Drug‐Induced Liver Injury Associated With Antidepressive Psychopharmacotherapy: An Explorative Assessment Based on Quantitative Signal Detection Using Different MedDRA Terms. (14th December 2015)

• Record Type: Journal Article
• Authors: Gahr, Maximilian; Zeiss, René; Lang, Dirk; Connemann, Bernhard J.; Hiemke, Christoph; Schönfeldt‐Lecuona, Carlos
• Is Part Of: Journal of clinical pharmacology. Volume 56:Number 6(2016)
• Page Start: 769
• Page End: 778
• Publication Date: 2015-12-14
• Subjects: adverse drug reaction -- antidepressant -- data mining -- disproportionality analysis -- drug safety -- liver enzymes -- pharmacovigilance; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1002/jcph.662
• Languages: English
• ISSNs: 0091-2700

Abstract

Abstract: Drug‐induced liver injury is a major problem of pharmacotherapy and is also frequent with antidepressive psychopharmacotherapy. However, there are only few studies using a consistent methodologic approach to study hepatotoxicity of a larger group of antidepress ants. We performed a quantitative signal detection analysis using data from the Uppsala Monitoring Centre from the WHO that records adverse drug reaction (ADR) data from worldwide sources; we retrieved substance‐ and country‐specific (Australia, France, Germany, Italy, Spain, the United Kingdom, and the United States) ADR data and calculated reporting odds ratios as measures for disproportionality within a case/noncase approach. To allow for identification of agents that cause severe forms of hepatotoxic ADRs, we used 2 terms of the MedDRA ("drug‐related hepatic disorders‐comprehensive search" [DRHD‐CS] and "… ‐severe events only" [DRHD‐SEO]). Distribution of signals was heterogeneous throughout the different data sets, and consistent findings were present for only a few substances: agomelatine (AGM) and tianeptine as well as both positive control agents (amineptine, nefazodone) generated signals related to DRHD‐CS and DRHD‐SEO in all analyzed data sets. Tri‐ and tetracyclic antidepressants (here amitriptyline, clomipramine, mianserin, mirtazapine, trimipramine) were associated with hepatotoxicity in several data sets. Using 2 MedDRA terms did not allow for detection of agents that cause severe hepatotoxic ADR. Our results support the findings of previous, primarily literature‐based, systematic analyses of hepatotoxicity related to antidepressive psychopharmacotherapy. No new safety information could be generated. Application of 2 MedDRA terms did not increase the substance‐specific safety information.