Clozapine pharmacovigilance in Croatia: Underreporting of specific adverse drug reactions and excellent reporting of suicide attempts: Clozapine Croatia suicide

Jose de Leon; Marina Sagud; Emilio J. Sanz; Carlos De las Cuevas

doi:10.1016/j.psychres.2025.116408

Clozapine pharmacovigilance in Croatia: Underreporting of specific adverse drug reactions and excellent reporting of suicide attempts: Clozapine Croatia suicide

Jose de Leon
, Marina Sagud
, Emilio J. Sanz
, Carlos De las Cuevas

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Croatia has implemented anti-suicide measures due to its high suicide rates. Clozapine has anti-suicidal effects. Using the international database (VigiBase), we explored Croatia's unusual clozapine pharmacovigilance. First, we compared the United Kingdom (UK) with Croatia for clozapine adverse drug reactions (ADRs) and fatal outcomes from clozapine's introduction through January 15, 2023. If the UK is considered 1, and after adjusting for population, Croatia had much lower rates (1 vs. 0.08 for clozapine ADR reports, 1 vs. 0.02 for fatal outcomes and 1 vs. 0.14 for percentage of clozapine reports out of all drug reports). Through 2023, the UK had 52,252 ADR reports and 6,567 fatal outcomes from clozapine-treated patients vs. Croatia with 395 reports and 6 fatal outcomes. The Croatian pharmacovigilance agency (and most national agencies) needs to learn from the UK's agency to better report clozapine ADRs. Second, we analyze suicide behaviors in Croatian clozapine-treated patients reported to VigiBase. Through 2023 the UK reported 537 clozapine-treated patients with at least 1 suicidal behavior versus 95 from Croatia. After adjusting for population, the UK reported a much smaller number of reports of suicidal behavior than Croatia (1 vs. 2.73). This overreporting by Croatian physicians may be a sign of the success of Croatia's anti-suicide measures. The percentage of fatal outcomes in 77 Croatian patients with an intentional overdose was 1.3 % (1/77) vs. 16.8 % in 411 non-Croatian patients, but this is possibly contaminated by early reporting (patients might die after the report). Longitudinal studies of clozapine overdoses in Croatia are needed.

Original language	English
Article number	116408
Journal	Psychiatry Research
Volume	347
DOIs	https://doi.org/10.1016/j.psychres.2025.116408
State	Published - May 2025

Bibliographical note

Publisher Copyright:
© 2025 Elsevier B.V.

Funding

The authors acknowledge Lorraine Maw, M.A. from the University of Kentucky Mental Health Research Center at Eastern State Hospital, who helped in editing the article. The authors are indebted to the national centers that make up the World Health Organization (WHO) Program for International Drug Monitoring and contribute reports to VigiBase at the Uppsala Monitoring Centre. The information comes from a variety of sources, and the probability that the suspected adverse effect is drug-related is not the same in all cases. However, the opinions and conclusions of this study are not necessarily those of the various centers nor of the WHO.

Funders
Lorraine Maw
University of Kentucky Mental Health Research Center at Eastern State Hospital
national centers that make up the World Health Organization
World Health Organization

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Clozapine
Drug overdose
Pharmacovigilance
Suicidal ideation
Suicide, attempted
Suicide, completed

ASJC Scopus subject areas

Psychiatry and Mental health
Biological Psychiatry

Access to Document

10.1016/j.psychres.2025.116408

Cite this

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title = "Clozapine pharmacovigilance in Croatia: Underreporting of specific adverse drug reactions and excellent reporting of suicide attempts: Clozapine Croatia suicide",

abstract = "Croatia has implemented anti-suicide measures due to its high suicide rates. Clozapine has anti-suicidal effects. Using the international database (VigiBase), we explored Croatia's unusual clozapine pharmacovigilance. First, we compared the United Kingdom (UK) with Croatia for clozapine adverse drug reactions (ADRs) and fatal outcomes from clozapine's introduction through January 15, 2023. If the UK is considered 1, and after adjusting for population, Croatia had much lower rates (1 vs. 0.08 for clozapine ADR reports, 1 vs. 0.02 for fatal outcomes and 1 vs. 0.14 for percentage of clozapine reports out of all drug reports). Through 2023, the UK had 52,252 ADR reports and 6,567 fatal outcomes from clozapine-treated patients vs. Croatia with 395 reports and 6 fatal outcomes. The Croatian pharmacovigilance agency (and most national agencies) needs to learn from the UK's agency to better report clozapine ADRs. Second, we analyze suicide behaviors in Croatian clozapine-treated patients reported to VigiBase. Through 2023 the UK reported 537 clozapine-treated patients with at least 1 suicidal behavior versus 95 from Croatia. After adjusting for population, the UK reported a much smaller number of reports of suicidal behavior than Croatia (1 vs. 2.73). This overreporting by Croatian physicians may be a sign of the success of Croatia's anti-suicide measures. The percentage of fatal outcomes in 77 Croatian patients with an intentional overdose was 1.3 \% (1/77) vs. 16.8 \% in 411 non-Croatian patients, but this is possibly contaminated by early reporting (patients might die after the report). Longitudinal studies of clozapine overdoses in Croatia are needed.",

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JO - Psychiatry Research

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M1 - 116408

ER -

Clozapine pharmacovigilance in Croatia: Underreporting of specific adverse drug reactions and excellent reporting of suicide attempts: Clozapine Croatia suicide

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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Cite this