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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pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies.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 Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009).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: In this article , the potential therapeutic strategies of different types of neuropathic pain (NP) and to summarize the cutting-edge novel approaches for NP treatment based on the clinical trials registered on ClinicalTrials.gov were explored.
Abstract: Purpose To explore the potential therapeutic strategies of different types of neuropathic pain (NP) and to summarize the cutting-edge novel approaches for NP treatment based on the clinical trials registered on ClinicalTrials.gov. Methods The relevant clinical trials were searched using ClinicalTrials.gov Dec 08, 2022. NP is defined as a painful condition caused by neurological lesions or diseases. All data were obtained and reviewed by the investigators to confirm whether they were related to the current topic. Results A total of 914 trials were included in this study. They were divided into painful diabetic neuropathy (PDN), postherpetic neuralgia (PHN), sciatica (SC), peripheral nerve injury-related NP (PNI), trigeminal neuralgia (TN), chemotherapy-induced NP (CINP), general peripheral NP (GPNP) and spinal cord injury NP (SCI-NP). Potential novel therapeutic strategies, such as novel drug targets and physical means, were discussed for each type of NP. Conclusion NP treatment is mainly dominated by drug therapy, and physical means have become increasingly popular. It is worth noting that novel drug targets, new implications of conventional medicine, and novel physical means can serve as promising strategies for the treatment of NP. However, more attention needs to be paid to the challenges of translating research findings into clinical practice.

1 citations

Journal ArticleDOI
06 Jan 2022
TL;DR: Cervicalgia diagnosis is directed primarily to eliminate symptomatic pains associated with severe somatic pathology, immune diseases, infections and oncology, andComorbid diseases and risk factors can combine with each other causing the polyetiologic pain syndrome.
Abstract: Neck pain is a fairly common complaint when visiting a doctor, its occurrence frequency is 10–21% per year, and neck pain takes the 4th place among the causes of disability; almost 50% of patients continue to experience unpleasant sensations or repeated pain episodes. The elderly people are the most prone to the neck pain, this is associated with the progressive degenerative changes in the facet joints and intervertebral discs. However, reasons of this symptom can be of different kinds. Cervicalgia diagnosis is directed primarily to eliminate symptomatic pains associated with severe somatic pathology, immune diseases, infections and oncology. Comorbid diseases and risk factors can combine with each other causing the polyetiologic pain syndrome. Main steps of the cervicalgia diagnostic algorithm are the following: collection of complaints and anamnesis in detail, physical and neurological examination, and also use of visualization methods. Visualization and electrodiagnostic methods are not always informative for patients with chronic cervicalgia and in the degenerative etiology of the syndrome. MRI and the surgeon consultation must be recommended to patients with deteriorating neurological symptoms or with long-term constant pain. Conservative therapy of cervicalgia implies a combination of non-drug methods (compliance with regime, orthopedic treatment, leaf, physiotherapy, etc.) and pharmacotherapy. The last depends on the presence of a neuropathic component of pain and the duration of pain syndrome. The pain therapy with a nociceptive nature is usually implies a combination of non-steroidal anti-inflammatory remedies, non-opioid analgesics and muscle relaxants. Whereas neuropathic pains first-line preparations are tricyclic antidepressants, duloxetine, venlafaxine, pregabalin, gabapentine. The therapy success depends on the proper individual estimation of the pain factors, pain chronization and possible treatment complications. The therapeutic forecast of the acute nonspecific cervicalgia is usually good, but it becomes less predictable if the pain acquires chronic character.

1 citations

Journal ArticleDOI
01 Oct 2016
TL;DR: The evidence to support the method used for transdermal buprenorphine rotation to tapentadol is weak and both drugs show particular pharmacodynamic and pharmacokinetic properties which reduce the risks of development of tolerance, opioid abuse, diversion and determine fewer hormone changes than the "classical opioids" making these opioids more attractive than other opioids in long term opioid treatment.
Abstract: Opioid analgesia continues to be the primary pharmacologic intervention for managing acute pain and malignant pain in both hospitalized and ambulatory patients. The increasing use of opioids in chronic nonmalignant pain is more problematic. Opioid treatment is complicated with the risks raised by adverse effects, especially cognitive disturbance, respiratory depression but also the risk of tolerance, opioid abuse and drug-disease interactions. Despite the growing number of available opioids within the last years, adequate trials of opioid rotation are lacking and most of the information is anecdotal. This article reviews the clinical evidence surrounding the switch from transdermal buprenorphine to tapentadol in malignant and non-malignant pain. Tapentadol acts on both the μ-opioid receptors (MOR) and on the neuronal reuptake of noradrenaline with a limited usefulness in acute pain management while buprenorphine is a mixed agonist-antagonist, and both present some advantages over other opioids. Both drugs show particular pharmacodynamic and pharmacokinetic properties which reduce the risks of development of tolerance, opioid abuse, diversion and determine fewer hormone changes than the "classical opioids" making these opioids more attractive than other opioids in long term opioid treatment. However, in the absence of powered clinical trials, the evidence to support the method used for transdermal buprenorphine rotation to tapentadol is weak.

1 citations


Cites background from "Pharmacotherapy for neuropathic pai..."

  • ...At the time of writing this article, despite a high Number Needed to Treat (NNT = 10·2) and an inconclusive recommendation for the treatment of neuropathic pain in adults according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE), tapentadol is widely used [22]....

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  • ...Examining the abuse potential, it was found that tapentadol was less likely to be abused than most other Schedule II analgesics examined [22, 23]....

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Book ChapterDOI
01 Jan 2019
TL;DR: The chapter describes in summary the main mechanism of pain based on peripheral receptors and biochemical mediators and the current hypothesis of pain modulation, sensitization, and manipulation.
Abstract: The chapter describes in summary the main mechanism of pain based on peripheral receptors and biochemical mediators. The pathways of pain and the central nervous system centers for pain are described. Different and the current hypothesis of pain modulation, sensitization, and manipulation are described. The concept of pain matrix based on the modern functional neuromaging in humans is reported. The descending control of brainstem on spinal mechanisms and the importance of attention and cognitive state on pain perception and elaboration are described.

1 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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