Systematic review and comparison of pharmacologic therapies for neuropathic pain associated with spinal cord injury

Abstract

Sonya J Snedecor,1 Lavanya Sudharshan,1 Joseph C Cappelleri,2 Alesia Sadosky,3 Pooja Desai,4 Yash J Jalundhwala,5 Marc Botteman1 1Pharmerit International, Bethesda, MD, USA; 2Global Research and Development, Pfizer, Groton, CT, USA; 3Biostatistics, Pfizer, New York, NY, USA; 4College of Pharmacy, University of Texas at Austin, Austin, TX, USA; 5Pharmacy Administration, University of Illinois at Chicago, Chicago, IL, USA Background: Management of neuropathic pain (NeP) associated with spinal cord injury (SCI) is difficult. This report presents a systematic literature review and comparison of the efficacy and safety of pharmacologic therapies for treating SCI-associated NeP. Methods: Medline, Embase, Cochrane, and Database of Abstracts of Reviews of Effects were searched through December 2011 for randomized, blinded, and controlled clinical trials of SCI-associated NeP meeting predefined inclusion criteria. Efficacy outcomes of interest were pain reduction on the 11-point numeric rating scale (NRS) or 100 mm visual analog scale and proportion of patients achieving ≥30% or ≥50% pain reduction. Discontinuations and adverse events (AEs) were also assessed, for which Bayesian meta-analytic indirect comparisons were performed. Results: Of the nine studies included in the analysis, samples were <100 patients, except for one pregabalin study (n = 136). Standard errors for the NRS outcome were often not reported, precluding quantitative comparisons across treatments. Estimated 11-point NRS pain reduction relative to placebo was –1.72 for pregabalin, –1.65 for amitriptyline, –1.0 for duloxetine, –1 (median) for levetiracetam, –0.27 for gabapentin, 1 (median) for lamotrigine, and 2 for dronabinol. Risk ratios relative to placebo for 30% improvement were 0.71 for levetiracetam and 2.56 for pregabalin, and 0.94 and 2.91, respectively, for 50% improvement. Meta-analytic comparisons showed significantly more AEs with pregabalin and tramadol compared with placebo, and no differences between placebo and any treatment for discontinuations. Conclusions: Studies of SCI-associated NeP were few, small, and reported insufficient data for quantitative comparisons of efficacy. However, available data suggested pregabalin was associated with more favorable efficacy for all outcome measures examined, and that the risks of AEs and discontinuations were found to be similar among the therapies. Keywords: neuropathic pain, spinal cord injury, systematic review, indirect comparison, pharmacologic management