Drug-induced megacolon in schizophrenia: a pharmacovigilance study of antipsychotic medications from the Japanese Adverse Drug Event database: a disproportionality analysis

Megacolon, characterized by colon dilation due to a nerve plexus disorder, can be fatal if untreated. Antipsychotic drugs for schizophrenia have anticholinergic effects that may cause chronic constipation and impaired gastrointestinal motility, potentially leading to megacolon. However, the megacolon risk associated with each antipsychotic drug has not been thoroughly evaluated. This study characterized the drug-induced megacolon using the Japanese adverse drug event database A retrospective pharmacovigilance disproportionality analysis was conducted using the Japanese Adverse Drug Event Report from April 2004 to April 2024. The study included 10,884 schizophrenia patients with, with 72 reports of antipsychotic-induced megacolon. Antipsychotic-induced megacolon was reported with 13 different antipsychotic drugs. Analysis of the reporting odds ratio for drug-induced megacolon for each antipsychotic revealed three drugs with statistically significant positive signals: zotepine = 7.25; sulpiride = 4.53; and quetiapine = 4.34. In addition, logistic regression analysis revealed that antipsychotic-induced megacolon is characterized by female sex. Zotepine, sulpiride, and quetiapine are associated with antipsychotic-induced megacolon in schizophrenia patients, and it is suggested that there is a gender difference. This study provides novel evidence for evaluating adverse drug events related to schizophrenia pharmacotherapy, contributing to improved quality of life for these patients.

巨结肠（Megacolon）是因神经丛障碍导致结肠扩张的疾病，若未及时治疗可能致命。用于精神分裂症治疗的抗精神病药物具有抗胆碱能效应，可能引发慢性便秘及胃肠动力障碍，进而潜在导致巨结肠。然而，每种抗精神病药物相关的巨结肠风险尚未得到全面评估。本研究通过日本药品不良反应数据库明确了药物诱导性巨结肠的特征，并基于2004年4月至2024年4月的《日本药品不良反应报告》开展了回顾性药物警戒不均衡性分析（disproportionality analysis）。研究纳入10884名精神分裂症患者，其中包含72例抗精神病药物诱导性巨结肠的报告。共有13种不同的抗精神病药物被报告与诱导性巨结肠相关。对每种抗精神病药物引发巨结肠的报告比值比（reporting odds ratio）分析显示，三种药物具有统计学意义的阳性信号：佐替平（zotepine）=7.25；舒必利（sulpiride）=4.53；喹硫平（quetiapine）=4.34。此外，逻辑回归分析（logistic regression analysis）表明，抗精神病药物诱导性巨结肠在女性群体中更为突出。佐替平、舒必利和喹硫平与精神分裂症患者的抗精神病药物诱导性巨结肠相关，且研究提示存在性别差异。本研究为评估精神分裂症药物治疗相关的药品不良反应提供了新证据，有助于改善该类患者的生活质量。