European clinical practice recommendations on opioids for chronic noncancer pain – Part 2: Special situations*
Katholieke Universiteit Leuven1, Queen's University Belfast2, King's College London3, University of Greifswald4, Imperial College Healthcare5, University of Antwerp6, University College Cork7, University of Münster8, University of Seville9, Ludwig Maximilian University of Munich10, Technische Universität München11
TL;DR: The European Clinical Practice Recommendations as discussed by the authors, developed by eight scientific societies and one patient self-help organization under the coordination of EFIC, provide guidance for combination with other medications, the management of frequent (e.g. nausea, constipation) and rare side effects, for special clinical populations and for special situations.
About: This article is published in European Journal of Pain.The article was published on 2021-03-02 and is currently open access. It has received 12 citations till now. The article focuses on the topics: Good clinical practice & Systematic review.
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Technische Universität München1, Katholieke Universiteit Leuven2, Queen's University Belfast3, King's College London4, University of Greifswald5, Imperial College Healthcare6, University of Antwerp7, University College Cork8, University of Münster9, University of Seville10, Ludwig Maximilian University of Munich11, University of Maribor12
TL;DR: In the absence of pan-European guidance on this issue, a position paper was commissioned by the European Pain Federation (EFIC) and the clinical practice recommendations were developed by eight scientific societies and one patient self-help organization under the coordination of EFIC.
38 citations
TL;DR: The European Pain Federation (EFIC) conducted a survey with its national chapter representatives on trends of opioid prescriptions and of drug-related emergency departments and substance use disorder treatment admissions and of deaths as proxies of opioidrelated harms over the last 20 years as discussed by the authors.
34 citations
TL;DR: In this article , the authors conducted a multi-stakeholder survey using a modified Delphi methodology focusing on policies, at the system level, rather than at the prescriber or patient level.
Abstract: Abstract Background This consensus statement was developed because there are concerns about the appropriate use of opioids for acute pain management, with opposing views in the literature. Consensus statement on policies for system-level interventions may help inform organisations such as management structures, government agencies and funding bodies. Methods We conducted a multi-stakeholder survey using a modified Delphi methodology focusing on policies, at the system level, rather than at the prescriber or patient level. We aimed to provide consensus statements for current developments and priorities for future developments. Results Twenty-five experts from a variety of fields with experience in acute pain management were invited to join a review panel, of whom 23 completed a modified Delphi survey of policies designed to improve the safety and quality of opioids prescribing for acute pain in the secondary care setting. Strong agreement, defined as consistent among> 75% of panellists, was observed for ten statements. Conclusions Using a modified Delphi study, we found agreement among a multidisciplinary panel, including patient representation, on prioritisation of policies for system-level interventions, to improve governance, pain management, patient/consumers care, safety and engagement.
8 citations
TL;DR: Evaluating the true dimension of prescription opioid misuse/abuse is complicated by statistical reporting which often does not differentiate between prescription and illicit opioid use, or between prescription opioid use by patients and nonpatients, highlighting a need for greater uniformity.
Abstract: Opioids are an important therapeutic option for severe resistant chronic pain but, in the absence of proper oversight, their use has risks. The level of prescription opioid misuse/abuse differs among countries, due to differences in healthcare systems and pain management approaches. However, evaluating the true dimension of prescription opioid misuse/abuse is complicated by statistical reporting which often does not differentiate between prescription and illicit opioid use, or between prescription opioid use by patients and nonpatients, highlighting a need for greater uniformity. Parallel efforts to educate patients and the general public about opioid risks, facilitate appropriate analgesic prescribing and identify alternative formulations or options to use instead of or with opioids, may contribute to optimizing prescription opioid use for pain management.
2 citations
TL;DR: In this article, the authors examined factors associated with higher doses of gabapentinentin receipt and determined if receipt varied by opioid use among 3,702 patients with HIV and found that high-dose gababentin receipt was associated with prescribed highdose opioids receipt and highdose benzodiazepine receipt.
Abstract: Gabapentin is commonly prescribed for chronic pain, including to patients with HIV (PWH). There is growing concern regarding gabapentin's potential for harm, particularly in combination with opioids. Among PWH, we examined factors associated with higher doses of gabapentin receipt and determined if receipt varied by opioid use. We examined data from the Veterans Aging Cohort Study, a national prospective cohort including PWH, from 2002 through 2017. Covariates included prescribed opioid dose, self-reported past year opioid use, and other sociodemographic and clinical variables. We used multinomial logistic regression to determine independent predictors of gabapentin receipt. Among 3,702 PWH, 902 (24%) received any gabapentin during the study period at a mean daily dose of 1,469 mg. In the multinomial model, high-dose gabapentin receipt was associated with high-dose benzodiazepine receipt (adjusted odds ratio [aOR], 95% confidence interval [CI]= 1.53, [1.03-2.27]), pain interference (1.65 [1.39-1.95]), and hand or foot pain (1.81, [1.45-2.26]). High-dose gabapentin receipt was associated with prescribed high-dose opioids receipt (2.66 [1.95-3.62]) but not self-reported opioid use (1.03 [0.89-1.21]). PWH prescribed gabapentin at higher doses are more likely to receive high-dose opioids and high-dose benzodiazepines, raising safety concerns.
2 citations
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Journal Article•
15,362 citations
TL;DR: This guideline is intended to improve communication about benefits and risks of opioids for chronic pain, improve safety and effectiveness of pain treatment, and reduce risks associated with long-term opioid therapy.
Abstract: Importance Primary care clinicians find managing chronic pain challenging. Evidence of long-term efficacy of opioids for chronic pain is limited. Opioid use is associated with serious risks, including opioid use disorder and overdose. Objective To provide recommendations about opioid prescribing for primary care clinicians treating adult patients with chronic pain outside of active cancer treatment, palliative care, and end-of-life care. Process The Centers for Disease Control and Prevention (CDC) updated a 2014 systematic review on effectiveness and risks of opioids and conducted a supplemental review on benefits and harms, values and preferences, and costs. CDC used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to assess evidence type and determine the recommendation category. Evidence Synthesis Evidence consisted of observational studies or randomized clinical trials with notable limitations, characterized as low quality using GRADE methodology. Meta-analysis was not attempted due to the limited number of studies, variability in study designs and clinical heterogeneity, and methodological shortcomings of studies. No study evaluated long-term (≥1 year) benefit of opioids for chronic pain. Opioids were associated with increased risks, including opioid use disorder, overdose, and death, with dose-dependent effects. Recommendations There are 12 recommendations. Of primary importance, nonopioid therapy is preferred for treatment of chronic pain. Opioids should be used only when benefits for pain and function are expected to outweigh risks. Before starting opioids, clinicians should establish treatment goals with patients and consider how opioids will be discontinued if benefits do not outweigh risks. When opioids are used, clinicians should prescribe the lowest effective dosage, carefully reassess benefits and risks when considering increasing dosage to 50 morphine milligram equivalents or more per day, and avoid concurrent opioids and benzodiazepines whenever possible. Clinicians should evaluate benefits and harms of continued opioid therapy with patients every 3 months or more frequently and review prescription drug monitoring program data, when available, for high-risk combinations or dosages. For patients with opioid use disorder, clinicians should offer or arrange evidence-based treatment, such as medication-assisted treatment with buprenorphine or methadone. Conclusions and Relevance The guideline is intended to improve communication about benefits and risks of opioids for chronic pain, improve safety and effectiveness of pain treatment, and reduce risks associated with long-term opioid therapy.
3,935 citations
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, Florey Institute of Neuroscience and Mental Health17, University of Edinburgh18, Greenwich Hospital19, University of Sydney20, 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.
2,512 citations
TL;DR: The short‐term efficacy of opioids was good in both neuropathic and musculoskeletal pain conditions, however, only a minority of patients in these studies went on to long‐term management with opioids, and conclusions concerning problems such as tolerance and addiction are not allowed.
Abstract: Opioids are used increasingly for chronic non-cancer pain. Controversy exists about their effectiveness and safety with long-term use. We analysed available randomised, placebo-controlled trials of WHO step 3 opioids for efficacy and safety in chronic non-cancer pain. The Oxford Pain Relief Database (1950-1994) and Medline, EMBASE and the Cochrane Library were searched until September 2003. Inclusion criteria were randomised comparisons of WHO step 3 opioids with placebo in chronic non-cancer pain. Double-blind studies reporting on pain intensity outcomes using validated pain scales were included. Fifteen randomised placebo-controlled trials were included. Four investigations with 120 patients studied intravenous opioid testing. Eleven studies (1025 patients) compared oral opioids with placebo for four days to eight weeks. Six of the 15 included trials had an open label follow-up of 6-24 months. The mean decrease in pain intensity in most studies was at least 30% with opioids and was comparable in neuropathic and musculoskeletal pain. About 80% of patients experienced at least one adverse event, with constipation (41%), nausea (32%) and somnolence (29%) being most common. Only 44% of 388 patients on open label treatments were still on opioids after therapy for between 7 and 24 months. The short-term efficacy of opioids was good in both neuropathic and musculoskeletal pain conditions. However, only a minority of patients in these studies went on to long-term management with opioids. The small number of selected patients and the short follow-ups do not allow conclusions concerning problems such as tolerance and addiction.
1,156 citations
TL;DR: Gabapentin and morphine combined achieved better analgesia at lower doses of each drug than either as a single agent, with constipation, sedation, and dry mouth as the most frequent adverse effects.
Abstract: From the Departments of Anesthesiology (I.G., J.M.B.) and Pharmacology and Tox- icology (I.G.), the Departments of Mathe- matics and Statistics and Community Health and Epidemiology (D.T.), the De- partment of Psychology (R.R.H.), and the Department of Medicine (Division of En- docrinology) (R.L.H.), Queen's Universi- ty, Kingston, Ont.; and the Departments background The available drugs to treat neuropathic pain have incomplete efficacy and dose-limit- ing adverse effects. We compared the efficacy of a combination of gabapentin and mor- phine with that of each as a single agent in patients with painful diabetic neuropathy or postherpetic neuralgia. methods In this randomized, double-blind, active placebo-controlled, four-period crossover trial, patients received daily active placebo (lorazepam), sustained-release morphine, gabapentin, and a combination of gabapentin and morphine — each given orally for five weeks. The primary outcome measure was mean daily pain intensity in patients re- ceiving a maximal tolerated dose; secondary outcomes included pain (rated according to the Short-Form McGill Pain Questionnaire), adverse effects, maximal tolerated dos- es, mood, and quality of life. results abstract
965 citations