Abstract
Agomelatine is an antidepressant with a unique mechanism of action. Since its marketing in 2009, concerns have been raised regarding its potential to induce liver injury. The authors therefore address the need to comprehensively evaluate the potential risk posed by agomelatine of inducing liver injury by reviewing data from published and unpublished clinical trials in both the pre- and postmarketing settings, as well as data from non-interventional studies, pharmacovigilance database reviews and one case report. Recommendations for clinicians are also provided.In this review, agomelatine was found to be associated with higher rates of liver injury than both placebo and the four active comparator antidepressants used in the clinical trials for agomelatine, with rates as high as 4.6% for agomelatine compared to 2.1% for placebo, 1.4% for escitalopram, 0.6% for paroxetine, 0.4% for fluoxetine, and 0% for sertraline. The review also provides evidence for the existence of a positive relationship between agomelatine dose and liver injury. Furthermore, rates of liver injury were found to be lower in non-interventional studies. Findings from pharmacovigilance database reviews and one case report also highlight the risk of agomelatine-induced liver injury.As agomelatine does pose a risk of liver injury, clinicians must carefully monitor liver function throughout treatment. However, agomelatine’s unique mechanism of action and favourable safety profile render it a valuable treatment option.A quantitative analysis of agomelatine-induced liver injury is lacking in the literature and would be welcomed.
Highlights
Synthesized for the first time in 1992 [1], agomelatine has been licensed for the treatment of Major Depressive Disorder (MDD) in adults since 2009 in the European Union [2] and since 2010 in Australia [3].Its short-term efficacy and tolerability have recently been systematically examined by Taylor et al [4] using data from both published and unpublished clinical trials
Findings from Gahr and colleagues [20] likewise highlight polypharmacy as a potential risk factor for agomelatineinduced hepatotoxicity. To our knowledge, this is the first review that solely provides an in-depth evaluation of agomelatine-induced liver injury compared to placebo and the four active comparator AD treatments used in the clinical trials for agomelatine by reviewing findings from both the preand postmarketing settings, and by including published and unpublished studies
When combining findings from pre- and postmarketing clinical trials, we find that significant elevations in liver enzymes (>3X upper limit of normal (ULN)) have been found to occur at a rate of up to 4.6% (25/50 mg) following the administration of agomelatine
Summary
Synthesized for the first time in 1992 [1], agomelatine has been licensed for the treatment of Major Depressive Disorder (MDD) in adults since 2009 in the European Union [2] and since 2010 in Australia [3]. In a six-week study by Kasper et al [28], where patients with MDD received either agomelatine (25/50 mg) or sertraline (50/100 mg), significant elevations in liver enzymes were noted in one patient (0.7%) receiving agomelatine (dosage not mentioned; percentage calculated using the safety set) The authors describe this patient as an alcoholic, and no additional information is provided. In an eight-week study in elderly MDD outpatients (aged ≥ 65 years) comparing agomelatine (25/50 mg) to placebo by Heun et al [41], two patients (1.3%; percentage calculated from safety set) receiving agomelatine (one aged ≥ 75 years; specific dosage not reported) with normal liver enzyme values at baseline showed significant elevations in liver enzymes during the study treatment. Findings from Gahr and colleagues [20] likewise highlight polypharmacy as a potential risk factor for agomelatineinduced hepatotoxicity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
