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Cover of The Effectiveness and Risks of Long-Term Opioid Treatment of Chronic Pain

The Effectiveness and Risks of Long-Term Opioid Treatment of Chronic Pain

Evidence Reports/Technology Assessments, No. 218

Investigators: , MD, FACP, , MD, MPH, , PharmD, PhD, MBA, , PharmD, PhD, , PhD, , MD, MPH, , MPH, , MLS, , MPH, and , PhD.

Author Information
Rockville (MD): Agency for Healthcare Research and Quality (US); .
Report No.: 14-E005-EF

Structured Abstract


Chronic pain is common and use of long-term opioid therapy for chronic pain has increased dramatically. This report reviews the current evidence on effectiveness and harms of opioid therapy for chronic pain, focusing on long-term (≥1 year) outcomes.

Data sources:

A prior systematic review (searches through October 2008), electronic databases (Ovid MEDLINE, Scopus, and the Cochrane Libraries January 2008 to August 2014), reference lists, and clinical trials registries.

Review methods:

Using predefined criteria, we selected randomized trials and comparative observational studies of patients with cancer or noncancer chronic pain being considered for or prescribed long-term opioid therapy that addressed effectiveness or harms versus placebo, no opioid use, or nonopioid therapies; different opioid dosing methods; or risk mitigation strategies. We also included uncontrolled studies ≥1 year that reported rates of abuse, addiction, or misuse, and studies on the accuracy of risk prediction instruments for predicting subsequent opioid abuse or misuse. The quality of included studies was assessed, data were extracted, and results were summarized qualitatively.


Of the 4,209 citations identified at the title and abstract level, a total of 39 studies were included. For a number of Key Questions, we identified no studies meeting inclusion criteria. Where studies were available, the strength of evidence was rated no higher than low, due to imprecision and methodological shortcomings, with the exception of buccal or intranasal fentanyl for pain relief outcomes within 2 hours after dosing (strength of evidence: moderate). No study evaluated effects of long-term opioid therapy versus no opioid therapy. In 10 uncontrolled studies, rates of opioid abuse were 0.6 percent to 8 percent and rates of dependence were 3.1 percent to 26 percent in primary care settings, but studies varied in methods used to define and ascertain outcomes. Rates of aberrant drug-related behaviors ranged from 5.7 percent to 37.1 percent. Compared with nonuse, long-term opioid therapy was associated with increased risk of abuse (one cohort study), overdose (one cohort study), fracture (two observational studies), myocardial infarction (two observational studies), and markers of sexual dysfunction (one cross-sectional study), with several studies showing a dose-dependent association. One randomized trial found no difference between a more liberal opioid dose escalation strategy and maintenance of current dose in pain or function, but differences between groups in daily opioid doses at the end of the trial were small. One cohort study found methadone associated with lower risk of mortality than long-acting morphine in a Veterans Affairs population in a propensity adjusted analysis (adjusted HR 0.56, 95 percent CI 0.51 to 0.62). Estimates of diagnostic accuracy for the Opioid Risk Tool were extremely inconsistent and other risk assessment instruments were evaluated in only one or two studies. No study evaluated the effectiveness of risk mitigation strategies on outcomes related to overdose, addiction, abuse, or misuse. Evidence was insufficient to evaluate benefits and harms of long-term opioid therapy in high-risk patients or in other subgroups.


Evidence on long-term opioid therapy for chronic pain is very limited but suggests an increased risk of serious harms that appears to be dose-dependent. More research is needed to understand long-term benefits, risk of abuse and related outcomes, and effectiveness of different opioid prescribing methods and risk mitigation strategies.


Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services1, Contract No. 290-2012-00014-I. Prepared by: Pacific Northwest Evidence-based Practice Center, Oregon Health and Science University, Portland, OR, University of Washington, Seattle, WA

Suggested citation:

Chou R, Deyo R, Devine B, Hansen R, Sullivan S, Jarvik JG, Blazina I, Dana T, Bougatsos C, Turner J. The Effectiveness and Risks of Long-Term Opioid Treatment of Chronic Pain. Evidence Report/Technology Assessment No. 218. (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 290-2012-00014-I.) AHRQ Publication No. 14-E005-EF. Rockville, MD: Agency for Healthcare Research and Quality; September 2014. DOI:

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. 290-2012-00014-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.

The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care 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 may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

This report may periodically be assessed for the urgency to update. If an assessment is done, the resulting surveillance report describing the methodology and findings will be found on the Effective Health Care Program Web site at: Search on the title of the report.

None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report.


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Bookshelf ID: NBK258809


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