| アブストラクト | BACKGROUND: Clozapine is associated with a high risk of central nervous system abnormalities. However, seizure risk related to interactions between clozapine and other antipsychotics remains poorly characterized, and the pharmacological mechanisms underlying these seizures are unclear. OBJECTIVES: We aimed to evaluate safety signals for seizures associated with clozapine augmentation by other antipsychotics and analyze the relationship between these signals and neurotransmitter receptor occupancy profiles. DESIGN: A pharmacovigilance-pharmacodynamic analysis using a spontaneous reporting system. METHODS: This pharmacovigilance study used VigiBase, an adverse drug reaction database maintained by the World Health Organization. Drug-drug interactions (DDIs) between clozapine and other antipsychotics were assessed using the Omega shrinkage measure model. The association between DDI signals and neurotransmitter receptor occupancy was evaluated using linear regression. Robustness was tested using four frequency statistical models: additive, multiplicative, combination risk ratio, and chi-square statistic models. RESULTS: Of 38,758,077 reports in VigiBase between 1990 and 2024, 230,371 involved clozapine. Among antipsychotics classified under ATC code N05A, DDIs with clozapine were detected for amisulpride, chlorpromazine, haloperidol, lurasidone, olanzapine, penfluridol, risperidone, sulpiride, zotepine, and zuclopenthixol. A significant association between dopamine D(4) receptor occupancy and the point estimates of signal values was observed in the Omega shrinkage measure model (beta = 0.295, 95% confidence interval: 0.119-0.471, p = 0.002) and replicated across all frequency statistical models. CONCLUSIONS: These findings suggest a potential role of dopamine D(4) receptor occupancy in seizures associated with clozapine augmentation by other antipsychotics. Further large-scale epidemiological studies are needed to validate these findings. |
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| ジャーナル名 | Therapeutic advances in psychopharmacology |
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| Pubmed追加日 | 2026/8/2 |
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| 投稿者 | Hatano, Masakazu; Hamano, Hirofumi; Kanda, Masaya; Koseki, Takenao; Nakai, Tsuyoshi; Horii, Rina; Yoshihara, Nozomi; Saito, Takeo; Takechi, Kenshi; Esumi, Satoru; Zamami, Yoshito; Yamada, Shigeki |
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| 組織名 | Department of Pharmacotherapeutics and Informatics, Fujita Health University;School of Medicine, 1-98 Dengakugakubo, Kutsukake, Toyoake 470-1192, Japan.;Department of Pharmacy, Okayama University Hospital, Okayama, Japan.;Department of Pharmacy, Asahikawa Medical University Hospital, Asahikawa, Japan.;School of Medicine, Toyoake, Japan.;Department of Advanced Medical Professional Development, Fujita Health University;Graduate School of Medical Sciences, Toyoake, Japan.;Department of Psychiatry, Fujita Health University School of Medicine, Toyoake,;Japan.;Department of Drug Information Analysis, College of Pharmaceutical Sciences,;Matsuyama University, Matsuyama, Japan.;The Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Japan. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/42540002/ |
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