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Introduction: Since pathogenesis of cholestatic pruritus is not fully elucidated, the treatment is a real challenge for the clinician. In case of the lack of efficiency, despite the treatment of the liver disease, one considers indications for the usage of drugs affecting the central nervous system, such as gabapentin; butorphanol, tetrahydrocannabinol, mirtazapine, naloxone, naltrexone, ondansetron and sertraline. Up to date, there has been a deficiency of randomized controlled trials (RCT) and meta-analyses concerning the usage of these medications. The aim of the study: To investigate efficiency of the usage of drugs affecting the central nervous system in the therapy of cholestatic pruritus based on a systematic review and meta-analysis of up-to-date studies. Material and methods: Randomized control trials (RCT) that investigated the usage of gabapentin; butorphanol, tetrahydrocannabinol, mirtazapine, naloxone, naltrexone, ondansetron and sertraline in the treatment of cholestatic pruritus were to be found. A statistical analysis was performed using MetaEasy, version 1.0.4. Meta-analysis was carried out based on the mean difference (MD) and lower and upper contingency interval (95% CI), in a random effects model. Results: The systematic review included 2 RCTs of naltrexone therapy conducted in 26 patients with cholestatic pruritus, 2 RCTs conducted in 22 patients undergoing naloxone therapy, 3 RTCs evaluating the usage of ondansetrone in 30 patients, 1 RCT assessing sertraline therapy in 12 patients, and 1 RCT assessing gabapentin therapy in 15 patients. Three case reports that concerned the usage of butorphanol, tetrahydrocannabinol and mirtazapine in cholestatic pruritus were not included in meta-analysis. Naltrexone for the treatment of cholestatic pruritus was statistically more effective in comparison with placebo in day time (MD=0.91 [95% CI=0.26-1.56]; MD=1.64 [95% CI=0.66-2.62]), and during the night (MD=0.85 [95% CI=0.2 -1.51]; MD=1.48 [95% CI=0.5-2.46]). In comparison with placebo naloxone was found to be more effective in relieving cholestatic pruritus (MD=0.74 [95% CI=0.22-1.26]; MD=0.06 [95% CI=-0.8-0.94). Two RCTs of ondansetrone showed no significant advantage over placebo and one RCT showing pruritus reduction (VAS decrease 1.34; 95%CI=0.12-2.56; p=0.033). In the group undergoing sertraline therapy (p<0.009), a significant reduction of pruritus was observed. In RCT assessing the usage of gabapentin no significant differences were found in reduction of the pruritus in comparison to the control group with placebo. Conclusions: Naltrexone, naloxone and sertraline are more effective than placebo for the treatment of cholestatic pruritus. There is a lack of convincing evidence of the advantage of the usage of gabapentin; butorphanol, tetrahydrocannabinol, mirtazapine and ondansetroneover placebo for cholestatic pruritus. [ABSTRACT FROM AUTHOR]

Introduction: Since pathogenesis of uremic pruritus is not fully elucidated, the treatment is a real challenge for a clinician. In case of the lack of treatment efficiency, despite the usage of emollients and phototherapy UV, one considers indications to the usage of drugs affecting the central nervous system, such as gabapentin, nalfurafine, butorphanol, naltrexone, ondansetron, mirtazapine and doxepin. Up to date there is a deficiency of randomized controlled trials (RCT) and meta-analyses concerning the usage of these medications. The aim of the study: To investigate efficiency of the usage of drugs affecting the central nervous system in the therapy of uremic pruritus based on the systematic review and meta-analysis of up-to-date studies. Material and methods: Randomized control trials (RCT) that investigated the usage of gabapentin, nalfurafine, butorphanol, naltrexone, ondansetron, mirtazapine, and doxepin in the treatment of uremic pruritus were enclosed to systematic review. A statistical analysis was performed using MetaEasy, version 1.0.4. Meta-analysis was carried out based on the mean difference (MD) and lower, and upper contingency interval (95% Cl), in a random effects model. Results: The systematic review included 3 RCT of gabapentin therapy conducted in 84 patients with uremic pruritus, 1 meta-analysis and 1 RCT conducted in 268 patients undergoing nalfurafine therapy, 2 RTCs evaluating the usage of naltrexone in 31 patients, 1 RCT assessing ondansetron therapy in 16 patients, and 1 RCT assessing doxepin therapy in 24 patients. Gabapentin for the treatment of uremic pruritus was statistically more effective in comparison with placebo (MD=-2.32 [lower 95%CI=-2.97, upper 95%CI=-1.66]). In comparison with placebo nalfurafine was found to be more effective in relieving uremic pruritus (MD=-0.49 [lower 95%CI=-0.66, upper 95%CI=-0.32]). One RCT showed significant decrease of pruritus in the group undergoing naltrexone therapy (p<0.001), however this investigation did not contain results of pruritus reduction in the control group with placebo, therefore it was not included in meta-analysis. In RCTs assessing the usage of naltrexone and ondansetron no significant differences were found in reduction of the pruritus in comparison to the control group with placebo. Conclusions: Gabapentin and nalfurafine for the tratment of uremic pruritus are more effective than placebo. There is a lack of convincing evidence of advantage of the usage of butophanol, naltrexone, ondansetrone, mirtazapine and doxepin over placebo for uremic pruritus. [ABSTRACT FROM AUTHOR]