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. 2016 Feb 15:5:125-34.
doi: 10.1016/j.ebiom.2016.02.020. eCollection 2016 Mar.

Clozapine-treated Patients Have Marked Gastrointestinal Hypomotility, the Probable Basis of Life-threatening Gastrointestinal Complications: A Cross Sectional Study

Susanna Every-Palmer  1 , Mike Nowitz  2 , James Stanley  3 , Eve Grant  4 , Mark Huthwaite  5 , Helen Dunn  6 , Pete M Ellis  5
Affiliations

Clozapine-treated Patients Have Marked Gastrointestinal Hypomotility, the Probable Basis of Life-threatening Gastrointestinal Complications: A Cross Sectional Study

Susanna Every-Palmer et al. EBioMedicine. .

Abstract

Background: 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.

Methods: 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.

Outcomes: 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.

Interpretation: Clozapine, unlike the other antipsychotics examined, causes marked gastrointestinal hypomotility, as previously hypothesized. Pre-emptive laxative treatment is recommended when starting clozapine.

Keywords: Antipsychotic agents; Clozapine; Constipation; Gastrointestinal motility; Gastrointestinal tract; Laxatives.

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Conflict of interest statement

We declare no competing interests.

Figures

Fig. 1
Fig. 1
Sitzmarks radiopaque markers: 0-rings; D-rings; and tri-rings.
Fig. 2
Fig. 2
ROM studies of a non-clozapine and clozapine-treated participant. Typical day four abdominal X-rays from a non-clozapine patient (left) and clozapine (right). The ROMs have almost all been excreted on the left, whereas on the right in the clozapine-treated patient all 72 ROMs are retained and scattered throughout the bowel in a pattern indicating global hypomotility.
Fig. 3
Fig. 3
Colonic transit time (in hours) for non-clozapine and clozapine-treated participants.
Fig. 4
Fig. 4
Survival analysis of colonic transit time (in hours) for clozapine and nonclozapine-treated participants.
Fig. 5
Fig. 5
Colonic transit time plotted by duration of clozapine treatment.
Fig. 6
Fig. 6
Colonic transit time plotted by clozapine dose and serum level.
See this image and copyright information in PMC

Comment in

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