Overview
Agomelatine is structurally closely related to melatonin. Agomelatine is a potent agonist at melatonin receptors and an antagonist at serotonin-2C (5-HT2C) receptors, tested in an animal model of depression. Agomelatine was developed in Europe by Servier Laboratories Ltd. and submitted to the European Medicines Agency (EMA) in 2005. The Committee for Medical Products for Human Use (CHMP) recommended refusal of marketing authorization on 27 July 2006. The major concern was that efficacy had not been sufficiently shown. In 2006 Servier sold the rights to develop Agomelatine in the US to Novartis. The development for the US market was discontinued in October 2011. It is currently sold in Australia under the Valdoxan trade name.
Indication
Agomelatine is indicated to treat major depressive episodes in adults.
Associated Conditions
- Major Depressive Episode
Research Report
Agomelatine (DB06594): A Comprehensive Monograph on a Novel Antidepressant
Abstract
Agomelatine is an atypical antidepressant characterized by a unique pharmacological profile that distinguishes it from conventional monoaminergic agents. As a potent agonist at melatonergic MT1 and MT2 receptors and a selective antagonist at serotonergic 5-HT2C receptors, it was developed to address both the circadian dysregulation and the neurochemical imbalances implicated in major depressive disorder (MDD). This dual mechanism theoretically offers advantages in treating core depressive symptoms, particularly anhedonia and sleep disturbances, without the common side effects of selective serotonin reuptake inhibitors (SSRIs), such as sexual dysfunction and discontinuation syndrome. However, its clinical development and adoption have been marked by significant controversy. The evidence for its efficacy, while demonstrating statistical superiority over placebo in some trials, has been questioned for its modest clinical relevance and has been affected by publication bias. This has led to a striking divergence in its global regulatory status: it is approved in Europe and Australia under strict risk management protocols but remains unapproved in the United States and Canada. The primary safety concern is a dose-dependent risk of hepatotoxicity, necessitating a rigorous liver function monitoring schedule that complicates its clinical use. This monograph provides a comprehensive analysis of agomelatine, covering its chemical properties, its novel synergistic mechanism of action, a critical appraisal of its clinical efficacy and safety data, its practical prescribing considerations, and the divergent regulatory philosophies it has exposed. Ultimately, agomelatine occupies a niche role in the psychiatric armamentarium, best suited for specific patient profiles where its unique benefits in tolerability and sleep regulation may outweigh its significant risks and monitoring burdens.
Clinical Trials
Title | Posted | Study ID | Phase | Status | Sponsor |
|---|---|---|---|---|---|
2025/06/10 | Phase 4 | Not yet recruiting | Xinyu Zhou | ||
2023/06/28 | Phase 2 | Recruiting | |||
2022/12/12 | Phase 4 | Recruiting | |||
2022/06/21 | Phase 4 | UNKNOWN | First Affiliated Hospital, Sun Yat-Sen University | ||
2020/10/19 | Phase 4 | Completed | Central South University | ||
2019/11/29 | Phase 4 | Completed | |||
2019/06/06 | Phase 4 | UNKNOWN | Second Affiliated Hospital of Soochow University | ||
2019/02/25 | Phase 3 | Withdrawn | |||
2017/06/20 | N/A | Completed | Kahramanmaras Sutcu Imam University | ||
2015/03/02 | Phase 3 | Terminated |
FDA Drug Approvals
Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
|---|---|---|---|---|---|
| No FDA approvals found for this drug. | |||||
EMA Drug Approvals
Approved Product | Authorization Holder | Status | Issued Date |
|---|---|---|---|
Authorised | 2/19/2009 |
HSA Drug Approvals
Approved Product | Manufacturer | Approval Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| VALDOXAN Tablet 25mg | SIN13770P | TABLET, FILM COATED | 25 mg | 2/26/2010 |
NMPA Drug Approvals
Approved Product | Company | Approval Number | Drug Type | Dosage Form | Approval Date |
|---|---|---|---|---|---|
| No NMPA approvals found for this drug. | |||||
PPB Drug Approvals
Approved Product | Registration No. | Company | Licence No. | Strength | Registration Date |
|---|---|---|---|---|---|
| No PPB approvals found for this drug. | |||||
TGA Drug Approvals
Approved Product | ARTG ID | Sponsor | Registration Type | Status | Registration Date |
|---|---|---|---|---|---|
| AGOMELATINE-WGR agomelatine 25 mg film coated tablet blister pack. | 439352 | Medicine | A | 5/8/2024 | |
| DOMION agomelatine 25 mg film-coated tablet blister pack. | 279057 | Medicine | A | 11/15/2016 | |
| NORTIM agomelatine 25 mg film-coated tablet blister pack. | 279058 | Medicine | A | 11/15/2016 | |
| VALDOXAN agomelatine 25 mg film coated tablet blister pack. | 159712 | Medicine | A | 8/9/2010 | |
| ARDIX AGOMELATINE agomelatine 25 mg film-coated tablet blister pack. | 279059 | Medicine | A | 11/15/2016 |
Health Canada Drug Approvals
Approved Product | Company | DIN | Dosage Form | Strength | Market Date |
|---|---|---|---|---|---|
| No Health Canada approvals found for this drug. | |||||
CIMA AEMPS Drug Approvals
Approved Product | Company | Registration Number | Pharmaceutical Form | Prescription Type | Status |
|---|---|---|---|---|---|
| VALDOXAN 25 MG COMPRIMIDOS RECUBIERTOS CON PELICULA | 08499008 | COMPRIMIDO RECUBIERTO CON PELÍCULA | Medicamento Sujeto A Prescripción Médica | Not Commercialized | |
| AGOMELATINA VISO FARMACEUTICA 25 MG COMPRIMIDOS RECUBIERTOS CON PELICULA EFG | 83833 | COMPRIMIDO RECUBIERTO CON PELÍCULA | Medicamento Sujeto A Prescripción Médica | Not Commercialized | |
| VALDOXAN 25 MG COMPRIMIDOS RECUBIERTOS CON PELICULA | 08499003IP | COMPRIMIDO RECUBIERTO CON PELÍCULA | Medicamento Sujeto A Prescripción Médica | Commercialized | |
| VALDOXAN 25 MG COMPRIMIDOS RECUBIERTOS CON PELICULA | 08499003 | COMPRIMIDO RECUBIERTO CON PELÍCULA | Medicamento Sujeto A Prescripción Médica | Commercialized | |
| THYMANAX 25 mg COMPRIMIDOS RECUBIERTOS CON PELICULA | Servier (Ireland) Industries Limited | 08498003 | COMPRIMIDO RECUBIERTO CON PELÍCULA | Medicamento Sujeto A Prescripción Médica | Not Commercialized |
| VALDOXAN 25 MG COMPRIMIDOS RECUBIERTOS CON PELICULA | 08499003IP2 | COMPRIMIDO RECUBIERTO CON PELÍCULA | Medicamento Sujeto A Prescripción Médica | Commercialized | |
| VALDOXAN 25 MG COMPRIMIDOS RECUBIERTOS CON PELICULA | 08499003IP1 | COMPRIMIDO RECUBIERTO CON PELÍCULA | Medicamento Sujeto A Prescripción Médica | Commercialized | |
| VALDOXAN 25 MG COMPRIMIDOS RECUBIERTOS CON PELICULA | 08499003IP3 | COMPRIMIDO RECUBIERTO CON PELÍCULA | Medicamento Sujeto A Prescripción Médica | Commercialized | |
| THYMANAX 25 mg COMPRIMIDOS RECUBIERTOS CON PELICULA | Servier (Ireland) Industries Limited | 08498008 | COMPRIMIDO RECUBIERTO CON PELÍCULA | Medicamento Sujeto A Prescripción Médica | Not Commercialized |
Philippines FDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Philippines FDA approvals found for this drug. | |||||
Saudi SFDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Saudi SFDA approvals found for this drug. | |||||
Malaysia NPRA Drug Approvals
Approved Product | Company | Registration Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Malaysia NPRA approvals found for this drug. | |||||
UK EMC Drug Information
Medicine Name | MA Holder | MA Number | Pharmaceutical Form | Active Ingredient | Authorization Date |
|---|---|---|---|---|---|
| No UK EMC drug information found for this drug. | |||||
Help Us Improve
Your feedback helps us provide better drug information and insights.