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Chiappini S, Schifano F, Corkery JM, et al. Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database. Brain Sci. 2020;10(2)doi: 10.3390/brainsci10020105.
Chiappini, S., Schifano, F., Corkery, J. M., & Guirguis, A. (2020). Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database. Brain sciences, 10(2), . https://doi.org/10.3390/brainsci10020105
Chiappini, Stefania, et al. "Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database." Brain sciences vol. 10,2 (2020). doi: https://doi.org/10.3390/brainsci10020105
Chiappini S, Schifano F, Corkery JM, Guirguis A. Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database. Brain Sci. 2020 Feb 16;10(2). doi: 10.3390/brainsci10020105. PMID: 32079135; PMCID: PMC7071448.
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Brain Sci. 2020 Feb 16;10(2). doi: 10.3390/brainsci10020105.

Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database.

Brain sciences

Stefania Chiappini, Fabrizio Schifano, John Martin Corkery, Amira Guirguis

Affiliations

  1. Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Hertfordshire AL10 9AB, UK.
  2. Swansea University Medical School, Institute of Life Sciences 2, Swansea University, Singleton Park, Swansea SA2 8PP, UK.

PMID: 32079135 PMCID: PMC7071448 DOI: 10.3390/brainsci10020105

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.

Keywords: adverse drug reactions; clozapine; dependence; misuse; overdose; withdrawal

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