Clozapine-induced gastrointestinal hypomotility and constipation can result in severe and sometimes fatal gastrointestinal complications. Laxatives should be prophylactically prescribed with clozapine, but this is inconsistently achieved. Digital clinical decision support (CDS) alerts can promote safer prescribing.

To evaluate whether a CDS alert could promote timely laxative use with clozapine in hospital.

Retrospective in-patient prescribing data was used to compare co-prescribing of laxatives for first clozapine prescriptions pre-alert (January 2017–September 2019) and post-alert (September 2019–December 2023) implementation across 1194 hospital admissions where clozapine was prescribed. Regular non-bulking laxative and any laxative co-prescribing for first clozapine prescriptions within 24 h were assessed. Multivariable logistic regression was performed to determine the impact of alert implementation on laxative co-prescribing.

Of the 1194 admissions included, 449 admissions had clozapine prescribed pre-alert implementation and 745 admissions had post-alert implementation. Regular non-bulking laxative co-prescription occurred for 67.0% of first clozapine prescriptions pre-alert and 76.1% post-alert (P < 0.001). Any laxative co-prescription occurred for 87.3% of first clozapine prescriptions pre-alert and 96.5% post-alert (P < 0.001). Alert implementation was associated with increased likelihoods of regular non-bulking laxative co-prescribing (odds ratio, 1.341; 95% CI, 1.021–1.756; P = 0.035) and any laxative co-prescribing (odds ratio, 3.487; 95% CI, 2.135–5.838; P < 0.001) for first clozapine prescriptions within 24 h.

CDS alert implementation was associated with increased and earlier laxative co-prescribing for clozapine. Our findings suggest that a CDS alert is an effective tool for promoting timely laxative use with clozapine in hospital.

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% (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.

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.