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 Table of Contents  
Year : 2019  |  Volume : 3  |  Issue : 2  |  Page : 171-172

Clozapine-induced massive hematemesis: A rare case report

Department of Psychiatry, Mental Health Hospital, Taif, KSA

Date of Submission19-Feb-2019
Date of Decision01-Apr-2019
Date of Acceptance04-Apr-2019
Date of Web Publication18-Dec-2019

Correspondence Address:
Dr. Javed Ather Siddiqui
Department of Psychiatry, Mental Health Hospital, P. O. Box. 2056, Taif 21944
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aip.aip_8_19

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Clozapine (CLZ) is a drug of choice for the treatment of resistant schizophrenia. It is always blamed probably due to its life-threatening side effects, such as agranulocytosis, constipation, cardiomyopathies, and rarely hematemesis. We report the case of a 65-year-old patient diagnosed with resistant schizophrenia and treated with CLZ later he developed sudden massive hematemesis. The aim of our case report is to describe the rarely seen and potentially life-threatening side effect related to CLZ. Physician, particularly psychiatrists and medical specialists, should not ignore, be aware, and alert or always need to be watchful to the fatality of CLZ-induced hematemesis in the management of psychiatric disorders and should take appropriate therapeutic measures in such a case.

Keywords: Clozapine, massive hematemesis, resistant-schizophrenia

How to cite this article:
Siddiqui JA, Qureshi SF, Ahmed Shawosh YB. Clozapine-induced massive hematemesis: A rare case report. Ann Indian Psychiatry 2019;3:171-2

How to cite this URL:
Siddiqui JA, Qureshi SF, Ahmed Shawosh YB. Clozapine-induced massive hematemesis: A rare case report. Ann Indian Psychiatry [serial online] 2019 [cited 2023 Mar 30];3:171-2. Available from: https://www.anip.co.in/text.asp?2019/3/2/171/262248

  Introduction Top

Clozapine (CLZ) is a tricyclic dibenzodiazepine, antipsychotic agent. It is first atypical antipsychotic known as the second-generation antipsychotic. It was first discovered in 1958, developed by Sandoz in 1961, and introduced in Europe in 1970. It is a drug of choice and the gold standard medication for the treatment of resistant schizophrenia,[1] but due to complicated side effect profile, it has limited use and needs necessary monitoring after initiation of medication.[2]

The side effects of CLZ reported could be serious and life-threatening and if not treated properly, can lead to dangerous consequences. These side effects are hematological such as agranulocytosis, cardiac side effects such as cardiomyopathies and pericarditis, neurological such as seizure, and metabolic such as diabetes and dyslipidemia. Other uncommon side effects affecting the gastrointestinal system are hematemesis, constipation, esophagitis, ischemic colitis, paralytic ileus, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudopheochromocytoma, periorbital edema, and parotitis.[3],[4],[5],[6] The potential reason for discontinuing CLZ is that some of the side effects are rare, fatal, miserable, and massive. It has been reported in the literature and some articles that around 11% of patients treated with CLZ develop gastrointestinal symptoms similar to reflux esophagitis within 6 weeks of treatment.[4]

The pathophysiology due to which CLZ causes severe esophagitis and subsequent hematemesis is at times difficult to understand. Anticholinergic activity plays an important role by causing antagonism of cholinergic receptors which may be responsible for the reduction or abolition of esophageal motility resulting in increased pressure in the lower sphincter tone and an overall reduction in esophageal tone. The incidence rate for gastrointestinal hypomotility has been reported to be 4–8/1000, which has a case fatality rate of 15%–27.5%.[7] We wish to report a rare case of clozapine induced hematemesis.

  Case Report Top

A 65-year-old male patient with good body built belonging to low-socioeconomic status, is admitted in a chronic rehabilitation ward since 15 years of a psychiatric hospital. He was diagnosed with schizophrenia 30 years back. He had been treated with multiple typical and atypical antipsychotics. At different times, he had been on haloperidol, olanzapine, chlorpromazine, amisulpride, and risperidone and depot preparations such as fluphenazine and haloperidol decanoate, risperidone consta for the past 30 years. Despite being treated with multiple antipsychotics, initially, he improved for 4 years, but as he never achieved full remission his diagnosis was revised to treatment-resistant schizophrenia and clozapine was considered. Baseline investigations, such as complete blood cell count, electrocardiography, serum electrolytes, and liver and kidney function tests, were all within the normal limits. There was a history of smoking since long and subsequently patient developed chronic obstructive pulmonary disease (COPD).

His milestones were normal. He had no substance abuse, other medical or gastrotrointestinal symptoms except for COPD. The patient had a significant improvement in his mental status within a month of starting CLZ and was maintained on 300 mg of CLZ in divided doses. 15 days later patient complained of constipation and gastroesophageal reflux and was accordingly treated with omeprazole and stool softener. He was noticed to have vomited about 200 ml of coffee-colored vomit on two occasions by the staff nurse.

Patient had epigastric pain and was treated with intravenous omeprazole 40 mg for 12 h and hydration was maintained. The patient was referred to the gastroenterologist. His upper gastrointestinal endoscopy showed evidence of esophagitis and pangastritis. The patient was assessed on Naranjo adverse drug reaction probability test, and the score was 7, suggesting possible adverse drug reaction. All other investigations were within the normal limits. The gastroenterologist made a diagnosis of the upper gastrointestinal bleeding secondary to CLZ use as the patient was on CLZ for 1 month. CLZ was tapered and discontinued over 2 months. It was restarted with caution at lower and slower dosage as the patient was refractory to other antipsychotics. There was no further episode of hematemesis and the patient maintained well.

  Discussion Top

CLZ is the first-line drug of choice for resistant schizophrenia, due to it's better efficacy over other typical and atypical antipsychotic drugs but needs monitoring due to its serious and fatal side effects, complications, and contraindications. Various literature and case studies reported that around 17% of patient those taking CLZ usually discontinue the treatment because of its fatal side effects or complications.[8] The risk of causing agranulocytosis and other life-threatening hematemesis due to CLZ is well established.[3] To the best of our knowledge, there is a similar case reported in Sub-Saharan Africa.[9] Our patient had gastrointestinal side effects such as constipation, gastroesophageal reflex, massive hematemesis and esophagitis without any prior history. It is important to be aware of this rare side effect to minimize the related mortality due to the loss of esophageal motility, increase in lower sphincter relaxation, and loss of lower esophageal tone and pressure. CLZ can also cause impairment of swallowing due to the the vagal regulation of esophageal peristaltic movement and hypersalivation.[10]

The gastrointestinal tract disorders, including cases of esophagitis with constipation, hiatal hernia, and hematemesis, have been reported with the use of CLZ, but very few articles have been published. These gastrointestinal disturbances arise in connection with hypomotility and changes in digestive secretion induced by CLZ, as a result of its antiserotoninergic and anticholinergic properties. It is the responsibility of physicians and psychiatrist to be aware of this life-threatening side effect and its consequences so that the morbidity and mortality could be prevented.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Schulte P. What is an adequate trial with clozapine? Therapeutic drug monitoring and time to response in treatment-refractory schizophrenia. Clin Pharmacokinet 2003;42:607-18.  Back to cited text no. 1
Meltzer HY, Ranjan R, Lee MA, Kenedy J. Emerging clinical uses of clozapine. Rev Contemp Pharmacother 1995;6:187-96.  Back to cited text no. 2
Fitzsimons J, Berk M, Lambert T, Bourin M, Dodd S. A review of clozapine safety. Expert Opin Drug Saf 2005;4:731-44.  Back to cited text no. 3
Laker MK, Cookson JC. Reflux oesophagitis and clozapine. Int Clin Psychopharmacol 1997;12:37-9.  Back to cited text no. 4
Townsend G, Curtis D. Case report: Rapidly fatal bowel ischaemia on clozapine treatment. BMC Psychiatry 2006;6:43.  Back to cited text no. 5
Nielsen J, Correll CU, Manu P, Kane JM. Termination of clozapine treatment due to medical reasons: When is it warranted and how can it be avoided? J Clin Psychiatry 2013;74:603-13.  Back to cited text no. 6
Cohen D, Bogers JP, van Dijk D, Bakker B, Schulte PF. Beyond white blood cell monitoring: Screening in the initial phase of clozapine therapy. J Clin Psychiatry 2012;73:1307-12.  Back to cited text no. 7
Young CR, Bowers MB Jr., Mazure CM. Management of the adverse effects of clozapine. Schizophr Bull 1998;24:381-90.  Back to cited text no. 8
Adebayo KO, Ibrahim N, Mosanya T, Eegunranti B, Suleiman B, Ayankunle A, et al. Life-threatening haematemesis associated with clozapine: A case report and literature review. Ther Adv Psychopharmacol 2013;3:275-7.  Back to cited text no. 9
Praharaj SK, Arora M, Gandotra S. Clozapine-induced sialorrhea: Pathophysiology and management strategies. Psychopharmacology (Berl) 2006;185:265-73.  Back to cited text no. 10


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