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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pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies.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 Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009).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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Journal ArticleDOI
TL;DR: In this article, the authors discuss the latest advances in the mechanisms of diabetic sensorimotor peripheral neuropathy and painful DSPN, originating both from the periphery and the central nervous system, as well as the emerging diagnostics and treatments.
Abstract: Diabetic sensorimotor peripheral neuropathy (DSPN) is a serious complication of diabetes mellitus and is associated with increased mortality, lower-limb amputations and distressing painful neuropathic symptoms (painful DSPN). Our understanding of the pathophysiology of the disease has largely been derived from animal models, which have identified key potential mechanisms. However, effective therapies in preclinical models have not translated into clinical trials and we have no universally accepted disease-modifying treatments. Moreover, the condition is generally diagnosed late when irreversible nerve damage has already taken place. Innovative point-of-care devices have great potential to enable the early diagnosis of DSPN when the condition might be more amenable to treatment. The management of painful DSPN remains less than optimal; however, studies suggest that a mechanism-based approach might offer an enhanced benefit in certain pain phenotypes. The management of patients with DSPN involves the control of individualized cardiometabolic targets, a multidisciplinary approach aimed at the prevention and management of foot complications, and the timely diagnosis and management of neuropathic pain. Here, we discuss the latest advances in the mechanisms of DSPN and painful DSPN, originating both from the periphery and the central nervous system, as well as the emerging diagnostics and treatments. This article discusses the latest advances in the mechanisms of diabetic sensorimotor peripheral neuropathy (DSPN) and painful DSPN, originating both from the periphery and the central nervous system, and outlines the emerging diagnostics and treatments.

107 citations

Journal ArticleDOI
06 Apr 2018
TL;DR: In those parts of the world with an opioid epidemic, coroners and medical examiners, private and public health agencies, and agencies that enforce the law need to cooperate in an effort to slow down and reverse the indiscriminate use of prescribing opioids in the long-term for chronic non-cancer pain.
Abstract: The opioid epidemic, with its noticeable increase in opioid prescriptions and related misuse, abuse and resultant deaths in the previous 12 years, is a particularly North American phenomenon. Europe, and particularly low- and middle-income countries, appear to be less influenced by this problem. There is undisputable value in using opioids not only in the treatment of acute pain, but in cancer pain as well. However, opioids are progressively being prescribed more and more for chronic non-cancer pain, despite inadequate data on their efficacy. In this paper, we describe the current prevalence of opioid misuse in a number of countries and the rationale for the commencement of opioid therapy. The safe initiation and monitoring of opioid therapy as well as the need for concurrent use of interdisciplinary multimodal therapy is discussed. The possible consequences of long-term use and predictors of high opioid use and overdose are presented. In particular, the management of opioid use disorders and the prevention of opioid abuse and dependence in the young, the old and the pregnant are discussed. Measures to prevent overprescribing and to alleviate risk are described, including the tapering of opioids and the use of opioid deterrents. Finally, the paper looks at the future development of pioneering medications and technologies to potentially treat abuse. In those parts of the world with an opioid epidemic, coroners and medical examiners, private and public health agencies, and agencies that enforce the law need to cooperate in an effort to slow down and reverse the indiscriminate use of prescribing opioids in the long-term for chronic non-cancer pain. Ongoing research is needed to create ways to minimise risks of opioid use, and to provide evidence for effective strategies for treating chronic pain.

107 citations


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

  • ...Regarding age, opioid use should be limited in the elderly due to adverse effects (low numbers needed to harm or NNH), and restricted in children [25, 45]....

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Journal ArticleDOI
TL;DR: There was no evidence to support or refute the use of oral NSAIDs to treat neuropathic pain conditions, and the adverse events associated with its use in clinical trials were low.
Abstract: Background Although often considered to be lacking adequate evidence, nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the management of neuropathic pain. Previous surveys found 18% to 47% of affected people reported using NSAIDs specifically for their neuropathic pain, although possibly not in the United Kingdom (UK). Objectives To assess the analgesic efficacy of oral NSAIDs for chronic neuropathic pain in adults, when compared to placebo or another active intervention, and the adverse events associated with its use in clinical trials. Search methods We searched CENTRAL, MEDLINE, and EMBASE from inception to 29 May 2015, together with reference lists of retrieved papers and reviews, and an online trials registry. Selection criteria We included randomised, double-blind studies of two weeks duration or longer, comparing any oral NSAID with placebo or another active treatment in chronic neuropathic pain. Data collection and analysis Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality. We did not carry out any pooled analysis. Main results We included two studies involving 251 participants with chronic low back pain with a neuropathic component or postherpetic neuralgia; 209 of these participants were involved in a study of an experimental NSAID not used in clinical practice, and of the remaining 42, only 16 had neuropathic pain. This represented only third tier evidence, and was of very low quality. There was no indication of any significant pain reduction with NSAIDs. Adverse event rates were low, with insufficient events for any analysis. Authors' conclusions There is no evidence to support or refute the use of oral NSAIDs to treat neuropathic pain conditions.

106 citations

Journal ArticleDOI
TL;DR: Evidence supports the redefinition of chronic pain as a distinct disease entity, not simply a symptom of injury or illness, and clinicians need to adopt a practical integrated management approach.
Abstract: Chronic pain is a common public health problem that has a detrimental impact on patient health, quality of life (QoL), and function, and poses a substantial socioeconomic burden. Evidence supports the redefinition of chronic pain as a distinct disease entity, not simply a symptom of injury or illness. Chronic pain conditions are characterized by three types of pain pathophysiology (i.e. nociceptive, neuropathic, and centralized pain/central sensitization) influenced by a cluster of coexisting psychosocial factors. Negative risk/vulnerability factors (e.g. mood or sleep disturbances) and positive resilience/protective factors (e.g. social/interpersonal relationships and active coping) interact with pain neurobiology to determine patients' unique pain experience. Viewing chronic pain through a biopsychosocial lens, instead of a purely biomedical one, clinicians need to adopt a practical integrated management approach. Thorough assessment focuses on the whole patient (not just the pain), including comorbidities, cognitive/emotional/behavioral characteristics, social environment, and QoL/functional impairment. As for other complex chronic illnesses, the treatment plan for chronic pain can be developed based on pain subtype and psychosocial profile, incorporating pharmacotherapy and self-management modalities. Preferred pharmacologic treatment of conditions primarily associated with nociception (e.g. osteoarthritis) includes acetaminophen and non-steroidal anti-inflammatory drugs, whereas preferred pharmacologic treatment of conditions primarily associated with neuropathy or central sensitization (e.g. fibromyalgia) includes tricyclic compounds, serotonin-norepinephrine reuptake inhibitors, and α2δ ligands. Education, exercise, cognitive behavioral therapy, and many other non-pharmacological approaches, alone or combined with pharmacotherapy, have been shown to be effective for any type of pain, although they remain underutilized due to lack of awareness of their benefits and reimbursement obstacles.

106 citations


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

  • ...diabetic peripheral neuropathy and fibromyalgia) tricyclic compounds, the serotonin-norepinephrine reuptake inhibitor duloxetine, and the α2δ ligands pregabalin and gabapentin are recommended pharmacologic treatment [129,191,192]....

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Journal ArticleDOI
TL;DR: The mechanisms involved in the occurrence and persistence of cancer-associated bone pain are discussed and the treatment methods recommended by experts in clinical practice are reviewed to improve quality of life (QoL).
Abstract: The skeletal system is the third most common site for cancer metastases, surpassed only by the lungs and liver. Many tumors, especially those of the breast, prostate, lungs, and kidneys, have a strong predilection to metastasize to bone, which causes pain, hypercalcemia, pathological skeletal fractures, compression of the spinal cord or other nervous structures, decreased mobility, and increased mortality. Metastatic cancer-induced bone pain (CIBP) is a type of chronic pain with unique and complex pathophysiology characterized by nociceptive and neuropathic components. Its treatment should be multimodal (pharmacological and non-pharmacological), including causal anticancer and symptomatic analgesic treatment to improve quality of life (QoL). The aim of this paper is to discuss the mechanisms involved in the occurrence and persistence of cancer-associated bone pain and to review the treatment methods recommended by experts in clinical practice. The final part of the paper reviews experimental therapeutic methods that are currently being studied and that may improve the efficacy of bone pain treatment in cancer patients in the future.

104 citations


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

  • ...Anticonvulsants are used widely and recommended for different neuropathic pain syndromes in humans [75]....

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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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