Updated Clinical Guidelines for Neuropathic Pain
Systematic review of trials on drug treatments for neuropathic pain yields updated clinical guidelines
January 8, 2015 (San Francisco, CA)
For people with neuropathic pain, damaged or dysfunctional nerve fibers cause chronic burning pain, tingling or numbness—frequently contributing to reduced quality of life. Previous studies suggest that many patients do not receive appropriate treatment, often from not recognizing the underlying nervous system injury, or insufficient knowledge of effective drugs and their appropriate use.
And while evidence-based recommendations are essential for ensuring appropriate treatment of patients with neuropathic pain, few clinical guidelines have been proposed over the past ten years.
Until now, with this week’s online publication in The Lancet Neurology of revised and unique Neuropathic Pain Special Interest Group (NeuPSIG) recommendations for the pharmacologic treatment of neuropathic pain, based on a systematic review and meta-analysis. The recommendations were updated based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).
“Inadequate response to drug treatments constitutes an unmet need in treating patients with neuropathic pain,” said Michael Rowbotham, M.D., Scientific Director of California Pacific Medical Center Research Institute (CPMCRI) and study co-author. “This review provides practical evidence-based recommendations that can be incorporated into clinical practice for treating stubbornly refractory chronic pain and improving quality of life.”
Dr. Rowbotham was part of an international group of pain experts including co-first authors Nadine Attal, M.D., Ph.D. (Director of the Pain Evaluation and Treatment Centre of Hôpital Ambroise Paré, France), and Nanna Finnerup, M.D. (Associate Professor in the Department of Clinical Medicine at the Danish Pain Research Center, Aarhus University).
The researchers conducted a meta-analysis of randomized double-blind studies of oral and topical drug treatments for neuropathic pain, including unpublished trials, published since 1966. The primary measure of the study was numbers needed to treat (NNT) for 50% pain relief (with NNT referring to the average number of patients requiring treatment to prevent one additional adverse outcome); difference in pain intensity was a secondary outcome.
After uncovering 229 studies for inclusion in the meta-analysis, assessment of publication bias suggested a 10% overstatement of treatment effects—especially for studies published in peer-reviewed journals compared with unpublished studies. Adding to the difficulty of estimating the true effect of treatments tested in clinical trials, other studies have shown that the placebo response has increased in recent neuropathic pain trials.
Trial outcomes were generally modest even for effective drugs: specifically, combined NNTs were 6.4 for the serotonin-noradrenaline reuptake inhibitors duloxetine and venlafaxine; 7.7 for pregabalin; 7.2 for gabapentin, including gabapentin extended release and enacarbil; and 10.6 for capsaicin high-concentration patches. NNTs were lower for tricyclic antidepressants, strong opioids, tramadol, and botulinum toxin A, and undetermined for lidocaine patches. There was no evidence that some types of neuropathic pain had different response patterns than others, although the amount of data on this aspect remains small.
After reviewing the trial outcomes for commonly used neuropathic pain medications, and based on GRADE, the study authors created a treatment algorithm supporting the use of:
• Tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin as first-line therapy;
• Lidocaine patches, capsaicin high-concentration patches, and tramadol as second-line therapy, and;
• Strong opioids and botulinum toxin A as third-line therapy.
“The strength of this review of studies on neuropathic pain pharmacotherapies is the analyses of publication bias and unpublished trials. Publication bias can occur if studies with positive results are published whereas those with no data or negative results are not–leading to a major overestimation of efficacy. This finding emphasizes the need to search these databases in systematic reviews and create repositories capturing availability of pain trial results,” said Dr. Rowbotham, citing his recent work with other researchers in developing the RReACT, RReMiT, and RReADS databases that yielded scorecards of publicly available pain trial results.
The study was funded by NeuPSIG.