Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis.
Nanna B. Finnerup,Nadine Attal,Simon Haroutounian,Ewan D McNicol,Ralf Baron,Robert H. Dworkin,Ian Gilron,Maija Haanpää,Per Hansson,Per Hansson,Troels S. Jensen,Troels S. Jensen,Peter R. Kamerman,Karen Lund,Andrew Moore,Srinivasa N. Raja,Andrew S.C. Rice,Andrew S.C. Rice,Michael C. Rowbotham,Emily S. Sena,Emily S. Sena,Philip J. Siddall,Philip J. Siddall,Blair H. Smith,Mark S. Wallace +24 more
TLDR
The results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain and allow a strong recommendation for use and proposal as first-line treatment in neuropathicPain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin.Abstract:
Summary Background New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of neuropathic pain. Using the Grading of Recommendations Assessment, Development, and E valuation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis. Methods Between April, 2013, and January, 2014, NeuPSIG of the International Association for the Study of Pain did a systematic review and meta-analysis of randomised, double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies. We used number needed to treat (NNT) for 50% pain relief as a primary measure and assessed publication bias; NNT was calculated with the fi xed-eff ects Mantel-Haenszel method. Findings 229 studies were included in the meta-analysis. Analysis of publication bias suggested a 10% overstatement of treatment eff ects. Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009). T rial outcomes were generally modest: in particular, combined NNTs were 6·4 (95% CI 5·2–8·4) for serotonin-noradrenaline reuptake inhibitors, mainly including duloxetine (nine of 14 studies); 7·7 (6·5–9·4) for pregabalin; 7·2 (5·9–9·21) for gabapentin, including gabapentin extended release and enacarbil; and 10·6 (7·4–19·0) for capsaicin high-concentration patches. NNTs were lower for tricyclic antidepressants, strong opioids, tramadol, and botulinum toxin A, and undetermined for lidocaine patches. Based on GRADE, fi nal quality of evidence was moderate or high for all treatments apart from lidocaine patches; tolerability and safety, and values and preferences were higher for topical drugs; and cost was lower for tricyclic antidepressants and tramadol. These fi ndings permitted a strong recommendation for use and proposal as fi rst-line treatment in neuropathic pain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin; a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin high-concentration patches, and tramadol; and a weak recommendation for use and proposal as third line for strong opioids and botulinum toxin A. Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only. Interpretation Our results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain. Inadequate response to drug treatments constitutes a substantial unmet need in patients with neuropathic pain. Modest effi cacy, large placebo responses, heterogeneous diagnostic criteria, and poor phenotypic profi ling probably account for moderate trial outcomes and should be taken into account in future studies. Funding NeuPSIG of the International Association for the Study of Pain.read more
Citations
More filters
Journal ArticleDOI
Effect of the T-type channel blocker KYS-05090S in mouse models of acute and neuropathic pain
Said M’Dahoma,Vinicius M. Gadotti,Fang Xiong Zhang,Byeongyeon Park,Ji Hye Nam,Valentina Onnis,Gianfranco Balboni,Jae Yeol Lee,Gerald W. Zamponi +8 more
TL;DR: Results indicate that KYS-05090S mediates a potent analgesic effect in inflammatory and neuropathic pain through T-type channel modulation, suggesting that its scaffold could be explored as a new class of analgesic compounds.
Journal ArticleDOI
Potentiation of Amitriptyline Anti-Hyperalgesic-Like Action By Astroglial Connexin 43 Inhibition in Neuropathic Rats
Tiffany Jeanson,Adeline Duchêne,Damien Richard,Sylvie Bourgoin,Christèle Picoli,Pascal Ezan,Franck Mouthon,Christian Giaume,Michel Hamon,Mathieu Charvériat +9 more
TL;DR: It was found that both mefloquine and amitriptyline inhibited Cx43-containing gap junctions, and that the drug combination acted synergically, and connexin inhibition in astroglia could represent a promising approach towards improving neuropathic pain therapy by antidepressants.
Journal ArticleDOI
Selective deficiencies in descending inhibitory modulation in neuropathic rats: implications for enhancing noradrenergic tone.
TL;DR: The extent to which the descending noradrenergic system is tonically active, how control of spinal neuronal excitability is integrated into thalamic relays within sensory-discriminative projection pathways, and how this inhibitory control is altered after nerve injury are examined are examined.
Journal ArticleDOI
Analgesic potential of PF-06372865, an α2/α3/α5 subtype-selective GABAA partial agonist, in humans
Guido van Amerongen,Pieter S. Siebenga,Rachel Gurrell,Pinky Dua,Mark Whitlock,Donal Gorman,Pieter Okkerse,Justin L. Hay,Richard P. Butt,Geert Jan Groeneveld +9 more
TL;DR: PF-06372865 has analgesic potential at doses that do not induce significant sedation or other intolerable adverse events limiting its clinical use, and is established as a tool in the development of analgesics with a novel mechanism of action.
Journal ArticleDOI
Evaluation of cebranopadol, a dually acting nociceptin/orphanin FQ and opioid receptor agonist in mouse models of acute, tonic, and chemotherapy-induced neuropathic pain
TL;DR: Cebranopadol may have significant potential for the treatment of various pain types, including inflammatory and chemotherapy-induced neuropathic pain.
References
More filters
Journal ArticleDOI
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement
TL;DR: Moher et al. as mentioned in this paper introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses, which is used in this paper.
Journal Article
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement.
TL;DR: The QUOROM Statement (QUality Of Reporting Of Meta-analyses) as mentioned in this paper was developed to address the suboptimal reporting of systematic reviews and meta-analysis of randomized controlled trials.
Journal ArticleDOI
Bias in meta-analysis detected by a simple, graphical test
TL;DR: Funnel plots, plots of the trials' effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials.
Journal ArticleDOI
Assessing the quality of reports of randomized clinical trials : is blinding necessary?
Alejandro R. Jadad,R. A. Moore,Dawn Carroll,C. Jenkinson,David Reynolds,David J. Gavaghan,Henry J McQuay +6 more
TL;DR: An instrument to assess the quality of reports of randomized clinical trials (RCTs) in pain research is described and its use to determine the effect of rater blinding on the assessments of quality is described.
Journal ArticleDOI
GRADE: an emerging consensus on rating quality of evidence and strength of recommendations
Gordon H. Guyatt,Andrew D Oxman,Gunn Elisabeth Vist,Regina Kunz,Yngve Falck-Ytter,Pablo Alonso-Coello,Holger J. Schünemann +6 more
TL;DR: The advantages of the GRADE system are explored, which is increasingly being adopted by organisations worldwide and which is often praised for its high level of consistency.