Risk of Acute Liver Injury in Agomelatine and Other Antidepressant Users in Four European Countries: A Cohort and...

Area of Science:

• Pharmacovigilance
• Hepatology
• Clinical Pharmacology

Background:

• Agomelatine, a melatonin and serotonin receptor agent for depression, carries a known risk of hepatotoxicity.
• Antidepressant-induced liver injury (ALI) is a concern, yet population studies are limited.
• Patients using antidepressants often have comorbidities increasing ALI risk.

Purpose of the Study:

• To assess the risk of acute liver injury (ALI) associated with agomelatine.
• To compare ALI risk of agomelatine and other antidepressants (fluoxetine, paroxetine, sertraline, escitalopram, mirtazapine, venlafaxine, duloxetine, amitriptyline) against citalopram.

Main Methods:

• A multinational nested case-control study (2009-2014) using electronic health records.
• Defined three ALI endpoints using ICD codes across inpatient and outpatient settings.
• Calculated adjusted odds ratios (ORs) for current antidepressant use versus citalopram.

Main Results:

• Over 3.2 million new antidepressant users were analyzed, including 74,440 agomelatine users.
• Agomelatine showed no increased risk of ALI hospitalization compared to citalopram (OR 0.48; 95% CI 0.13-1.71).
• Most other evaluated antidepressants also suggested a lower ALI risk than citalopram, though with wider confidence intervals.

Conclusions:

• Agomelatine was not linked to a higher risk of ALI hospitalization when compared to citalopram.
• European risk minimization measures for agomelatine may influence prescribing patterns and observed risk.
• Further research is needed to confirm the observed lower risks for agomelatine and other antidepressants versus citalopram.