Oral and Topical Pharmacological Agents for Neuropathic Pain
EBM Focus - Volume 10, Issue 4
Neuropathic pain can be due to disease or damage to the somatosensory nervous system by numerous clinical factors including infection, metabolic disease, trauma, and autoimmune disease (CMAJ 2006 Aug 1;175(3):265, Continuum (Minneap Minn) 2012 Feb;18(1):161). Current estimates suggest that 7-10% of the general population experience chronic neuropathic pain and ineffective treatment is associated with poor physical and mental health, pain-related disability, high health care use, and a high socioeconomic burden (Pain 2014 Apr;155(4):654,Pain 2013 May;154(5):690). Proper pain management is crucial for improving patients quality of life, but determining the best treatment can be difficult. A recent systematic review of 229 randomized trials compared oral and topical pharmacological treatments vs. placebo in patients with neuropathic pain. One of the aims of the systematic review was to update the International Association for the Study of Pain/Neuropathic Pain Special Interest Group (IASP/NeuPSIG) guideline on neuropathic pain.
The included trials investigated a wide variety of drugs with different dosages and trial durations. Although these trials included a number of different patient populations, 55% investigated patients with diabetic neuropathy or postherpetic neuralgia. The number needed to treat (NNT) for at least a moderate reduction in pain and the number needed to harm (NNH) (the number needed to treat for 1 patient to drop out due to adverse events) were calculable for 77% of trials and the combined results for each drug or drug class were reported. Most treatments had a moderate effect size, with high to moderate quality of evidence available for several first, second, and third line drugs. All first-line treatment options had an NNT of 9 or less, with the lowest NNT reported for tricyclic antidepressants (4, 95% CI 3-4.4). Serotonin-noradrenaline reuptake inhibitors had an NNT of 7 (95% CI 5.2-8.4), however this drug class was also associated with the highest discontinuation rate of first-line drugs with a NNH of 11. Pregabalin, gabapentin, and gabapentin extended release or enacarbil had NNTs of 8, 7, and 9 respectively, though gabapentins had the lowest NNHs of all drugs reported (25-32). Second-line drugs tramadol and capsaicin 8% patches had moderate to low effect sizes, but only low quality evidence was available for lidocaine patches and the NNT could not be calculated. Evaluated third-line drugs included strong opioids and botulinum toxin A, and although botulinum toxin A had a low NNT, only 4 trials contributed to the analysis.
This systematic review suggests a number of pharmacological agents may provide at least moderate pain relief in patients with neuropathic pain, however there is no one size fits all treatment option. While NNT numbers suggest most oral medications have a moderate effect size, most were also accompanied by tolerability that was moderate at best, as demonstrated by a low NNH. These findings are also supportive of recommendations made by the European Federation of Neurological Science (EFNS) with the most notable difference being the systematic review adding capsaicin as a second-line agent and botulinum toxin A as a third-line agent for all patients with neuropathic pain. One of the persistent areas of uncertainty is whether certain causes of neuropathic pain may respond more favorably, or develop more adverse effects, to specific treatments. Also, all included trials were performed in adult neuropathic pain populations, so trials in children are needed to determine best therapy in that age group.