title: Life-threatening clozapine-induced gastrointestinal hypomotility: an analysis of 102 cases.
abstract: OBJECTIVE
  To raise awareness of potentially lethal clozapine-induced gastrointestinal hypomotility (CIGH) by reviewing cases from the literature and unpublished pharmacovigilance data and to offer strategies aimed at prevention and early treatment.
  
  
  METHODS
  Databases (PsycINFO, 1967-2007; MEDLINE, 1950-2007; and EMBASE, 1988-2007) were searched using the term clozapine together with each of the following: gastrointestinal, dysmotility, constipation, obstipation, fecal impaction, fecaloma, paralytic ileus, adynamic ileus, subileus, ischemic colitis, colon ischemia, bowel ischemia, gastrointestinal ischemia, gut ischemia, obstruction, necrosis, gangrene, bowel perforation, micro-perforation, megacolon, toxic megacolon, acquired megacolon, pseudo-obstruction, Ogilvie, and Ogilvie's syndrome. We analyzed the electronic database entries held by the Adverse Drug Reactions Advisory Committee and the New Zealand Intensive Medicines Monitoring Program, which cited suspected clozapine-related gastrointestinal side effects, as well as all relevant published case reports. We reviewed the literature on the treatment of gastrointestinal hypomotility and constipation.
  
  
  RESULTS
  We compiled a database of 102 cases of suspected life-threatening CIGH. There was a mortality rate of 27.5% and considerable morbidity, largely due to bowel resection. Within Australasia, at least 15 patients have died of CIGH. Probable risk factors are identified as recent instigation of clozapine, high clozapine dose or serum level, concomitant anticholinergic use, or intercurrent illness.
  
  
  CONCLUSIONS
  The paucity of literature on CIGH suggests that the significance of this uncommon but important and frequently fatal side effect has not been recognized. Clozapine can affect the entire gastrointestinal system, from esophagus to rectum, and may cause bowel obstruction, ischemia, perforation, and aspiration. The mechanism is likely to be anticholinergic and antiserotonergic. Clozapine prescribing should be accompanied by regular physical monitoring, appropriate and timely use of laxatives, and early referral of constipated patients--before life-threatening pathologic processes develop.
authors.affiliation: Te Korowai Whariki Mental Health Services, Capital and Coast District Health Board, Wellington, New Zealand. susanna.palmer@ccdhb.org.nz
authors.forename: Susanna E
authors.initials: SE
authors.lastname: Palmer
authors.forename: Rachael M
authors.initials: RM
authors.lastname: McLean
authors.forename: Peter M
authors.initials: PM
authors.lastname: Ellis
authors.forename: Mira
authors.initials: M
authors.lastname: Harrison-Woolrych
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects*; D003024:Clozapine / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000401:mortality / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D045823:Ileus / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D015995:Prevalence
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine