Life-Threatening Clozapine-Induced Gastrointestinal Hypomotility: An Analysis of 102 Cases
J Clin Psychiatry 2008;69(5):759-768
© Copyright 2014 Physicians Postgraduate Press, Inc.
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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unpublished pharmacovigilance data and to offer strategies aimed at prevention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.
Method: 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
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.
Conclusion: 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.