Phenytoin in Topical Formulations Augments Pain Reduction of Other Analgesics in the Treatment of Neuropathic Pain

Topical analgesic formulations are gaining interest for the treatment of peripheral neuropathic pain since the beginning of 2000. Advantages of topical analgesics over oral medication are the absence of systemic side effects and drug-drug interactions, higher concentrations of active compound at the pain area, fast onset on action, improvement of compliance, and no risk of abuse. In many peripheral neuropathic pain states the pain area is small and thus topical analgesics are suitable. Most patients experience pain reducing effect within 30 minutes after application of compounded topical analgesics, such as creams containing amitriptyline, ketamine, baclofen, or clonidine. This helps to quickly identify responders on selected analgesic creams. Unfortunately, in some patients the duration of topical applied analgesic formulations is short and/or the reduction of pain is insufficient. Therefore, strategies to prolong the duration and intensify the analgesic effect are needed. We discovered that phenytoin augments the effects of topical analgesics, leading to a faster onset of action, a longer duration of analgesia, and an intensified pain relieving effect. We will present 6 cases in which phenytoin 5% or 10% lead to enhanced therapeutic effects of topical applied amitriptyline 10%, ketamine 10%, baclofen 5%, or clonidine 0.2% creams in the treatment of neuropathic pain. We also present a fast topical analgesic response-test to identify responders within a 30 minutes’ assessment period after a test application. Responders are defined as experiencing at least 2 points reduction of pain intensity, as measured with the 11-point numerical rating scale. Responders subsequently are treated with the analgesic cream as tested. sics have a number of advantages over oral medication, such as the absence of systemic side effects and drugdrug interactions, fast onset of pain relief, high concentration of the active compound at the application area, improvement of compliance, and no risk of abuse [1]. These advantages are based on the fact that topical analgesics have a peripheral mechanism of action, without the need to enter the bloodstream. Especially in geriatric patients with neuropathic pain, with high risk of undesirable side effects, drug-drug interactions and/or altered metabolization due to intake of multiple medications, topical analgesics should be considered as a first line treatment option [2]. In our Institute for Neuropathic Pain we developed and tested topical compounded analgesics, such as ketamine 10%, amitriptyline 10%, and baclofen 5% creams [3-10]. Most responders experience pain reducing effect within 30 minutes after application. Using a topical analgesic response-test, responders can be identified within a 30 minutes assessment period after a test application. A responder is defined as least 2 points reduction of pain intensity, as measured with the 11-point numerical rating scale (NRS). After identifying the responder as such, we prescribe the topical analgesic which was tested. Unfortunately, some of our patients experience pain relief only for a short period of time (e.g. 1 to 2 hours). In our search to solve this problem we discovered that the old anticonvulsant phenytoin has remarkable properties. Phenytoin added to other active compounds in topical formulations leads to augmentation of effects, such as a faster onset of action, a longer duration of Case RepoRt