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Journal ArticleDOI

Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis.

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pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies.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 Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009).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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Citations
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Journal ArticleDOI
TL;DR: The findings of this study suggest JM-20 can decrease persistent pain and a transient activity of its BDZ portion on nociceptive pathways mediated by GABA/BZD receptors in association with its anti-inflammatory properties could be at least partially involved in this effect.

3 citations

Journal ArticleDOI
TL;DR: IPL combined with DCBE drop therapy was effective for DED patients with ocular pain and with such treatment, both DED symptoms and the sensation of ocularPain may be improved.
Abstract: Purpose: To investigate the efficacy of intense pulsed light (IPL) combined with deproteinized calf blood extract (DCBE) eye drops for dry eye disease (DED) patients with nociceptive ocular pain. Methods: In this prospective, one-center, interventional study, 23 subjects with DED and ocular pain were treated with a combination of IPL and DCBE eye drops for four sessions at a four-week interval. Subjective and objective assessments on nociceptive pain and dry eye were examined and analyzed. Results: The visual analog scale (VAS), ocular surface disease index, ocular pain assessment survey (OPAS), patient health questionnaire-9 items, generalized anxiety disorder (GAD-7), Athens insomnia scale, corneal fluorescein staining score, meibomian gland secretion quality, and expressibility scores were significantly reduced after the treatment. Tear break-up time and Schirmer I test increased significantly. The brand density of corneal nerves and neuropeptide substance P also significantly increased. OPAS, GAD-7, meibomian gland secretion quality, and expressibility scores were essential factors affecting the VAS changes. Conclusions: IPL combined with DCBE drop therapy was effective for DED patients with ocular pain. With such treatment, both DED symptoms and the sensation of ocular pain may be improved.

3 citations

Patent
11 Feb 2016
TL;DR: In this article, the authors proposed methods and compositions for preventing, reducing, mitigating and treating neuropathic pain by the combined administration of an agent that increases EETs and an inhibitor of endoplasmic reticulum stress.
Abstract: Provided are methods and compositions for preventing, reducing, mitigating and treating pain, particularly neuropathic pain by the combined administration of an agent that increases EETs and an agent that reduces/inhibits endoplasmic reticulum (ER) stress. In one aspect, provided are methods of preventing, reducing, ameliorating, mitigating, inhibiting and/or reversing pain in a subject in need thereof. In some embodiments, the methods comprise co-administering to the subject an agent that increases the production and/or level of epoxygenated fatty acids and an inhibitor of endoplasmic reticulum stress. In varying embodiments, the pain comprises inflammatory pain. In varying embodiments, the pain comprises neuropathic pain.

3 citations

Book ChapterDOI
01 Jan 2020
TL;DR: Multimodal therapy through various medications described in this chapter is also essential to creating a balanced treatment plan that reduces risk and side effects from any single agent, especially opioids.
Abstract: Chronic pain related to painful medical diseases is an extensive field that requires more awareness and large clinical research trials into optimal treatments that can increase patient satisfaction and quality of life. Using a multidisciplinary approach requires an array of medications, in addition to behavioral/psychological, interventional, and physical therapy treatments. Multimodal therapy through various medications described in this chapter is also essential to creating a balanced treatment plan that reduces risk and side effects from any single agent, especially opioids. The opioid epidemic is no doubt prevalent at this time, and recent guidelines reinforce the need for improved patient and physician education and access to safer and more effective options. When opioids are essential for certain medical conditions, increased awareness of long-term side effects and associated comorbidities can optimize the balance between risks and benefits.

3 citations

Book ChapterDOI
05 Nov 2018
TL;DR: The scope of this chapter would be to update the knowledge regarding serotonin involving in pain pathways and to highlight the importance and contribution of serotonin reuptake inhibitors in the multimodal pain management schemes.
Abstract: Serotonin has a particular place in the modulation of pain. Experimental studies have described 5-HT1–7 receptors and their effects on facilitation or inhibition of nociceptive input. Selective serotonin reuptake inhibitors (SSRIs) and serotoninnorepinephrine reuptake inhibitors showed efficient and safer than tricyclic antidepressants in neuropathic pain. Although there is evidence regarding the beneficial impact of SSRIs in the multimodal acute pain management, studies are still searching for the potentially favorable effect of these drugs in the prevention of chronic postoperative pain. The scope of this chapter would be to update the knowledge regarding serotonin involving in pain pathways and to highlight the importance and contribution of serotonin reuptake inhibitors in the multimodal pain management schemes.

3 citations

References
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Journal ArticleDOI
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

Journal ArticleDOI
13 Sep 1997-BMJ
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

Journal ArticleDOI
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

Journal ArticleDOI
24 Apr 2008-BMJ
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

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