanceSun Z, Chen S, Zhang H et al. · Clinical neuropharmacology · 2023 · PMID 37748002
- Clinical trial publication Vortioxetine in patients with major depressive disorder and high levels of anxiety symptoms: An updated analysis of efficacy and tolerabilityAdair M, Christensen MC, Florea I et al. · Journal of affective disorders · 2023 · PMID 36708956
- Cochrane review A comprehensive review and meta-analysis of neurological side effects related to second-generation antidepressants in individuals with major depressive disorderZhou Q, Li X, Yang D et al. · Behavioural brain research · 2023 · PMID 37044221
- Cochrane review Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase: a systematic review and network meta-analysisKishi T, Ikuta T, Sakuma K et al. · Molecular psychiatry · 2023 · PMID 36253442
- Clinical trial publication The Relationship Between Depression and Pain During Acute Electroconvulsive Therapy and Follow-Up Period for Patients With Treatment-Resistant DepressionLin CH, Yang WC, Chan MH et al. · The journal of ECT · 2022 · PMID 35220359
- Cochrane review Agomelatine: An Astounding Sui-generis Antidepressant?Naveed M, Li LD, Sheng G et al. · Current molecular pharmacology · 2022 · PMID 34886787
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 Agomelatine approved for Major Depressive Disorder?
Agomelatine 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 Agomelatine in clinical trials for Major Depressive Disorder?
ClinicalTrials.gov lists 8 registered trials linking Agomelatine to Major Depressive Disorder: 7 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT04589143). The largest enrolment is 837 participants (NCT01156415). Registration activity spans 2006 to 2020.
What does the evidence show for Agomelatine in Major Depressive Disorder?
Agomelatine 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.