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European Child & Adolescent Psychiatry
Article . 2024 . Peer-reviewed
License: Springer Nature TDM
Data sources: Crossref
https://dx.doi.org/10.5167/uzh...
Other literature type . 2025
Data sources: Datacite
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Evaluating the adverse drug reactions to clozapine in populations of children and adolescents: insights from VigiBase data

Authors: De las Cuevas, Carlos; Sanz, Emilio J; Jiménez-Fernández, Sara; Schoretsanitis, Georgios; Ruan, Can-Jun; de Leon, Jose;

Evaluating the adverse drug reactions to clozapine in populations of children and adolescents: insights from VigiBase data

Abstract

Pharmacovigilance findings have marked clozapine use. Prescribers and package inserts worldwide focus on clozapine-induced neutropenia. The literature on clozapine adverse drug reactions (ADRs) for those under age 18 and their associated fatal outcomes is limited. Reports to the World Health Organization's global pharmacovigilance database (VigiBase) were analyzed among patients under 18 years of age extending from clozapine's introduction to June 1, 2022. There were 2825 reports of clozapine, including 42 fatal outcomes (relative lethality = 1.5% vs. 11.7% in all ages). After 280 cases were excluded (clozapine exposure during pregnancy, accidental exposure or unclear age), 2455 were included with ADRs during therapeutic use. Decreased white blood cell (WBC) count provided the most frequent aggregated ADR, accounting for 934 cases (37% of 2545), with only 1 fatal outcome (0.01%, 1/934). Suicide explained 7 of 27 (26%) non-duplicated fatal outcomes. Next in importance was clozapine-induced gastrointestinal hypomotility (CIGH) with 3 cases (11% of 27) and neuroleptic malignant syndrome with 2 cases (7% of 27). Agranulocytosis, aspiration, myocarditis, myocardiopathy and ventricular arrythmia led to single fatal cases. Based on these new findings and recent literature in all ages, to prevent fatal outcomes, child and adolescent psychiatrists need to shift their focus from severe neutropenia to other ADRs including pneumonia, respiratory aspiration and CIGH. In spite of its potential toxicity during overdoses, clozapine may have specific and strong anti-suicidal effects when compared with other antipsychotics. Child and adolescent psychiatrists need to take extreme precautions to avoid intentional overdoses when prescribing clozapine to patients with suicide risk.

Keywords

3204 Developmental and Educational Psychology, 2738 Psychiatry and Mental Health, 10054 Clinic for Psychiatry, Psychotherapy, and Psychosomatics, 610 Medicine & health, 2735 Pediatrics, Perinatology and Child Health

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
4
Top 10%
Top 10%
Average
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