High Doses of Topical Amitriptyline in Neuropathic Pain: Two Cases and Literature Review

Abstract

Severe chronic neuropathic pain is a challenge to treat, and due to adverse effects of classical oral medication, optimal and effective dose levels are difficult to reach. Therefore, administration of topical analgesics might be an option, due to reduced adverse effects, and increased patient compliance. The aim of this article is to describe two cases treated effectively with topical amitriptyline 5% and 10%, the highest dosage described to date. The first patient was a 39-year-old man, suffering from severe intractable neuropathic pain in feet and hands, due to diabetes mellitus type II (DM-II). After application of amitriptyline 5% the patient experienced a complete relieve only in the hands, whereas after application of amitriptyline 10%, a total reduction of pain occurred within 20 minutes, lasting the whole day. The second patient was a 57-year-old man, suffering for 10 years from progressive sensory disturbances in both feet and increasing pain due to chronic idiopathic axonal polyneuropathy (CIAP). Amitriptyline 5% cream reduced pain in the toes nearly completely, but this was not the case in the heels. Amitriptyline 10% reduced pain in the feet, however, systemic adverse effects occurred, mainly drowsiness. The patient decided to stop topical treatment because of these adverse effects. These two cases suggest an analgesic dose-response effect of topical amitriptyline in painful neuropathy. Systemic adverse effects should be taken into account.

Targeting the glial-derived neurotrophic factor and related molecules for controlling normal and pathologic pain

“…If one considers the picture emerged from a more precise dissection of the nociceptive circuitries in the substantia gelatinosa of the spinal cord (Figure2), amitriptyline has the potential to target at the same time a pro-(BDNF) and an antinociceptive (GDNF) factor at this very important relay station. Notably, a very recent study has shown that systemic (intraperitoneal) amitriptyline reversed the effects of allodynia and hyperalgesia induced by chronic constriction injury (CCI) in mice [93], and case reports in the clinical literature indicate that high doses of topical amitriptyline are beneficial in the treatment of neuropathic pain although systemic adverse effects should be taken into account [94] .…”

The Use of Topical Compounded Analgesic Creams in Neuropathic Pain by the Primary Care Physician

“…In the period 2008-2011 we started compounding a number of creams based on amitriptyline and ketamine and found out that most of the approaches at that time selected a dose too low, based on only 1% to 5%. We found that such analgesics needed to be compounded in creams containing at least 5% and preferably 10% of the active ingredient [7]. The same holds true for phenytoin, where we also prefer a 10% compounded cream [8].…”

Topical Treatment in Pain Medicine: From Ancient Remedies to Modern Usage

“…[137] Although not effective in every trial [138], amitriptyline at concentrations between 2-10%, along with some other antidepressant agents has been successfully used as a topical agent in a number of neuropathic pain states including complex regional pain syndrome (CRPS), multiple sclerosis and vulvodynia. [139][140][141] Amitriptyline has been employed as a sole agent or in combination with other topical agents such as ketamine and baclofen. [142][143][144][145][146][147] Although the topical application of antidepressant drugs can reduce their unwanted central side effects, this form of administration can occasionally lead to adverse toxicity.…”