Topical analgesics for neuropathic pain in the elderly: current and future prospects

Neuropathic pain (NeP) is a significant medical and socioeconomic burden with limited therapeutic options. Elderly patients exhibit a higher incidence of several NeP conditions and pose a particular challenge due to age-related pharmacokinetic and pharmacodynamic issues, comorbid conditions, and polypharmacy, as well as frailty and cognitive decline. Topical analgesics are of interest because of their comparable efficacy to oral agents, good tolerability and safety, and potential to be add-on therapies to oral treatments. In recent years, two topical formulations for NeP have been approved (5% lidocaine medicated plaster, 8% capsaicin patch) but are not available in all countries. There are controlled trials and a growing body of open-label reports on their use in clinical care. Some studies provide a post hoc analysis of data in relation to older age (≥65 years), which is useful. The body of evidence relating to topical investigational agents is growing and involves controlled trials as well as individual cases. The largest single body of information is for topical ketamine, administered either alone or combined with other agents (particularly amitriptyline), and some large randomized controlled trials report efficacy. Other large trials involve topical clonidine and further ketamine combinations. Compounding analgesics involves challenges, including uncertain composition (two to five ingredients are used) and concentrations (range 0.5-5%), as well as the heterogeneity of data that support choices. Nevertheless, case reports and acceptable response rates in larger cohorts are intriguing, and this area merits further investigation in controlled settings as well as continued documentation of clinical experiences.