(196) Successful continuation of clozapine treatment during liver transplantation

Abstract:

Background: Evidence suggests that patients with psychotic disorders can successfully undergo solid organ transplantation without significant adverse medical outcomes.1 However, experience with the use of clozapine in the post-transplant setting is limited. Clozapine use post-transplant requires careful consideration given the risk of synergistic medication-induced agranulocytosis, seizures, QT prolongation, hyperglycemia, and other potential drug-drug interactions between clozapine, immunosuppressants, and infection prophylaxis medications. We present a case of clozapine use in the perioperative period for a liver transplant recipient.



Case: A 59 year old man with treatment-resistant schizophrenia stable on clozapine for many years and cirrhosis secondary to non-alcoholic steatohepatitis underwent successful liver transplantation. He was continued on his home psychotropics clozapine 100 mg daily and sertraline 100 mg daily perioperatively. He received methylprednisolone bolus intraoperatively, followed by tacrolimus, mycophenolate mofetil, and prednisone postoperatively. On postoperative day 7, the patient displayed disorientation, hyperverbal speech, disorganized thought process, and visual hallucinations secondary to sleep deprivation that was treated with lorazepam 1 mg nightly. On postoperative day 10, he developed elevated mood, increased energy, and tangential thought process that was treated by increasing his clozapine dose to 150 mg daily. Seven months later, he is psychiatrically stable and has had no adverse drug reactions.



Discussion: Our case adds to other case reports demonstrating that clozapine can be safely continued through solid organ transplantation2 and bone marrow transplantation3 without adverse medical outcome but does require significant monitoring. We monitored for agranulocytosis by checking complete blood count and absolute neutrophil count daily for 1 week post-transplant, followed by weekly for 4 weeks, and then monthly thereafter. If moderate neutropenia were to develop after liver transplantation, considerations might include discontinuing prophylaxis medication, reducing the dose of mycophenolate mofetil, and/or initiating filgrastim prior to discontinuing clozapine.4



Conclusion: It is possible to continue clozapine for chronic psychotic disorders during the perioperative liver transplant period. Clinicians should be vigilant of monitoring and managing side effects in clozapine-treated patients to reduce the risk of overlapping toxicity between immunosuppressants and infectious prophylaxis medications.



References:

1. Zimbrean P, Emre S. Patients with psychotic disorders in solid-organ transplant. Prog Transplant Aliso Viejo Calif. 2015;25(4):289-296. doi:10.7182/pit2015296
   


2. Lim AM, Dhillon R, Tibrewal P, Bastiampillai T, Nguyen BDH. Clozapine, immunosuppressants and renal transplantation. Asian J Psychiatry. 2016;23:118. doi:10.1016/j.ajp.2016.07.018
   


3. Wright TC, Du S, Hedrick RM, Cho SH. Successful continuation of clozapine treatment during hematopoietic stem cell transplantation: A step toward health equity in the oncologic care of people with severe mental illness. Psychooncology. 2021;30(12):2082-2086. doi:10.1002/pon.5782
   


4. Keles M, Yildirim R, Uyanik A, et al. Neutropenia related to valacyclovir and valganciclovir in 2 renal transplant patients and treatment with granulocyte colony stimulating factor: a case report. Exp Clin Transplant Off J Middle East Soc Organ Transplant. 2010;8(2):181-183.