Clozapine and Gastrointestinal Hypomotility

Gastrointestinal hypomotility (GIH) is an under-reported but highly prevalent and potentially dangerous side effect of clozapine. In a comprehensive meta-analysis of clozapine-treated patients, the prevalence of GIH was 32%. In general, GIH has consistently been reported to have a negative impact on quality of life, and there is no reason to believe this will be different in clozapine-treated patients with therapy-resistant schizophrenia. GIH is dangerous; in a comparative review of lethal side effects of clozapine, the mortality of agranulocytosis was 2.2-4.2% compared with 15.0-27.5% for GIH. The mortality rate in our review of all published case reports of ileus was 43.7%. (Co-)Prescription of anticholinergic drugs in patients treated with clozapine should be avoided as anticholinergics are associated with increased incidence and fatality of ileus. Prevention of GIH can best be obtained by frequent and targeted questioning by the mental healthcare providers of the patients' defecation pattern and this is therefore strongly recommended for timely detection and treatment of treatment-emergent GIH throughout clozapine treatment. Treatment approaches can be either preventive laxative prescription with every clozapine prescription in all clozapine-treated patients or targeted treatment of treatment-emergent GIH. First-line treatments of GIH are the osmotic laxative macrogol, stool softener docusate and bowel stimulant senna. As the occurrence of severe cases of GIH is not restricted to a certain treatment duration, alertness for and/or treatment of GIH is required for the whole duration of clozapine treatment.