Ondansetron and pruritus in chronic liver disease: a controlled study.

BACKGROUND/AIMS: Increased central opioidergic neurotransmission, mediated by endogenous opioid peptide agonists, contributes to the pruritus of cholestasis. There are interrelationships between the opioid and serotonin neurotransmitter systems. The serotonin 5-HT3 receptor subtype antagonist, ondansetron, has been reported to ameliorate centrally-mediated pruritus induced by exogenously administered opiates. This study was designed to determine whether long-term oral administration of ondansetron is efficacious in ameliorating pruritus complicating chronic liver disease. METHODOLOGY: Seventeen patients with severe pruritus complicating established chronic liver disease were randomized to receive, double-blind, ondansetron (8 mg) or a placebo orally; each was administered thrice daily for a 4-week period. Endpoints were subjective scores of pruritus and objective 24-hour measurements of scratching activity. Analysable data were generated in 13 of the patients. RESULTS: Ondansetron therapy was associated with ameliorations of pruritus that appeared to be clinically significant in 5 patients (38%); in these 5 patients the mean decrease in a subjective score of pruritus was 27% of the scale of the score. However, these apparent ameliorations were not associated with robust decreases in scratching activity. For the whole group of 13 patients mean scratching activity during ondansetron therapy was not significantly less than that during treatment with placebo (p = 0.19). The total time that patients were not scratching was similar during treatment with ondansetron and placebo (p = 0.57). CONCLUSIONS: The findings suggest that serotoninergic neurotransmission, in neurons bearing receptors of the 5-HT3 subtype, plays no more than a minor role in the mediation of pruritus complicating chronic liver disease. The lack of an association between the results of applying subjective scores of pruritus and scratching activity emphasizes the need to include an objective quantitative efficacy endpoint in the design of trials of new therapies for pruritus.

Reduced corneal swelling and deswelling response in the iridocorneal endothelial syndrome.

PURPOSE: Despite severe abnormalities of the corneal endothelium in the iridocorneal endothelial (ICE) syndrome, the cornea can remain clear and maintain its normal thickness for years before corneal decompensation occurs. The aim of this study is to analyze this discrepancy by studying corneal hydration control in the ICE syndrome. METHODS: In four subjects with unilateral ICE syndrome, without signs of corneal decompensation, a "corneal stress test" was performed in both the affected and the unaffected eye. The stress test measures the recovery of corneal thickness after swelling induced by wearing a soft contact lens with the eyes closed. Corneal thickness was measured by noncontact pachymetry. RESULTS: Mean baseline corneal thickness of affected eyes (535+/-56 microm) was not different from unaffected eyes (526+/-39 microm). On the other hand, the corneal stress test showed a smaller induced swelling in affected eyes (33+/-15 microm) compared with unaffected eyes (67+/-11 microm) and a slower recovery of corneal thickness in affected eyes. In one of four subjects, the cornea of the affected eye was calculated not yet to have recovered its original thickness before midnight. After this finding, although the cornea of this subject did not show any signs of clinical decompensation, the study was discontinued. CONCLUSIONS: Corneal hydration control is altered in the ICE syndrome. The ICE cornea can maintain its normal thickness despite severe morphologic abnormalities of the endothelium. Because we found that recovery of corneal thickness can be extremely slow, it cannot be guaranteed that such corneal "stress tests" are completely safe for subjects with the ICE syndrome, and we therefore feel that they should no longer be performed in these subjects.