Paralytic Ileus in a 45-Year-Old Female with Schizophrenia on Clozapine Therapy

Abstract

A 45-year-old woman who comes with complains of recurrent paradoxical loose stools and abdominal distension for 3 days. She had type II diabetes, schizophrenia, and a history of left below-knee amputation. While there was no indication of a mechanical blockage, imaging tests revealed paralytic ileus. A potentially fatal gastrointestinal side effect that is frequently associated with anticholinergic drugs, such as clozapine, is paralytic ileus. Full recovery was achieved with conservative treatment and a reduction in the dosage of clozapine. This instance highlights how important it is to identify and treat drug-induced gastrointestinal dysmotility as soon as possible.

INTRODUCTION

Paralytic ileus, which is characterized by a disruption of normal intestinal peristalsis without mechanical obstruction, is sometimes caused by the adverse effects of drugs, particularly those that have anticholinergic properties. Strong anticholinergic and anti-serotonergic effects of clozapine, a major ingredient in treatment-resistant schizophrenia, can impair gastrointestinal motility, resulting in constipation and, in severe cases, bowel obstruction and paralytic ileus.[1,2,3] Although constipation is common in clozapine patients, paralytic ileus remains a rare but dangerous side effect with significant morbidity and death if managed.[4,5] According to this article, clozapine caused paralytic ileus in a middle-aged woman with multiple comorbidities. It also discusses the challenges associated with this illness’s diagnosis and treatment.

CASE REPORT

A 45-year-old woman with a history of schizophrenia who had been taking clozapine for more than 5 years showed signs of growing distension in her abdomen and 4 days of paradoxical loose stools. Her medical history included a left below-knee amputation from trauma 10 years ago, hypothyroidism on thyroxine, and well-controlled type 2 diabetes mellitus treated with metformin 500 mg once a day and vildagliptin 50 mg once a day. Due to sedation, her dose of clozapine was recently lowered from 400 mg to 300 mg. She was found to be haemodynamically steady and afebrile. Significant distension without tenderness or guarding was found during the abdominal examination; the bowel sounds were hypoactive.

Laboratory tests showed mild hyponatremia, leukocytosis (white blood cell 13,660/μL with 92% neutrophils), severe microcytic hypochromic anemia (hemoglobin 6.4 g/dL), increased C-reactive protein (120 mg/L), and hypoalbuminemia (2.0 g/dL). Thyroid function tests revealed low levels of T3 and T4, as well as suppressed thyroid-stimulating hormone. Viral serologies and stool cultures used in infectious screening came out negative.

Investigations

An initial abdominal X-ray showed markedly dilated bowel loops consistent with paralytic ileus but no mechanical obstruction [Figure 1]. Further imaging with computed tomography (CT) abdomen confirmed diffuse bowel dilatation without a transition point. Contrast-enhanced CT of the abdomen demonstrated diffuse dilatation of the duodenum, jejunum, and ileum with air-fluid levels and a small bowel feces sign, without a transition point, confirming paralytic ileus [Figures 2-4]. Sequential laboratory and diagnostic parameters during the hospital stay are summarized in Table 1.

Figure 1.

The chest radiograph, though mildly rotated to the left, reveals a well-positioned radiopaque nasogastric/OG tube descending smoothly through the esophagus without coiling. No abnormalities are detected, with clear lung fields, normal mediastinal structures, and intact bony and soft-tissue anatomy

Figure 2.

Contrast-enhanced CT abdomen shows dilatation of the ileum, jejunum, and duodenum (2^nd to 4^th sections) with air-fluid levels and small bowel feces sign. No transition point or obstructive lesion noted. Findings consistent with paralytic ileus

Figure 4.

Axial CT image showing duodenal loop dilatation with small bowel feces sign

Table 1.

Sequential laboratory and diagnostic parameter changes from admission to discharge

Test category	Parameter (reference range)	Day 1	Day 2	Day 3	Day 4	Day 5	Day 6
Complete blood count	Hb (11.6–15 g/dl)	7.0	8.6	10.2	-	-	10.8
	Total WBC (4000–10,000/µL)	13,600	12,400	11,200	-	-	8,900
	Neutrophils (40%–80%)	92	88	82	-	-	68
	Lymphocytes (20%–40%)	6	8	10	-	-	25
	Platelets (1.5–4.1 lakh/µL)	3.9 L	3.8L	3.7L	-	-	3.85L
Liver function test	Bilirubin total (0.2–1.2 mg/dL)	1.2	1.0	0.9	-	-	0.6
	Bilirubin direct (≤0.5 mg/dL)	0.6	0.5	0.5	-	-	0.2
	SGOT (8–43 U/L)	25	22	25	-	-	17
	SGPT (7–45 U/L)	10	12	14	-	-	20
	ALP (35–104 U/L)	152	140	98	-	-	100
	Albumin (3.5–5.2 g/dL)	2.0	2.3	3.3	-	-	3.8
Renal function test	Urea (15–40 mg/dL)	50	48	38	30	28	26
	Creatinine (0.6–1.2 mg/dL)	2.1	1.8	1.0	0.8	1.12	0.7
Serum electrolyte	Sodium (135–145 mmol/L)	132	135	138	136	140	142
	Potassium (3.5–5.0 mmol/L)	2.9	3.4	3.6	4.8	4.6	4.5
	Chloride (98–106 mmol/L)	98	96	100	99	98	102
	CRP<6 mg/L	46	-	32	-	18	9
Urine analysis	Appearance (clear)	Clear	Clear	Clear			Clear
	Protein (nil)	Trace	Trace	Nil			Nil
	Sugar (nil)	1-2	Nil	Nil			Nil
Thyroid function	T3 (80–200 ng/dL)	70	80			95
	T4 (5.1–14.1 µg/dL)	5.8	6.0			6.5
	TSH (0.3–4.5 µIU/mL)	3.8	4.2			3.0
	Ultrasound imaging	Dilated bowel loops					Normal

TSH=Thyroid-stimulating hormone, CRP=C-reactive protein, ALP=Alkaline phosphatase, Hb=Hemoglobin, WBC=White blood cell, SGOT=Serum glutamate oxaloacetate transaminase, SGPT=Serum glutamate pyruvate transaminase

Figure 3.

Contrast-enhanced CT showing dilated jejunal and ileal loops with air-fluid levels, no transition point

Additional assessment using contrast-enhanced abdominal CT verified fecalization of the distal small bowel and diffuse dilatation of the duodenum, jejunum, and ileum with air–fluid levels. There was no discernible obstructive lesion or transition point. The Grade 1 fatty liver and dilated bowel loops showed to-and-fro peristalsis on abdominal ultrasonography. During admission, two-dimensional echocardiography showed a maintained ejection fraction and normal cardiac anatomy and function.

Management

To relieve gastrointestinal distension and avoid aspiration, the patient was first treated conservatively with nasogastric (NG) decompression using a Ryle’s tube. Initial chest radiograph showed proper positioning of the nasogastric tube without coiling or pulmonary complications [Figure 5]. To address dehydration and electrolyte imbalances while reducing gut stimulation, rigorous bowel rest (nil per os) and intravenous fluid resuscitation were implemented. The placement of a Foley catheter allowed for precise urine output monitoring. Two units of packed red blood cells were transfused to treat anemia, and diuretics were given to avoid fluid overload. Intravenous 20% albumin infusions were administered for 5 days to treat hypoalbuminemia to support vascular stability and restore oncotic pressure. Due to increased inflammatory indicators, empirical intravenous antibiotics, such as monocef and metronidazole, were initiated, and oral probiotics were administered to support a healthy gut flora.[6,7]

Figure 5.

On the day of admission, the abdominal radiograph shows multiple dilated, gas-filled bowel loops, raising suspicion for intestinal obstruction. No free air is seen under the diaphragm, and both fat planes, lumbar spine, and soft-tissues appear normal; further evaluation with ultrasonography or contrast-enhanced computed tomography of the abdomen and pelvis was recommended

To increase gastrointestinal motility, the patient’s thyroxine dosage was decreased from 100 μg to 25 μg after consulting with endocrinology as part of endocrine optimization. To balance the risk of psychotic relapse with the requirement to lessen anticholinergic side effects that contribute to paralytic ileus, psychiatric therapy involved a slow tapering of clozapine from 300 mg to 50 mg under close psychiatric care.[4,8] A repeat abdominal X-ray performed after clozapine dose reduction continued to show dilated gas-filled bowel loops without free air [Figure 6]. Within 72 h, the abdomen circumference shrank and the bowel sounds returned to normal, indicating clinical recovery. Five days later, follow-up imaging confirmed that the intestinal dilatation had resolved. An abdominal X-ray obtained on the day of discharge showed resolution of bowel dilatation with no abnormal air–fluid levels [Figure 7]. The patient complied with the treatment plan and maintained mental stability during the hospital stay.

Figure 6.

On 3^rd day of admission, after decreasing clozapine dosage the abdominal radiograph shows multiple dilated, gas-filled bowel loops, raising suspicion for intestinal obstruction. No free air is seen under the diaphragm, and both fat planes, lumbar spine, and soft-tissues appear normal; further evaluation with ultrasonography or contrast-enhanced computed tomography of the abdomen and pelvis was recommended

Figure 7.

X-ray erect abdomen on the day of discharge showed nasogastric/orogastric tube tip is in situ. The properitoneal fat planes seem normal, and there is no free air beneath the diaphragmatic domes or aberrant air-fluid levels. No aberrant radiopaque densities are visible in the belly, soft tissues, or bones. No glaring anomaly was found

Post-discharge care focuses on continued multidisciplinary follow-up involving internal medicine, gastroenterology, endocrinology, and psychiatry to monitor bowel function, optimize comorbidities, and maintain psychiatric stability. Dietary modifications promoting fiber intake and hydration, along with the cautious use of stool softeners, help prevent recurrence of ileus. Ongoing psychiatric assessments and laboratory monitoring of clozapine levels ensure safe medication use. Patient education regarding early signs of gastrointestinal dysfunction and medication adherence is emphasized, with social support and lifestyle interventions to enhance recovery and long-term outcomes.

DISCUSSION

Clozapine-induced paralytic ileus represents a rare but potentially life-threatening adverse effect associated with the anticholinergic properties of clozapine, which inhibit parasympathetic stimulation of the gastrointestinal tract and result in a significant reduction of intestinal motility.[1,3,5] A comparison with previously reported cases of clozapine-induced paralytic ileus is shown in Table 2. This pathophysiological disruption leads to functional obstruction due to impaired peristalsis rather than mechanical blockage. Clinically, patients may present with paradoxical overflow diarrhea, a manifestation of severe constipation or fecal impaction, which can obscure the diagnosis and delay appropriate intervention. Comorbid conditions, including diabetes mellitus with autonomic neuropathy, hypothyroidism, anemia, immobility, and concomitant use of other anticholinergic agents, further predispose patients to gastrointestinal hypomotility and increase the risk of developing paralytic ileus.

Table 2.

Comparative summary with similar reported cases of clozapine-induced paralytic ileus

Parameter/feature	Present case	Case 1 (van Weringh, et al. 2024)[9]	Case 2 (Kumar et al., 2019)[10]	Case 3 (Lee et al., 2020)[11]
Age/sex	45 female	50 male	42 female	47 male
Clozapine dose at onset	300 mg/day	400 mg/day	350 mg/day	450 mg/day
Major symptoms	Abdominal distension, paradoxical diarrhea	Constipation, distension	Distension, vomiting	Abdominal pain, no stool
Imaging findings	Diffuse bowel dilatation, no transition point	Small bowel dilatation	Generalized ileus	Colonic pseudo-obstruction
Comorbidities	DM2, hypothyroid, anemia, BKA	HTN, DM2	Hypothyroid, depression	DM2, hyperlipidemia
Clozapine adjustment	Gradual taper to 50 mg	Discontinued	Tapered to 100 mg	Switched to olanzapine
Outcome	Full recovery	Full recovery	Recovery, mild constipation	Recovery

DM2=Type 2 diabetes mellitus, BKA: Below-knee amputation, HTN=Hypertension

Optimal management requires early identification and a multidisciplinary approach to balance the resolution of gastrointestinal complications with the continuation of essential psychiatric treatment. The key stone of initial therapy consists of supportive measures like keeping the patient nothing per mouth, careful monitoring, abdominal girth monitoring, and correction of fluid and electrolyte imbalances. To avoid psychotic symptoms from recurring, the dosage of clozapine must be gradually reduced while being closely monitored by a psychiatrist. To guarantee comprehensive care, coordination between primary care physicians, gastroenterologists, and psychiatrists is essential. To reduce morbidity and mortality linked to this significant complication, recent research emphasizes the significance of proactive monitoring for gastrointestinal side effects in patients receiving clozapine and the need for prompt intervention.[7]

CONCLUSION

Clozapine induced paralytic ileus is a serious and fatal which ultimately had a lethal side effect requiring closer therapeutic monitoring. This case report brings to the fore the issue of how abdominal distension, paradoxical diarrhea, and gastrointestinal hypomobility, can mask the underlying condition, ultimately to delay the timely intervention. One of the most common side effects of chronic clozapine users who also have comorbid conditions such as diabetes mellitus, hypertension, and hypothyroidism had such symptoms of abdominal distension and loose stools.[1] Prompt early diagnosis due to clinical approach and proper imaging modalities, and successful nonsurgical treatment, such as fluid resuscitation, decompression with NG tube, bowel rest, and monitored medical alteration saved the patient. Stepwise tapering of clozapine was utilized to preserve mental stability and reduce gastrointestinal side effects.

The success of this guarded approach proves the worth of a multidisciplinary collaboration that involves gastrointestinal, endocrinology, psychiatry, and internal medicine. Need for regular monitoring measures among long-term clozapine users must involve early evaluation for gastrointestinal symptoms, dissemination of awareness against patient, and regular evaluation of bowel habits, if necessary, imaging, and metabolic function that will benefit the patient. Taking steps to avoid the problem returning, like consuming more fiber, staying hydrated with lots of water, and avoiding excessive anticholinergic medication, can significantly reduce the chances of it occurring again.[8] The conclusion of this research discusses the fine line that must be struck between regulating the therapeutic effects of clozapine and lessening its systemic risks. Through proactive monitoring, patient-focused care, and early identification, physicians are able to ensure that patients with both physical and mental ailments are well.

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.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.