Roger Chou, MD; Judith A. Turner, PhD; Emily B. Devine, PharmD, PhD, MBA; Ryan N. Hansen, PharmD, PhD; Sean D. Sullivan, PhD; Ian Blazina, MPH; Tracy Dana, MLS; Christina Bougatsos, MPH; Richard A. Deyo, MD, MPH
Disclaimer: The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Acknowledgment: The authors thank Jeffrey Jarvik, MD, MPH, from the University of Washington; Suchitra Iyer, PhD, Agency for Healthcare Research and Quality task order officer; and the members of the National Institutes of Health Working Group.
Financial Support: This project was funded under contract HHSA290201200014I from the Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services.
Disclosures: Dr. Chou reports grants from the Agency for Healthcare Research and Quality during the conduct of the study and consultancies for the U.S. Department of Health and Human Services, the Physicians' Clinical Support System for Opioids (funded by the Substance Abuse and Mental Health Services Administration), the Mayday Foundation, the Collaborative Opioid Prescribing Education for REMS (funded by the University of Washington), and the University of Wisconsin outside the submitted work. Dr. Turner reports support from a contract to the University of Washington from the Agency for Healthcare Research and Quality during the conduct of the study. Dr. Hansen reports grants from the Agency for Healthcare Research and Quality during the conduct of the study and grants and personal fees from Mallinckrodt Pharmaceuticals and Pacira Pharmaceuticals outside the submitted work. Mr. Blazina reports support from the Agency for Healthcare Research and Quality for a larger report on which this manuscript is based. Ms. Dana reports grants from the Agency for Healthcare Research and Quality during the conduct of the study and outside the submitted work. Ms. Bougatsos reports support from the Agency for Healthcare Research and Quality for a larger report on which this manuscript is based. Dr. Deyo reports a contract from the Agency for Healthcare Research and Quality during the conduct of the study, personal fees from the Informed Medical Decisions Foundation and UpToDate outside the submitted work, and an endowment from Kaiser Permanente outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-2559.
Requests for Single Reprints: Roger Chou, MD, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code BICC, Portland, OR 97239; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Chou, Mr. Blazina, Ms. Dana, and Ms. Bougatsos: Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code BICC, Portland, OR 97239.
Dr. Turner: Department of Psychiatry and Behavioral Sciences, University of Washington, Box 356560, Seattle, WA 98195-6560.
Drs. Devine and Hansen: University of Washington, Box 357630, Seattle, WA 98195-7630.
Dr. Sullivan: University of Washington, 1959 NE Pacific Street, H-364, Box 357631, Seattle, WA 98195-7630.
Dr. Deyo: Oregon Health & Science University, Mail Code FM, 3181 SW Sam Jackson Park Road, Portland, OR 97239.
Author Contributions: Conception and design: R. Chou, J.A. Turner, R.N. Hansen, S.D. Sullivan.
Analysis and interpretation of the data: R. Chou, J.A. Turner, E.B. Devine, R.N. Hansen, S.D. Sullivan, I. Blazina, T. Dana, C. Bougatsos, R.A. Deyo.
Drafting of the article: R. Chou, J.A. Turner, E.B. Devine, R.N. Hansen, I. Blazina, T. Dana, C. Bougatsos.
Critical revision of the article for important intellectual content: R. Chou, J.A. Turner, E.B. Devine, R.N. Hansen, S.D. Sullivan, I. Blazina, T. Dana, R.A. Deyo.
Final approval of the article: R. Chou, J.A. Turner, E.B. Devine, R.N. Hansen, S.D. Sullivan, I. Blazina, T. Dana, R.A. Deyo.
Statistical expertise: R. Chou.
Obtaining of funding: R. Chou, J.A. Turner, S.D. Sullivan.
Administrative, technical, or logistic support: I. Blazina, T. Dana, C. Bougatsos.
Collection and assembly of data: R. Chou, J.A. Turner, E.B. Devine, R.N. Hansen, S.D. Sullivan, I. Blazina, T. Dana, C. Bougatsos.
Increases in prescriptions of opioid medications for chronic pain have been accompanied by increases in opioid overdoses, abuse, and other harms and uncertainty about long-term effectiveness.
To evaluate evidence on the effectiveness and harms of long-term (>3 months) opioid therapy for chronic pain in adults.
MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, PsycINFO, and CINAHL (January 2008 through August 2014); relevant studies from a prior review; reference lists; and ClinicalTrials.gov.
Randomized trials and observational studies that involved adults with chronic pain who were prescribed long-term opioid therapy and that evaluated opioid therapy versus placebo, no opioid, or nonopioid therapy; different opioid dosing strategies; or risk mitigation strategies.
Dual extraction and quality assessment.
No study of opioid therapy versus no opioid therapy evaluated long-term (>1 year) outcomes related to pain, function, quality of life, opioid abuse, or addiction. Good- and fair-quality observational studies suggest that opioid therapy for chronic pain is associated with increased risk for overdose, opioid abuse, fractures, myocardial infarction, and markers of sexual dysfunction, although there are few studies for each of these outcomes; for some harms, higher doses are associated with increased risk. Evidence on the effectiveness and harms of different opioid dosing and risk mitigation strategies is limited.
Non–English-language articles were excluded, meta-analysis could not be done, and publication bias could not be assessed. No placebo-controlled trials met inclusion criteria, evidence was lacking for many comparisons and outcomes, and observational studies were limited in their ability to address potential confounding.
Evidence is insufficient to determine the effectiveness of long-term opioid therapy for improving chronic pain and function. Evidence supports a dose-dependent risk for serious harms.
Agency for Healthcare Research and Quality.
Summary of evidence search and selection.
* Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews.
† Includes reference lists of relevant articles and systematic reviews.
‡ Some studies have multiple publications, and some are included for >1 key question.
§ Includes 5 studies on acute exacerbations of pain, which are discussed in the full report (20).
Appendix Table 1. Uncontrolled Studies of Long-Term Opioid Use and Abuse, Misuse, and Related Outcomes
Appendix Table 2. Studies of Harms
Appendix Table 3. Head-to-Head Trials and Observational Studies of Different Long-Acting Opioids
Appendix Table 4. Studies of Risk Assessment Instruments
Appendix Table 5. Predictive Value of Risk Assessment Instruments
Table. Strength of Evidence
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Michael Lubrano, MD, MPH; Jonathan P. Wanderer, MD, MPhil; Jesse M. Ehrenfeld, MD, MPH
Dr Lubrano, Dept. of Medicine, NYU School of Medicine; Dr Wanderer, Dept. of Anesthesiology, Vanderbilt University
February 5, 2015
Long-Term Opioid Therapy for Chronic Pain: But What Drives Prescribing?
There is no doubt that opioid prescribing has increased over the past several decades. As detailed in Chou and colleague’s recent review (1), improving risk mitigation strategies for negative outcomes from long term opioid use is likely warranted. The authors highlight an absence of adequate, scientific evidence for long-term opioid therapy and note that this paucity of data is in “striking contrast” to the widespread use of opiates. While the Chou et. al. describe the consequences of current opioid prescribing patterns, they do not address what is driving this practice.
In the late 1990s, The Joint Commission (TJC) made well-intended recommendations that pain be better recognized (2). The American Pain Society subsequently developed a Pain Care Bill of Rights and promoted pain as a “fifth vital sign.” Other organizations followed suit, including the Veterans Administration which published a “Pain as the 5th Vital Sign Toolkit” in 2000, further justifying the use of opiates for non-malignant pain. The opiate-boom began.
With this modern culture of opiate prescribing, we have seen an incongruity between physician treatment goals and the perceptions that patients have regarding the management of their pain (3). These situations inevitably result in patient-provider conflict. Face-to-face requests for opiates by patients often contradict a number of practice guidelines suggesting non-pharmacologic or non-opioid alternatives for pain. Most patients do not have formal medical training and are largely unaware of what constitutes “quality” medical care, or of adverse medication effects.
In the world of pain management, patient satisfaction surveys may lead to unintended consequences. Government programs now look to patient satisfaction as a surrogate for healthcare quality. For example, Medicare reimbursements partially rely on this metric as part of the CMS Hospital Inpatient Value-Based Purchasing program (4). Not only are physician salaries subject to adjustment based on these data but promotion delays or termination may occur as a result. Overworked physicians with very little time are therefore heavily incentivized to meet their patient’s expectations by prescribing opiates (5). Pain is a vital sign, after all.
While Chou and colleagues make a number of salient suggestions for reducing harms of long-term opioid therapy, we may never be fully successful in curbing these risks without addressing the causes of opiate prescribing. Concerns regarding patient demand, patient satisfaction, and quality measures serve to further complicate this, and deserve attention as our government moves to alter reimbursement without consideration for clinical reality.
1. Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I, Dana T, Bougatsos C, Deyo RA.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 Jan 13. [Epub ahead of print]
2. Joint Commission on Accreditation of Healthcare Organizations. Pain assessment and management: an organizational approach. Oakbrook Terrace, IL: Joint Commission on Accreditation of Healthcare Organizations, 2000.
3. Frantsve LME, Kerns RD. Patient-provider interactions in the management of chronic pain: current findings within the context of shared medical decision making. Pain Med. 2007; 8(1):25–35.
4. Hospital Inpatient Value-Based Purchasing Program [Centers for Medicare & Medicaid Services web site]. Available at:http://www.gpo.gov/fdsys/pkg/FR-2011-05-06/pdf/2011-10568.pdf
5. Zgierska A, Miller M, Rabago D. Patient satisfaction, prescription drug abuse, and potential unintended consequences. JAMA. 2012 Apr 4;307(13):1377-8.
J Walden Retan MD
The Pain Clinic, Cooper Green/Mercy Health Services, Birmingham, AL
March 8, 2015
Narcotic Prescribing, Benefits and Risks
Prescriptions of narcotic medications for chronic pain have increased dramatically over the past three decades. The trend has been accompanied by greatly increased levels of prescription narcotic overdose, abuse, addiction and diversion.The trend is commonly blamed on irresponsible prescribing. As an unintended consequence of the blame, many younger physicians refuse to prescribe narcotics for people with chronic pain. Not for anyone. Not for any pain. The result is that pain is the only treatable condition I can think of that many physicians deliberately will not treat."The Effectiveness and Risks of Long-Term Opioid Therapy for Chronic Pain" (Ann Intern Med 2015;162:276-286) perpetuates the negative image of narcotic prescriptions for chronic pain. In a review of 4209 English-language articles, the authors could find no study of the long-term outcomes related to pain, function, or quality of life. Not one. The article is then given over entirely to a discussion of risks. But risk, alone, is never the basis for a physician's or a patient's decision. It is always the balance of risk versus benefit. Omission of discussion of benefit from an article on the effectiveness and risks of therapy is, at a minimum…curious.There are other curious problems with the article. It speaks of overdose deaths as if all deaths were the same. There’s no mention of the tragic deaths of children who sample parent’s medicines with lethal results. It doesn’t recognize that some overdose deaths are suicides. Chronic pain can cause patients to lose jobs, self-sufficiency, family, all their belongings and hope. Suicides in patients with chronic pain are not surprising.There’s no mention of diverted narcotics, prescribed for pain, becoming gateway drugs for heroin.The article speaks of heightened ED drug use in narcotic-treated patients as a possible indicator of opoid-induced sexual dysfunction. Another hypothesis is that pain impairs sexual appetite. Treatment of that pain can allow sexual activity to rebound, uncovering the ED problem.The article speaks of increased risk of myocardial infarction in narcotic-treated people. Is it the narcotic? Or the changes in activity and diet, forced by pain, that increases the risk?And so on.In the end, the article might have closed by pointing out the similarities between narcotics and alcohol. The great majority of people who use alcohol, and of people who are prescribed narcotics, use them responsibly. A minority don’t. The minority attracts all the attention.Many older physicians…and I…still prescribe narcotics for our patients who have significant chronic pain, despite acknowledged risks. We believe it’s the right thing to do.
Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University
April 4, 2015
Conflict of Interest:
Research funding from the Agency for Healthcare Research and Quality to conduct the review that is the subject of the correspondence
We agree with Dr. Lubrano and colleagues that effectively managing the risks of long-term prescribing opioids will not just be based on evidence regarding benefits and harms (the subject of our systematic review), but also will require that clinicians and policymakers understand and address policy and factors related to the physician-patient interaction that may drive less appropriate prescribing practices.1As Dr. Retan notes, we identified no studies meeting pre-defined inclusion criteria on the effectiveness of long-term opioid therapy for chronic pain. He does not describe any studies that we overlooked. Therefore, it is unclear what evidence he believes should have been included to discuss long-term benefits. For mortality and overdose-related events, it was generally not possible for studies to exclude cases due to intentional suicide attempts, though the authors controlled for psychological diagnoses and psychiatric medication use.2, 3 For these and other harms, we described limitations of the evidence, including the inability to completely address potential confounders and (in the case of endocrine-related adverse events) the reliance on a surrogate outcome (use of medications for erectile dysfunction and testosterone replacement).4 We describe the associations as reported in the studies and did not speculate about the underlying causes of myocardial infarction or other harms.High levels of scrutiny for opioid prescribing are warranted based on the substantial increases in opioid-related deaths and prescription opioid abuse.5 It does not seem appropriate, as Dr. Retan states, to equate alcohol use, a substance used recreationally, with long-term opioid therapy, a drug prescribed for medical purposes. Curiously, while downplaying the harms of opioids, Dr. Retan at the same time notes additional harms related to diversion and sampling of opioids by family members and friends and critiques our review for not addressing them. To clarify, our review focused on benefits and harms in persons prescribed opioids. However, we are unaware of any study that has attempted to estimate the harms related to diversion and sampling of opioids from persons prescribed versus not prescribed opioids, or evaluated dose-dependent effects on such outcomes.1. Reuben DB, Alvanzo AA, Ashikaga T, et al. National Institute of Health Pathways to Prevention Workshop: The rold of opioids in the treatment of chronic pain. Ann Intern Med 2015;162:295-300.2. Dunn KM, Saunders DW, Rutter CM et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med 2010;152:85-92.3. Gomes T, Mamdani MM, Dhalla IA et al. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med 2011;17:686-91.4. Deyo RA, Smith DH, Johnson E, et al. Prescription opioids for back pain and use of medications for erectile dysfunction. Spine 2013;38:909-15.5. Okie S. A flood of opioids, a rising tide of deaths. N Engl J Med 2010;363:1981-5
Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I, et al. 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;162:276–286. doi: 10.7326/M14-2559
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Published: Ann Intern Med. 2015;162(4):276-286.
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