Clozapine induced gastrointestinal hypomotility: A potentially life threatening adverse event. A review of the literature

Stephen West, David Rowbotham, Glen Xiong, Chris Kenedi

Research output: Contribution to journalReview article

12 Citations (Scopus)

Abstract

Objective The haematological and cardiac complications of clozapine have been well documented. Recent evidence from pharmacovigilance databases suggests that gastrointestinal (GI) complications are the leading cause of clozapine related deaths. This review aims to describe clinical features along with preventative and treatment options. Method A review of MEDLINE via PubMed searching for all articles published up to February of 2016. Inclusion criteria were articles that provided clinical or epidemiological information relating to the diagnosis, outcome, management or pathophysiology of clozapine related gastrointestinal disorders in humans. Results Three large case series were identified with 104 cases, 20 of these reported clinical details. A further 52 cases reports were included. Median age was 40, with 79% being male, mean daily clozapine dose was 453 mg. Mortality was 38% with survivors being younger (39 vs. 42), on lower daily doses (400 mg vs. 532 mg), more likely to be female (32% vs. 6%). Four patients were re-challenged with clozapine following CIGH, two suffered a recurrence. Conclusion Risk factors for CIGH appear to be older age, male gender, patients in the first four months of treatment, co-prescription of constipating agents, higher daily dose of clozapine, and previous CIGH. Risk factors for death were older age and male gender. Patients receiving clozapine should be counselled about the dangers of constipation and to report new GI symptoms. Once CIGH has occurred clozapine should be halted and bowel symptoms managed promptly. Re-challenging with clozapine may present substantial risks due to the severity of CIGH and a paucity of evidence. From the available evidence a treatment strategy has been proposed. Further prospective data regarding CIGH are needed to allow a better assessment of the scale of the problem with the development and testing of treatment strategies.

Original languageEnglish (US)
Pages (from-to)32-37
Number of pages6
JournalGeneral Hospital Psychiatry
Volume46
DOIs
StatePublished - May 1 2017

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Clozapine
Pharmacovigilance
Constipation
Therapeutics
PubMed
MEDLINE
Prescriptions
Survivors
Databases
Recurrence
Mortality

Keywords

  • Clozapine
  • Constipation
  • Gastrointestinal hypomotility
  • Ileus

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Clozapine induced gastrointestinal hypomotility : A potentially life threatening adverse event. A review of the literature. / West, Stephen; Rowbotham, David; Xiong, Glen; Kenedi, Chris.

In: General Hospital Psychiatry, Vol. 46, 01.05.2017, p. 32-37.

Research output: Contribution to journalReview article

West, Stephen ; Rowbotham, David ; Xiong, Glen ; Kenedi, Chris. / Clozapine induced gastrointestinal hypomotility : A potentially life threatening adverse event. A review of the literature. In: General Hospital Psychiatry. 2017 ; Vol. 46. pp. 32-37.
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title = "Clozapine induced gastrointestinal hypomotility: A potentially life threatening adverse event. A review of the literature",
abstract = "Objective The haematological and cardiac complications of clozapine have been well documented. Recent evidence from pharmacovigilance databases suggests that gastrointestinal (GI) complications are the leading cause of clozapine related deaths. This review aims to describe clinical features along with preventative and treatment options. Method A review of MEDLINE via PubMed searching for all articles published up to February of 2016. Inclusion criteria were articles that provided clinical or epidemiological information relating to the diagnosis, outcome, management or pathophysiology of clozapine related gastrointestinal disorders in humans. Results Three large case series were identified with 104 cases, 20 of these reported clinical details. A further 52 cases reports were included. Median age was 40, with 79{\%} being male, mean daily clozapine dose was 453 mg. Mortality was 38{\%} with survivors being younger (39 vs. 42), on lower daily doses (400 mg vs. 532 mg), more likely to be female (32{\%} vs. 6{\%}). Four patients were re-challenged with clozapine following CIGH, two suffered a recurrence. Conclusion Risk factors for CIGH appear to be older age, male gender, patients in the first four months of treatment, co-prescription of constipating agents, higher daily dose of clozapine, and previous CIGH. Risk factors for death were older age and male gender. Patients receiving clozapine should be counselled about the dangers of constipation and to report new GI symptoms. Once CIGH has occurred clozapine should be halted and bowel symptoms managed promptly. Re-challenging with clozapine may present substantial risks due to the severity of CIGH and a paucity of evidence. From the available evidence a treatment strategy has been proposed. Further prospective data regarding CIGH are needed to allow a better assessment of the scale of the problem with the development and testing of treatment strategies.",
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N2 - Objective The haematological and cardiac complications of clozapine have been well documented. Recent evidence from pharmacovigilance databases suggests that gastrointestinal (GI) complications are the leading cause of clozapine related deaths. This review aims to describe clinical features along with preventative and treatment options. Method A review of MEDLINE via PubMed searching for all articles published up to February of 2016. Inclusion criteria were articles that provided clinical or epidemiological information relating to the diagnosis, outcome, management or pathophysiology of clozapine related gastrointestinal disorders in humans. Results Three large case series were identified with 104 cases, 20 of these reported clinical details. A further 52 cases reports were included. Median age was 40, with 79% being male, mean daily clozapine dose was 453 mg. Mortality was 38% with survivors being younger (39 vs. 42), on lower daily doses (400 mg vs. 532 mg), more likely to be female (32% vs. 6%). Four patients were re-challenged with clozapine following CIGH, two suffered a recurrence. Conclusion Risk factors for CIGH appear to be older age, male gender, patients in the first four months of treatment, co-prescription of constipating agents, higher daily dose of clozapine, and previous CIGH. Risk factors for death were older age and male gender. Patients receiving clozapine should be counselled about the dangers of constipation and to report new GI symptoms. Once CIGH has occurred clozapine should be halted and bowel symptoms managed promptly. Re-challenging with clozapine may present substantial risks due to the severity of CIGH and a paucity of evidence. From the available evidence a treatment strategy has been proposed. Further prospective data regarding CIGH are needed to allow a better assessment of the scale of the problem with the development and testing of treatment strategies.

AB - Objective The haematological and cardiac complications of clozapine have been well documented. Recent evidence from pharmacovigilance databases suggests that gastrointestinal (GI) complications are the leading cause of clozapine related deaths. This review aims to describe clinical features along with preventative and treatment options. Method A review of MEDLINE via PubMed searching for all articles published up to February of 2016. Inclusion criteria were articles that provided clinical or epidemiological information relating to the diagnosis, outcome, management or pathophysiology of clozapine related gastrointestinal disorders in humans. Results Three large case series were identified with 104 cases, 20 of these reported clinical details. A further 52 cases reports were included. Median age was 40, with 79% being male, mean daily clozapine dose was 453 mg. Mortality was 38% with survivors being younger (39 vs. 42), on lower daily doses (400 mg vs. 532 mg), more likely to be female (32% vs. 6%). Four patients were re-challenged with clozapine following CIGH, two suffered a recurrence. Conclusion Risk factors for CIGH appear to be older age, male gender, patients in the first four months of treatment, co-prescription of constipating agents, higher daily dose of clozapine, and previous CIGH. Risk factors for death were older age and male gender. Patients receiving clozapine should be counselled about the dangers of constipation and to report new GI symptoms. Once CIGH has occurred clozapine should be halted and bowel symptoms managed promptly. Re-challenging with clozapine may present substantial risks due to the severity of CIGH and a paucity of evidence. From the available evidence a treatment strategy has been proposed. Further prospective data regarding CIGH are needed to allow a better assessment of the scale of the problem with the development and testing of treatment strategies.

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