By Michael Rubin, MD
Professor of Clinical Neurology,
Weill Cornell Medical College

Dr. Rubin reports no financial relationships relevant to this field of study.

SYNOPSIS: In an exhaustive review of the literature with a meta-analysis, the following medications were found to be most efficacious in the treatment of neuropathic pain: gabapentin, pregabalin, serotonin-noradrenaline reuptake inhibitors including duloxetine or venlafaxine, and tricyclic antidepressants.

SOURCE: Finnerup NB, et al. Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis. Lancet Neurol 2015;14:162-173.

Which agents are most efficacious for the treatment of neuropathic pain? Given new drug treatments, novel methods of delivering old ones, and new clinical trials, meta-analysis and systematic review of the literature was undertaken by Finnerup et al to address this question.

Adhering to the 23-item AGREE II: Appraisal of Guidelines for Research and Evaluation, for reporting and evaluating health care recommendations, the authors conducted a literature review using PubMed, Medline, the Cochrane Central Register of Controlled Trials, and Embase, searching from January 1966 to April 2013. Published reviews and reference lists of selected papers were additionally gathered, as were primary registries in the World Health Organization Network and those approved by the International Committee of Medical Journal Editors. PubMed and the ClinicalTrials.gov website searches brought the study up to date as of January 31, 2014. Inclusion criteria comprised patients of any age with neuropathic pain, defined as pain caused by a lesion affecting the somatosensory nervous system, including diabetic or non-diabetic painful neuropathy, post-herpetic neuralgia, post-amputation, post-traumatic, or post-surgical neuropathic pain, plexus avulsion injuries and complex regional pain syndrome type 2, central post-stroke pain, spinal cord injury pain, and multiple sclerosis-associated pain. As they do not meet the current definition of neuropathic pain, complex regional pain syndrome type 1, low back pain without radicular pain, fibromyalgia, and atypical face pain were excluded. Interventions studied included systemic or topical treatments, and single-administration treatments with long-term efficacy. Studies that were randomized, double-blind, or placebo-controlled, with parallel group or crossover study designs, were included, but studies published only as abstracts were excluded, as were studies in which the primary outcome included a score for paraesthesia only or pain and paraesthesia. Final recommendations were made using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) classification. Numbers needed-to-treat (NNT) for 50% pain reduction, calculated with the fixed-effects Mantel-Haenszel method, was the primary effect measure, with secondary outcome being the difference in pain intensity.

Among 1634 records screened, 1361 were excluded by abstract, leaving 273 full-text articles assessed for eligibility; 229 of these articles or trials were ultimately incorporated for meta-analysis. Based on GRADE, strong first-line recommendations could be given for gabapentin, pregabalin, serotonin-noradrenaline reuptake inhibitors including duloxetine or venlafaxine, and tricyclic antidepressants. Weak second-line recommendations were given for capsaicin 8% patches, lidocaine patches, and tramadol, with third-line recommendations for botulinum toxin A (subcutaneously) and strong opioids, including sustained release oxycodone and morphine. Given these findings, a revision of current recommendations for control of neuropathic pain should be considered.

COMMENTARY

Multiple mechanisms, at both the level of the peripheral and central nervous systems, appear to underlie neuropathic pain, suggesting that simultaneous targeting may improve treatment outcome. Inconsistent results from the few clinical trials undertaken using drug combinations, including morphine and gabapentin, gabapentin and nortriptyline, pregabalin and duloxetine, and doxepin and capsaicin, have been disappointing, but this option requires further investigation.1

REFERENCE

1. Eisenberg E, Suzan E. Drug combinations in the treatment of neuropathic pain. Curr Pain Headache Rep 2014;18:463; DOI 10.1007/s11916-014-0463-y.