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

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.