GI, Pulmonary Illnesses: Most Cited for Hospitalizing Clozapine Patients

When prescribing clozapine—the only antipsychotic that has been FDA-approved for treatment-resistant schizophrenia—clinicians are required by an FDA boxed warning to closely monitor patients’ blood to reduce the risk of agranulocytosis and other adverse events. A study published online on November 18, 2016, in Psychosomatics now suggests pulmonary and gastrointestinal illnesses may be the most likely reason for patients taking clozapine to be hospitalized.

“The new study gives a clear profile of medical vulnerabilities faced by some patients treated with clozapine,” said Mark Olfson, M.D., M.P.H., a professor of psychiatry at Columbia University Medical Center, who was not involved in the study.

For the study, Jonathan Leung, Pharm.D., of the Mayo Clinic in Minnesota and colleagues conducted a retrospective chart review of patients with schizophrenia or schizoaffective disorder who were taking clozapine and admitted to an inpatient medical unit at the Mayo Clinic for nonpsychiatric illness between January 1, 2003, and August 1, 2005. A total of 104 adults aged 18 and older was included in the analysis. They were admitted into the hospital a total of 248 times, and the mean clozapine dose prescribed at the index admission was 407.2 mg.

Pulmonary illness and gastrointestinal illness were the most common reasons for hospitalizations at 32.2 percent and 19.8 percent, respectively. The most common pulmonary diagnosis was pneumonia, accounting for 58 percent of pulmonary admissions. The most common reason for gastrointestinal diagnosis was hypomotility, at 61.2 percent. The authors noted that clozapine was discontinued due to neutropenia in two patients; there were no patients admitted for myocarditis. (Agranulocytosis can lead to neutropenia when the bone marrow fails to make enough neutrophils.)

“In our sample, the primary reasons for admission were not related to the FDA boxed warnings, but rather to pulmonary and gastrointestinal illnesses,” the authors wrote. “This is not unexpected given that clozapine-related neutropenia and myocarditis have the highest incidence within several months after first exposure and are likely to be discovered through vigilant monitoring. Discovery then allows for early clozapine discontinuation and resolution of the adverse event, potentially avoiding medical hospitalization.”

Psychiatric consultation was obtained in 25 percent of the hospitalizations, “most frequently for ‘clozapine management,’ retitration recommendations, or possible clozapine toxicity. Clozapine dosage adjustment infrequently occurred, and complete discontinuation was rare,” the authors wrote.

In an interview with Psychiatric News, Leung said that current findings are congruent with other published information and highlight two important aspects of clozapine therapy. First, all clinicians should vigilantly monitor bowel function in order to prevent potentially fatal complications; and second, pneumonia associated with clozapine is an underappreciated event.

Leung continued that it will be important for future investigations to include control populations such as patients on other antipsychotics to understand the proportion of adverse events potentially attributable to clozapine. “We can then focus on developing improved monitoring procedures and interventions that can minimize morbidity and mortality associated with pulmonary and gastrointestinal complications.”

No financial support was received for this study. ■

An abstract of “Characterization of Admission Types in Medically Hospitalized Patients Prescribed Clozapine” can be accessed here.