Pharmacology Update: Pruritus in Palliative Care With Focus on Naltrexone

BackgroundPruritus is a common and often distressing symptom in palliative care, affecting a significant fraction of patients and significantly impairing sleep, mood, and quality of life. Common etiologies include chronic kidney disease, cholestatic liver disease, hematologic malignancies, solid tumors, medication-related syndromes, and paraneoplastic processes. Conventional treatments, including antihistamines, antidepressants, gabapentinoids, ondansetron, and ultraviolet-B phototherapy, are frequently limited by adverse effects, cost, or practicality in seriously ill patients.ObjectiveTo review the pathophysiology of pruritus relevant to palliative care and evaluate the emerging role of naltrexone as a therapeutic option for refractory pruritus.MethodsNarrative review of the literature addressing the mechanisms of pruritus, current treatment approaches, and clinical evidence supporting the use of naltrexone across various pruritic conditions encountered in palliative medicine.ResultsIncreasing evidence implicates dysregulation of the endogenous opioid system in the pathogenesis of several forms of chronic pruritus. As a competitive opioid receptor antagonist, naltrexone may mitigate "itch" through μ-opioid receptor blockade and restoration of opioid signaling balance. The strongest evidence supports its use in cholestatic pruritus, where randomized placebo-controlled trials demonstrated significant reductions in symptom severity with 50 mg daily dosing. Evidence in uremic pruritus is mixed, with some studies showing benefit and others finding no superiority over placebo. Case reports and small series suggest potential efficacy in malignancy-associated pruritus, polycythemia vera, and selected dermatologic disorders. Limitations include contraindication in patients receiving opioid therapy, potential precipitation of withdrawal, and adverse effects such as nausea, gastrointestinal distress, dizziness, fatigue, and sleep disturbance.ConclusionsNaltrexone represents a mechanistically rational and potentially effective option for selected patients with refractory pruritus in palliative care. Current evidence is most compelling for cholestatic pruritus, while data for other etiologies remain limited and heterogeneous. Larger prospective studies are needed to define optimal dosing strategies, identify patients most likely to benefit, and better characterize its role in opioid-exposed palliative care populations.