Tacrolimus-induced psychosis in liver transplant recipients: A systematic review of all published cases

Abstract

Objective

This systematic review aims to better characterize the clinical patterns, potential protective and risk factors, prognosis, and management of tacrolimus-induced psychosis in liver transplant recipients.

Method

We reviewed all published cases of severe psychiatric complications associated with tacrolimus in liver transplant recipients from 1998 to 2024. In total, 17 case reports, 1 case-control study, 3 retrospective studies, and 2 prospective studies were identified.

Results

Tacrolimus-induced psychosis presented with a wide range of symptoms, including tremor, speech difficulties, seizures, delusions, and paranoia. Of the 17 case reports, only 10 documented symptoms aligning with a clinical, DSM-based definition of psychosis. Affected patients varied in age, and a significant proportion had no prior psychiatric history. Symptom onset after tacrolimus initiation varied, though 15 of 17 cases developed psychosis within the first 6 months of treatment. Of these cases, 13 saw resolution of symptoms within one month of stopping tacrolimus. We differentiated cases by a strict, DSM-based definition of psychosis versus a broader categorization. The 10 cases fitting the classic definition showed a higher rate of symptom resolution within the first month.

Conclusion

Presentation of tacrolimus-induced psychosis varied considerably across reviewed studies, with rapid resolution upon drug discontinuation in most cases. However, a standardized approach to balancing risks of drug withdrawal against the need for immunosuppression remains absent. This review underscores the need for standardized diagnostic criteria.