Severe antipsychotic-associated gastrointestinal hypomotility: AMSP pharmacovigilance data from 333,175 psychiatric inpatients

Abstract Background Severe courses of gastrointestinal hypomotility (GIH) are rare but potentially life-threatening adverse drug reactions (ADRs) associated with antipsychotic drugs (APDs). This study aimed to investigate the frequency, clinical characteristics, and associated drugs of severe APD-associated GIH. Methods Severe cases of GIH reported within the multicentred observational pharmacovigilance project “Arzneimittelsicherheit in der Psychiatrie” (AMSP) between 1993 and 2016 were retrospectively analysed. Among 495,615 psychiatric inpatients, 333,175 were treated with APDs. Severe GIH (including severe constipation, subileus and ileus) associated with APDs, were identified and analysed. Descriptive statistics and Fisher’s exact tests or chi-squared tests were performed where appropriate. Results A total of 41 cases of severe GIH was documented among 333,175 APD-treated patients (0.012%). Severe constipation accounted for 46.3% of all documented cases, followed by subileus (31.7%) and ileus (22.0%). Clozapine was the APD most frequently implicated among reported severe GIH cases (48.8% of all cases), followed by quetiapine (31.7%). Most cases involved a combination of imputed drugs (70.7%), frequently including drugs with strong anticholinergic properties. Particularly, concomitant treatment with pirenzepine was associated with a higher reporting frequency ( p = 0.027) of severe GIH among clozapine treated patients. Three patients (7.3% of GIH cases) died following paralytic ileus associated with clozapine treatment. Conclusion Severe APD-associated GIH seems to be rare but potentially fatal, although the true incidence may be underestimated due to the focus on severe cases and pharmacovigilance-based reporting. Clozapine and concomitant anticholinergic drugs were frequently implicated in severe GIH cases and may contribute to increased vulnerability. Careful assessment, clinical monitoring, and patient education regarding early symptoms are important in prevention.