Several neurological side effects induced by tacrolimus are described in the scientific literature, ranging from mild neurological symptoms to delirium and psychosis. We report the case of a 46-year-old man with no prior psychiatric history who suddenly manifested manic-like psychosis associated with elevated trough tacrolimus blood concentrations 17 years after kidney transplant. The use of antipsychotics may improve the severity of symptoms; but in order to obtain a complete remission, the reduction in the dose of tacrolimus, or its replacement with alternative immunosuppressant therapies, is recommended. 1. Introduction Calcineurin-inhibitor Tacrolimus (FK506; Fujisawa, Deerfield, IL, USA) is considered one of the mainstays of posttransplant immunosuppression [1]. Discovered in 1984, it is a macrolide lactone extracted from Streptomyces tsukubaensis as an alternative to cyclosporine [2]. Tacrolimus mechanism of action is fulfilled through the binding with the cytoplasmic protein macrophilin 12 and the consequent inhibition of calcium-dependent phosphatase calcineurin, which is followed by the blockade of the transcription factor NF-AT [3]. Tacrolimus has a narrow therapeutic window with wide interindividual variability in pharmacokinetics and clearance [4, 5]. Its availability mostly depends on the activity of hepatic and intestinal CYP3A4, and its active transport is mediated by intestinal P-glycoprotein [6]. Less than 1% of the drug is excreted unchanged in the urine [7]. Based on FK506 consensus reports by Jusko et al. [8] and Wong [9], its therapeutic ranges in kidney transplanted patients should be 10–15？μg/L in the first 6 months of treatment; 8–12？μg/L in the following semester; and 5–10？μg/L as maintenance therapy after 1 year. Even if this highly beneficial drug is critical for post-transplant survival, a significant number of transplant recipients experience neurological side effects, with potential severe impact on mental status and cognition. Numerous cases of mild neurological side effects including tremors, paresthesias, and headache [10] have been described, while more severe neurological and psychiatric side effects seem to occur more rarely (Table 1). Table 1: Neurologic complications of tacrolimus therapy in transplants patients (1, 2, 3). Later, we describe the case of a 46-year-old man who developed a manic-like psychosis as a consequence of high blood concentrations of tacrolimus. 2. Case Report Mr. MP was a 46-year-old man who underwent left kidney transplant in 1996; therefore, he was treated with the following
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