Clozapine-related gastrointestinal perforation: four case reports

Nakajima, Nobuko; Misawa, Fuminari; Fujii, Yasuo; Takeuchi, Hiroyoshi

doi:10.1177/0004867419887231

Cited by 3 publications

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“…One case report is from our hospital 18 . After that case report, we published 4 cases with clozapine-related gastrointestinal perforation, including the first case that we had previously reported 19 ; of these, 3 patients had appendicitis. The other case series reported 6 patients who had perforated appendicitis associated with clozapine treatment over a 14-year period 12 .…”

Section: Discussionmentioning

confidence: 99%

“…22 In addition, the blood clozapine concentration can be elevated by inflammation, which may contribute to the following 2 vicious cycles accelerating the progression of appendicitis. 19 First, because clozapine can increase proinflammatory cytokines, 23,24 a self-enhancing cycle of toxic inflammation can develop. 12 Second, because constipation can be a dose-dependent adverse effect of clozapine, an increased blood clozapine concentration can worsen constipation, 4 leading to progression of inflammation via increased intraluminal pressure, which can further elevate the blood clozapine concentration.…”

Section: Discussionmentioning

confidence: 99%

“…The increased pressure can lead to structural inflammation, such as appendicitis, and eventually result in mucosal ischemia and necrosis, which may induce perforation 22 . In addition, the blood clozapine concentration can be elevated by inflammation, which may contribute to the following 2 vicious cycles accelerating the progression of appendicitis 19 . First, because clozapine can increase proinflammatory cytokines, 23,24 a self-enhancing cycle of toxic inflammation can develop 12 .…”

Section: Discussionmentioning

confidence: 99%

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Appendicitis Associated With Clozapine

Misawa

Nakajima

Fujii

et al. 2023

J Clin Psychopharmacol

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BackgroundAn association between appendicitis and clozapine has recently been reported; however, few studies other than case reports have investigated this association. Therefore, we aimed to investigate the association between appendicitis and clozapine, using a large spontaneous reporting database in Japan.MethodsJapanese Adverse Drug Event Report data were used in this study, and patients who had received clozapine or nonclozapine second-generation antipsychotics (NC-SGAs) available in Japan were included. To compare the reporting frequency of appendicitis associated with clozapine and NC-SGAs, we calculated the adjusted reporting odds ratio using logistic regression models, adjusting for age group, sex, and anticholinergic use. We conducted a time-to-event analysis to examine the time to onset of appendicitis associated with clozapine.ResultsIn total, 8921 patients were included in this study, of whom 85 (1.0%) had appendicitis. Of these, 83 patients had received clozapine. Appendicitis was significantly more frequently reported with clozapine than with NC-SGAs. Time-to-event analysis showed that the risk of developing appendicitis associated with clozapine increased over time.ConclusionsClozapine was associated with a higher risk of appendicitis than NC-SGAs, which increased with time. These findings suggest that clinicians need to pay greater attention to the risk of developing appendicitis during clozapine treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Appendicitis Associated With Clozapine

Misawa

Nakajima

Fujii

et al. 2023

J Clin Psychopharmacol

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The prevalence of constipation in adult psychiatric out‐patients on clozapine treatment at a regional public hospital in Hong Kong

Lam,

2024

Human Psychopharmacology

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ObjectiveTo determine the occurrence of constipation in local patients on clozapine treatment, and to compare the demographical and clinical characteristics of patients on clozapine treatment with or without constipation.MethodsThis is a cross‐sectional, observational study. All adult psychiatric out‐patients on clozapine treatment attending follow‐up at a regional hospital were recruited for clinical interview and medical record review. The Enhanced Asian Rome III Questionnaire (EAR3Q) was used to define patients with constipation. The Bristol Stool Form Scale (BSFS) was used to assess stool form. The Brief Psychiatric Rating Scale‐Anchored (BPRS‐A) was used to measure psychiatric symptoms. The Brief Medication Adherence Scale (BMAS) was used to assess treatment adherence. Logistic regression was conducted to identify independent associating factors of constipation in patients on clozapine treatment.ResultsThe prevalence of constipation in patients on clozapine treatment was 26.3%, (95% CI [21.5%, 31.6%]). Independent associating factors included disorder of psychological development (aOR = 6.98, 95% CI [1.24, 39.18]), anxiety (very mild: aOR = 9.23, 95% CI [2.59, 32.87]; mild: aOR = 2.66, 95% CI [1.26, 5.62]), prescription with combination of laxatives (aOR = 0.40, 95% CI [0.17, 0.95]), and concomitant use of amisulpride (aOR = 2.52, 95% CI [1.09, 5.82]), quetiapine (aOR = 5.92, 95% CI [1.11, 31.56]) and metamucil (aOR = 9.30, 95% CI [1.53, 56.58]).ConclusionThis study examined the prevalence of clozapine‐associated constipation in Hong Kong using a validated questionnaire. The identification of independent factors associated with constipation could facilitate better risk stratification and risk modification in clinical practice.

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Clozapine

2020

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Clozapine-related gastrointestinal perforation: four case reports

Cited by 3 publications

References 3 publications

Appendicitis Associated With Clozapine

Appendicitis Associated With Clozapine

The prevalence of constipation in adult psychiatric out‐patients on clozapine treatment at a regional public hospital in Hong Kong

Clozapine

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