A systematic review of agomelatine-induced liver injury

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evaluate the potential risk posed by agomelatine of inducing liver injury by reviewing data from published and unpublished clinical trials in both the pre- and postmarketing settings, as well as data from non-interventional studies, pharmacovigilance database reviews and one case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.

Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis

“…Agomelatine (based on our small cumulative samples) was the only drug with established effectiveness among the new pharmacologic options to treat GAD, and showed improved acceptability compared to active drugs including benzodiazepine, quetiapine and paroxetine. In practice however, agomelatine may have limited use on account of concerns about liver toxicity [25].…”

The Safety, Tolerability and Risks Associated with the Use of Newer Generation Antidepressant Drugs: A Critical Review of the Literature

“…On the other hand, the risk of liver toxicity for nefazodone was so high that it was subsequently withdrawn from the market [45]. A recent systematic review found that the incidence of agomelatine-induced liver injury was as high as 4.6% and the risk of liver injury appeared to be dose dependent [46]. Case reports of life-threatening liver toxicity, in some cases requiring liver transplantation, have been described in the literature for nefazodone, duloxetine, venlafaxine and agomelatine [41].…”

Comparison of the effects of sertraline and agomelatine on sleep quality, sexual functioning and metabolic parameters in patients with major depressive disorder

“…agomelatine, and duloxetine [30]. In a systematic review of agomelatine-induced liver injuries [31], agomelatine was found to be associated with higher rates of liver injury than a placebo, escitalopram, paroxetine, fluoxetine, and sertraline, and a positive relationship was evidenced between agomelatine dose and liver injury. In a recent study of 896 patients with depression using agomelatine [32], liver enzymes (AST, ALT, GGT, ALP) were found to be elevated after 12 weeks of treatment, although these elevations did not exceed three times the upper limits of the established norms.…”