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

Abstract

Clozapine-induced gastrointestinal hypomotility (CIGH) affects some 75% of patients treated with clozapine. To document the incidence of potentially harmful CIGH in the UK. We studied spontaneous UK pharmacovigilance reports recorded as clozapine-related gastrointestinal adverse drug reactions, 1992-2017. There were 527 patients reported with potentially harmful CIGH; 33% (<i>n</i> = 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 <i>v.</i> 49 years) and had been prescribed clozapine for longer than those who recovered (median 11.3 years <i>v</i>. 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% (<i>n</i> = 5) were fatal. At 10-14 years there were 63 reports of CIGH, of which 25% (<i>n</i> = 16) were fatal. Among the deaths, males were younger (median 51, range 22-89 <i>v</i>. median 57, range 24-89 years) with higher clozapine doses (median 450, range 100-900 <i>v</i>. median 300, range 12.5-800 mg/d) than females. In non-fatal CIGH, surgery was the most frequent outcome (<i>n</i> = 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. 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.