Comparison of gabapentin and doxepin in the management of uremic pruritus: A randomized crossover clinical trial

Abstract

Gabapentin and doxepin are well-known treatments of uremic pruritus in hemodialysis patients but no head-to-head studies were conducted to date. The aim of this trial is to compare the efficacy and the tolerability of gabapentin and doxepin in the treatment of uremic pruritus in hemodialysis patients. A single-blind crossover randomized trial was conducted that included hemodialysis patients with uremic pruritus. Patients were randomized to receive 10 mg doxepin daily or 100 mg gabapentin for 4 weeks and the two groups were treated conversely for another 4 weeks after a 4-week washout period. Eighty-five patients were screened for eligibility. Thirty-one met the inclusion criteria and four were excluded. Sixteen patients agreed and signed the consent and two withdrew from the study. VAS scores at baseline were 6.71 and 6.14, and dropped to 0.57 and 2.35 at week 4 in the gabapentin and doxepin groups, respectively. Mean scores of the 5-Domain Itch Scale (5-D) at baseline were 14.71

Chronic Kidney Disease-Associated Itch (CKD-aI) in Children—A Narrative Review

“…An experimental study by Kim [ 312 ] reported that first-generation H 1 -antihistamines exert their effects on various subcortical and cortical regions of the brain which results in decreased pleasure associated with scratching. Regarding CKD-aI treatment in adults, the usage of hydroxyzine [ 313 , 314 ], doxepin [ 315 , 316 ] and ketotifen [ 185 , 317 ] is supported by the available literature. Concerning second generation of H 1 -antihistamines, desloratadine diminished CKD-aI in a prospective, crossover, open-label trial ( n = 22).…”

“…Notably, they have also proven useful in the management of psychiatric disorders (such as bipolar disorder) and neuropathic pain [ 322 , 323 ]. Up to date, gabapentin [ 314 , 316 , 317 , 324 , 325 , 326 , 327 , 328 , 329 , 330 , 331 , 332 ] and pregabalin [ 315 , 327 , 328 , 332 , 333 , 334 , 335 , 336 ] constitute the most effective systemic treatment of CKD-aI in adults, with several hundred reported patients in the literature. Direct comparison between both drugs revealed no difference between their effectiveness [ 327 , 328 , 332 ], although gabapentin may be switched to pregabalin in case of insufficient tolerance.…”

Topical gabapentin 10% in the treatment of epidermolysis bullosa pruritus: A pilot, double‐blind, split‐site, randomized controlled trial

“…Gabapentin is an antiseizure drug approved for treating epileptic seizures and peripheral neuropathic pain, including vulvodynia, herpes neuralgia, and painful diabetic peripheral neuropathy 6,7 . This drug can mitigate chronic uremic and nephropathic itching and burn‐related itching 8–14 . This effect appears to be due to its high affinity for binding to the α2δ subunit of voltage‐gated calcium channels in the nervous system, 15 thereby regulating the release of substance‐P (SP) and the calcitonin gene‐related peptide (CGRP) 15,16 .…”

“…6,7 This drug can mitigate chronic uremic and nephropathic itching and burn-related itching. [8][9][10][11][12][13][14] This effect appears to be due to its high affinity for binding to the α2δ subunit of voltage-gated calcium channels in the nervous system, 15 thereby regulating the release of substance-P (SP) and the calcitonin gene-related peptide (CGRP). 15,16 It can also directly inhibit interleukin (IL)-2 and reduce its binding to the neurokinin-1 receptor, thus improving the itch's severity.…”