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Clozapine-induced gastrointestinal hypomotility: presenting features and outcomes, UK pharmacovigilance reports, 1992-2017

Citation

Handley, SA and Every-Palmer, S and Ismail, A and Flanagan, RJ, Clozapine-induced gastrointestinal hypomotility: presenting features and outcomes, UK pharmacovigilance reports, 1992-2017, British Journal of Psychiatry pp. 1-9. ISSN 0007-1250 (2022) [Refereed Article]

Copyright Statement

Copyright 2022 The Authors

DOI: doi:10.1192/bjp.2022.24

Abstract

Background: Clozapine-induced gastrointestinal hypomotility (CIGH) affects some 75% of patients treated with clozapine.

Aims: To document the incidence of potentially harmful CIGH in the UK.

Method: We studied spontaneous UK pharmacovigilance reports recorded as clozapine-related gastrointestinal adverse drug reactions, 1992-2017.

Results: There were 527 patients reported with potentially harmful CIGH; 33% (n = 172) died. Deaths averaged 1 per year 1992-1999, 5 per year 2000-2009 and 15 per year 2010-2017. Those who died were older (median 52 years v. 49 years) and had been prescribed clozapine for longer than those who recovered (median 11.3 years v. 4.8 years), but there was no difference in prescribed dose. Within the first 4 years of clozapine treatment, there were 169 reports of CIGH, of which 3% (n = 5) were fatal. At 10-14 years there were 63 reports of CIGH, of which 25% (n = 16) were fatal. Among the deaths, males were younger (median 51, range 22-89 v. median 57, range 24-89 years) with higher clozapine doses (median 450, range 100-900 v. median 300, range 12.5-800 mg/d) than females. In non-fatal CIGH, surgery was the most frequent outcome (n = 92). The procedures included appendectomy, ileostomy, total/partial colectomy, colostomy/stoma and proctosigmoidectomy. Clozapine dosage was reduced in 6 patients, stopped and restarted in 23, 'continued' in 6 and discontinued permanently in at least 76 patients.

Conclusions: The risk of serious morbidity/mortality from CIGH is substantial. The need to actively monitor bowel function and give laxatives to patients treated with clozapine is clear.

Item Details

Item Type:Refereed Article
Keywords:clozapine, adverse drug reactions, gastrointestinal hypomotility, constipation, pharmacovigilance
Research Division:Health Sciences
Research Group:Health services and systems
Research Field:General practice
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Handley, SA (Dr Simon Handley)
ID Code:149571
Year Published:2022
Web of Science® Times Cited:1
Deposited By:Medicine
Deposited On:2022-04-04
Last Modified:2022-05-13
Downloads:0

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