(199) Delayed-Onset Psychosis After Lung Transplant Secondary to Tacrolimus Neurotoxicity

Location: Griffin Hall

Trainee Involvement: Yes

Presenting Author(s)

Matthew Gunther, MD, MA (he/him/his)

Clinical Assistant Professor
Stanford University
Palo Alto, California, United States

Co-Author(s)

Yelizaveta Sher, MD, FACLP

Clinical Professor of Psychiatry
Stanford School of Medicine
Stanford, California, United States
Shixie Jiang, MD

Assistant Professor
University of Florida
Gainesville, Florida, United States

Background/Significance: Tacrolimus is the most common immunosuppressant used after transplant, yet it can result in moderate-to-severe neurotoxicity in up to 32% of patients (Bechstein, 2000). Signs of neurotoxicity can vary (from tremor to catatonia) with recognition and management leading to prompt resolution.

Case: Mr. M had a history of interstitial lung disease with subsequent bilateral lung transplant. One year after his transplant, he was admitted for pancytopenia and RSV infection. The psychiatry team was consulted due to a change in personality, refusal of interventions and some medications, and a focus on controlling his room temperature.
On evaluation, patient presented with a profound, fixed delusion that the room temperature was too cold. Mr. M’s delusion remained fixed, despite room temperature adjustments, to the point that the patient expressed a willingness to forego any medical care and pass away. There was no evidence of delirium, posterior reversible encephalopathy syndrome (PRES) (although both were on the differential), or deficits in cognitive testing. Tacrolimus levels were between 4.4 to 8.7 the month leading up to consultation. Renal function had decreased with dialysis initiation the month prior to consult.
Diagnosis was suspected to be tacrolimus-induced neurotoxicity, with notable contribution from declining renal function. Intravenous haloperidol was started and titrated with some clinical improvement. The transplant team transitioned patient from tacrolimus to cyclosporine. While Mr. M declined a few dialysis sessions, it was restarted. Mr. M had complete symptom resolution, including disappearance of his obsession over the room temperature, six days after change in immunosuppressant therapy.

Discussion: The data on isolated psychotic symptoms in the setting of tacrolimus-induced neurotoxicity are quite limited (Uvais, 2022). Current literature addresses more common presentations including tremor or delirium. PRES is also a well-documented, but rare, finding of tacrolimus use (Braithwaite, 2021; Bechstein, 2000). Our case is unique not only in the clinical symptomatology, but in its delayed presentation one year after transplant. With our case, we present what is known on tacrolimus-induced psychosis as well as further distinguish it from other conditions, including delirium. Risk factors for development of this syndrome and differential diagnosis formulation are emphasized. These findings should inform medical psychiatrists and transplant teams alike to consider tacrolimus-induced neurotoxicity as an etiology for any new psychiatric symptoms in their patients.
Conclusion/Implications: Tacrolimus-induced psychosis is a unique presentation of tacrolimus-related neurotoxicity and can present without the cardinal symptoms of other encephalopathies. Development can occur later in the treatment course and at normal tacrolimus serum levels. It improves with antipsychotic therapies, but primary management should include cross-titration to an alternate immunosuppressant regimen.

References:

1. Braithwaite HE, et al. . Identifying the association between tacrolimus exposure and toxicity in heart and lung transplant recipients: A systematic review. Transplantation Reviews. 2021 Apr;35(2):100610.
2. Bechstein WO. Neurotoxicity of calcineurin inhibitors: impact and clinical management. Transplant Int. 2000 Sep;13(5):313–26.
3. Uvais NA, et al. . Psychosis Associated With Tacrolimus at Therapeutic Serum Levels. Prim Care Companion CNS Disord. 2022 Dec 8;24(6).