Systematic review of topical amitriptyline for the treatment of neuropathic pain

What is known and objectiveNeuropathic pain is a common disorder for which patients seek treatment. The most common causes of neuropathic pain are diabetes, herpetic infection and chemotherapy-induced neuropathy. Oral administration of amitriptyline has traditionally been used for treating neuropathic pain; however, it has dose-related anticholinergic effects, which may limit its use in some individuals. Pharmacotherapeutic agents that are commonly used to treat neuropathic pain include antidepressants, anticonvulsants, opioids and opioid-like substances, and topical medications. The objective of this paper is to review the effectiveness of topical amitriptyline in patients with neuropathic pain. MethodsWe utilized the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to provide a systematic and transparent reporting method. The literature search was performed using PubMed (1966 through October 2014) applying the MeSH amitriptyline' and drug administration, topical' and neuropathy'. Web of Science (1945 through October 2014) was searched using the text words amitriptyline' and neuropathy'. Bibliographies of retrieved articles were scanned for relevant articles. Cochrane databases were also searched for methods to treat neuropathic pain. Broad subject headings, including neuropathic pain', were used to search the database for review articles. All data sources in English and in humans were considered for inclusion. Results and discussionTopical application of amitriptyline has the theoretical advantage of local effects with fewer systemic side effects. The clinical trials and case reports describing the use of topical amitriptyline we reviewed show mixed results concerning the efficacy and the presence of adverse reactions. Controlled clinical trials reveal that topical amitriptyline is not effective in treating neuropathic pain. The uncontrolled clinical trials did support efficacy of topical amitriptyline; however, the data from these trials may be biased due to the nature of the study design. Finally, there have been several case reports that claim patients achieved pain relief with the use of topical amitriptyline. Data from these cases are limited due to the fact that there were no controls to which the amitriptyline treatments could be compared, and the majority of the patients in these cases were on other analgesics. What is new and conclusionAlthough there are reports that describe the benefits of topical amitriptyline for neuropathic pain, data from evidence-based controlled clinical trials do not support efficacy in patients who use topical amitriptyline for neuropathic pain control.