Unmet medication need in neuropathic pain
medwireNews: A systematic review and meta-analysis reveals that current treatments for neuropathic pain achieve only a moderate response in patients.
Nadine Attal (Hôpital Ambroise Paré, Paris, France) and study co-authors included 196 published papers in their analysis, as well as 33 unpublished studies identified in clinical trial registries.
Based on Grading of Recommendations Assessment, Development, and Evaluation (GRADE) recommendations, the team says there is strong evidence for first-line use of tricyclic antidepressants, serotonin–noradrenaline reuptake inhibitors (duloxetine or venlafaxine), pregabalin and gabapentin in patients with neuropathic pain.
For these medications, the average number needed to treat (NNT) to obtain a 50% reduction in pain ranged from 3.6 for tricyclic antidepressants to 7.7 for pregabalin. The quality of evidence was high for most treatments, with the exception of tricyclic antidepressants, for which it was moderate.
However, further analysis indicated publication bias, suggesting about 34 missing studies and a 10% overstatement of the treatment effect. Likewise, the treatment effects found in published studies were significantly greater than those found in unpublished studies. But the effect of the putative missing studies did not risk negating the treatment effect, except in the case of capsaicin 8% patches, in which the NNT would have increased to more than 11, and therefore become clinically nonsignificant, if a missing study was negative.
“This finding lends support to the robustness of a meta-analysis that includes unpublished trials and suggests that effect sizes were overestimated in previous meta-analyses of pharmacotherapy for neuropathic pain”, write Attal et al in The Lancet Neurology.
Capsaicin 8% patches therefore had a weak GRADE recommendation, as did lidocaine patches, tramadol, botulinum toxin A and strong opioids due to poor evidence, high expense or safety concerns.
Four drugs had weak (cannabinoids, valproate) or strong (levetiracetam, mexiletine) recommendations against use because of negative trials or side effects, and a further 12 therapies had inconclusive recommendations.
Treatments with inconclusive evidence included combination therapy, a point picked up on by David Bennett (University of Oxford, UK) in a linked commentary, saying that although combining treatments is “intellectually appealing”, studies to date have been mostly small, with the only large study so far being negative.
“Because so many patients in clinical practice are on more than one analgesic, more studies are needed in this area”, he says. “Overall, present options are far from ideal and new and more efficacious treatments than exist at present are needed for neuropathic pain.”
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