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of potentially lethal clozapine-induced gastrointestinal hypomotility (CIGH) by reviewing cases from the literature and unpublished pharmacovigilance data and to offer strategies aimed at prevention and early treatment.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 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. 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.
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of potentially lethal clozapine-induced gastrointestinal hypomotility (CIGH) by reviewing cases from the literature and unpublished pharmacovigilance data and to offer strategies aimed at prevention and early treatment.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 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. 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 constipatedpatients--before life-threatening pathologic processes develop.
Authors: Domenico De Berardis; Gabriella Rapini; Luigi Olivieri; Domenico Di Nicola; Carmine Tomasetti; Alessandro Valchera; Michele Fornaro; Fabio Di Fabio; Giampaolo Perna; Marco Di Nicola; Gianluca Serafini; Alessandro Carano; Maurizio Pompili; Federica Vellante; Laura Orsolini; Giovanni Martinotti; Massimo Di Giannantonio Journal: Ther Adv Drug Saf Date: 2018-02-06
Authors: Madeleine S A Tan; Faraz Honarparvar; James R Falconer; Harendra S Parekh; Preeti Pandey; Dan J Siskind Journal: Psychopharmacology (Berl) Date: 2021-01-07 Impact factor: 4.530
Authors: Marc DE Hert; Christoph U Correll; Julio Bobes; Marcelo Cetkovich-Bakmas; Dan Cohen; Itsuo Asai; Johan Detraux; Shiv Gautam; Hans-Jurgen Möller; David M Ndetei; John W Newcomer; Richard Uwakwe; Stefan Leucht Journal: World Psychiatry Date: 2011-02 Impact factor: 49.548
Authors: Susanna Every-Palmer; Pete M Ellis; Mike Nowitz; James Stanley; Eve Grant; Mark Huthwaite; Helen Dunn Journal: CNS Drugs Date: 2017-01 Impact factor: 5.749