Clozapine-induced Paralytic Ileus: A Case Report

Sir, Clozapine is generally used for patients with treatment-resistant schizophrenia, usually defined as the failed trial of two other antipsychotics of optimal dose and duration.[1] Despite this, clozapine is used less commonly because of the side-effects burden associated with it. Some potentially life-threatening side effects of clozapine include agranulocytosis, myocarditis, and diabetic ketoacidosis. Although constipation is a frequent adverse effect of clozapine, it is often overlooked. Life-threatening complications such as paralytic ileus can result from constipation unless it is appropriately managed.[2] Paralytic ileus is one of the rare but potentially fatal side effects of clozapine.[3,4] The primary mechanism by which clozapine is linked to paralytic ileus is because of its muscarinic anticholinergic action. Risk factors for paralytic ileus include old age and female sex.[5] Here, we describe a patient with treatment-resistant schizophrenia who developed paralytic ileus 1 year after the initiation of clozapine. A 45-year-old married woman was admitted to the emergency medicine department complaining of difficulty in passing stools, abdominal pain, and distension for 1 week. She was diagnosed with paranoid schizophrenia 11 years ago and was treated with multiple first and second-generation antipsychotics with no relief of symptoms. She was started on clozapine 300 mg/day for the past year with relief of symptoms. There was no history of similar complaints. She was a known case of diabetes mellitus and hypothyroidism on regular treatment for the past 3 years and has normal blood sugar and thyroid hormone levels. The patient denied a history of substance use. There was no family history of psychiatric illnesses. Physical examination revealed a distended abdomen with reduced bowel sounds. The patient’s complete blood count, biochemistry, urinalysis, thyroid function tests, and inflammatory markers were normal. Abdominal ultrasonography and X-ray of the erect abdomen revealed dilated bowel loops [Figure 1]. After doing a computed tomography scan, the patient was diagnosed with paralytic ileus [Figure 2]. The patient’s symptoms were thought to be due to the use of clozapine; therefore, oral intake was stopped, and feeding was provided by a nasogastric tube. Clozapine was tapered off. The patient experienced an improvement in her constipation and a decrease in her stomach pain and distention over 3 days. After 2 weeks, the patient was discharged against medical advice due to financial reasons and was lost to follow-up.Figure 1: X-ray of the abdomen showing dilated small and large bowel loops with multiple diffuse, air-fluid levels typical of paralytic ileus, and the presence of gas in the rectum and distal colon, which rules out complete mechanical obstructionFigure 2: Computed tomography abdomen showing generalized uniform gaseous distension of small and large bowel loops. Lack of any transition point noted. Findings suggestive of paralytic ileusPeople with schizophrenia and their first-degree relatives have been found to have autonomic dysfunction of the enteric nervous system, specifically dysmotility of the gastrointestinal tract because of abnormal sympathetic reflexes.[6] Antipsychotics’ anticholinergic and antiserotonergic effects have been associated with contributing to the onset of paralytic ileus.[7] Paralytic ileus may be caused by trauma, following abdominal surgery, hypokalaemia, uremia, or toxemia, but none of these was seen in our patient. Clozapine’s highest anticholinergic property is thought to be the leading cause of paralytic ileus. The mean time from initiation of clozapine to the onset of ileus is 4 years.[3] Compared with these cases, the clinical findings in our patient are unique: In our patient, paralytic ileus was considered to be due to the use of clozapine and promptly responded to drug withdrawal. In the present case, anticholinergic drugs were not used, and long-standing constipation was not an issue. No other cause of paralytic ileus was apparent. Patients using antipsychotic medications should be monitored regularly to ensure they are implementing the recommended precautions against constipation. It is crucial to start anticholinergic medications cautiously and increase dosages gradually. Ileus should be treated with caution because common clinical signs, particularly in those with mental illnesses, can be obscured or changed. Since early detection can prevent life-threatening pathologic processes and fatal outcomes and allow for appropriate management, patients receiving clozapine and/or other psychotropics associated with significant muscarinic properties should have their bowel function closely monitored, laxatives should be used promptly, and constipated patients should be referred as soon as possible. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.