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pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies.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 Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009).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.
Citations
More filters
TL;DR: Lidocaine 5% medicated plaster was successful in relieving itching and other symptoms in this case of NP, and the patient reported an associated improvement in her quality of life throughout therapy.
Abstract: Notalgia paresthetica (NP) is a sensory neuropathy characterized by chronic, localized pruritus in a circumscribed area on the upper back. Pruritus, frequently resistant to treatment, may be accompanied by pain, paresthesia, allodynia and alloknesis. There is a paucity of data in the NP literature about the use of lidocaine 5% medicated plaster. This case involves a 75-year-old woman with NP and a history of many unsuccessful local or systemic treatments. The patient was treated with lidocaine 5% medicated plaster, while other therapies were progressively retired. After 11 weeks of therapy, a significant reduction in the intensity of itching was achieved and the itching area was reduced. The patient also reported an associated improvement in her quality of life throughout therapy. In conclusion, lidocaine 5% medicated plaster was successful in relieving itching and other symptoms in this case of NP.
2 citations
TL;DR: An in-depth characterization of this optimized QuilA-EAE model is made, describing for the first time somatic thermal hyperalgesia associated with mechanical and cold allodynia and showing an anti-hyperalgesic thermal effect on this model.
Abstract: Among the many symptoms (motor, sensory, and cognitive) associated with multiple sclerosis (MS), chronic pain is a common disabling condition. In particular, neuropathic pain symptoms are very prevalent and debilitating, even in early stages of the disease. Unfortunately, chronic pain still lacks efficient therapeutic agents. Progress is needed (i) clinically by better characterizing pain symptoms in MS and understanding the underlying mechanisms, and (ii) preclinically by developing a more closely dedicated model to identify new therapeutic targets and evaluate new drugs. In this setting, new variants of experimental autoimmune encephalomyelitis (EAE) are currently developed in mice to exhibit less severe motor impairments, thereby avoiding confounding factors in assessing pain behaviors over the disease course. Among these, the optimized relapsing-remitting EAE (QuilA-EAE) mouse model, induced using myelin oligodendrocyte glycoprotein peptide fragment (35–55), pertussis toxin, and quillaja bark saponin, seems very promising. Our study sought (i) to better define sensitive dysfunctions and (ii) to extend behavioral characterization to interfering symptoms often associated with pain during MS, such as mood disturbances, fatigue, and cognitive impairment, in this optimized QuilA-EAE model. We made an in-depth characterization of this optimized QuilA-EAE model, describing for the first time somatic thermal hyperalgesia associated with mechanical and cold allodynia. Evaluation of orofacial pain sensitivity showed no mechanical or thermal allodynia. Detailed evaluation of motor behaviors highlighted slight defects in fine motor coordination in the QuilA-EAE mice but without impact on pain evaluation. Finally, no anxiety-related or cognitive impairment was observed during the peak of sensitive symptoms. Pharmacologically, as previously described, we found that pregabalin, a treatment commonly used in neuropathic pain patients, induced an analgesic effect on mechanical allodynia. In addition, we showed an anti-hyperalgesic thermal effect on this model. Our results demonstrate that this QuilA-EAE model is clearly of interest for studying pain symptom development and so could be used to identify and evaluate new therapeutic targets. The presence of interfering symptoms still needs to be further characterized.
2 citations
TL;DR: Treatment of pain in patients with CLI in an out-patient setting is ineffective because it is based on medications used in the treatment of nociceptive pain and not neuropathic pain.
Abstract: Introduction: Critical limb ischemia (CLI) is a condition resulting from chronic impaired limb perfusion by arterial blood, which is always accompanied by rest pain. The key objectives of treatment are to prevent high-level amputations and to manage pain. Currently there are no strong recommendations regarding pharmacotherapy for pain in patients with CLI. The aim of the study was to evaluate analgesics currently used in patients with CLI on an outpatient basis and to assess their effectiveness in pain treatment. Materials and methods: The study included 88 patients diagnosed with CLI, who declared taking a painkiller in the past 12 h. Patients were asked for the name of the drug. The truth of the declaration was verified by the presence of the drug in the serum of 45 randomly selected patients. All patients rated pain intensity on a numerical scale (NRS) before and after treatment. Their mental state was evaluated by Mini-Mental State Examination (MMSE) test. Results: The most commonly used analgesics were ketoprofen, ibuprofen and acetaminophen. Pain management was successful in 11.4% of patients. Average pain intensity before taking the drug was 8.34 points (SD 1.27) and 5.85 (SD 1.57) after. In only 11 patients the presence of the declared drug was confirmed in serum. In 22 patients other drugs were found. For patients who reported that analgesic medication was ineffective, MMSE value averaged 22.1 (SD 4.95) and 25.1 (SD 4.25) for the group reporting effective treatment, p = 0.07. Patients reporting ineffectiveness of medications had suffered for an average duration of 8.2 weeks (SD 1.39), while the effective group average 5.2 weeks (SD 5.13), p = 0.06. Conclusions: Treatment of pain in patients with CLI in an outpatient setting is ineffective because it is based on medications used in the treatment of nociceptive pain and not neuropathic pain. There is an urgent need to improve the treatment of pain in patients with CLI by educating family doctors.
2 citations
Cites background from "Pharmacotherapy for neuropathic pai..."
...The treatment of neuropathic pain is not within the traditional WHO pain pyramid; it is different from the treatment of nociceptive pain [19, 20]....
[...]
...Tricyclic antidepressants, serotonin and noradrenaline reuptake inhibitors, pregabalin or gabapentins may be used [19, 20]....
[...]
TL;DR: In this paper, a series of guidelines aimed at reducing the risk of infection of health personnel, other patients and the community are included in this manuscript, including the Pain Treatment Units, patients with suspected or confirmed SARS-CoV-2 infection may be waiting for medical consult or interventional procedures for the management of chronic pain refractory to other therapies.
Abstract: SARS-CoV-2 infection has evolved into a pandemic and a Public Health Emergency of International Importance that has forced health organizations at the global, regional and local levels to adopt a series of measures to address to COVID-19 and try to reduce its impact, not only in the social sphere but also in the health sphere, modifying the guidelines for action in the health services. Within these recommendations that include the Pain Treatment Units, patients with suspected or confirmed SARS-CoV-2 infection may be waiting for medical consult or interventional procedures for the management of chronic pain refractory to other therapies. A series of guidelines aimed at reducing the risk of infection of health personnel, other patients and the community are included in this manuscript.
2 citations
TL;DR: Wang et al. as mentioned in this paper proposed a novel framework to provide treatment recommendations by integrating resting-state functional connectivity and advanced machine learning technique in a large data set, which is able to objectively and automatically cluster patients into different subgroups and recommends the optimal treatment strategies based on specific brain circuits and clinical symptoms.
Abstract: Background: Major depressive disorder (MDD) is a highly prevalent and disabling disease. Currently, patients’ treatment choices depend on their clinical symptoms observed by clinicians, which are subjective. Rich evidence suggests that different functional networks’ dysfunctions correspond to different intervention preferences. In this study, we aimed to develop a prediction model based on data-driven subgroups to provide treatment recommendations. Methods: All 630 participants enrolled from four sites underwent functional magnetic resonances imaging at baseline. In the discovery data set (n = 228), we first identified MDD subgroups by the hierarchical clustering method using the canonical variates of resting-state functional connectivity (FC) through canonical correlation analyses. The demographic symptom improvement and FC were compared among subgroups. The preference intervention for each subgroup was also determined. Next, we predicted the individual treatment strategy. Specifically, a patient was assigned into predefined subgroups based on FC similarities and then his/her treatment strategy was determined by the subgroups’ preferred interventions. Results: Three subgroups with specific treatment recommendations were emerged, including (1) a selective serotonin reuptake inhibitors-oriented subgroup with early improvements in working and activities, (2) a stimulation-oriented subgroup with more alleviation in suicide, and (3) a selective serotonin noradrenaline reuptake inhibitors-oriented subgroup with more alleviation in hypochondriasis. Through cross-dataset testing, respectively, conducted on three testing data sets, results showed an overall accuracy of 72.83%. Conclusions: Our works revealed the correspondences between subgroups and their treatment preferences and predicted individual treatment strategy based on such correspondences. Our model has the potential to support psychiatrists in early clinical decision making for better treatment outcomes. This study proposes a novel framework to provide treatment recommendations by integrating resting-state functional connectivity and advanced machine learning technique in a large data set. Our data-driven approach is able to objectively and automatically cluster patients into different subgroups and recommends the optimal treatment strategies based on specific brain circuits and clinical symptoms. Our results have the potential to support psychiatrists in early clinical decision making for better treatment outcomes.
2 citations
References
More filters
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