Clozapine-induced gastrointestinal hypomotility poses serious morbidity, mortality risks

Around 75 percent of patients on clozapine develop treatment-induced gastrointestinal hypomotility (CIGH), which contributes to substantial risks of serious morbidity and mortality, a study reports.

Researchers looked at spontaneous UK pharmacovigilance reports (1992–2017) of clozapine-related gastrointestinal adverse drug reactions to record the incidence of potentially harmful CIGH in the UK.

A total of 527 patients were reported to have developed potentially harmful CIGH, of whom 172 (33 percent) died. The average number of deaths per year was one in 1992–1999, five in 2000–2009, and 15 in 2010–2017.

Compared with survivors, the patients who died tended to be older (median, 52 vs 49 years) and had been prescribed clozapine for longer (median, 11.3 vs 4.8 years). However, there was no significant difference in the prescribed dose.

During the first 4 years of clozapine treatment, a total of 169 incident CIGH were documented. Of these, five (3 percent) led to death. At 10–14 years, there were 63 reports of incident CIGH, of which 16 (25 percent) were fatal.

Among the patients who died, men were younger (median, 51 vs 57 years) and had higher clozapine doses (median, 450 vs 300 mg/d) compared with women.

In nonfatal CIGH, the most common outcome was surgery (n=92). The surgical procedures included appendectomy, ileostomy, total/partial colectomy, colostomy/stoma, and proctosigmoidectomy. Clozapine dosage was decreased in six patients, stopped and restarted in 23, continued in six, and ceased permanently in at least 76 patients.

The findings underscore the need to actively monitor bowel function and administer laxatives to patients treated with clozapine.