Agomelatine-induced hepatotoxicity

Štuhec, Matej

doi:10.1007/s00508-013-0344-0

Cited by 22 publications

(11 citation statements)

References 10 publications

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“…In any case, such data are helpful in identifying potential risk factors associated with agomelatine and liver injury, and here Gahr et al [20] highlight the female gender, increased aged, and polypharmacy. Interestingly, two of these potential risk factors (i.e., female gender and increased age) figure in the one published case report of agomelatine-induced hepatotoxicity found during the writing of this article [47]. …”

Section: Discussionmentioning

confidence: 99%

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A systematic review of agomelatine-induced liver injury

Freiesleben

Furczyk

2015

J Mol Psychiatr

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evaluate the potential risk posed by agomelatine of inducing liver injury by reviewing data from published and unpublished clinical trials in both the pre- and postmarketing settings, as well as data from non-interventional studies, pharmacovigilance database reviews and one case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

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Section: Discussionmentioning

confidence: 99%

“…We found one published case report of agomelatine-induced liver injury [47]. After 3 weeks of agomelatine treatment (dose increased from 25 mg to 50 mg in one week; no concurrent medications listed), a female patient aged 44 years old showed significant elevations in liver enzyme.…”

Section: Reviewmentioning

confidence: 99%

A systematic review of agomelatine-induced liver injury

Freiesleben

Furczyk

2015

J Mol Psychiatr

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“…It is rapidly absorbed orally and mainly metabolized via CYP1A2 hepatic isoenzymes, has no active metabolites. AG's mechanism of action (MT 1 and MT 2 receptor agonist) and its effects on the increase of noradrenaline level in the frontal prefrontal cortex (antagonizing 5HT 2C receptors in brainstem and release of noradrenaline and dopamine in prefrontal cortex) may explain its benefits in the treatment of MDD [6,7]. From a pharmacodynamic perspective, the combination of AG and MOC acts on different types of receptors (5HT 2C , MT 1 , MT 2 and MAO) and this can be possible therapeutic tools in the fight against treatment of treatment-resistant MDD, where many proven treatment strategy have not been effective.…”

Section: Introductionmentioning

confidence: 99%

Moclobemide as add-on therapy to agomelatine in a patient with treatment-resistant major depressive disorder: a psychopharmacological case

Štuhec

Oravecz

2015

Wien Klin Wochenschr

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“…Especially with regard to tricyclic antidepressants, a transient increase of liver enzymes is a frequent ADR [ 40 ] . Considering AGM-related hepatotoxic ADR there is a considerable discrepancy between the common clinical knowledge of the potential of AGM to cause hepatotoxic ADR and the factual availability of published data regarding AGM-related hepatotoxicity [ 41 ] . Nevertheless, results of a recent non-interventional, observational study involving n = 3 317 depressed outpatients treated with AGM for 12 weeks indicated a comparatively low incidence of elevation of liver enzymes (> 3-fold upper the limit of normal range) of 0.2 % [ 42 ] .…”

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confidence: 99%

Agomelatine and Hepatotoxicity: Implications of Cumulated Data Derived from Spontaneous Reports of Adverse Drug Reactions

et al. 2013

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Considering the antidepressant agomelatine (AGM) there is a discrepancy between the widespread knowledge of the potential of AGM to cause hepatotoxic adverse drug reactions (ADR) and the availability of corresponding published data. This impedes an adequate assessment of the hepatotoxicity profile of AGM. We conducted a query of the database of a German Medical Regulatory Body (BfArM) and analyzed spontaneous reports of hepatotoxic ADR. We identified n=58 cases of AGM-related hepatotoxic ADR. Most frequent ADR was asymptomatic increase of liver enzymes (79%); n=6 patients (10%) with AGM-related toxic hepatitis were reported. Characteristics of patients: female sex (69%), age > 50 years (mean 54 years), polypharmacy (57%), and presence of cardiovascular risk factors (58.5%). Most of the hepatotoxic ADR (90%) were reported to have improved/recovered after discontinuation of AGM. Our evaluation suggests that AGM features a potential to cause severe forms of hepatotoxicity and emphasizes that a pre-existing liver disease is a contraindication for treatment with AGM. Secondly, increased age, female sex and polypharmacy may be risk factors for the development of AGM-related hepatotoxic ADR.

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Agomelatine-induced hepatotoxicity

Cited by 22 publications

References 10 publications

A systematic review of agomelatine-induced liver injury

A systematic review of agomelatine-induced liver injury

Moclobemide as add-on therapy to agomelatine in a patient with treatment-resistant major depressive disorder: a psychopharmacological case

Agomelatine and Hepatotoxicity: Implications of Cumulated Data Derived from Spontaneous Reports of Adverse Drug Reactions

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