Hepatotoxicity associated with agomelatine and other antidepressants: Disproportionality analysis using pooled pharmacovigilance data from the Uppsala Monitoring Centre. (9th March 2015)

• Record Type: Journal Article
• Authors: Gahr, Maximilian; Zeiss, René; Lang, Dirk; Connemann, Bernhard J.; Schönfeldt‐Lecuona, Carlos
• Is Part Of: Journal of clinical pharmacology. Volume 55:Number 7(2015:Jul.)
• Page Start: 768
• Page End: 773
• Publication Date: 2015-03-09
• Subjects: Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1002/jcph.475
• Languages: English
• ISSNs: 0091-2700

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="jcph475-sec-0001" sec-type="section"> <p>Since its marketing approval, the attention to the hepatic side‐effect profile of the antidepressant agomelatine (AGM) has gradually increased. Several cases of severe hepatotoxic adverse drug reactions (ADR) have been reported and the European Medicines Agency has released a safety warning regarding AGM‐associated hepatotoxicity. However, there are insufficient data for an adequate safety assessment of AGM‐related hepatotoxicity. Therefore, we performed a quantitative signal detection analysis using pharmacovigilance data from the Uppsala Monitoring Centre from the WHO that records ADR data from worldwide sources; we calculated reporting odds ratios (ROR) as measures for disproportionality within a case/non‐case approach for AGM and several other antidepressants. AGM was statistically associated with an increased risk of hepatotoxicity (ROR 6.4 [95%CI 5.7–7.2]) as well as both positive controls: amineptine (ROR 38.4 [95%CI 33.8–43.6]) and nefazodone (ROR 3.2 [95%CI 3.0–3.5]). Following amineptine, AGM was associated with the second highest ROR, followed by tianeptine (ROR 4.4 [95%CI 3.6–5.3]), mianserin (ROR 3.6 [95%CI 3.3–3.9]), and nefazodone. These results support the hypothesis that AGM is associated with relevant hepatotoxicity. However, the used data and applied method do not allow a quantitative evaluation of hepatotoxicity or assessment of substance‐specific differences regarding the extent of hepatotoxicity.</p> </sec> </abstract>