Clozapine-Induced GI Hypomotility: from Constipation to Bowel Obstruction
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Pearls Clozapine-induced GI hypomotility: From constipation to bowel obstruction Andrew Cruz, MD, and Oliver Freudenreich, MD Dr. Cruz is a PGY-2 resident, MGH/ Table McLean Adult Psychiatry Residency atients who are treated with clozap- Program, and Dr. Freudenreich ine—a second-generation antipsy- Bowel regimen for chronic is Co-Director, Schizophrenia chotic approved for treatment-resistant constipation Clinical and Research Program, P Massachusetts General Hospital, schizophrenia—require monitoring for seri- Stool softener (daily) Boston, Massachusetts. ous adverse effects. Many of these adverse Docusate sodium 100 mg twice daily Disclosures effects, such as agranulocytosis or seizures, Stimulant laxative (weekly and as needed) The authors report no financial relationships with any company are familiar to clinicians; however, gastro- Bisacodyl, 5 to 15 mg/d, as needed whose products are mentioned in intestinal (GI) hypomotility is not always Senna glycoside, 15 mg/d, as needed this article, or with manufacturers of competing products. recognized as a potentially serious adverse effect, even though it is one of the most common causes for hospital admission.1 Its Staff who care for patients taking clozapine manifestations range from being relatively who live in a supervised setting should be benign (nausea, vomiting, constipation) to educated about the relevance of a patient’s potentially severe (fecal impaction) or even changing bowel habits or GI complaints. life-threatening (bowel obstruction, ileus, Also, teach patients about simple lifestyle toxic megacolon).2 modifications they can make to counteract GI hypomotility is caused by clozapine’s constipation, including increased physical strong anticholinergic properties, which activity, adequate hydration, and consum- lead to slowed smooth muscle contrac- ing a fiber-rich diet. Acknowledgment tions and delayed bowel transit time. It is The authors thank Travis Baggett, MD, Department of further compounded by clozapine’s 5-HT3 Avoid anticholinergics, consider Medicine, Massachusetts General antagonism, which is also known to slow a bowel regimen Hospital, Boston, Massachusetts, for reviewing the medical bowel transit time. To avoid the potentially If possible, avoid prescribing anticholin- management of constipation. serious risks associated with GI hypomo- ergic medications to a patient receiving References tility, we offer simple approaches for clini- clozapine because such agents may add 1. Stroup TS, Gerhard T, Crystal S, cians to follow when treating patients with to clozapine’s anticholinergic load. Some et al. Comparative effectiveness of clozapine and standard clozapine. patients may require medical manage- antipsychotic treatment in adults with schizophrenia. Am J ment of chronic constipation with stool Psychiatry. 2016;173(2):166-173. Teach patients to watch for softeners and stimulant laxatives. The 2. Every-Palmer S, Ellis PM. Clozapine-induced GI symptoms Table outlines a typical bowel regimen we gastrointestinal hypomotility: Before starting a patient on clozapine, use for patients at our clinic. Some clini- a 22-year bi-national pharmacovigilance study and at all subsequent visits, ask him or cians may prefer earlier and more regu- of serious or fatal ‘slow gut’ reactions, and comparison her about bowel habits and GI symptoms. lar use of senna glycoside. Also, patients with international drug safety Because the onset of GI hypomotility can be might need a referral to their primary advice. CNS Drugs. 2017; 31(8):699-709. subtle, ask patients to pay close attention to care physician if prevention has failed their bowel habits and keep a diary to docu- and fecal impaction requires enemas ment GI symptoms and bowel movements. or mechanical disimpaction. An urgent Signs of bowel obstruction can include an referral to the emergency department is inability to pass stool, nausea, vomiting, needed if a patient has a suspected bowel Current Psychiatry 44 August 2018 abdominal pain, and a bloated abdomen. obstruction..