Citation

Chiappini S, Schifano F, Corkery JM, Guirguis A. Brain Sci. 2020; 10(2).

Copyright

(Copyright © 2020, Switzerland Molecular Diversity Preservation International (MDPI) AG)

DOI

10.3390/brainsci10020105

PMID

unavailable

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.

METHOD: A descriptive analysis of clozapine-related ADRs was performed when available, data on ADRs' outcome, dosage, and possible concomitant drug(s) were considered.

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.

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.

Language: en

Keywords

adult; human; suicide; female; male; aged; Overdose; schizophrenia; suicidal behavior; clozapine; Clozapine; drug overdose; major clinical study; drug dependence; drug withdrawal; drug misuse; withdrawal syndrome; Withdrawal; Article; Dependence; Misuse; Adverse drug reactions; neutrophil count