Drug-Induced Psychosis: A Drastic Turn After a Kidney Transplant

Drug-induced psychosis is an uncommon but clinically significant complication in solid-organ transplant recipients, particularly those receiving calcineurin inhibitors such as tacrolimus. Neuropsychiatric toxicity can occur even at therapeutic drug levels, and concurrent corticosteroid use may further increase vulnerability. Early recognition is essential, as symptoms may be mistakenly attributed to metabolic disturbances, primary psychiatric illness, or postoperative delirium, thereby delaying appropriate intervention. We report the case of a previously healthy 34-year-old man with end-stage renal disease who underwent a living-donor kidney transplant and subsequently developed profound behavioral and cognitive changes. Despite no prior psychiatric history, he experienced progressive social withdrawal, auditory hallucinations with running commentary, persecutory delusions toward family members, disrupted sleep-wake patterns, weight loss, and significant functional decline. At the time, he was receiving tacrolimus, mycophenolate mofetil, and low-dose prednisolone for graft maintenance. His family observed a marked deterioration following an episode of acute kidney injury and hyponatremia several months earlier. Mental status examination revealed preserved orientation and attention but prominent psychotic features and poor insight. Tacrolimus trough levels remained within the reported therapeutic range; however, variability in oral absorption and the inability of whole-blood concentrations to reflect the active unbound fraction may have masked neurotoxic exposure. Prednisolone, though prescribed at a low dose, may have contributed synergistically to symptom onset. Alternative etiologies, including primary psychotic disorders, delirium, and mood disorders with psychotic features, were considered but were not supported clinically. This case underscores the importance of maintaining a high index of suspicion for calcineurin inhibitor-related neurotoxicity in transplant recipients who develop new-onset psychosis, even when tacrolimus levels appear therapeutic. In this patient, psychotic symptoms were managed through a multidisciplinary approach that prioritized graft preservation while addressing neuropsychiatric safety. Prednisolone was discontinued, and antipsychotic therapy was initiated, while tacrolimus was continued due to its necessity in preventing rejection. This case highlights that meaningful clinical improvement can be achieved without altering essential immunosuppressive therapy when teams collaborate closely and monitor both psychiatric status and graft function. Early recognition and prompt intervention are crucial to reducing morbidity in this vulnerable population.