de Leon Jose, Sagud Marina, Sanz Emilio J, De Las Cuevas Carlos
Mental Health Research Center at Eastern State Hospital, Lexington, KY, USA; Biomedical Research Centre in Mental Health Net (CIBERSAM), Santiago Apóstol Hospital, University of the Basque Country, Vitoria, Spain.
School of Medicine, University of Zagreb, Zagreb, Croatia; University Hospital Centre Zagreb, Zagreb, Croatia.
Psychiatry Res. 2025 May;347:116408. doi: 10.1016/j.psychres.2025.116408. Epub 2025 Feb 17.
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.
由于自杀率较高，克罗地亚已实施了反自杀措施。氯氮平具有抗自杀作用。我们利用国际数据库（VigiBase），探究了克罗地亚不同寻常的氯氮平药物警戒情况。首先，我们将英国与克罗地亚在氯氮平药物不良反应（ADR）以及自氯氮平引入至2023年1月15日期间的致命后果方面进行了比较。若将英国的情况视为1，在对人口进行调整后，克罗地亚的发生率要低得多（氯氮平ADR报告：1比0.08；致命后果：1比0.02；氯氮平报告占所有药物报告的百分比：1比0.14）。截至2023年，英国有52252份氯氮平治疗患者的ADR报告和6567例致命后果，而克罗地亚分别为395份报告和6例致命后果。克罗地亚药物警戒机构（以及大多数国家机构）需要向英国机构学习，以更好地报告氯氮平ADR。其次，我们分析了向VigiBase报告的克罗地亚氯氮平治疗患者的自杀行为。截至2023年，英国报告了537例至少有1次自杀行为的氯氮平治疗患者，而克罗地亚为95例。在对人口进行调整后，英国报告的自杀行为报告数量比克罗地亚少得多（1比2.73）。克罗地亚医生的这种过度报告可能是克罗地亚反自杀措施成功的一个迹象。77例克罗地亚故意过量服药患者的致命后果百分比为1.3%（1/77），而411例非克罗地亚患者为16.8%，但这可能受到早期报告的影响（患者可能在报告后死亡）。克罗地亚需要对氯氮平过量情况进行纵向研究。
