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pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies.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 Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009).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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TL;DR: A high prevalence of CP is demonstrated in OMPs, three to four-fold than in the general population, as assessed using the capture-recapture method applied to the French nationwide healthcare database.
Abstract: Few studies all based on classical surveys have provided prevalence estimates of chronic pain (CP) in opioid-maintained patients (OMPs) but often had a limited patient sample size and a great variability in the prevalence estimates. This study sought to assess the prevalence of CP in the exhaustive population of OMPs using the capture-recapture method applied to the French nationwide health care database. Capture-recapture methods are increasingly used to estimate the prevalence of chronic conditions but have never been used in the specific context of CP in OMPs. Three large medical-administrative sources were used: the prescription drug database (A-list), the national hospital discharge database (M-list), and the pain center database (C-list). Between 2015 and 2016, 160,429 OMPs aged 15 years and older were identified and age- and sex-matched with 160,429 non-OMPs. All patients treated with analgesic drugs for ≥6 months (A-list) or diagnosed with CP (M- and C-list) were included. Capture-recapture analyses were performed to yield CP estimates with their 95% confidence intervals using log-linear models. In 2015 to 2016, 12,765 OMPs and 2938 non-OMPs with CP were captured. Most patients were male (67%) in OMPs and non-OMPs; median ages for OMPs and non-OMPs were 46 (interquartile range: 38-51) and 48 (41-53) years, respectively. The CP prevalence estimated in OMPs and non-OMPs ranged from 23.6% (14.9-46.2) to 32.1% (28.6-36.3) and from 7.28% (3.98-18.4) to 9.32% (7.42-12.1), respectively. This first study on CP in the exhaustive population of OMPs using the capture-recapture method demonstrated a high prevalence of CP in OMPs, 3- to 4-fold than in the general population.
3 citations
01 Mar 2022
TL;DR: In this article , the authors compared the effectiveness and tolerability of topical lidocaine 700 mg medicated plaster (LMP) compared with oral systemic first-line medications (OSM) in postherpetic neuralgia treatment.
Abstract: Aim: To provide real-world evidence for the effectiveness and tolerability of lidocaine 700 mg medicated plaster (LMP) compared with oral systemic first-line medications (OSM) in postherpetic neuralgia treatment. Patients & methods: Retrospective cohort study in patients refractory to at least one recommended OSM (single drug or a combination of drugs) using anonymized routine medical care data from the German Pain e-Registry. A matched pair approach using propensity score matching was employed. Results: A total of 1711 data sets of postherpetic neuralgia patients were identified per treatment group. The majority (>60%) had experienced pain for more than a year and reported a high burden of pain and reduced quality of life. Six months of LMP treatment provided significantly greater pain reductions, improvements in pain-related impairments and quality of life than OSM treatment (p < 0.001 for all parameters). Drug-related adverse events and treatment discontinuation due to drug-related adverse events also occurred less frequently under LMP treatment (p < 0.001). Conclusion: These real-world data confirm the effectiveness and good tolerability of LMP under routine medical care. The treatment was significantly more effective when compared with first-line oral systemic medications.Lay abstract Postherpetic neuralgia is the most common complication of shingles. It is a chronic condition causing burning pain that persists long after the shingles rash disappears. There are several oral and topical medications available for pain treatment. Our study compared the effectiveness and tolerability of the topical lidocaine 700 mg medicated plaster with oral medications using anonymized patient data from German clinical practices collected in a pain registry (1711 patient data sets per treatment). Six months of treatment with the lidocaine plaster resulted in better pain relief, fewer restrictions in daily life activities, and better quality of life for the patients than the oral medications investigated. The lidocaine plaster was also significantly better tolerated. The lidocaine 700 mg medicated plaster is effective and well tolerated in routine medical practice.
3 citations
31 Mar 2019
TL;DR: Deep brain stimulation (DBS) is a modern neuromodulation method used in the treatment of advanced movement disorders such as Parkinson’s disease and dystonia, but insufficient evidence-based strategies for managing psychiatric symptoms in PD patients with DBS exist.
Abstract: Deep brain stimulation (DBS) is a modern neuromodulation method used in the treatment of advanced movement disorders such as Parkinson’s disease (PD) and dystonia. Patients with PD may have multiple psychiatric comorbidities, notably anxiety, depression, mania or hypomania, and psychosis. DBS surgery may indirectly alleviate psychiatric symptoms by allowing reduction of dopaminergic medications, or as a result of functional improvement. Patients who are considering DBS for PD often have more advanced disease and may be more vulnerable to perioperative psychiatric decline. Albeit infrequently, increased depression, apathy, irritability, hypomania or mania, and suicidal behavior have been observed after DBS surgery. Objective: This review aimed to present current evidence and empirical recommendations for the management of the psychiatric symptoms in patients with PD treated with DBS. Method: Relevant literature was reviewed and synthesized, along with recommendations informed by the authors’ clinical experience in a large, academic DBS center.Careful evaluation of DBS candidacy, including assessing the risk for perioperative psychiatric decompensation is advised. Maintaining at least eight weeks of psychiatric stability prior to DBS surgery is strongly recommended. Postoperative management can be challenging due to advanced disease, concurrent psychiatric comorbidities, and possible DBS stimulation-related effects on mood and impulse control. Stimulation-induced elevated mood states (mania, hypomania) have started to be recognized as distinct clinical entities, although not included in the current psychiatric nomenclature.Insufficient evidence-based strategies for managing psychiatric symptoms in PD patients with DBS exist at this time. Further research is necessary to uncover best practices in this complex, expanding field.
3 citations
01 Jan 2018
TL;DR: Medication management is the mainstay of treatment for painful neuropathy, and the most widely studied class of medications is the antidepressants; tricyclic antidepressants (TCAs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and selective serotonin reuptakes inhibitors (SSRIs) are all used in the treatment of neuropathic pain.
Abstract: Neuropathic pain, defined as pain caused by a lesion or disease of the somatosensory nervous system, affects up to 10% of the population. There are a number of proposed mechanisms thought to be responsible for the development of neuropathic pain, however, injury to the afferent sensory pathways appears to be a common etiologic mechanism. Common causes for painful peripheral neuropathy include metabolic disorders, particularly diabetes; nutritional deficiencies; toxin exposure, especially chemotherapeutic agents; genetic disorders; infectious and inflammatory disorders, such as HIV and herpes zoster virus; and idiopathic small fiber neuropathy. Medication management is the mainstay of treatment for painful neuropathy. The most widely studied class of medications is the antidepressants; tricyclic antidepressants (TCAs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and selective serotonin reuptake inhibitors (SSRIs) are all used in the treatment of neuropathic pain. Anticonvulsants, such as gabapentin, pregabalin, and carbamazepine, are also widely used. Second- and third-line agents include topical lidocaine, capsaicin, botulinum toxin A, NMDA antagonists, and opioids. Interventional treatment options for neuropathic pain include sympathetic nerve blocks, neurolytic sympathetic blocks, spinal cord stimulation, and deep brain stimulation. Transcutaneous electrical nerve stimulation and repetitive transcranial magnetic stimulation may also have a role in treating neuropathic pain.
3 citations
01 Jan 2017
TL;DR: A psychophysiological approach to chronic physical illness embraces the understanding that sexuality can be an important part of living and a crucial element for integrated holistic health care to maximize function and quality of living is needed.
Abstract: Chronic physical illness can have a devastating impact for the individual, family, and significant others. The fact is that illness over time carries an additional burden upon the individual and one’s psychosocial world. At times, a person’s life desires and expectations are pushed aside. Fortitude and strength are now channeled into finding one’s resiliency to endure and carry out day-to-day activities of daily living. A psychophysiological approach to chronic physical illness embraces the understanding that sexuality can be an important part of living. Thus, it is a necessary part of assessment and intervention, and a crucial element for integrated holistic health care to maximize function and quality of living is needed.
3 citations
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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