NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
Structured Abstract
Objectives:
Chronic pain is common, and opioid therapy is frequently prescribed for this condition. This report updates and expands on a prior Comparative Effectiveness Review on long-term (≥1 year) effectiveness and harms of opioid therapy for chronic pain, including evidence on shorter term (1 to 12 months) outcomes.
Data sources:
A prior systematic review (searches through January 2014), electronic databases (Ovid MEDLINE®, Embase®, PsycINFO®, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews through August 2019), reference lists, and clinical trials registries.
Review methods:
Predefined criteria were used to select studies of patients with chronic pain prescribed opioids that addressed effectiveness or harms versus placebo, no opioid use, or nonopioid pharmacological therapies; different opioid dosing methods; or risk mitigation strategies. Effects were analyzed at short-term (1 to <6 months), intermediate-term (≥6 to <12 months), and long-term (≥12 months) followup. Studies on the accuracy of risk prediction instruments for predicting opioid use disorder or misuse were also included. Random effects meta-analysis was conducted on short-term trials of opioids versus placebo, opioids versus nonopioids, and opioids plus nonopioids versus an opioid or nonopioid alone. Magnitude of effects was classified as small, moderate, or large using predefined criteria, and strength of evidence was assessed.
Results:
We included 115 randomized controlled trials (RCTs), 40 observational studies, and 7 studies of predictive accuracy; 134 were new to this update. Opioids were associated with small benefits versus placebo in short-term pain, function, and sleep quality. There was a small dose-dependent effect on pain, and effects were attenuated at longer (3 to 6 month) versus shorter (1 to 3 month) followup. Opioids were associated with increased risk of discontinuation due to adverse events, gastrointestinal adverse events, somnolence, dizziness, and pruritus versus placebo. In observational studies, opioids were associated with increased risk of an opioid abuse or dependence diagnosis, overdose, all-cause mortality, fractures, falls, and myocardial infarction versus no opioid use; there was evidence of a dose-dependent risk for all outcomes except fracture and falls.
There were no differences between opioids and nonopioid medications in pain, function, or other short-term outcomes. Opioid plus nonopioid combination therapy was associated with little improvement in pain at short-term followup versus an opioid alone. Co-prescription of benzodiazepines or gabapentinoids was associated with increased risk of overdose versus an opioid alone. No RCT evaluated intermediate- or long-term benefits of opioids versus placebo. One trial found stepped therapy starting with opioids to be associated with higher pain intensity and no difference in function or other outcomes versus stepped therapy starting with nonopioid therapy.
Limited evidence indicated no differences between long- and short-acting opioids in effectiveness, but long-acting opioids were associated with increased risk of overdose. One RCT found a taper support intervention associated with greater improvement in function but no difference in pain versus usual care.
Estimates of diagnostic accuracy for various risk prediction instruments were highly inconsistent, and there was no evidence on the effectiveness of risk mitigation strategies for improving clinical outcomes, with the exception of one study that found provision of naloxone associated with decreased emergency department visits.
Trials of patients with prescription opioid dependence found buprenorphine maintenance associated with better outcomes than buprenorphine taper and similar effects of methadone versus buprenorphine. Evidence was insufficient to evaluate benefits and harms of opioid therapy in patients at higher risk for opioid use disorder.
Conclusions:
At short-term followup, for patients with chronic pain, opioids are associated with small beneficial effects versus placebo but are associated with increased risk of short-term harms and do not appear to be superior to nonopioid therapy. Evidence on intermediate-term and long-term benefits remains very limited, and additional evidence confirms an association between opioids and increased risk of serious harms that appears to be dose-dependent. Research is needed to develop accurate risk prediction instruments, determine effective risk mitigation strategies, clarify risks associated with co-prescribed medications, and identify optimal opioid tapering strategies.
Contents
- Key Messages
- Preface
- Acknowledgments
- Technical Expert Panel
- Peer Reviewers
- Summary of Changes Since the Previous Report
- Evidence Summary
- Introduction
- Methods
- Results
- Results of Literature Search
- Key Question 1a. In patients with chronic pain, what is the effectiveness of opioids versus placebo or no opioid for outcomes related to pain, function, and quality of life after short-term followup (1 to <6 months), intermediate-term followup (6 to <12 months), and long-term followup (≥12 months)?
- Key Question 1b. How does effectiveness vary depending on: (1) the specific type or cause of pain, (2) patient demographics, (3) patient comorbidities, or (4) the mechanism of action of opioids used?
- Key Question 1c. In patients with chronic pain, what is the comparative effectiveness of opioids versus nonopioid therapies (pharmacologic or nonpharmacologic, including cannabis) on outcomes related to pain, function, and quality of life after short-term followup (1 to <6 months), intermediate-term followup (6 to <12 months), and long-term followup (≥12 months)?
- Key Question 1d. In patients with chronic pain, what is the comparative effectiveness of opioids plus nonopioid interventions (pharmacologic or nonpharmacologic, including cannabis) versus opioids or nonopioid interventions alone on outcomes related to pain, function, quality of life, and doses of opioids used after short-term followup (1 to <6 months), intermediate-term followup (6 to <12 months), and long-term followup (≥12 months)?
- Key Question 2a. In patients with chronic pain, what are the risks of opioids versus placebo or no opioid on: (1) opioid use disorder, abuse, or misuse; (2) overdose (intentional and unintentional); and (3) other harms, including gastrointestinal-related harms, falls, fractures, motor vehicle accidents, endocrinological harms, infections, cardiovascular events, cognitive harms, and psychological harms (e.g., depression)?
- Key Question 2b. How do harms vary depending on: (1) the specific type or cause of pain, (2) patient demographics, (3) patient comorbidities, (4) the dose of opioids used and duration of therapy, (5) the mechanism of action of opioids used, (6) use of sedative hypnotics, (7) use of gabapentinoids, (8) use of cannabis?
- Key Question 2c. In patients with chronic pain, what are the comparative risks of opioids versus nonopioid therapies on: (1) opioid use disorder, abuse, or misuse; (2) overdose (intentional and unintentional); and (3) other harms including gastrointestinal-related harms, falls, fractures, motor vehicle accidents, endocrinological harms, infections, cardiovascular events, cognitive harms, and mental health harms (e.g., depression)?
- Key Question 2d. In patients with chronic pain, what are the comparative risks of opioids plus nonopioid interventions (pharmacologic or nonpharmacologic, including cannabis) versus opioids or nonopioid interventions alone on: (1) opioid use disorder, abuse, or misuse; (2) overdose (intentional and unintentional); and (3) other harms, including gastrointestinal-related harms, falls, fractures, motor vehicle accidents, endocrinological harms, infections, cardiovascular events, cognitive harms, and mental health harms (e.g., depression)?
- Key Question 3a. In patients with chronic pain, what is the comparative effectiveness of different methods for initiating and titrating opioids for outcomes related to pain, function, and quality of life; risk of opioid use disorder, abuse, or misuse; overdose; and doses of opioids used?
- Key Question 3b. In patients with chronic pain, what is the comparative effectiveness of short-acting versus long-acting opioids on outcomes related to pain, function, and quality of life; risk of opioid use disorder, abuse, or misuse; overdose; and doses of opioids used?
- Key Question 3c. In patients with chronic pain, what is the comparative effectiveness of different long-acting opioids on outcomes related to pain, function, and quality of life; risk of opioid use disorder, abuse, or misuse; and overdose?
- Key Question 3d. In patients with chronic pain, what is the comparative effectiveness of short- plus long-acting opioids versus long-acting opioids alone on outcomes related to pain, function, and quality of life; risk of opioid use disorder, abuse, or misuse; overdose; and doses of opioids used?
- Key Question 3e. In patients with chronic pain, what is the comparative effectiveness of scheduled, continuous versus as-needed dosing of opioids on outcomes related to pain, function, and quality of life; risk of opioid use disorder, abuse, or misuse; overdose; and doses of opioids used?
- Key Question 3f. In patients with chronic pain, what is the comparative effectiveness of opioid dose escalation versus dose maintenance or use of dose thresholds on outcomes related to pain, function, and quality of life?
- Key Question 3g. In patients with chronic pain, what is the comparative effectiveness of opioid rotation versus maintenance of current opioid therapy on outcomes related to pain, function, and quality of life, and doses of opioids used?
- Key Question 3h. In patients with chronic pain, what is the comparative effectiveness of different strategies for treating acute exacerbations of chronic pain on outcomes related to pain, function, and quality of life?
- Key Question 3i. In patients with chronic pain, what are the effects of decreasing opioid doses or of tapering off opioids versus continuation of opioids on outcomes related to pain, function, quality of life, and opiate withdrawal symptoms?
- Key Question 3j. In patients with chronic pain, what is the comparative effectiveness of different tapering protocols and strategies on measures related to pain, function, quality of life, opiate withdrawal symptoms, and likelihood of opioid cessation?
- Key Question 3k. In patients with chronic pain, what is the comparative effectiveness of different opioid dosages and durations of therapy for outcomes related to pain, function, and quality of life?
- Key Question 4a. In patients with chronic pain being considered for opioid therapy, what is the accuracy of instruments and tests (including metabolic and/or genetic testing) for predicting risk of opioid use disorder, abuse, or misuse; and overdose?
- Key Question 4b. In patients with chronic pain, what is the effectiveness of use of risk prediction instruments and tests (including metabolic and/or genetic testing) on outcomes related to opioid use disorder, abuse, or misuse, and overdose?
- Key Question 4c. In patients with chronic pain who are prescribed opioid therapy, what is the effectiveness of risk mitigation strategies, including (1) opioid management plans, (2) patient education, (3) urine drug screening, (4) use of prescription drug monitoring program data, (5) use of monitoring instruments, (6) more frequent monitoring intervals, (7) pill counts, (8) use of abuse-deterrent formulations, (9) consultation with mental health providers when mental health conditions are present, (10) avoidance of co-prescribing of sedative hypnotics, and (11) co-prescribing of naloxone on outcomes related to opioid use disorder, abuse, or misuse, and overdose?
- Key Question 4d. In patients with chronic pain, what is the comparative effectiveness of treatment strategies for managing patients with opioid use disorder related to prescription opioids on outcomes related to pain, function, quality of life, opioid use disorder, abuse, misuse, and overdose?
- Contextual Question 1. What are clinician and patient values and preferences related to opioids and medication risks, benefits, and use?
- Contextual Question 2. What are the costs and cost-effectiveness of opioid therapy and risk mitigation strategies?
- Discussion
- References
- Abbreviations and Acronyms
- Appendixes
- Appendix A. Search Strategies
- Appendix B. Inclusion and Exclusion Criteria
- Appendix C. List of Excluded Studies
- Appendix D. Quality Rating Criteria
- Appendix E. Detailed Statistical Methods
- Appendix F. List of Included Studies
- Appendix G. Quality Tables
- Appendix H. Data Abstraction
- Appendix I. Strength of Evidence
Suggested citation:
Chou R, Hartung D, Turner J, Blazina I, Chan B, Levander X, McDonagh M, Selph S, Fu R, Pappas M. Opioid Treatments for Chronic Pain. Comparative Effectiveness Review No. 229. (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 290-2015-00009-I.) AHRQ Publication No. 20-EHC011. Rockville, MD: Agency for Healthcare Research and Quality; April 2020. DOI: https://doi.org/10.23970/AHRQEPCCER229. Posted final reports are located on the Effective Health Care Program search page.
This report is based on research conducted by the Pacific Northwest Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2015-00009-I). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.
None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report.
The information in this report is intended to help healthcare decision makers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of healthcare services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.
This report is made available to the public under the terms of a licensing agreement between the author and the Agency for Healthcare Research and Quality. This report may be used and reprinted without permission except those copyrighted materials that are clearly noted in the report. Further reproduction of those copyrighted materials is prohibited without the express permission of copyright holders.
AHRQ or U.S. Department of Health and Human Services endorsement of any derivative products that may be developed from this report, such as clinical practice guidelines, other quality enhancement tools, or reimbursement or coverage policies, may not be stated or implied.
This report may periodically be assessed for the currency of conclusions. If an assessment is done, the resulting surveillance report describing the methodology and findings will be found on the Effective Health Care Program website at www.effectivehealthcare.ahrq.gov. Search on the title of the report.
People using assistive technology may not be able to fully access information in this report. For assistance contact vog.shh.qrha@CPE.
- NLM CatalogRelated NLM Catalog Entries
- Review The Effectiveness and Risks of Long-Term Opioid Treatment of Chronic Pain.[Evid Rep Technol Assess (Full ...]Review The Effectiveness and Risks of Long-Term Opioid Treatment of Chronic Pain.Chou R, Deyo R, Devine B, Hansen R, Sullivan S, Jarvik JG, Blazina I, Dana T, Bougatsos C, Turner J. Evid Rep Technol Assess (Full Rep). 2014 Sep; (218):1-219.
- Review Treatments for Acute Pain: A Systematic Review[ 2020]Review Treatments for Acute Pain: A Systematic ReviewChou R, Wagner J, Ahmed AY, Blazina I, Brodt E, Buckley DI, Cheney TP, Choo E, Dana T, Gordon D, et al. 2020 Dec
- Review Screening for Cognitive Impairment in Older Adults: An Evidence Update for the U.S. Preventive Services Task Force[ 2020]Review Screening for Cognitive Impairment in Older Adults: An Evidence Update for the U.S. Preventive Services Task ForcePatnode CD, Perdue LA, Rossom RC, Rushkin MC, Redmond N, Thomas RG, Lin JS. 2020 Feb
- Review Noninvasive Treatments for Low Back Pain[ 2016]Review Noninvasive Treatments for Low Back PainChou R, Deyo R, Friedly J, Skelly A, Hashimoto R, Weimer M, Fu R, Dana T, Kraegel P, Griffin J, et al. 2016 Feb
- Review The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop.[Ann Intern Med. 2015]Review The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop.Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I, Dana T, Bougatsos C, Deyo RA. Ann Intern Med. 2015 Feb 17; 162(4):276-86.
- Opioid Treatments for Chronic PainOpioid Treatments for Chronic Pain
- Chromosome neighbors for GEO Profiles (Select 132487130) (20)GEO Profiles
- Taxonomy Links for Protein (Select 1958762159) (1)Taxonomy
Your browsing activity is empty.
Activity recording is turned off.
See more...