Tuesday, February 26, 2013

Myths and Facts About Chronic Opioid Therapy (COT)

In a letter to the editor of the New England Journal of Medicine, Jane Ballantyne, M.D. and Mark Sullivan, M.D. of the University of Washington Medicine in Seattle, Washington, reply to a previous article by Lembke:
"Lembke asks why doctors prescribe opioids
when 'fully aware that their patients are abusing
these medications or diverting them.'

(Anna Lembke, M.D. "Why Doctors Prescribe Opioids to Known Opioid Abusers."
N Engl J Med 2012; 367:1580-1581. October 25 2012)
"One answer is that once a commitment to long-term pain treatment with opioids has been made, it is not at all easy to stop. Does a patient's pain that once justified a commitment to opioids diminish in significance because aberrant behaviors come to light?
"Modern societies, to their credit, do pay attention to pain. It is not possible to verify a patient's report of pain, but it is possible to select the appropriate therapy. Evidence increasingly suggests that gains from long-term opioid therapy are small and may not justify the risk. The problem facing the United States now is how to change the culture into one that recognizes pain without conflating pain relief with opioid therapy. The treatment of pain with any number of approaches other than opioids can be held up as compassionate care. But most of them require more time than writing a prescription, and time is, as Lembke points out, 'medicine's least valued commodity.'”
(Jane C. Ballantyne, M.D. and Mark D. Sullivan, M.D., Ph.D. "Why Doctors Prescribe
Opioids to Known Opioid Abusers." N Engl J Med 2013; 368:484-485. January 31 2013)

In commenting about the editorial, Anna Lembke, M.D. of Stanford University School of Medicine, Stanford, California, points out the following:

"Physicians don't hesitate to switch antibiotics
when the first one isn't working, or stop chemotherapy
when side effects outweigh benefits. Why should it be
different for the treatment of pain with opioids?
Cessation of opioids in the context of addiction
 is not reneging on a “commitment” to treat pain
but recognizing and targeting the long-term pain
 caused by addiction. It is also compassionate care."

"Furthermore, as the authors point out, opioids are not a very effective treatment for chronic pain that is not related to cancer. Effective treatments for chronic pain syndromes involve behavioral interventions in combination with somatic therapies. Both addictive disorders and chronic pain syndromes are long-lasting conditions that require and deserve the best treatments we have to offer; one should not be sacrificed for the other."

Myths and Facts about Chronic Opioid
Therapy (COT) 

The following information is found in the "Myths and Facts Brochure for Cautious, Evidence-based, Opioid Prescribing" written by the Physicians For Responsible Opioid Prescribing.

Here is a link to their website: http://prescriptionopioidreform.com/Home_Page.html

Myth: COT for chronic pain is supported by strong  evidence.
Fact: Evidence of long-term efficacy for chronic non-cancer pain (≥16 weeks) is limited, (1,2,3) and of low quality. (4,5) Opioids are effective for short-term pain management. But, for many patients with chronic pain, analgesic efficacy is not maintained over long time periods. (6)

Myth: Physical dependence only happens with high doses over long periods of time.

Fact: With daily opioid use, physical dependence and tolerance can develop in days or weeks. (7,8)

Myth: Patients who develop physical dependence on opioids can easily be tapered off.

Fact: Successfully tapering chronic pain patients from opioids can be difficult – even for patients who are motivated to discontinue opioid use. (33)

Myth: Addiction is rare in patients receiving medically prescribed COT.

Fact: Estimates vary. Between 4% and 26% of patients receiving COT have an opioid use disorder. (9-12) Among patients without an opioid use disorder, more than one in ten misuse opioids by: intentional over-sedation; concurrently using alcohol for pain relief; hoarding medications; increasing dose on their own; and borrowing opioids from friends. (9,15)

Myth: Addiction is the main risk to be concerned about when prescribing opioids.

Fact: Opioids have significant risks besides addiction and misuse. (18,19) These risks include respiratory depression and unintentional overdose; (20,21) serious fractures from falls; (22,23) hypogonadism and other endocrine effects that can cause a spectrum of adverse effects; (24) increased pain sensitivity, (25) sleep-disordered breathing, (26) chronic constipation and serious fecal impaction, (27,28) and chronic dry mouth which can lead to tooth decay. (29)

Myth: Extended-release opioids are better than short-acting opioids for managing chronic pain.

Fact: Extended-release opioids have not been proto be safer or more effective than short-acting opioids for managing chronic pain. (30)

Myth: Prescribing high-dose opioid therapy (>120 mg morphine equivalents/day) is supported by strong evidence that benefits outweigh risks.

Fact: No randomized trials show long-term effectiveness of high opioid doses for chronic non-cancer pain. Many patients on high doses continue to have substantial pain and related dysfunction. (32) Higher doses come with increased risks for adverse events and side effects including overdose, fractures, hormonal changes, and increased pain sensitivity. (18-26)

Myth: Opioid overdoses only occur among drug abusers and patients who attempt suicide.

Fact: Patients using prescription opioids are at risk of unintentional overdose and death. (20) This risk increases with dose and when opioids are combined with other CNS depressants like benzodiazepines and alcohol. (21)

Myth: Dose escalation is the best response when patients experience decreased pain control.

Fact: When treating chronic pain, dose escalation has not been proven to reduce pain or increase function, but it can increase risks. (32)

1. Kalso E, Edwards JE, Moore RA, McQuay HJ. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain. 2004;112:372-80.

2. 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.

3. Martell BA, O’Connor PG, Kerns RD, Becker WC, Morales KH, Kosten TR, et al. Systematic review: opioid treatment for chronic back pain: prevalence, efficacy, and association with addiction.

Ann Intern Med. 2007;146:116-27.

4. Chou R, Fanciullo GJ, Fine PG, Adler JA, Ballantyne JC, Davies P, Donovan MI, Fishbain DA, Foley KM, Fudin J, Gilson AM, Kelter A, Mauskop A, O’Connor PG, Passik SD, Pasternak GW, Portenoy RK, Rich BA,

Roberts RG, Todd KH, Miaskowski C; American Pain Society-American Academy of Pain Medicine Opioids Guidelines Panel. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain.

J Pain 2009; 10:113-130.

5. American Geriatrics Society Panel on the Pharmacological Management of Persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons. JAGS 2009; 57:1331–1346, 2009.

6. Ballantyne JC, Shin NS. Efficacy of opioids for chronic pain: a review of the evidence. Clin J Pain 2008;24:469-78.

7. McQuay H. Opioids in pain management. Lancet 1999, 353: 2229-2232.

8. Baily CP and Connor M. Opioids: Cellular mechanisms of tolerance and physical dependence. Current Opinion in Pharmacology 2005; 5:60-80.

9. Fleming MF, Balousek SL, Klessig CL, Mundt MP, Brown DD. Substance Use Disorders in a Primary Care Sample Receiving Daily Opioid Therapy. J Pain 2007; 8:573-582. Banta-Green CJ, Merrill JO, Doyle SR,

Boudreau DM, Calsyn DA. Measurement of opioid problems among chronic pain patients in a general medical population. Drug and Alcohol Dependence 2009; 104:43-49. Becker WC, Fiellin DA, Gallagher RM,

Barth KS, Ross JT, Oslin DW. The association between chronic pain and prescription drug abuse in Veterans. Pain Medicine 2009; 10:531-536.

10. Banta-Green CJ, Merrill JO, Doyle SR, Boudreau DM, Calsyn DA. Measurement of opioid problems among chronic pain patients in a general medical population. Drug and Alcohol Dependence 2009; 104:43-49.

11. Becker WC, Fiellin DA, Gallagher RM, Barth KS, Ross JT, Oslin DW. The association between chronic pain and prescription drug abuse in Veterans. Pain Medicine 2009; 10:531-536.

12. Boscarino JA, Rutstalis M, Hoffman SN, Han JJ, Erlich PM, Gerhard GS, Stewart WF. Risk factors for drug dependence among out-patients on opioid therapy in a large US health-care system.

Addiction 2010; 105:1776-1782.

13. Manchikanti L., Fellows B., Damron K.S., Pampati V., McManus C.D. Prevalence of illicit drug use among individuals with chronic pain in the Commonwealth of Kentucky: an evaluation of patterns and trends.

J Ky Med Assoc 2005; 103: 55-62.

14. Ives TJ, Chelminski PR, Hammett-Stabler CA, Malone RM, Perhac JS, Potisek NM, Shilliday BB, DeWalt DA, Pignone MP. Predictors of opioid misuse in patients with chronic pain: a prospective cohort study.

BMC Health Services Research 2006; 6:46-55.

15. Banta-Green CJ, Merrill JO, Doyle SR, Boudreau DM, Calsyn DA. Opioid use behaviors, mental health and pain—Development of a typology of chronic pain patients.

Drug and Alcohol Dependence 2009; 104:34-42.

16. Goldsworthy RC, Schwartz NC, Mayhorn CB. Beyond Abuse and Exposure: Framing the Impact of Prescription-Medication Sharing. Am J Public Health. 2008;98:1115–1121.

17. Sullivan MD, Von Korff M, Banta-Green C, Merrill JA, Saunders K. Problems and concerns of patients receiving chronic opioid therapy for chronic non-cancer pain. Pain 2010; 149:345-353.

18. Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J Med 2003;349:1943-53.

19. Von Korff M. Commentary on Boscarino et al. (2010): Understanding the spectrum of opioid abuse, misuse and harms among chronic opioid therapy patients. Addiction 2010; 105:1783-1784.

20. Paulozzi LJ, Ryan GW. Opioid analgesics and rates of fatal drug poisoning in the United States. Am J Prev Med. 2006;31:506-11.

21. Dunn KM, Saunders KW, Rutter CM, Banta-Green CJ, Merrill JO, Sullivan MD, Weisner CM, Silverberg MJ, Campbell CI, Psaty BM, Von Korff M. Opioid prescriptions for chronic pain and overdose: a cohort study.

Annals of Internal Medicine 2010; 152:85-92.

22. Saunders KW, Dunn KM, Merrill JO, Sullivan MD, Weisner CM, Braden JB, Psaty BM, Von Korff M. Relationship of opioid use and dosage levels to fractures in older chronic pain patients.

Journal of General Internal Medicine 2010; 25:310-315.

23. Takkouche B, Montes-Martinez A, Gill S, Etminan M. Psychotropic medications and the risk of fracture. Drug Safety. 2007;30(2):171-84.

24. Vuong C, Van Uum SH, O’Dell LE, Lutfy K, Friedman TC. The effects of opioids and opioid analogs on animal and human endocrine systems. Endocr Rev. 2010; 31:98-132.

25. Zhou HY, Chen SR, Chen H, Pan HL. Opioid-induced long-term potentiation in the spinal cord is a presynaptic event. Neuroscience 2010; 30:4460-4466.

26. Walker JM, Farney RJ, Rhondeau SM, Boyle KM, Valentine K, Cloward TV, Shilling KC, Chronic Opioid Use is a Risk Factor for the Development of Central Sleep Apnea and Ataxic Breathing.

J Clin Sleep Medicine 2007; 3:455-461.

27. Tuteja AK, Biskupiak J, Stoddard GJ, Lipman AG. Opioid-induced bowel disorders and narcotic bowel syndrome in patients with chronic non-cancer pain. Neurogastroenterol Motil 2010; 22:424-30.

28. Bell TJ, Panchal SJ, Miaskowski C, Bolge SC, Milanova T, Williamson R. The prevalence, severity and impact of opioid-induced bowel dysfunction: results of a US and European Patient Survey (PROBE 1).

Pain Medicine 2009; 10:35-42.

29. Murray Thomson W, Poulton R, Mark Broadbent J, Al-Kubaisy S: Xerostomia and medications among 32-year olds. Acta Odontol Scand 64:249-254, 2006

30. Chou R, Clark E, Helfand M. Comparative efficacy and safety of long-acting oral opioids for chronic non-cancer pain: a systematic review. J Pain Symptom Manage 2003;26:1026-1048.

31. Lusher J, Elander J, Bevan D, Telfer P, Burton B: Analgesic addiction and pseudoaddiction in painful chronic illness. Clin J Pain 2006; 22:316–324.

32. Franklin GM, Rahman EA, Turner JA, Daniell WA, Fulton-Kehoe D. Opioid use for chronic low back pain. A prospective, population-based study among injured workers in Washington State, 2002-2005.

Clin J Pain 2009; 25:743-751.

33. Blondell RD, Ashrafioun L, Dambra CM, Foschio EM, Zielinski AL, Salcedo DM. A clinical trial comparing tapering doses of buprenorphine with steady doses for chronic pain and co-existent opioid addiction.

J Addict Med 2010; 4:140-146.

34. Caudill-Slosberg MA, Schwartz LM, Woloshin S. Office visits and analgesic prescriptions for musculoskeletal pain in US: 1980 vs 2000. Pain. 2004;109(3):514-519.

35. Boudreau D, Von Korff M, Rutter CM, et al. Trends in long-term opioid therapy for chronic non-cancer pain. Pharmacoepidemiol Drug Saf. 2009;18(12):1166-1175.

36. Sullivan MD, Edlund MJ, Fan MY, et al. Trends in use of opioids for non-cancer pain conditions 2000-2005 in commercial and Medicaid insurance plans: the TROUP study. Pain. 2008;138(2):440-449.

37. Zacny J, Bigelow G, Compton P, Foley K, Iguchi M, Sannerud C. College on Problems of Drug Dependence taskforce on prescription opioid non-medical use and abuse: position statement.

Drug and alcohol dependence 2003;69:215-232.



Andrew Kolodny, MD
Gary Franklin, MD, MPH
Stephen Gelfand, MD
Petros Levounis, MD, MA
Rosemary Orr, MD

External Reviewers:

Jane Ballantyne, MD
Roger Chou, MD
Mark Edlund, MD, PhD
Richard A. Deyo, MD, MPH
Thomas Kosten, MD

Patient/Family Advocates:

Peter Jackson
Len Paulozzi, MD, MPH Betts Tully
Jon Streltzer, MD
Art Van Zee, MD
Michael Von Korff, ScD
Mark Sullivan, MD, PhD
Judith Turner, PhD

For additional information, please contact Physicians for Responsible Opiod Prescribing: Andrew Kolodny, MD, akolodny@maimonidesmed.org or Michael Von Korff, ScD, vonkorff.m@ghc.org

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