Clozapine-treated Patients Have Marked Gastrointestinal Hypomotility, the Probable Basis of Life-threatening Gastrointestinal Complications: A Cross Sectional Study
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-03-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396416300536 |
| _version_ | 1818199405562429440 |
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| author | Susanna Every-Palmer Mike Nowitz James Stanley Eve Grant Mark Huthwaite Helen Dunn Pete M. Ellis |
| author_facet | Susanna Every-Palmer Mike Nowitz James Stanley Eve Grant Mark Huthwaite Helen Dunn Pete M. Ellis |
| author_sort | Susanna Every-Palmer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T02:21:15Z |
| format | Article |
| id | doaj.art-3a16886636b542d0a980367d1c3ca8f1 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-12T02:21:15Z |
| publishDate | 2016-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-3a16886636b542d0a980367d1c3ca8f12022-12-22T00:41:41ZengElsevierEBioMedicine2352-39642016-03-015C12513410.1016/j.ebiom.2016.02.020Clozapine-treated Patients Have Marked Gastrointestinal Hypomotility, the Probable Basis of Life-threatening Gastrointestinal Complications: A Cross Sectional StudySusanna Every-Palmer0Mike Nowitz1James Stanley2Eve Grant3Mark Huthwaite4Helen Dunn5Pete M. Ellis6Te Korowai Whāriki Central Regional Forensic Service, Capital and Coast District Health Board, New ZealandDepartment of Medicine, University of Otago, Wellington, PO Box 7343, Wellington 6242, New ZealandBiostatistics Group, University of Otago, Wellington, PO Box 7343, Wellington 6242, New ZealandTe Korowai Whāriki Central Regional Forensic Service, Capital and Coast District Health Board, New ZealandDepartment of Psychological Medicine, University of Otago, Wellington, PO Box 7343, Wellington 6242, New ZealandPharmacy Department, Capital and Coast District Health Board, Private Bag 7902, Wellington South, New ZealandDepartment of Psychological Medicine, University of Otago, Wellington, PO Box 7343, Wellington 6242, New ZealandBackground: 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.http://www.sciencedirect.com/science/article/pii/S2352396416300536Antipsychotic agentsClozapineGastrointestinal tractLaxativesConstipationGastrointestinal motility |
| spellingShingle | Susanna Every-Palmer Mike Nowitz James Stanley Eve Grant Mark Huthwaite Helen Dunn Pete M. Ellis Clozapine-treated Patients Have Marked Gastrointestinal Hypomotility, the Probable Basis of Life-threatening Gastrointestinal Complications: A Cross Sectional Study EBioMedicine Antipsychotic agents Clozapine Gastrointestinal tract Laxatives Constipation Gastrointestinal motility |
| title | Clozapine-treated Patients Have Marked Gastrointestinal Hypomotility, the Probable Basis of Life-threatening Gastrointestinal Complications: A Cross Sectional Study |
| title_full | Clozapine-treated Patients Have Marked Gastrointestinal Hypomotility, the Probable Basis of Life-threatening Gastrointestinal Complications: A Cross Sectional Study |
| title_fullStr | Clozapine-treated Patients Have Marked Gastrointestinal Hypomotility, the Probable Basis of Life-threatening Gastrointestinal Complications: A Cross Sectional Study |
| title_full_unstemmed | Clozapine-treated Patients Have Marked Gastrointestinal Hypomotility, the Probable Basis of Life-threatening Gastrointestinal Complications: A Cross Sectional Study |
| title_short | Clozapine-treated Patients Have Marked Gastrointestinal Hypomotility, the Probable Basis of Life-threatening Gastrointestinal Complications: A Cross Sectional Study |
| title_sort | clozapine treated patients have marked gastrointestinal hypomotility the probable basis of life threatening gastrointestinal complications a cross sectional study |
| topic | Antipsychotic agents Clozapine Gastrointestinal tract Laxatives Constipation Gastrointestinal motility |
| url | http://www.sciencedirect.com/science/article/pii/S2352396416300536 |
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