Opioids for Chronic Pain: The Status Quo is Not an Option

Michael Von Korff ScD, Senior Investigator, Group Health Research Institute

Roger A Rosenblatt MD, MPH, MFR, Professor & Vice Chair, Department of Family Medicine, University of Washington

**Editor's Note: NWRPCA seeks to provide a forum for discussion by all competent participants with a reasonable point of view expressed respectfully and professionally and in good faith. We do not profess to have a "position" or "correct answers" about clinical and care issues. We are serving here as conveners and facilitators, inviting all reasonable perspectives and willing to present evidence from all responsible sources.**

America’s Prescription Drug Abuse Epidemic

The United States is experiencing an unprecedented epidemic caused by prescription drug abuse and misuse [1]. This epidemic is notable for rapid increases in the number of unintentional overdose deaths involving prescription opioids and in the occurrence of prescription opioid addiction.  These increases in morbidity and mortality were precipitated by large increases in per capita dispensing of oxycodone, hydrocodone, morphine and methadone since the mid-1990’s [2].  From 1999-2009, overdose deaths involving prescription opioids increased four fold, with over 100,000 deaths in that time span [3].  Over the same years, admissions for prescription opioid addiction treatment increased more than four fold; almost three-quarters of a million persons were treated for this addiction from 1999 to 2009 [4].  Our communities are awash in prescription narcotics, largely dispensed to patients with chronic pain.  More than 85% of opioids, as measured by total morphine equivalents, are dispensed to patients with chronic pain, with more than half dispensed to patients on regimens exceeding 50 milligrams average daily dose (morphine equivalents) [5]. These drugs are often misused by patients, frequently diverted for non-medical use, and contribute to tragic cases of prescription drug addiction and fatal drug overdose affecting patients, their families, and the community-at-large.


Does Opioid Rx = Compassionate Care?

Compassionate care of chronic pain patients has been inappropriately equated with access to opioids [6].  A recent meta-analysis of randomized trials of chronic opioid therapy reached a more reserved conclusion about opioid effectiveness: “Short-term use of opioids (for chronic pain) is associated with modest but favorable effects on pain and physical function.” [7] The typical benefit of chronic opioid therapy is a one-third reduction in pain intensity (e.g. reducing pain from a 7 to a 5 on a 0-to-10 rating scale), but analgesic benefits vary widely [5,8].  Furthermore, it is unknown whether short-term benefits are sustained long-term, particularly at higher dosage levels.  Observational studies call into question whether extended opioid use is helpful [9].

Compared to other medication regimens commonly used for long-term management of chronic conditions, evidence for the long-term effectiveness and safety of opioids is negligible.  Research has produced about 1.8 million person-years of observation in randomized trials of anti-hypertensive medications [10], three-quarters of a million person-years in trials of lipid-lowering agents [11], and about 100,000 person-years in trials of NSAIDs [12].  In contrast, we have only a meager 1500 person-years of observation in randomized trials of opioids for chronic non-cancer pain management [13].  The available trials of chronic opioid therapy are too short to evaluate long-term effectiveness, and too small and selective to adequately evaluate safety.

While overdose mortality and prescription drug addiction morbidity have received the most attention, substantial knowledge-gaps exist regarding the safety of long-term opioid use, particularly at higher dosage levels.   Such long-term opioid use, inadequately studied to date, entails many potential medical risks in addition to overdose and addiction, including: falls and fractures; chronic constipation and serious intestinal blockage; breathing difficulties during sleep; hormonal and endocrine dysregulation (potentially contributing to sexual dysfunction, osteoporosis, depression); immunosuppressive effects that may contribute to infection risk; cardiovascular disease risks; increased risks of motor vehicle accidents; and risks of cognitive and neuropsychologic impairments such as delirium and dementia [14].  While it can be difficult for patients who desire immediate relief from chronic pain, or who may have become addicted, to adequately weigh uncertain, long-term health risks against short-term rewards, the prescribing physician has a duty to balance the potential harms of long-term use of opioids against the often modest benefits.

Given epidemic levels of opioid-related morbidity and mortality, and substantial uncertainty about a broad spectrum of medical risks, there is insufficient evidence to support claims that chronic opioid therapy represents compassionate treatment of chronic non-cancer pain.  It is not surprising that the most vocal opponents of commonsense restraints on opioid prescribing for chronic non-cancer pain have been individuals and organizations supported by opioid manufacturers.


The Status Quo is Not an Option

In the June issue of QuickNotes, Malcolm Butler eloquently argued that achieving greater restraint in opioid prescribing for chronic non-cancer pain is a public health imperative [15].  America’s prescription drug crisis is an epidemic in which the agents (opioids) are obtained largely from community physicians.  Characteristics of the host (i.e. patient liability to opioid misuse and abuse) modify individual risks. To date, efforts to reduce opioid-related morbidity and mortality have largely focused on patient (host) factors, through identification of high risk patients and through ongoing monitoring to identify opioid abuse and misuse.  Given current levels of opioid-related morbidity and mortality, the exclusively patient-focused methods of risk reduction appear to have failed.  It is not reasonable to expect community physicians to accurately sort out which chronic pain patients will misuse, abuse or divert opioid medications.  We cannot depend solely on closer monitoring of chronic opioid therapy patients and more frequent use of urine drug screens to prevent addiction and overdose.  While careful screening and close monitoring are prudent when prescribing opioids long-term, no compelling evidence demonstrates that these practices alone are sufficient to ensure patient safety [5], even if careful screening and close monitoring were consistently practiced, which they are not.

We need to expand efforts to prevent opioid-related morbidity and mortality from largely patient-oriented strategies, to include controlling exposure to opioids and altering environmental factors influencing opioid exposure—particularly physician prescribing norms and practices.  Patient risks of opioid-related adverse events increase with opioid dose prescribed [16-19].  Community risks increase with the total volume of opioids dispensed in the population-at-large, because they increase the quantity of opioids available for diversion and non-medical use. Clinical decisions of community physicians about how many of their patients will use opioids long-term, and the opioid dose these patients receive, influence opioid-related morbidity and mortality, including direct risks to patients and indirect risks to the larger community.  Without reducing the volume of opioids in community medicine cabinets and available on our streets, it will be difficult to reverse trends in opioid-related morbidity and mortality.


Finding the Way without a Roadmap

Lowering patient and community risks of opioid-related morbidity and mortality is likely to depend on reducing how often physicians prescribe chronic opioid therapy, and what doses they prescribe to patients using opioids long-term.  While it would be desirable to understand the trade-offs between risks and benefits of more selective and cautious opioid prescribing, steps to control risks of addiction and overdose cannot wait five or ten years for research results to show the way.  Given the scope of opioid-related morbidity and mortality, prescribing norms will change whether or not research is available to adequately define best practices.

As evidence mounts that benefits of chronic opioid therapy were overstated and harms and risks understated, a new set of prescribing principles is likely to emerge to guide more cautious and selective opioid prescribing.  In the previous issue of this newsletter, Malcolm Butler [15] suggested that: (1) In the absence of high quality research, be skeptical of unsubstantiated claims for the long-term effectiveness and safety of opioids for chronic non-cancer pain. Opioids can be an excellent option for acute pain management, but they are often the wrong choice for chronic non-cancer pain.  (2) Don’t be afraid to say “no” to prescribing opioids long-term. And, (3) when opioids are used long-term, avoid escalation from initial cautious dose levels, as risks and problems increase with dose, and opioid discontinuation becomes more difficult.   Reaching agreement on prescribing principles such as these may be contentious and controversial at times.  To the extent that research sheds light on consequences of more selective and cautious opioid prescribing, the pace of adoption of uniform best practices that serve patients well will accelerate.

It will be important to try out approaches to achieving more cautious and selective opioid prescribing, and then to learn from the experience gained through clinical observation and community-based research evaluating practice change.  Practical approaches that might be considered to achieve more selective and cautious use of opioids for chronic non-cancer pain include the following:

(1)  Begin treatment of chronic pain with non-opioid modalities, including encouragement to resume rewarding life activities, gradual increases in physical activities such as walking, physical therapy, massage, cognitive behavioral therapy, chronic pain support groups, and safer medications such as anti-depressants.  Learning to manage chronic pain can take time, so don’t give up on safer modalities too soon.

(2)  If opioids are considered, start with short-term or intermittent opioid use for severe pain flare-ups as an alternative to sustained opioid use.  The claimed benefits of long-acting opioids and time-scheduled opioid dosing for management of chronic non-cancer pain have not been proven by controlled studies, and they lead to higher opioid dose [20].

(3)  Long-term use of opioids for chronic pain is not an evidence-based therapy, and it carries significant risks for patients.  Observational research has raised questions about whether efficacy is sustained long-term [9].  For these reasons, when chronic opioid therapy is considered, initiate treatment cautiously as a time-limited therapeutic trial.  Agree upon criteria for decisive improvement in performance of activities in work, family and social life, and for pain control, to test whether the therapeutic trial achieves hoped-for benefits.  Set expectations that the therapeutic trial will not be continued unless decisive benefits are observed.

(4)   Avoid opioid dose escalation to levels where discontinuation becomes difficult and risks of adverse events are increased. Taper patients off opioids if benefits are limited, problems arise, or benefits for quality of life are not sustained over time.  Continually revisit whether the patient is ready to discontinue opioid use or reduce dose.  Many patients using opioids long-term remain ambivalent about opioid use [21], so opportunities to discontinue use or lower dose may arise over time.

(5)  Do not overestimate your ability to predict which patients will misuse or abuse prescription opioids, or even to detect opioid misuse or abuse among patients using opioids long-term.  Remain vigilant for adverse medical effects of opioids as well as indications of abuse, misuse or diversion.

At this juncture, we cannot predict to what extent more selective and cautious opioid prescribing will enhance patient and community safety.   However, the status quo is not an option--current opioid-related morbidity and mortality is unacceptable, particularly since the benefits of long-term opioid use for chronic pain are unknown.  As prescribing norms and practices change, it will be important to share experiences about what is working, and what is not.  It will be essential for research and surveillance to monitor how changes in opioid prescribing affect patient health outcomes and their quality of life. Caring, compassion and encouragement for patients with chronic pain need not depend on opioid prescribing. (See editor's note below regarding such an opportunity for sharing.)



1.  Office of National Drug Control Policy.  Epidemic: Responding to America’s Prescription Drug Abuse Crisis.   Prepared by the Office of National Drug Control Policy, the Food and Drug Administration, and the Drug Enforcement Agency.   http://www.whitehousedrugpolicy.gov/publications/pdf/rx_abuse_plan.pdf.     Accessed on June 3, 2011.

2.   Kenan K, Mack K, Paulozzi L.  Open Medicine 2012; 6:e41.

3.  Paulozzi L.  Epidemiology of the overdose epidemic.  Common Threads in Pain and Addiction.  Pain and Addiction Common Threads XIII.  43rd Annual Meeting of the American Society of Addiction Medicine, Atlanta, GA, April, 19, 2012.

4.  Center for Behavioral Health Statistics and Quality.  Substance Abuse and Mental Health Services Administration.  Treatment Episodes Data Set (TEDS).  Data received through 11/3/2010.

5.   Von Korff M, Kolodny A, Deyo RA, Chou R.  Long-term opioid therapy reconsidered.  Annals Internal Medicine 2011; 155:325-328.

6.  Christopher M.  Rise above the ‘Opioid Wars” to manage chronic pain.  Seattle Times, December 22, 2011.

7.   Papaleontiou M, Henderson CR, Turner BJ, Moore AA, Olkhovskaya Y, Amanfo L, Reid MC.  Outcomes associated with opioid use in the treatment of chronic noncancer pain in older adults: a systematic review and meta-analysis.  JAGS 2010; 58:1353-1369.

8.  Raja S.  What is the evidence for the efficacy of opioid analgesics for chronic pain from randomized controlled trials.  Assessment of Analgesic Treatment of Chronic Pain: A Scientific Workshop.  Sponsored by the Food and Drug Administration.   Bethesda MD, May 31, 2012.

9   Ballantyne J.  What is the evidence for the effectiveness of opioid analgesics for chronic pain from other clinical and administrative data?  Assessment of Analgesic Treatment of Chronic Pain: A Scientific Workshop.  Sponsored by the Food and Drug Administration.   Bethesda MD, May 31, 2012.

10.   Law MR, Morris JK, Wald NJ.  Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies.  BMJ 2009; 338:b1665.

11.   Cholesterol Treatment Trialists (CTT) Collaboration.  Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials.  Lancet 2010; 376:1670-1681.

12.   Trelle S, Reicherback S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, Egger M, Juni P.  Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis.  BMJ 2011; 342:c7086.

13.  Furlan AD, Chaparro LE, Irvin E, Mailis-Gagnon A.  A comparion between enriched and nonenriched enrollment randomized withdrawal trials of opioids for chronic noncancer pain.  Pain Research and Management: The Journal of the Candian Pain Society 2011; 16:337-351.

14.  Baldini A, Von Korff M, Lin EHB.  A review of potential adverse effects of long-term opioid therapy: A practitioner’s guide.  Primary Care Companion CNS 2012; 14 (3):doi.4088/PCC.11m01326.

15.  Butler M.  Opioid Redux.  Northwest Regional Primary Care Association Newsletter.  http://www.nwrpca.org/health-center-news/239-opioid-redux.html.  Accessed on July 7, 2012.

16.  Dunn KM, Saunders KW, Rutter CM, et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med. 2010;152(2):85-92.

17.   Saunders KW, Dunn KM, Merrill JO, et al. Relationship of opioid use and dosage levels to fractures in older chronic pain patients. J Gen Intern Med. 2010;25(4):310-315.

18.   Bohnert ASB, Valenstein M, Bair MJ, Ganoczy D, McCarthy JF, Ilgen MA, Blow FC.  Association Between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths.  JAMA  2011; 305:1315-1321.

19.   Gomes T, Mamdani MM, Dhalla IA,  Paterson JM, Juurlink DN. Opioid Dose and Drug-Related Mortality in Patients With Nonmalignant Pain.  Arch Intern Med 2011;171: 686-691.

20,   Von Korff M, Merrill JO, Rutter CM, Sullivan M, Campbell CI, Weisner C.   Time-scheduled vs. pain-contingent opioid dosing in chronic opioid therapy. Pain 2011; 152:1256-12622.

21.  Howe CQ, Sullivan MD, Saunders KW, Merrill JO, Banta-Green CJ, Weisner C, Campbell CI, Von Korff M.  Depression and ambivalence toward chronic opioid therapy for chronic noncancer pain.  Clin J Pain 2012; In press.

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