title: Drug-Induced Liver Injury Associated With Antidepressive Psychopharmacotherapy: An Explorative Assessment Based on Quantitative Signal Detection Using Different MedDRA Terms.
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.
authors.affiliation: University of Ulm, Department of Psychiatry and Psychotherapy III, Ulm, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Gahr
authors.affiliation: University of Ulm, Department of Psychiatry and Psychotherapy III, Ulm, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Zeiss
authors.affiliation: University of Ulm, Department of Psychosomatic Medicine and Psychotherapy, Ulm, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Lang
authors.affiliation: University of Ulm, Department of Psychiatry and Psychotherapy III, Ulm, Germany.
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Connemann
authors.affiliation: University Medical Center of Mainz, Department of Psychiatry and Psychotherapy, Mainz, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
authors.affiliation: University of Ulm, Department of Psychiatry and Psychotherapy III, Ulm, Germany.
authors.forename: Carlos
authors.initials: C
authors.lastname: Schönfeldt-Lecuona
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000592:standards* / Q000639:trends; D000928:Antidepressive Agents / Q000009:adverse effects*; D001315:Australia / Q000453:epidemiology; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis* / Q000453:epidemiology*; D016208:Databases, Factual / Q000592:standards* / Q000639:trends; D005060:Europe / Q000453:epidemiology; D006801:Humans; D038622:Internationality; D014481:United States / Q000453:epidemiology
chemical_list: D000928:Antidepressive Agents
keywords: adverse drug reaction; antidepressant; data mining; disproportionality analysis; drug safety; liver enzymes; pharmacovigilance