Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebo-controlled study

Background & Aims: The efficacy of currently available therapeutic: agents for cholestatic pruritus is often disappointing. The aim of this study was to assess the antipruritic effect of naltrexone, an oral opiate receptor antagonist. Methods: Sixteen patients with pruritus of chronic cholestasis were randomized to receive naltrexone (4-week course of 50 mg naltrexone daily) or placebo, Pruritus, duality of sleep, fatigue (using visual analogue scales), side effects, and liver function were assessed every 2 weeks. Serum naltrexone and 6 beta-naltrexol concentrations in all patients and 5 healthy controls were measured during the first day of naltrexone treatment. Results: Mean changes with respect to baseline were significantly different, in favor of the naltrexone group, for daytime itching (-54% vs, 8%; P < 0.001) and nighttime itching (-44% vs. 7%, P = 0.003). In 4 naltrexone-treated patients, side effects (transient in 3 cases) consistent with an opiate withdrawal syndrome were noted. No deterioration of the underlying disease was observed. Naltrexone and 6 beta-naltrexol levels did not differ between patients and controls, and there was no significant association with treatment response. Conclusions: For patients with cholestatic liver disease and itching, refractory to regular antipruritic therapy, oval naltrexone may be an effective and well-tolerated alternative.