RANDOMIZED CROSSOVER TRIAL OF NALTREXONE IN UREMIC PRURITUS

Background Most dialysis patients develop pruritus, for which current treatment is unsatisfactory. Endogenous opioids may be involved in thi s pruritus. We studied the effect of the opioid antagonist naltrexone on the pruritus of haemodialysis patients. Methods Naltrexone 50 mg pe r day by mouth was given to 15 haemodialysis patients with severe resi stant pruritus in a randomised, double-blind, placebo-controlled cross over trial. The naltrexone or placebo periods lasted 7 days each with a 7-day washout between the two periods. Pruritus was assessed by the patients on a visual analogue scale from 0 (no pruritus) to 10 (maximu m), and mean daily scores were calculated. Plasma histamine and beta-e ndorphin levels were measured, and spontaneous and stimulated basophil histamine-release were determined. Findings The median pruritus score s at the end of the naltrexone treatment were 2.1 (interquartile range 1.5-2.15) for the naltrexone-placebo sequence and 1.0 (0.4-1.15) for the placebo-naltrexone sequence. The respective values before naltrexo ne was given were 9.9 (9.85-9.95) and 9.9 (9.3-10.0). Plasma beta-endo rphin levels were normal and remained unchanged during the study. Plas ma histamine levels were high (mean 2.32 [SD 0.11] ng/mL, normal <1.0) and decreased after naltrexone (to 1.8 [0.09], p<0.01). Basophils fro m haemodialysis patients stimulated by interleukin-3 plus IgE antibodi es released high amounts of histamine. The increase was 78.3 (19.3)% c ompared with 26.6 (16.3)% for five normal controls (p<0.01). Incubatio n of the basophils with naloxone, another opioid antagonist, prevented this effect. Interpretation Our data suggest short-term efficacy with few side-effects for the amelioration of uraemic pruritus with naltre xone.