Methadone for neuropathic pain in adults
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TLDR
This review serves to update the original and includes only studies of neuropathic pain, and found methadone to be statistically superior to placebo for the outcomes of categorical pain intensity and evoked pain.Abstract:
Background
This review replaces an earlier review, "Methadone for chronic non-cancer pain in adults". This review serves to update the original and includes only studies of neuropathic pain. Methadone belongs to a class of analgesics known as opioids, that are considered the cornerstone of therapy for moderate-to-severe postsurgical pain and pain due to life-threatening illnesses; however, their use in neuropathic pain is controversial. Methadone has many characteristics that differentiate it from other opioids, which suggests that it may have a different efficacy and safety profile.
Objectives
To assess the analgesic efficacy and adverse events of methadone for chronic neuropathic pain in adults.
Search methods
We searched the following databases: CENTRAL (CRSO), MEDLINE (Ovid), and Embase (Ovid), and two clinical trial registries. We also searched the reference lists of retrieved articles. The date of the most recent search was 30 November 2016.
Selection criteria
We included randomised, double-blind studies of two weeks’ duration or longer, comparing methadone (in any dose, administered by any route, and in any formulation) with placebo or another active treatment in chronic neuropathic pain.
Data collection and analysis
We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. There were insufficient data to perform pooled analyses. We assessed the overall quality of the evidence for each outcome using GRADE and created a 'Summary of findings' table.
Main results
We included three studies, involving 105 participants. All were cross-over studies, one involving 19 participants with diverse neuropathic pain syndromes, the other two involving 86 participants with postherpetic neuralgia. Study phases ranged from 20 days to approximately eight weeks. All administered methadone orally, in doses ranging from 10 mg to 80 mg daily. Comparators were primarily placebo, but one study also included morphine and tricyclic antidepressants.
The included studies had several limitations related to risk of bias, particularly incomplete reporting, selective outcome reporting, and small sample sizes.
There were very limited data for our primary outcomes of participants with at least 30% or at least 50% pain relief. Two studies reported that 11/29 participants receiving methadone achieved 30% pain relief versus 7/29 participants receiving placebo. Only one study presented data in a manner that allowed us to calculate the number of participants with at least 50% pain relief. None of the 19 participants achieved a 50% reduction in pain intensity, either when receiving methadone or when receiving placebo. No study provided data for our other primary outcomes of Patient Global Impression of Change scale (PGIC) much or very much improved (equivalent to at least 30% pain relief) and PGIC very much improved (equivalent to at least 50% pain relief).
For secondary efficacy outcomes, one study reported maximum and mean pain intensity and pain relief, and reported statistically significant improvements versus placebo for all outcomes with 20 mg daily doses of methadone, but not with 10 mg daily doses. The second study reported differences in pain reduction between methadone (n = 26) and morphine (n = 38) and found morphine to be statistically superior. The third study reported the number of responders (variously defined) for several pain and functional outcomes and found methadone to be statistically superior to placebo for the outcomes of categorical pain intensity and evoked pain. In the two studies that reported data, 0/29 participants withdrew due to lack of efficacy, whereas 4/29 participants withdrew due to adverse events while taking methadone versus 3/29 while taking placebo.
One study reported incidences for several individual adverse events, but found a statistically significant increased incidence for methadone over placebo for only one event, dizziness. The other studies did not report data in a manner that enabled us to analyze adverse events. There were no serious adverse events or deaths reported.
We assessed the quality of the evidence as very low for all efficacy and safety outcomes using GRADE, primarily because of the heterogeneity of study designs and populations, short durations, cross-over methodology, and few participants and events.
Authors' conclusions
The three studies provide very limited, very low quality evidence of the efficacy and safety of methadone for chronic neuropathic pain, and there were too few data for pooled analysis of efficacy or harm, or to have confidence in the results of the individual studies. No conclusions can be made regarding differences in efficacy or safety between methadone and placebo, other opioids, or other treatments.read more
Citations
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Palliative Care and the Management of Common Distressing Symptoms in Advanced Cancer: Pain, Breathlessness, Nausea and Vomiting, and Fatigue.
Lesley A. Henson,Matthew Maddocks,Catherine J Evans,Martin Davidson,Stephanie C. Hicks,Irene J Higginson +5 more
TL;DR: The role of palliative care in supporting a holistic approach to symptom management throughout the cancer trajectory is discussed and the management of four common and distressing symptoms commonly experienced by people with advanced cancer is reviewed.
ReportDOI
Opioid Treatments for Chronic Pain
Roger Chou,Daniel M. Hartung,Judith A. Turner,Ian Blazina,Brian Chan,Ximena A. Levander,Marian McDonagh,Shelley Selph,Rongwei Fu,Miranda Pappas +9 more
TL;DR: Outcomes of interest were pain, function, health status/quality of life, mental health outcomes, sleep, doses of opioid used (for comparisons involving opioids and nonopioid therapy) and harms.
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Trends in Medical Use of Opioids in the U.S., 2006-2016.
TL;DR: With the exception of buprenorphine, used to treat an opioid use disorder, prescription opioid use has been decreasing over the past 5 years in the U.S.
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Perioperative Pain Management and Opioid Stewardship: A Practical Guide
Sara J. Hyland,Kara K Brockhaus,William R. Vincent,Nicole Z. Spence,Michelle M. Lucki,Michael J. Howkins,Robert K. Cleary +6 more
TL;DR: In this article, the authors present a brief review of applicable statistics and definitions as impetus for prioritizing both analgesia and opioid exposure in surgical quality improvement and highlight the value of interprofessional collaboration in implementing and sustaining perioperative performance measures related to pain management and analgesic exposure, including those from the patient perspective.
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Why mu-opioid agonists have less analgesic efficacy in neuropathic pain?
TL;DR: Up‐to‐day research exploring the contribution of mu‐opioid receptor (MOR) on the pathophysiology of neuropathic pain and on analgesic opioid actions under these conditions is reviewed, focusing on the specific contributions of MOR populations at peripheral, spinal and supraspinal level.
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Chapter 8: Assessing risk of bias in included studies
TL;DR: The Cochrane Handbook for Systematic Reviews of Interventions (ISBN 978-0470057964) is published by John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England.
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TL;DR: A consensus meeting was convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to provide recommendations for interpreting clinical importance of treatment outcomes in clinical trials of the efficacy and effectiveness of chronic pain treatments as discussed by the authors.
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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.
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