title: Clozapine-treated Patients Have Marked Gastrointestinal Hypomotility, the Probable Basis of Life-threatening Gastrointestinal Complications: A Cross Sectional Study.
abstract: Gastrointestinal side effects are particularly common with clozapine and occur with other antipsychotics, ranging from mild constipation to fatal bowel obstruction and/or ischemia. While this adverse-effect spectrum has been attributed to 'gastrointestinal hypomotility', gastrointestinal transit times in antipsychotic-treated patients have not previously been measured, making this mechanism speculative.
  
  
  
  Using standardized radiopaque marker ('Metcalf') methods we established colonic transit times of antipsychotic-treated psychiatric inpatients and compared them with population normative values. We analyzed results by antipsychotic type, antipsychotic dose equivalent, anticholinergic load, duration of treatment, gender, ethnicity, and age.
  
  
  
  For patients not prescribed clozapine, median colonic transit time was 23 h. For patients prescribed clozapine, median transit time was 104.5 h, over four times longer than those on other antipsychotics or normative values (p < 0.0001). Eighty percent of clozapine-treated patients had colonic hypomotility, compared with none of those prescribed other antipsychotics (olanzapine, risperidone, paliperidone aripiprazole, zuclopenthixol or haloperidol). In the clozapine group, right colon, left colon and rectosigmoid transit times were all markedly abnormal suggesting pan-colonic pathology. Hypomotility occurred irrespective of gender, age, ethnicity, or length of clozapine treatment. Transit times were positively correlated with clozapine plasma level (rho = 0.451, p = 0.045), but not with duration of treatment, total antipsychotic load or demographic factors.
  
  
  
  Clozapine, unlike the other antipsychotics examined, causes marked gastrointestinal hypomotility, as previously hypothesized. Pre-emptive laxative treatment is recommended when starting clozapine.
authors.affiliation: Te Korowai Whāriki Central Regional Forensic Service, Capital and Coast District Health Board, New Zealand; Department of Psychological Medicine, University of Otago, Wellington, PO Box 7343, Wellington 6242, New Zealand.
authors.forename: Susanna
authors.initials: S
authors.lastname: Every-Palmer
authors.affiliation: Department of Medicine, University of Otago, Wellington, PO Box 7343, Wellington 6242, New Zealand.
authors.forename: Mike
authors.initials: M
authors.lastname: Nowitz
authors.affiliation: Biostatistics Group, University of Otago, Wellington, PO Box 7343, Wellington 6242, New Zealand.
authors.forename: James
authors.initials: J
authors.lastname: Stanley
authors.affiliation: Te Korowai Whāriki Central Regional Forensic Service, Capital and Coast District Health Board, New Zealand.
authors.forename: Eve
authors.initials: E
authors.lastname: Grant
authors.affiliation: Department of Psychological Medicine, University of Otago, Wellington, PO Box 7343, Wellington 6242, New Zealand.
authors.forename: Mark
authors.initials: M
authors.lastname: Huthwaite
authors.affiliation: Pharmacy Department, Capital and Coast District Health Board, Private Bag 7902, Wellington South, New Zealand.
authors.forename: Helen
authors.initials: H
authors.lastname: Dunn
authors.affiliation: Department of Psychological Medicine, University of Otago, Wellington, PO Box 7343, Wellington 6242, New Zealand.
authors.forename: Pete M
authors.initials: PM
authors.lastname: Ellis
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D003938:Diagnostic Techniques, Digestive System; D004305:Dose-Response Relationship, Drug; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging*; D041981:Gastrointestinal Tract / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D007297:Inpatients; D008297:Male; D008875:Middle Aged; D011860:Radiography, Abdominal / Q000379:methods; D013997:Time Factors; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: Antipsychotic agents; Clozapine; Constipation; Gastrointestinal motility; Gastrointestinal tract; Laxatives