Delayed onset tacrolimus-induced neuropsychiatric symptoms in a pancreas-after-kidney transplant recipient

The introduction of tacrolimus as an anti-rejection medication has markedly improved the outcomes of patients receiving organ transplants. While the use of tacrolimus has been instrumental in preventing organ rejection, especially in the case of pancreas and multi-organ transplants, the neuropsychiatric side effects are less commonly reported. Here, we present the complicated psychiatric and behavioral presentation of a 38-year-old woman with a psychiatric history of treatment-resistant depression, anxiety, and an unspecified eating disorder, who had been maintained uneventfully on tacrolimus after receiving a living-donor kidney transplant two years earlier. The patient then underwent an isolated pancreas transplant. Psychiatry was consulted six days after transplant for hyperactivity, disruptive behaviors, physical agitation, impaired cognition, disorientation, disorganized speech, and occasional hallucinations; these symptoms were refractory to multiple trials of psychiatric medications. After extensive medical and neurological work-up, and several instances of critically elevated tacrolimus levels, the patient was transitioned to cyclosporine, with gradual improvement, and eventual return to cognitive baseline. In exploring the possible causes of this complicated psychiatric presentation, we highlight the correlation between tacrolimus use and psychiatric symptoms, even when levels are in the therapeutic range, and emphasize the need to consider switching to an alternate agent. To our knowledge, this is the first case of tacrolimus-induced psychotic symptoms in the setting of a second organ transplant, years after initiation of tacrolimus for an initial transplant. Considering this, clinicians should remain vigilant in monitoring patients with chronic tacrolimus use, while awaiting more research into the neurotoxic implications of its long-term use.