Case Report: The Challenges of Assessing and Managing Dysphagia in Two Patients on Long-term Clozapine

Abstract

<h3>Introduction</h3> Introduction: The risk of clozapine associated dysphagia is between 1/1000 and 1/10000 (1). The associated complications of aspiration, pneumonia and mortality are also observed to be elevated with clozapine use(2). There is also limited evidence suggesting that risk is dose and age dependent (2), We present two cases illustrating the potential complex presentations of dysphagia in patients on clozapine. <h3>Methods</h3> Methods: The first case is a 61-year-old male veteran with history of chronic schizophrenia admitted for worsening psychosis. He has been on clozapine up to 550mg since 2001, with clozapine/norclozapine levels at 452/232. Exam was remarkable for an AIMS score of 25. During admission patient reported odynophagia, dysphagia and a 40-pound weight loss. Initial workup revealed candida esophagitis. 21-day course of fluconazole yielded no improvement. Inpatient team did not increase dose due to concern for esophageal dysmotility. Manometry is pending at the writing of this case report, hydroxyzine was reduced and benztropine discontinued to reduce anticholinergic burden. The second patient was a 51-year-old female with history of schizoaffective disorder, chronic PTSD, alcohol use disorder, bulimia nervosa, temporal lobe epilepsy, iron deficiency anemia, and GERD. Patient was on clozapine from 2009 until 2016. In 2015, she reported dysphagia worsening for one year with solid food dysphagia, choking, and sialorrhea. Subsequent manometry revealed type II achalasia and clozapine was discontinued within one year and switched to aripiprazole and eventually olanzapine. Over subsequent years, patient's dysphagia worsened and led to severe malnutrition. In 2020, she underwent Heller's myotomy with Dor fundoplication, with the expectation that dysphagia may remain given multifactorial etiology including polypharmacy. Patient also received a PEG tube. In 2020-2021, patient had more than 20 admissions for recurrent aspiration pneumonitis. In July 2021, she was admitted for replacement of a PEG tube and patient went into pulseless electrical arrest. Aspiration was cited as a factor in her death. <h3>Results</h3> Discussion: Dysphagia with antipsychotics can be mediated by multiple mechanisms including parkinsonism, acute dystonic reactions, tardive dyskinesia, sialorrhea, xerostomia, and sedation. Management approaches include reduction of clozapine and switching to another antipsychotic although these interventions may not reduce dysphagia. Aspiration on clozapine leads to a release of cytokines which can increase serum concentration of clozapine and in turn, side-effects (3). <h3>Conclusions</h3> Conclusion: These two cases illustrate the challenges in assessing and managing dysphagia in patients on clozapine. In both cases, dysphagia became an issue years after initiation of clozapine. In the first case, the veteran's dysphagia was likely mediated by tardive dyskinesia and oversedation. In the second case, dysphagia was likely mediated by sialorrhea, oversedation and other multiple comorbidities. More systematic studies are needed to better characterize risk of clozapine associated dysphagia and treatment approaches. <h3>This research was funded by</h3> none