Antipsychotic-Related DRESS Syndrome: Analysis of Individual Case Safety Reports of the WHO Pharmacovigilance Database

Renato de Filippis; John M Kane; Elena Arzenton; Ugo Moretti; Emanuel Raschi; Gianluca Trifirò; Corrado Barbui; Pasquale De Fazio; Chiara Gastaldon; Georgios Schoretsanitis

doi:10.1007/s40264-024-01431-7

Antipsychotic-Related DRESS Syndrome: Analysis of Individual Case Safety Reports of the WHO Pharmacovigilance Database

Drug Saf. 2024 May 9. doi: 10.1007/s40264-024-01431-7. Online ahead of print.

Authors

Renato de Filippis¹, John M Kane^{2

3

4}, Elena Arzenton⁵, Ugo Moretti⁵, Emanuel Raschi⁶, Gianluca Trifirò⁵, Corrado Barbui⁷, Pasquale De Fazio⁸, Chiara Gastaldon^#^{7

9}, Georgios Schoretsanitis^#^{2

3

10}

Affiliations

¹ Psychiatry Unit, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100, Catanzaro, Italy. rdefilippis@unicz.it.
² The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, NY, USA.
³ Department of Psychiatry, Zucker School of Medicine at Northwell/Hofstra, Hempstead, NY, USA.
⁴ Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA.
⁵ Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
⁶ Pharmacology Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
⁷ WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy.
⁸ Psychiatry Unit, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100, Catanzaro, Italy.
⁹ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
¹⁰ Department of Psychiatry, Psychotherapy and Psychosomatics, Hospital of Psychiatry, University of Zurich, Zurich, Switzerland.

^# Contributed equally.

PMID: 38722481
DOI: 10.1007/s40264-024-01431-7

Abstract

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is gaining attention in pharmacovigilance, but its association with antipsychotics, other than clozapine, is still unclear.

Methods: We conducted a case/non-case study with disproportionality analysis based on the World Health Organization (WHO) global spontaneous reporting database, VigiBase®. We analyzed individual case safety reports of DRESS syndrome related to antipsychotics compared to (1) all other medications in VigiBase®, (2) carbamazepine (a known positive control), and (3) within classes (typical/atypical) of antipsychotics. We calculated reporting odds ratio (ROR) and Bayesian information component (IC), with 95% confidence intervals (CIs). Disproportionate reporting was prioritized based on clinical importance, according to predefined criteria. Additionally, we compared characteristics of patients reporting with serious/non-serious reactions.

Results: A total of 1534 reports describing DRESS syndrome for 19 antipsychotics were identified. The ROR for antipsychotics as a class as compared to all other medications was 1.0 (95% CI 0.9-1.1). We found disproportionate reporting for clozapine (ROR 2.3, 95% CI 2.1-2.5; IC 1.2, 95% CI 1.1-1.3), cyamemazine (ROR 2.3, 95% CI 1.5-3.5; IC 1.2, 95% CI 0.5-1.7), and chlorpromazine (ROR 1.5, 95% CI 1.1-2.1; IC 0.6, 95% CI 0.1-1.0). We found 35.7% of cases with co-reported anticonvulsants, and 25% with multiple concurrent antipsychotics in serious compared to 8.6% in non-serious cases (p = 0.03). Fatal cases were 164 (10.7%).

Conclusions: Apart from the expected association with clozapine, chlorpromazine and cyamemazine (sharing an aromatic heteropolycyclic molecular structure) emerged with a higher-than-expected reporting of DRESS. Better knowledge of the antipsychotic-related DRESS syndrome should increase clinicians' awareness leading to safer prescribing of antipsychotics.