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

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.