Multiple spontaneous small bowel perforations due to clozapine—Case report

Rodrigues, Ângela; Duarte, Ana Filipa; Marques, Ary de Azevedo; Magalhães, Maria João; Camarneiro, R.; Silva, R.; Ferreira, Álvaro; Dionísio, I.; Flores, L. Val; Melo, M. Brito e

doi:10.1016/j.ijscr.2018.10.067

Cited by 5 publications

(7 citation statements)

References 11 publications

(16 reference statements)

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“…A meta-analysis showed clozapine-associated constipation was approximately 3 times more likely to occur than with other antipsychotics, 21 which is considered to be due to the stronger anticholinergic and antiserotonergic properties of clozapine 4 . Constipation can cause fecal impaction 3 that can increase colonic intraluminal pressure 22 . The increased pressure can lead to structural inflammation, such as appendicitis, and eventually result in mucosal ischemia and necrosis, which may induce perforation 22 .…”

Section: Discussionmentioning

confidence: 99%

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%

Appendicitis Associated With Clozapine

Misawa

Nakajima

Fujii

et al. 2023

J Clin Psychopharmacol

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“…[3] Ischemic colitis is an uncommon adverse effect of antipsychotic agents, more commonly found with phenothiazine drugs and atypical neuroleptics such as clozapine. Clozapine is the atypical antipsychotic drug most commonly described in the literature as the cause of ischemic colitis [4,5]. The risk of developing ischemic colitis increases in 2 situations: when anti-cholinergic drugs are associated with neuroleptics or when a highdose treatment is used.…”

Section: Discussionmentioning

confidence: 99%

“…The risk of developing ischemic colitis increases in 2 situations: when anti-cholinergic drugs are associated with neuroleptics or when a highdose treatment is used. [4,5] The mechanism most often mentioned in psychiatry, is the effect of anticholinergic medication responsible for digestive atony. Constipation resulting from parasympatholytic treatment effect and sedentary lifestyle of patients in psychiatric hospitals would be responsible for chronic digestive distension and intracolonic hypertension that can lead to ischemia.…”

Section: Discussionmentioning

confidence: 99%

Severe Neuroleptic Induced Ischemic Colitis: A Case Report

et al. 2021

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Ischemic colitis (IC) is a rare adverse effect of antipsychotic medications and is most commonly associated with the phenothiazine class of neuroleptics. Different cases reported in patients without other obvious risk factors led to the link between taking neuroleptics and acute ischemic colitis. The severe form is acute necrotizing colitis. This entity is characterized by sudden onset of abdominal pain and bloody diarrhea, progressing rapidly to produce severe illness with general peritonitis and shock.We report a case of a 26 years old Moroccan man, treated for four years for chronic psychosis, admitted to the emergency for abdominal pain and diarrhea. Clinical examination showed a conscious patient, tachycardia at 120 beats/min, febrile to 38.5 ° C, with generalized abdominal defense. Laboratory tests revealed: GB 33400, CRP 290 mg/l, abdominal tomography revealed colonic distension. The patient was prepared and admitted to the operating room. During the intervention, a colonoscopy was performed and shown ulcerated lesions with a purplish background without interval healthy mucosa. A subtotal colectomy with ileostomy and sigmoidostomy were performed. The histological examination of the surgical specimen showed superficial and extended ulcerations without interval healthy mucosa. Thus, no factors for IC were detected by appropriate workup other than the long-time use of neuroleptics. The restoration of continuity by ileorectal anastomosis was achieved two months later with a good clinical outcome, and the patient was recommended for psychiatry to reevaluate his antipsychotic regimen given the association with IC.Our case supports that neuroleptics can promote IC in patients under antipsychotic medications. It should alert physicians who prescribe neuroleptics and colorectal surgeons to the possibility of intestinal ischemia. Although the clinical presentation is non-specific, abdominal pain and distension should be headed, and endoscopy carried out. A better knowledge of this condition should promote earlier diagnosis and improve management.

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“…We speculate that these cases indicate the underlying relationship among clozapine treatment, structural inflammation and intestinal perforation, although it remains unclear. Constipation due to clozapine can lead to fecal impaction (Every-Palmer and Ellis, 2017), which can result in increased colonic intraluminal pressure (Rodrigues et al, 2018). The increased pressure can cause structural inflammation such as appendicitis and cause mucosal ischemia and necrosis, which may induce intestinal perforation (Rodrigues et al, 2018).…”

mentioning

confidence: 99%

“…Constipation due to clozapine can lead to fecal impaction (Every-Palmer and Ellis, 2017), which can result in increased colonic intraluminal pressure (Rodrigues et al, 2018). The increased pressure can cause structural inflammation such as appendicitis and cause mucosal ischemia and necrosis, which may induce intestinal perforation (Rodrigues et al, 2018). Moreover, inflammation can elevate serum clozapine levels (Haack et al, 2003) and may contribute to two vicious circles that accelerate the pathway to perforation: (a) clozapine has direct proinflammatory effects, further increasing serum clozapine levels and promoting structural inflammation; and (b) increased serum clozapine levels worsen intestinal hypomotility, a dose-dependent side effect of clozapine (Haack et al, 2003) leading to progression of inflammation, ischemia and necrosis via increased intraluminal pressure.…”

mentioning

confidence: 99%