title: Hepatic injury and pancreatitis during treatment with serotonin reuptake inhibitors: data from the World Health Organization (WHO) database of adverse drug reactions.
abstract: Severe hepatic adverse drug reactions have been occasionally reported in the literature for the selective serotonin reuptake inhibitors (SSRIs), venlafaxine and nefazodone. In addition, a few case reports have suggested a possible association between SSRI treatment and pancreatitis. To further investigate this issue, a Bayesian confidence propagation neural network (BCPNN) method was applied on the World Health Organization database of adverse drug reactions. This method identifies whether a drug/adverse drug reaction combination is reported more frequently to the database than expected on the basis of chance alone compared to general reporting in the database. A statistically significant unexpected high number of reports were found for nefazodone and hepatic injury, relative to the generality of the dataset but, for the other drug/adverse drug reaction combinations, no such association was found. The nefazodone finding is in accordance with data from other publications, suggesting that the risk of hepatic injury is increased. However, because of the nature of the BCPNN, the negative findings do not necessarily prove that there is no excess risk for hepatic injury/pancreatitis during treatment with drugs other than nefazodone. Further studies are required using alternative methodologies to demonstrate whether the selective serotonin reuptake inhibitors or venlafaxine may cause hepatic injury or pancreatitis.
authors.affiliation: Department of Clinical Pharmacology, St Olav's University Hospital, Trondheim, Norway. olav.spigset@legemidler.no
authors.forename: Olav
authors.initials: O
authors.lastname: Spigset
authors.forename: Staffan
authors.initials: S
authors.lastname: Hägg
authors.forename: Andrew
authors.initials: A
authors.lastname: Bate
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D001499:Bayes Theorem; D056486:Chemical and Drug Induced Liver Injury; D003511:Cyclohexanols / Q000009:adverse effects* / Q000627:therapeutic use; D016208:Databases, Factual; D006801:Humans; D016571:Neural Networks, Computer; D010195:Pancreatitis / Q000139:chemically induced*; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D014230:Triazoles / Q000009:adverse effects* / Q000627:therapeutic use; D000069470:Venlafaxine Hydrochloride; D014944:World Health Organization
chemical_list: D003511:Cyclohexanols; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; D014230:Triazoles; D000069470:Venlafaxine Hydrochloride; C051752:nefazodone