Calcineurin Inhibitor-Induced Psychosis following Kidney Transplantation: Complete Resolution by Switching to Balatacept

Dear Editor,

Calcineurin inhibitors (CNI) are the mainstay of immunosuppression following organ transplantation. Neurological side effects like tremors are common with CNI use. Rare, more serious neurologic and behavioral adverse effects include akinetic mutism, dementia, psychosis, seizures, and leukoencephalopathy.¹ We present a kidney transplant recipient who developed CNI-induced psychosis that completely resolved after switching to belatacept.

A 66-year-old female with bipolar disorder and chronic lithium exposure was well controlled on lamotrigine and escitalopram. She underwent preemptive living donor kidney transplantation with thymoglobulin induction and tacrolimus/mycophenolate mofetil maintenance with standard infection prophylaxis. She experienced immediate graft function and was discharged on the 4^th post-operative day. A week later, she was re-admitted with encephalopathy, confusion, catatonia, and psychosis. Tacrolimus levels were in the therapeutic range (8-10 ng/mL). Hematologic, biochemical, infectious, and neurological workup, including brain MRI scan and EEG, were inconclusive. Psychiatric evaluation revealed new, psychotic features with delusional suspiciousness. Tacrolimus was thought to be the culprit and was switched to cyclosporine. The patient was transferred to the inpatient psychiatric unit on ziprasidone and sodium valproate. Due to a lack of improvement one month post-transplant, it was felt that psychosis was due to a class effect from CNI. Cyclosporine was switched to belatacept. Psychosis completely resolved within 2 weeks. She was weaned off sodium valproate and ziprasidone. Five months post-transplant, the patient is fully functional and independent with stable allograft function and no signs of psychosis.

The neurobehavioral side effects are thought to be related to the modulatory effects of CNI agents on glutamate pathways, and dopamine signal transduction and can happen with therapeutic drug levels.^1-3 Switching to belatacept, a co-stimulation blocking agent⁴ with no significant transport across the blood-brain barrier, led to complete resolution of CNI-induced psychosis.