Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis.
Aarhus University1, French Institute of Health and Medical Research2, Washington University in St. Louis3, Tufts Medical Center4, University of Rochester5, Queen's University6, Helsinki University Central Hospital7, Oslo University Hospital8, Karolinska Institutet9, Aarhus University Hospital10, University of the Witwatersrand11, Churchill Hospital12, Johns Hopkins University13, Imperial College London14, Chelsea and Westminster Hospital NHS Foundation Trust15, California Pacific Medical Center16, University of Edinburgh17, Florey Institute of Neuroscience and Mental Health18, University of Sydney19, Greenwich Hospital20, University of Dundee21, University of California, San Diego22
TL;DR: 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pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies.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 Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009).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.
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13 Mar 2021
TL;DR: In this paper, a modified Delphi study was conducted to generate consensus statements for the diagnosis, management, and prognosis of chronic low back pain (LBP) by a panel of five experts.
Abstract: Low back pain (LBP) is a common reason for adults to seek medical care and is associated with important functional limitation and patient burden. Yet, heterogeneity in the causes and presentation of LBP and a lack of standardization in its management impede effective prevention and treatment. We conducted a modified Delphi study to generate consensus statements for the diagnosis, management, and prognosis of LBP. A panel of five experts proposed 19 statements that were subsequently evaluated by physicians who treat LBP in their everyday clinical practice. Physicians were asked to validate statements in the form of a web survey assessing level of agreement on a five-point Likert-like scale. Consensus (≥ 70% agreement) was obtained for all 19 statements. Strength of agreement and physician comments highlighted the importance of pain management, but also strategies to ameliorate functional limitation and prevent future LBP episodes. Respondents favored multidisciplinary approaches and multimodal management for LBP, although there was some ambiguity as to how multidisciplinary strategies could be feasibly incorporated into daily practice. Finally, the results indicated some conflict regarding the use of imaging for the diagnosis of LBP and how to classify LBP for targeted treatment. The results of this study provide a summary of favored clinical practice for the management of chronic LBP. While the consensus statements were generally agreeable to survey respondents, some areas of ambiguity, including how to increase the feasibility of multidisciplinary strategies, when and how to use diagnostic imaging in LBP, and LBP classification, necessitate clarification in future studies and guidelines.
5 citations
TL;DR: In this article, the authors developed recommendations on the diagnosis and management of pudendal nerve entrapment (PNE) syndrome based on a literature review and expert consensus, and incorporated these recommendations into 10 sections to describe diagnosis of PNE, patients advice and precautions, drugs treatments, physiotherapy, psychotherapy, injections, surgery, pulsed radiofrequency, and Neuromodulation.
5 citations
TL;DR: Thenaissances sur les douleurs pelvi-perineales apres chirurgie du prolapsus genital sont encore limitees a ce jour, anders selon l’International Association for the Study of Pain.
Abstract: Resume Introduction Les douleurs pelvi-perineales postchirurgie du prolapsus genital sont des complications postoperatoires graves et frequentes dont le diagnostic et le traitement peuvent etre complexes. Materiels et methodes Nous avons realise une revue de la litterature sur la base de donnees Pubmed en utilisant les mots et MeSH suivants : genital prolapse, pain, dyspareunia, genital prolapse and pain, genital prolapse and dyspareunia, genital prolapse and surgery, pain and surgery. Resultats Parmi les 133 articles trouves, 74 ont ete retenus. Les douleurs pelvi-perineales chroniques evoluent depuis plus de 3 mois selon l’International Association for the Study of Pain, et peuvent etre de type nociceptif, neuropathique ou dysfonctionnel. Leur definition est avant tout clinique. Leur incidence varie de 1 a 50 % et les facteurs de risques suspectes sont un âge jeune, des comorbidites, un antecedent de chirurgie de prolapsus, un stade eleve de prolapsus, des douleurs preoperatoires, une voie d’abord chirurgicale invasive, la pose simultanee de plusieurs protheses, une moindre experience de l’operateur, une duree importante d’intervention et des douleurs postoperatoires precoces. La voie vaginale peut favoriser une modification de la compliance ou de la longueur vaginale, des lesions des nerfs pudendaux, sciatiques ou obturateurs ou un syndrome myofascial pelviens ; la voie cœlioscopique est a risque de lesion des nerfs parietaux ; la chirurgie prothetique implique des complications liees aux modifications de prothese. La prise en charge therapeutique est complexe et doit etre multimodale et pluridisciplinaire. Conclusion Les connaissances sur les douleurs pelvi-perineales apres chirurgie du prolapsus genital sont encore limitees a ce jour.
5 citations
TL;DR: A narrative review hopes to supplement the available treatment options for children with recurrent or chronic pain and headache by reviewing the pediatric and adult literature for analgesic properties of medications that also have psychiatric indication.
Abstract: Children and adolescents with recurrent or chronic pain and headache are a complex and heterogenous population. Patients are best served by multi-specialty, multidisciplinary teams to assess and create tailored, individualized pain treatment and rehabilitation plans. Due to the complex nature of pain, generalizing pharmacologic treatment recommendations in children with recurrent or chronic pains is challenging. This is particularly true of complicated patients with co-existing painful and psychiatric conditions. There is an unfortunate dearth of evidence to support many pharmacologic therapies to treat children with chronic pain and headache. This narrative review hopes to supplement the available treatment options for this complex population by reviewing the pediatric and adult literature for analgesic properties of medications that also have psychiatric indication. The medications reviewed belong to medication classes typically described as antidepressants, alpha 2 delta ligands, mood stabilizers, anti-psychotics, anti-sympathetic agents, and stimulants.
5 citations
Cites background or result from "Pharmacotherapy for neuropathic pai..."
...For mixed neuropathic pain states, the calculated NNTB was 7–8 for 30% and 50% reduction in pain, and patient global impression of change [76,80]....
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...For other neuropathic pain states, the results are mixed, but generally trend towards similar outcomes [76,77]....
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TL;DR: The findings indicate that the antihyperalgesic and antiallodynic effects of reboxetine are mediated by the catecholaminergic system; β 2 -adrenoceptors; D 1 -, D 2 /D 3 -dopaminergic receptors; and δ-opioid receptors.
Abstract: Current data indicate that the noradrenergic system plays a critical role in neuropathic pain treatment. Notably, drugs that directly affect this system may have curative potential in neuropathy-associated pain. The aim of this study was to evaluate the potential therapeutic efficacy of reboxetine, a potent and selective noradrenaline reuptake inhibitor, on hyperalgesia and allodynia responses in rats with experimental diabetes. Furthermore, mechanistic studies were performed to elucidate the possible mode of actions. Experimental diabetes was induced by a single dose of streptozotocin. Mechanical hyperalgesia, mechanical allodynia, thermal hyperalgesia, and thermal allodynia responses in diabetic rats were evaluated by Randall–Selitto, dynamic plantar, Hargreaves, and warm plate tests, respectively. Reboxetine treatment (8 and 16 mg/kg for 2 weeks) demonstrated an effect comparable to that of the reference drug, pregabalin, improving the hyperalgesic and allodynic responses secondary to diabetes mellitus. Pretreatment with phentolamine, metoprolol, SR 59230A, and atropine did not alter the abovementioned effects of reboxetine; however, the administration of α-methyl-para-tyrosine methyl ester, propranolol, ICI-118,551, SCH-23390, sulpiride, and naltrindole significantly inhibited these effects. Moreover, reboxetine did not induce a significant difference in the rat plasma glucose levels. Our findings indicate that the antihyperalgesic and antiallodynic effects of reboxetine are mediated by the catecholaminergic system; β2-adrenoceptors; D1-, D2/D3-dopaminergic receptors; and δ-opioid receptors. The results suggest that this analgesic effect of reboxetine, besides its neutral profile on glycemic control, may be advantageous in the pharmacotherapy of diabetic neuropathy–induced pain.
5 citations
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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.
Abstract: David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses
62,157 citations
Journal Article•
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.
Abstract: Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field,1,2 and they are often used as a starting point for developing clinical practice guidelines. Granting agencies may require a systematic review to ensure there is justification for further research,3 and some health care journals are moving in this direction.4 As with all research, the value of a systematic review depends on what was done, what was found, and the clarity of reporting. As with other publications, the reporting quality of systematic reviews varies, limiting readers' ability to assess the strengths and weaknesses of those reviews.
Several early studies evaluated the quality of review reports. In 1987, Mulrow examined 50 review articles published in 4 leading medical journals in 1985 and 1986 and found that none met all 8 explicit scientific criteria, such as a quality assessment of included studies.5 In 1987, Sacks and colleagues6 evaluated the adequacy of reporting of 83 meta-analyses on 23 characteristics in 6 domains. Reporting was generally poor; between 1 and 14 characteristics were adequately reported (mean = 7.7; standard deviation = 2.7). A 1996 update of this study found little improvement.7
In 1996, to address the suboptimal reporting of meta-analyses, an international group developed a guidance called the QUOROM Statement (QUality Of Reporting Of Meta-analyses), which focused on the reporting of meta-analyses of randomized controlled trials.8 In this article, we summarize a revision of these guidelines, renamed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which have been updated to address several conceptual and practical advances in the science of systematic reviews (Box 1).
Box 1
Conceptual issues in the evolution from QUOROM to PRISMA
46,935 citations
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.
Abstract: Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 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 Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure
37,989 citations
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.
15,740 citations
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.
Abstract: Guidelines are inconsistent in how they rate the quality of evidence and the strength of recommendations. This article explores the advantages of the GRADE system, which is increasingly being adopted by organisations worldwide
13,324 citations