Clozapine-associated pericarditis and pancreatitis in children and adolescents: A systematic literature review and pharmacovigilance study using the VigiBase database

Renato de Filippis; Carlos De Las Cuevas; Emilio J Sanz; Georgios Schoretsanitis; Christoph U Correll; Jose de Leon

doi:10.1016/j.schres.2023.10.027

Clozapine-associated pericarditis and pancreatitis in children and adolescents: A systematic literature review and pharmacovigilance study using the VigiBase database

Schizophr Res. 2023 Nov 18:S0920-9964(23)00387-0. doi: 10.1016/j.schres.2023.10.027. Online ahead of print.

Authors

Renato de Filippis¹, Carlos De Las Cuevas², Emilio J Sanz³, Georgios Schoretsanitis⁴, Christoph U Correll⁵, Jose de Leon⁶

Affiliations

¹ Psychiatry Unit, Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy. Electronic address: rdefilippis@unicz.it.
² Department of Internal Medicine, Dermatology and Psychiatry, School of Medicine, University of La Laguna, Canary Islands, Spain; Instituto Universitario de Neurociencia (IUNE), Universidad de La Laguna, San Cristóbal de La Laguna, Spain.
³ Department of Physical Medicine and Pharmacology, School of Medicine, Universidad de La Laguna, Canary Islands, Spain; Hospital Universitario de Canarias, Tenerife, Spain.
⁴ Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zürich, Zürich, Switzerland; Department of Psychiatry Research, Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, USA.
⁵ Department of Psychiatry Research, Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, USA; Department of Psychiatry and Molecular Medicine, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, NY, USA; Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany. Electronic address: CCorrell@northwell.edu.
⁶ Mental Health Research Center at Eastern State Hospital, Lexington, KY, USA; Biomedical Research Centre in Mental Health Net (CIBERSAM), Santiago Apostol Hospital, University of the Basque Country, Vitoria, Spain. Electronic address: jdeleon@uky.edu.

PMID: 37981478
DOI: 10.1016/j.schres.2023.10.027

Abstract

Background: The literature has paid very little attention to pericarditis, pericardial effusion and pancreatitis during clozapine treatment in children and adolescents.

Methods: Cases of clozapine-associated pericarditis and pancreatitis in children were studied using searches in: 1) PubMed (June 16, 2023), and 2) the World Health Organization's pharmacovigilance database (June 1, 2022), VigiBase. VigiBase uses a logarithmic measure of disproportionality called the information component (IC).

Results: The PubMed search yielded 3 clozapine-associated pericarditis cases, 1 pancreatitis case and 1 with both. VigiBase provided a significant clozapine-associated pericarditis IC = 3.6 with an IC₀₂₅ = 2.9 (only 3 cases were expected while 22 were observed). VigiBase provided a significant clozapine-associated pancreatitis IC = 2.2 with an IC₀₂₅ = 1.4 (only 3 cases were expected while 16 were observed). In VigiBase clozapine-associated pericarditis and pericardial effusion in youth looked similar and on a continuum with myocarditis, as myocarditis, pericarditis and pancreatitis appeared to occur mainly during clozapine titration. Combining PubMed and VigiBase we identified: 1) 29 cases of at least possible clozapine-associated pericarditis/pericardial effusion (6 probable and 23 possible) including 7 cases with and 22 without myocarditis, and 2) 17 cases of clozapine-associated pancreatitis (1 definite and 16 possible). Two of the pancreatitis cases occurred during overdoses. No fatal outcomes were found in any clozapine-associated pericarditis and pancreatitis cases.

Conclusions: Despite the lack of attention in the literature to clozapine-associated pericarditis and pancreatitis, results demonstrate that they can happen in youth, particularly during titration. Pericarditis and pancreatitis appear to be forms of clozapine-associated inflammation during dose titration.

Keywords: Clozapine/administration and dosage; Clozapine/adverse effects; Clozapine/toxicity; Pancreatitis; Pericardial effusion; Pericarditis.