(129) Clozapine in the Medically Ill, Between a Rock and a Hard Place: A Case Report of Initiating Clozapine in a Burn Patient.

Abstract:

Background: Different international guidelines and safety programs have been developed for clozapine treatment in the general population. No specific guidelines exist for treatment initiation and monitoring of clozapine in medically ill individuals admitted for non-psychiatric reasons. We describe clozapine initiation in a patient with treatment-resistant schizoaffective disorder admitted after self-immolation. We discuss the challenges of clozapine treatment in this population while proposing adjustments to current guidelines.





Case: A 38-year-old male with a history of schizoaffective disorder and 10 prior involuntary psychiatric hospitalizations due to psychosis, aggression, and suicidality, was admitted to the Burn Intensive Care Unit with 65% total body surface area burns after dousing himself with gasoline and setting himself on fire. He underwent multiple debridements with grafting and his hospital course was complicated by pneumonia, respiratory failure requiring intubation, osteomyelitis, C. Difficile colitis, urinary tract infections, and delirium. He was continued on his home medications consisting of olanzapine, haloperidol and haloperidol decanoate; his home lithium was held. After extubation, his delirium persisted and he experienced marked agitation, also developing auditory hallucinations, delusions and suicidal ideations. Four weeks later, his auditory hallucinations, delusions and suicidal ideations persisted despite resolution of delirium. We initiated clozapine treatment following Food and Drug Administration (FDA)monitoring guidelines. The patient became febrile and white blood cells (WBC) increased on multiple occasions during clozapine titration, but all incidents were attributed to infection. Psychotic symptoms and suicidal ideations significantly improved after introducing clozapine. However, the patient became heavily sedated and delirium worsened despite an improvement in his medical conditions. When the clozapine dose was decreased, his delirium eventually resolved. After a total of 16-weeks of hospitalization, his psychiatric symptoms significantly improved to the point where he could be discharged to a subacute rehabilitation facility.



Discussion: Clinicians face many challenges with clozapine treatment in medically ill patients admitted to medical units. This may include: 1) significant increases in clozapine levels and toxicity with inflammation (Clark, 2018) (Lenoir, 2021), 2) infection-related changes in WBC and temperature which affect the validity of safety parameters, 3) increased incidence of delirium (Centorrino, 2003) and, 4) difficulties in optimizing the clozapine dose after medical conditions resolve.



Conclusion: This case shows the limitations of current clozapine guidelines in medically compromised patients and illustrates the need for consensus on different approaches and safety parameters in this vulnerable population.











Reference:



1. Clark SR et al. Elevated clozapine levels associated with infection: A systematic review. Schizophrenia Research, 2018, 192:50–56.



2. Lenoir C, Rollason V, Desmeules JA and Samer CF. Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature. Front. Pharmacol. 2021, 12:733935.



3. Centorrino F et al. Delirium During Clozapine Treatment: Incidence and Associated Risk Factors. Pharmacopsychiatry, 2003;36:156-160.