@article{ref1,
title="Focus on clozapine withdrawal-and misuse-related cases as reported to the european medicines agency (EMA) pharmacovigilance database",
journal="Brain sciences",
year="2020",
author="Chiappini, S. and Schifano, F. and Corkery, J.M. and Guirguis, A.",
volume="10",
number="2",
pages="-",
abstract="BACKGROUND: Clozapine is of high clinical relevance for the management of both treatment-resistant schizophrenia and psychotic disturbances with concurrent drug misuse. Although the molecule presents with a range of well-known side-effects, its discontinuation/withdrawal syndrome has been only anecdotally described. Aims: the 2005-2018 European Medicines Agency (EMA) dataset of Adverse Drug Reactions (ADRs) was analyzed to identify and describe possible clozapine withdrawal-and misuse-/abuse-/dependence-related issues. <br><br>METHOD: A descriptive analysis of clozapine-related ADRs was performed when available, data on ADRs' outcome, dosage, and possible concomitant drug(s) were considered. <br><br>RESULTS: Out of 11,847 clozapine-related ADRs, some 599 (5.05%) were related to misuse/abuse/dependence/withdrawal issues, including 258 withdrawal-related (43.1%); 241 abuse-related (40.2%); and 80 intentional product misuse-related (13.3%) ADRs. A small number of overdose-and suicide-related ADRs were reported as well. Clozapine was typically (69.2%) identified alone, and most (84.7%) fatalities/high-dosage intake instances were reported in association with a history of substance abuse. <br><br>CONCLUSIONS: Previous suggestions about the possibility of a clozapine discontinuation/withdrawal occurrence are here supported, but further studies are needed. However, the misuse/abuse cases here identified might be difficult to interpret, given the lack of studies highlighting the possible recreational use of clozapine. The high-dosage intake, fatal outcomes and clozapine/polydrug abuse issues reported here may, however, be a reason for concern. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.<p /><p>Language: en</p>",
language="en",
issn="2076-3425",
doi="10.3390/brainsci10020105",
url="http://dx.doi.org/10.3390/brainsci10020105"
}