Tacrolimus-Induced Parasomnia Posttransplantation

Tacrolimus, a potent calcineurin inhibitor, is widely prescribed to prevent organ rejection after allogenic transplantation and to manage autoimmune conditions like rheumatoid arthritis and lupus nephritis. Despite its immunosuppressive advantages, tacrolimus can cause significant systemic side effects, including rare but notable neurotoxic effects such as psychosis.^1,2 However, parasomnias linked to tacrolimus have not been documented in the literature. Here, we present a rare case of tacrolimus-induced parasomnia, adding to the body of evidence on its neurotoxic potential.

Case Report

Ms D, a 58-year-old woman with bronchiectasis, chronic obstructive pulmonary disease, and hypertension, underwent a bilateral lung transplant for hypoxemia. Her past psychiatric history included depression managed with citalopram and alprazolam, with no family history of psychiatric or cognitive disorders. Postoperatively, she was initiated on tacrolimus, mycophenolate mofetil, and prednisone.

Three days after transplant, Ms D began experiencing vivid auditory and visual hallucinations, describing voices of family members and a man whispering by her window. She also displayed significant sleep disturbances, including loud sleep-talking without subsequent recollection. Various medications, including gabapentin, prednisone, ribavirin, and voriconazole, were held due to potential neuropsychiatric side effects with no improvement.

On evaluation, she showed impaired attention, concentration, and executive function, along with bradyphrenia and distractibility. Imaging revealed no acute abnormalities. A diagnosis of delirium with mixed features was considered, and she was started on haloperidol, guanfacine, and melatonin. Although her cognitive functioning improved over 4 days, she continued to have episodes of sleep-talking and morning hallucinations.

A temporal connection emerged between her tacrolimus dosing and symptom onset. Sleep-talking occurred within 1 to 2 hours of her nighttime dose; similarly, morning hallucinations appeared within the same timeframe after her morning dose. Tacrolimus’s peak onset typically falls within 1 to 4 hours after administration, which coincided with Ms D’s symptoms. Despite her tacrolimus levels remaining within the therapeutic range, these observations strongly suggested tacrolimus-induced neurotoxicity. In collaboration with the transplant team, tacrolimus was switched to cyclosporine. Within 2 days, her hallucinations and parasomnias resolved entirely.

Discussion

Parasomnias are sleep disorders characterized by abnormal motor, verbal, or behavioral events during sleep or at transitions between sleep and wakefulness. Somniloquy (sleep-talking) can range from isolated words to full conversations without recall. Various triggers—including sleep disorders (eg, sleep apnea), jet lag, or medications—can disrupt the sleep-wake boundary and precipitate parasomnias.³

This case highlights a potential association between tacrolimus and parasomnias, likely attributable to its neurotoxic properties as a calcineurin inhibitor.³ Tacrolimus influences neurotransmitter pathways by increasing glutamate (via inhibition of calcium ion channels in synaptosomes) and reducing γ-aminobutyric acid (GABA) (through inhibition of dephosphorylation of l-glutamate decarboxylase).³ Elevated glutamate enhances wakefulness by activating neurons in the ascending reticular activating system, while reduced GABA diminishes inhibitory control, destabilizing sleep regulation.⁴ Consequently, patients may experience fragmented sleep and heightened vulnerability to parasomnias.³ Importantly, postoperative delirium, which can increase blood-brain barrier permeability, likely amplified the neurotoxic effects of tacrolimus in this case.⁵

Management could initially involve reducing the dose of tacrolimus, although neurotoxic effects have been observed even at therapeutic levels. Switching to alternative immunosuppressants (eg, cyclosporine or mechanistic target of rapamycin [mTOR] inhibitors) is another option, though mTOR inhibitors are associated with impaired wound healing early posttransplant.¹ Tacrolimus also boasts lower rejection rates during the first year after liver transplant compared to other immunosuppressants.¹

In our patient, the cessation of tacrolimus and the transition to cyclosporine led to a complete resolution of her parasomnias and hallucinations, underscoring the importance of recognizing tacrolimus-induced parasomnias as a possible yet rare complication. Clinicians should remain vigilant for neuropsychiatric side effects in transplant patients, particularly when delirium is present. Early detection and prompt modification of immunosuppressant therapy can be crucial to optimizing safety and therapeutic efficacy.

Article Information

Published Online: March 17, 2026. https://doi.org/10.4088/PCC.25cr04108
© 2026 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2026;28(2):25cr04108
Submitted: October 13, 2025; accepted December 15, 2025.
To Cite: Tacrolimus-induced parasomnia posttransplantation. Prim Care Companion CNS Disord 2026;28(2):25cr04108.
Author Affiliations: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California (Nolasco, Gunther); Department of Psychiatry, University of Florida College of Medicine, Gainesville, Florida (Jiang); Department of Psychiatry and Behavioral Neurosciences, University of South Florida, Tampa, Florida (House); Edward Hines Jr. Veterans Administration Hospital, Hines, Illinois (Czuma); Department of Pulmonary, Critical Care and Sleep Medicine, University of Florida College of Medicine, Gainesville, Florida (Janssen).
Corresponding Author: Diego Nolasco, MD, Stanford University, Department of Psychiatry and Behavioral Sciences, 401 Quarry Rd, Palo Alto, CA 94304 ([email protected]).
Financial Disclosure: None.
Funding/Support: None.
Patient Consent: Informed consent was obtained from the patient to publish the case report, and information has been de-identified to protect patient anonymity.