The Dilemma of Clozapine in the Medically Ill: Challenges and Solutions.

Abstract:
Background: Different guidelines and safety programs were developed for clozapine treatment in the general population. No specific guidelines exist for treatment initiation and monitoring of clozapine in medically ill individuals admitted to the hospital for non-psychiatric reasons. In this presentation, we discuss the challenges of clozapine treatment in this population and propose adjustments to the current guidelines based on available evidence.

Method: We will briefly present a literature review to address four main challenges that Consultation-Liaison (CL) psychiatrists usually face in managing clozapine patients when they become medically ill. These challenges are: 1- The impact of medical illness on the validity of CBC for agranulocytosis monitoring. 2- The difficulty in detecting clozapine induced myocarditis. 3- The substantial increase in clozapine level and clozapine toxicity in cases of severe inflammation and infection. 4- clozapine induced delirium and how to distinguish it from other causes of delirium.

We will start the presentation with brief review of clozapine history and the different guidelines around the globe, that will be followed by 2 clinical scenarios which we usually encounter as CL psychiatrists in these patients, then the bulk of the presentation will be on discussing and addressing the challenges mentioned above. Finally, we will summarize recommendations for managing patients taking clozapine admitted to the medical unit along with proposing adjustments to the current clozapine guidelines.

Discussion: Clinicians face many challenges with clozapine treatment in medically ill patients admitted to medical units. This may include 1) significant increase in clozapine level and toxicity with inflammation (Clark et al 2018) (Lenoir C et al 2021) 2) Infection-related changes in ANC and temperature which affect the validity of safety monitoring parameters for both agranulocytes and myocarditis 3) increased incidence of delirium (Centorrino et al 2003) and 4) difficulty optimizing clozapine dose after stabilizing the medical condition.

Conclusion: This presentation sheds the light on the limitations of current clozapine guidelines when they are applied to medically compromised patients and illustrates the need for consensus on different approaches and safety parameters such as monitoring clozapine levels, Troponin, and EKG in this vulnerable population. CL psychiatrists play a pivotal role in managing these complex clinical cases.