Death from clozapine-induced constipation: case report and literature review.

Received October 16, 2001; accepted October 16, 2001. From the Department of Consultation Liaison Psychiatry, Long Island Jewish Medical Center, New Hyde Park, NY. Address correspondence and reprint requests to Dr. Levin, Department of Consultation Liaison Psychiatry, Long Island Jewish Medical Center, 270-05 76th Ave, New Hyde Park, NY 11040. E-mail: tlevin@lij.edu Copyright 2002 The Academy of Psychosomatic Medicine. Clozapine is commonly used in the therapy of patients with treatment-resistant schizophrenia and schizophrenia with prominent negative symptoms. Constipation occurs in 14% of patients receiving clozapine and is believed to be an anticholinergic side effect. A recent edition of the Australian Adverse Drug Reactions Bulletin highlighted the common nature of this side effect. However, this is not a trivial side effect. Of the 15 cases of serious constipation reported in Australia, 4 involved fecal impaction, 2 involved subacute bowel obstruction, 1 involved rectal prolapse requiring ileostomy, and there was 1 fatality secondary to inhalation of feculent vomitus. The aforementioned fatality, described by Drew and Herdson, occurred in a 49-year-old man with paranoid schizophrenia who was treated with clozapine (500 mg/day) for 2 years. He died unexpectedly in a psychiatric ward. Postmortem examination revealed severe pulmonary edema secondary to inhalation of feculent vomitus. Extensive, severe fecal impaction was found, involving the entire large bowel with feculent fluid extending all the way to the stomach. There was also evidence of reflux esophagitis. Of note, in the month before his death, the patient had complained of intermittent nausea, vomiting, indigestion, and chest pain, but had complained of constipation only once, 11 days before his death. Hayes and Gibler described a similar death in a 29-year-old man receiving clozapine (up to a dose of 400 mg/day) for 36 days, who also died of aspiration of vomitus secondary to constipation and bowel obstruction. A French report of 30 cases of clozapine-induced constipation documented three cases of intestinal obstruction that required surgical laparotomy. One of the cases was fatal. A further case of a 36-year-old man treated with clozapine (600 mg/day) for 4 months was documented by Shammi and Remington. Their patient had previously documented constipation and upper gastrointestinal complaints. He presented with nausea and an acute abdomen, and laparotomy revealed a grossly dilated colon. Autopsy showed marked dilation and necrosis of the entire large bowel. More recently, Freudenreich and Goff described a 49-year-old man who developed colon perforation and feculent peritonitis 6 weeks after commencing clozapine (400 mg/day). The patient had complained of constipation, but did not receive treatment. He required an emergency hemicolectomy and perioperatively sustained a dense cerebrovascular accident. We describe a further death secondary to clozapineinduced constipation and fecal impaction. We believe this is the fifth fatality described in the literature. The ramifications of this complication for patients receiving clozapine are discussed.