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pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies.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 Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009).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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10 Mar 2020
TL;DR: This review will elaborate on the short history of Kampo, its basic concepts, and use for the treatment of pain in Japan.
Abstract: Kampo, a branch of traditional Japanese herbal medicine, has been the backbone of Japanese medicine for more than 1500 years. The health insurance system in Japan allows patients to access both Western and Kampo medical care at the same time in the same medical institution. Kampo has been used for the treatment of not only acute but also chronic pain in Japan. In this review, we will elaborate on the short history of Kampo, its basic concepts, and use for the treatment of pain.
10 citations
TL;DR: This meta-analysis indicates the effectiveness of the treatments based on duloxetine, gabapentin and pregabalin, as well as other drugs, such as tapentadol and topic clonidine, whose use is better prescribed in more specific situations.
Abstract: Background One of the most frequent problems caused by diabetes is the so called painful diabetic neuropathy. This condition can be treated through numerous types of therapy. The purpose of this study was to analyze, as a meta-analysis, different treatments used to alleviate painful diabetic neuropathy, with the aim of generating results that help making decisions when applying such treatments to tackle this pathology. Methods A search was conducted in the main databases for Health Sciences, such as PUBMED, Web of Science (WOS), and IME biomedicina (Spanish Medical Reports in Biomedicine), to gather randomized controlled trials about treatments used for painful diabetic neuropathy. The analyzed studies were required to meet the inclusion criteria selected, especially those results related to pain intensity. Results Nine randomized controlled trials were chosen. The meta-analysis shows significant positive effects for those treatments based on tapentadol [g: -1.333, 95% CI (-1.594; -1.072), P < 0.05], duloxetine [g: -1.622, 95 % CI (-1.650; -1.594), P < 0.05], pregabalin [g: -0.607, 95% CI (-0.980; -0.325), P < 0.05], and clonidine [g: -0.242, 95 % CI (-0.543; -0.058), P < 0.05]. Conclusions This meta-analysis indicates the effectiveness of the treatments based on duloxetine, gabapentin and pregabalin, as well as other drugs, such as tapentadol and topic clonidine, whose use is better prescribed in more specific situations. The results provided can help increase the knowledge about the treatment of painful diabetic neuropathy and also in the making of clinical practice guidelines for healthcare professionals.
10 citations
TL;DR: The IASP special interest group on NeP has recently refined their previous identification algorithm for NeP and emphasizes the neuroanatomical distribution of pain and findings of sensory aberrations in the painful area.
Abstract: Neuropathic pain (NeP) conditions have received considerable attention from the pain community in the past decades. However, when addressing NeP, chronic NeP (CNeP) is usually implied. The literature contains a multitude of studies characterizing the clinical phenomenology of CNeP, including both symptoms and signs. In addition, numerous clinical trials have been reported, and recently, a systematic review and metaanalysis was published as a basis for guidelines on treatment recommendations of topical and oral medication. Also, central neurostimulation techniques have recently been reviewed and presented with guidelines. In contrast to CNeP, NeP which is associated with the acute phase after a lesion or onset of a disease of the somatosensory nervous system has received conspicuously little attention. All NePs that are labelled as chronic obviously have a history of an acute phase, that is, before the first 3 months have elapsed, a time line agreed upon by the IASP and the WHO. Hence, acute NeP (ANeP) may start after trauma, including surgery, and develop in parallel with any disease or lesion affecting the somatosensory nervous system, for example, infections as in herpes zoster, polyneuropathy, oxaliplatin induced neuropathy, stroke, or multiple sclerosis. There are fundamental knowledge gaps regarding the prevalence of ANeP, clinical characteristics, diagnostic criteria, prognosis, and, most importantly, treatment. In addition, we do not know whether ANeP and CNeP form a continuum or represent distinct conditions. The IASP has in 2011 renewed the definition of NeP to “Pain caused by a lesion or disease of the somatosensory nervous system.” The IASP special interest group on NeP has recently refined their previous identification algorithm for NeP and emphasizes the neuroanatomical distribution of pain and findings of sensory aberrations in the painful area. With such a perspective, identifying a projected NeP in a geographically distant area to a surgical incision is fairly straightforward. A characteristic example is ANeP in the innervation territory of the intercostobrachial nerve after breast cancer surgery including axillary dissection. To infer a NeP contribution in the surgical area poses, however, a significant diagnostic challenge in the acute and subacute phase since nerve injury always is present in such an area and hence may or may not contribute to the generation of activity in nociceptive afferents. In addition, there are no reports from studies on ANeP conditions and the use of questionnaires such as painDETECT or DN4 that have been validated in such acute pain states. Published questionnaires targeting NeP have all been validated only in the CNeP scenario. Reports on randomized controlled treatment trials of ANeP are lacking in the literature. In the postoperative scenario, it is clinically widely appreciated that anticonvulsants and antidepressants recommended for treatment of CNeP are also used in the acute and subacute phase after surgery. Based on available literature, the efficacy of such drugs are difficult to determine. Studies on anticonvulsants have been short term in the postoperative period unlike the relatively long-term use in studies on CNeP treatment. Initially, after surgery, anticonvulsants or antidepressants or both are usually employed with the combined use of opioids and acetaminophen or antiinflammatory drugs. If antidepressants and anticonvulsants are effective in this early stage of NeP, which again has not been systematically studied, one should keep in mind the relatively high number needed to treat reported from studies on CNeP. It would be reasonable to suggest that repeated disappointing efficacy when using such medication would not have survived clinical scrutiny over time in the postoperative scenario. One should remember, however, that anti-inflammatory drugs have been shown to be used as first-line prescription for NeP in the general practitioner setting. Such a treatment strategy lacks both scientific foundation and expertise endorsement. Furthermore, to what extent regular treatment of postoperative pain of nociceptive/inflammatory nature by anti-inflammatory drugs/ acetaminophen and opioids is efficacious also in ANeP is not reported on in the literature. In addition, many ANePs may vanish spontaneously before becoming chronic which may obscure nonsystematic clinical treatment experience of single physicians. Animal studies based on nerve injury models have intermittently over the past 3 decades been put into question as suitable reflections of human NeP. Both the relevance of models and behavioral testing approaches have been probed. Interestingly, Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. a Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, b Division of Emergencies and Critical Care, Department of Pain Management and Research, Oslo University Hospital, Oslo, Norway, c Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany, d Faculty of Medicine, University of Oslo and Department of Pain Management and Research, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway
10 citations
Cites background from "Pharmacotherapy for neuropathic pai..."
...In addition, numerous clinical trials have been reported, and recently, a systematic review and metaanalysis was published as a basis for guidelines on treatment recommendations of topical and oral medication.(7) Also, central neurostimulation techniques have recently been reviewed and presented with guidelines....
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10 citations
TL;DR: Evidence is offered about a synergistic antinociceptive effect between opioidergic and dopaminergic drugs that may relieve painful conditions resistant to conventional treatments, and it may reduce the adverse effects of chronic opioid administration.
10 citations
References
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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