Low Dose Naltrexone for the Treatment of Pruritus Associated with Dermatological Conditions: A Systematic Review

Naltrexone is a long-acting opioid receptor antagonist approved by the U.S. Food and Drug Administration in 1984 for opioid and alcohol dependence. Low-dose naltrexone (LDN), defined as 1.5 to 4.5 mg daily, produces an intermittent opioid receptor blockade that is thought to upregulate opioid growth factor and reduce proinflammatory cytokine production, contributing to its immunomodulatory effects. Dermatologic use of LDN has expanded significantly, with reported efficacy in inflammatory and autoimmune skin conditions including Hailey-Hailey disease (HHD), Darier disease, lichen planopilaris (LP), dermatomyositis, and psoriasis. LDN is initiated at 1.5 mg with gradual 1 mg titration to a typical target dose of 4.5 mg daily, optimizing tolerability and individualized response. Building on the demonstrated efficacy of LDN in various dermatologic conditions, this systematic review aims to evaluate its use in the treatment of pruritus associated with dermatologic disease.

Following Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines, PubMed, Embase, Web of Science, and ClinicalTrials.gov databases were searched using predefined keywords. Eligible studies were published in English and evaluated LDN for the treatment of pruritus in dermatologic conditions. Titles and abstracts were screened for relevance, followed by full-text review. Data on LDN dosing, pruritus improvement, clinical outcomes, and adverse effects were extracted by two independent reviewers. Inclusion criteria consisted of original human studies available in full text and addressing off-label LDN use for pruritus in dermatologic indications.