Meta-Analysis of Randomized Controlled Trials on GABA Analogues and Opioid-Based Therapies for CKD-Associated Pruritus

Chronic kidney disease (CKD)-associated pruritus (CKD-aP) is one of the most distressing symptoms of patients with CKD, adversely affecting their quality of life and survival. This study aimed to investigate the efficacy and safety of gamma-aminobutyric acid (GABA) analogues and opioid-based therapies in patients with CKD-aP. The eligible studies were searched from PubMed, Embase, and Scopus up to January 22, 2025. Only randomized controlled trials (RCTs) that reported the treatment effect on pruritus severity scores were included, focusing on both unidimensional scales and multidimensional scales. The results were synthesized using a random-effect model and provided weighted mean difference (WMD) and relative risk (RR) with a 95% confidence interval (CI). A total of 27 RCTs involving 2836 patients with CKD-aP were analyzed. Treatment with GABA analogues was associated with significantly greater reductions in 10-cm visual analog scale (VAS) and 5-D itch scores with nonsignificant increased incidence of adverse events (AEs) or adverse drug reactions (ADRs). In addition, opioid receptor-targeting treatments significantly decreased worst itch numeric rating scale (WI-NRS), 5-D itch, Skindex-10, and 100-mm VAS, but showed significantly higher rates of AEs or ADRs, particularly related to gastrointestinal issues, as well as neurological disorders such as sleep disturbances. Our results suggest that GABA analogues and opioid-based therapies, particularly difelikefalin, have significant potential in alleviating itch intensity and improving the quality of life of patients with CKD-aP. However, opioid-based therapies, especially those involving μ-receptor antagonists such as naltrexone and nalbuphine, are associated with a higher incidence of AEs or ADRs. Given the substantial heterogeneity observed in most of the results, interpretation should be approached with caution.