CLOZAPINE INDUCED CONSTIPATION: A CASE REPORT

Ali Mahmood Khan 1 , Javeria Sahib Din 1 , Faiza Farooq 1 , Ashraf Farooq Arain 2 , Mohammad Mustafa Ahmed 2 , Shanila Shagufta 1 and Abdul Mohit 3 . 1. Kings County Hospital Center, NY, USA. 2. Ziauddin University, Karachi, Pakistan. 3. Behavioral Health, Kings County Hospital Center, NY, USA. ..................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History


ISSN: 2320-5407
Int. J. Adv. Res. 5 (7), 1863-1865 1864 11/26/16.At the time of development of small bowel obstruction his medication regimen included Fluphenazine 5mg morning, 10 qhs, Clozapine 100 mg morning, 300 qhs, Depakote 1000 mg BID.The patient went through an exploratory laparotomy secondary to small bowel obstruction, reduction of volvulus was performed, and 2 days later he was taken back to operating room for reduction of abdominal hypertension, which was successful. Post-surgeryClozapine was discontinued and his medication regimen was changed to monotherapy Prolixin. On the 12 th post-operative day he was transferred back to the psychiatry unit for continuation of his psychiatric treatment and stabilization. The patient's symptoms had not been controlled hence Prolixin with Loxapine was tried. However due to unacceptable extrapyramidal side effects patient was switched to Prolixin and Zyprexa. This combination was clinically in-effective therefore Seroquel was added. Although his psychosis were better controlled his affect was still dysregulated hence Depakote 1500mg BID was added.
After arriving to the unit he was found to be very weak with unstable gait and selectively mute. Patient appeared to be internally preoccupied and psychotic. Additionally patient stated that he tried to commit suicide when he was younger but denied any current suicidal and homicidal ideations on the unit. On mental status evaluation the patient's insight was poor; judgment was impaired; attention span was poor by interview; memory was grossly intact;intellectual functioning was intact; affect was labile.
Patienthas no history of substance abuse or intoxications, which was confirmed by a negative urine toxicology. Patient had poor social support, and has had problems with keeping relationships due to his aggression. The protective factors for the patient are his supportive sister and stable housing. On the unit, patient was counselled for medication adherence, attending groups and to learn coping skills for his aggressive behavior.
Gradually patient's behavior regressed on the unit, his thought process became more linear and his affect stabilized. He became selectively mute, stayed in his room most of the times, but did come out and participated in groups few times. Patient's bowel movement was continuously assessed by the medical and psychiatric team. Patient had some constipation but his bowel movements were recorded to be every 2-3days by the time of his discharge. Patient was offered to be re-started on Clozapine since it had good effect for him but he refused. Treatment team did not ask for court-override since his psychosis and affect symptoms were well controlled with medication regimen at the time of discharge which was Zyprexa 40mg per-oral qhs, Depakote 1500 mg BIDper-oral and Seroquel 300 mg per-oral in the morning and 400mg qhs per-oraland Prolxin 5mg per-oral BID. At the time of discharge he had no suicidal ideation, plan, or intent and was not an imminent danger to himself or others. Pt was discharged back to her sister's house and with follow up appointment in the out-patient.

Discussion:-
Clozapine is a tricyclic dibenzodiazepine and it is classified as an atypical antipsychotic agent, which binds to various types of Central Nervous System receptors. It is a serotonin antagonist and binds to 5-HT 2A/2C receptor subtype. It has weak antagonism for dopamine D2 receptor as well. It is used to treat patients with treatmentresistant schizophrenia, suicidal behavior and advanced dopaminomimetic psychosis. The drug is metabolized by hepatic enzymes and has a half-life of around 8 hours. It is the only atypical antipsychotic which is better than all other antipsychotics [2]. Schizophrenia patients who do not improve with other atypical antipsychotics, show improved results by switching to Clozapine [3].
Constipation is a clinical manifestation which has different ways of presenting itself, some of the symptoms include hard stools, infrequent defecation and feeling of incomplete bowel movement. It is caused by a variety of reasons with low intake of fiber a very common one along with drugs such as antipsychotics, diuretics and calcium channel blockers, known to cause hypomotility. Stress and anxiety is also considered to be one of the factors for causing constipation.
The gut has innervations from cholinergic and serotonergic receptors (5-HT3) so Clozapine induces constipation using its strong antagonist effects on serotonin receptors (5-HT2, 5-HT3, 5-HT6, 5-HT7), leading to hypomotility [8]. Although a number of antipsychotics cause constipation, studies indicate Clozapine induced constipation is quite common and is "approximately three times more likely to occur than with other antipsychotics" [1]. Though constipation is not a serious side effect of Clozapine, reports state that if left undiagnosed and untreated, it may potentially prove to be fatal and cause death [4]. There are a number of complications due to increased gastrointestinal hypo-motility which can prove fatal [9]. Some of the complications due to gastrointestinal hypomotility include severe fecal impaction which may lead to vomiting or bowel necrosis [10]. It is difficult for 1865 physicians to diagnose such severe complications at times as patients with schizophrenia could have decreased sensitivity to pain [5]. The lowered sensitivity may cause the patient to not recognize the pain being caused due to the increased hypomotility [6]. Even if pain perception is normal, expression of pain is considered to be difficult for patients suffering from schizophrenia [7]. Approximately 40% of cases that were reported of severe clozapine induced gastrointestinal motility took place within a span of 4 months since treatment was initiated [9].
Patients with clozapine induced constipation should be educated about the risk of constipation and warned about usage of drugs which may elevate the risk of hypomotility [10]. Laxatives such as Senna, Docusate, lactulose or Polyethylene glycol may be used for treatment of clozapine induced constipation [9] [11].

Conclusion:-
In light of previous researches, it can be said that constipation is a common side effect of clozapine but may progress to life threatening complications if left untreated. Patients should be monitored closely while being treated with clozapine to avoid the risk of constipation being left undiagnosed.