The safety of agomelatine in standard medical practice in depressed patients: A 26-week international multicentre cohort study

Hum Psychopharmacol. 2021 Jan;36(1):1-11. doi: 10.1002/hup.2759. Epub 2020 Sep 25.


Objective: The present observational cohort study documented the safety of agomelatine in current medical practice in out-patients suffering from major depressive disorder.

Method: The 6-month evolution of agomelatine-treated patients was assessed with a focus on safety (emergent adverse events, liver acceptability), severity of depression using the Clinical Global Impression Severity (CGI-S) score, and functioning measured by the Sheehan Disability Scale (SDS).

Results: A total of 8453 depressed patients from 761 centres in 6 countries were analysed (female: 67.7%; mean age: 49.1 ± 14.8 years). Adverse events reported were in accordance with the known safety profile of agomelatine. Cutaneous events were reported in 1.7% of the patients and increased hepatic transaminases values were reported in 0.9 % of the patients. The incidence of events related to suicide/self-injury was 1.0%. Two completed suicides, not related to the study drug, were reported. CGI-S total scores and SDS sub-scores improved and numbers of days lost or underproductive decreased over the treatment period.

Conclusions: In standard medical practice, agomelatine treatment was associated with a low incidence of side effects. No unexpected events were reported. A decrease in the severity of the depressive episode and improved functioning were observed.

Trial registration name: Observational cohort study to evaluate the safety of agomelatine in standard medical practice in depressed patients. A prospective, observational (non-interventional), international, multicentre cohort study.

Trial registration number: ISRCTN53570733.

Keywords: agomelatine; liver acceptability; observational; safety-medical practice; skin events.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / adverse effects*
  • Acetamides / therapeutic use*
  • Antidepressive Agents / adverse effects
  • Cohort Studies
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / psychology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Suicide / statistics & numerical data
  • Treatment Outcome


  • Acetamides
  • Antidepressive Agents
  • agomelatine