Top-Accessed Article: Combination Gel of 1% Amitriptyline and 0.5% Ketamine to Treat Refractory Erythromelalgia Pain

Abstract

Sandroni P, Davis MP. Combination gel of 1% amitriptyline and 0.5% ketamine to treatrefractoryerythromelalgiapain:anewtreatmentoption?ArchDermatol.2006; 142(3):283-286. Erythromelalgia is a rare skin disorder characterized by severe burning pain, warmth, and erythema that is aggravated by heat and exercise. It is considered to be a neurovascular disorder associated with a small nerve fiber neuropathy and alteredvoltage-gatedsodiumchannels.Inrecentyears,neuromodulatingagents,such as gabapentin and pregabalin, as well as topical lidocaine, were found to be useful therapies. However, there are cases of erythomelalgia that remain resistant to these conventionaltherapiesandcauseextremesuffering.SandroniandDavisreportusing a novel treatment featuring combination gel of 1% amitryptiline hydrochloride and 0.5% ketamine hydrochloride in lecithin pluronic organogel applied 4 to 5 times a day in 5 patients with intractable erythromelalgia. In 4 of these patients, a significant response was noted, with the improvement rate ranging from 50% to 95%. The rationale for this combination can be explained by specific pathways that aretargeted.KetamineisanN-methyl-Daspartate(NMDA)receptorantagonistand a modulator of glutamatergic receptors. This is important since NMDA and glutamate are known to play a key role in neuropathic pain. Amitriptyline is a tricyclic antidepressant, which helps reduces pain in various disorders owing to its ability to block voltage-gated sodium ion channels. While topical application in limited body areas in this study did not lead to systemic absorption, the safety profile of thispreparationhasnotbeenfullyassessed.Nonetheless,thisanecdotalreportholds