clozapine and Ileus

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of potentially lethal clozapine-induced gastrointestinal hypomotility (CIGH) by reviewing cases from the literature and unpublished pharmacovigilance data and to offer strategies aimed at prevention and early treatment.. 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.. 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.. 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.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Female; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Ileus; Male; Middle Aged; Prevalence

Topics: Antipsychotic Agents; Clozapine; Humans; Ileus

Purpose of the article: Clozapine is the only evidence based treatment for treatment-resistant schizophrenia. Constipation is a well known side effect of clozapine treatment. The aims of this study are to describe the prevalence of constipation and ileus during clozapine treatment of patients with schizophrenia in Iceland and to assess the concomitant use of medication that can cause constipation, and laxatives used to treat constipation.. We identified 188 patients treated with clozapine by searching the electronic health records of Landspitali, the National University Hospital, during the study period 1.1.1998 - 21.11.2014. Cases of constipation and ileus were identified using an electronic search with keywords related to ileus in the patients' electronic health records. Detailed medication use was available for 154 patients that used clozapine for at least one year.. Four out of 188 patients were diagnosed with ileus that resulted in admission to hospital. Two of these required a permanent stoma as a consequence of their ileus. Laxatives were prescribed for 24 out of 154 patients (15.4%) while on clozapine. In total 40.9% of the patients either had laxatives prescribed or had constipation documented in the medical records. Apart from clozapine, other medications known to cause constipation were prescribed to 28 out of 154 patients (18.2%).. Constipation is a common problem during clozapine treatment which can progress to full-blown ileus which can be fatal. Clinicians need to monitor signs of constipation during treatment with clozapine and respond to it with lifestyle advice and laxative treatment.

Topics: Adult; Antipsychotic Agents; Clozapine; Cohort Studies; Constipation; Female; Follow-Up Studies; Humans; Iceland; Ileus; Laxatives; Male; Middle Aged; Prevalence; Retrospective Studies; Schizophrenia; Treatment Outcome; Young Adult

Constipation is a known side effect of psychotropics that possess high affinity for muscarinic cholinergic receptors. In severe cases, constipation progresses to ileus and bowel ischemia, with multiple fatalities related to sepsis and perforation described in the literature, primarily among patients with schizophrenia. A historical prospective database study was performed using registry data from psychiatric and somatic hospitals, combined with the prescription database to examine associations between medications and ileus. Only cases with an ICD-10 diagnosis of schizophrenia (F20) and a concurrent diagnosis of ileus in the years 1996-2007 were included in the study. A total of 26,720 patients with schizophrenia were identified with 123 cases of ileus noted in the study period. Increasing age (OR: 1.03 CI: 1.01-1.04) and female sex (OR: 1.60 CI: 1.10-2.31) were associated with an increased risk of ileus. Treatment with clozapine (OR: 1.99 CI: 1.21-3.29), high-potency first-generation antipsychotics (OR: 1.81 CI: 1.01-3.23), tricyclic antidepressants (OR: 2.29 CI: 1.29-4.09), anticholinergics (OR: 1.48 CI: 1.00-2.19), and opioids (OR: 2.14 CI: 1.36-3.36) were associated with an increased risk of ileus. The onset of ileus occurred on average more than 3 years after the first prescription of the offending drug. Aripiprazole and amisulpride were not associated with ileus. Nine of the ileus cases (7.3%) had a fatal course. Treatment with clozapine (OR: 6.73 CI: 1.55-29.17) or anticholinergics (OR: 5.88 CI: 1.47-23.58) were associated with increased risk of fatal ileus. Patients receiving psychotropics associated with significant anticholinergic properties should undergo proper monitoring and interventions in order to minimize the burden of constipation and the risk of ileus.

Topics: Antidepressive Agents, Tricyclic; Antipsychotic Agents; Cholinergic Antagonists; Clozapine; Female; Humans; Ileus; Male; Middle Aged; Prospective Studies; Registries; Risk Factors; Schizophrenia; Sex Factors

Topics: Aged; Antipsychotic Agents; Clozapine; Fatal Outcome; Humans; Ileus; Male; Schizophrenia

Topics: Antipsychotic Agents; Clozapine; Gastrointestinal Motility; Humans; Ileus; Intestinal Obstruction; New Zealand; United Kingdom