Questions about tolerance with use of opioids

I was very interested in the article "Chronic pain update: Addressing abuse and misuse of opioid analgesics" by Ross et al (The Journal of Musculoskeletal Medicine, June 2008, page 268) because pain management and addiction medicine is my specialty.The article was interesting, useful, and well written and referenced. However, it perpetuated one myth about opioid prescribing for chronic pain when the authors wrote, "Tolerance develops in most patients who receive long-term opioid therapy."

Not surprisingly, this statement-in contrast to most other declarations of fact in the article-was not referenced. In my many years of experience treating patients with chronic pain with opioids, as well as the experience of other clinicians who prescribe opioids over long periods, tolerance to the pain-relieving effect of opioids is uncommon.^1-3 After initial titration that most often is related to increased activity once patients experience some pain relief, most patients can be stabilized on some opioid dose, on which they tend to stay for long periods, unless their disease process worsens. I suspect that this also has been the authors' experience, because in the article they said, "Most patients with pain who have been prescribed a stable dose of opioids . . . can be referred back to their primary care physician." This statement implies that such patients do achieve a stable dose.

In addition, the authors wrote that some patients who have adverse effects with the use of opioids improve after "detoxification." Given the current Drug Enforcement Administration (DEA) scrutiny of pain physicians' prescribing habits, avoiding the term "detoxification" when referring to weaning or tapering pain patients off opioids is advisable.

1. Schneider JP. Opioids, pain management, and addiction. Pain Practitioner. 2006;16:17-24.
2. Scimeca MM, Savage SR, Portenoy R, Lowinson J. Treatment of pain in methadone-maintained patients. Mt Sinai J Med. 2000;67:412-422.
3. Portenoy RK. Using opioids for chronic nonmalignant pain: current thinking. Intern Med. 1996;17(suppl):S25-S31.

JENNIFER P. SCHNEIDER, MD, PhDTucson.

The authors respond:

We are grateful for Dr Schneider's comments.As we define "tolerance" in our article, it is a diminution of one or more of a drug's effects over time and is a common experience of all mammals that take opioids for an extended period. This phenomenon has been well documented and well referenced and cannot be considered "uncommon."^1-4

This is not to mean that there are not some persons who can be maintained on the same dose of opioids for an extended period. However, most patients with pain receiving long-term opioid therapy report that the benefit of their opioid medication in reducing their pain is diminished with time.

Dr Schneider implies that patients experience more pain not because of tolerance but because of increased activity. Although we acknowledge that there can be an interactive effect,we disagree with the notion that increased activity rather than tolerance accounts for most of the increase in self-reported noncancer pain in patients receiving opioid therapy.There is little evidence in the literature to support this belief.

It also should be pointed out that there are individual differences in tolerance to opioids. Some studies suggest that tolerance to opioids may develop in persons who are prone to substance misuse more rapidly than in those at low risk for opioid misuse.⁵ Additional research would help in our understanding of tolerance and why it is that some develop a more rapid tolerance to opioids than others.

Dr Schneider also takes issue with the word "detoxification" in our article. We recognize that the word can be pejorative and may imply the presence of addiction. However, patients with pain often are referred to detoxification centers when they elect to be tapered off their opioids and seek assistance in doing so. In addition, we think that the fear of investigation of prescribing physicians by DEA officials often is unfounded and taking steps to assess risk and to document progress and outcome would avoid reprisals. As a result, we remain less concerned about the use of this term than Dr Schneider.

1. Cohen SP, Christo PJ, Wang S, et al. The effect of opioid dose and treatment duration on the perception of a painful standardized clinical stimulus. Reg Anesth Pain Med. 2008;33:199-206.
2. Chang G, Chen L, Mao J. Opioid tolerance and hyperalgesia. Med Clin North Am. 2007;91:199-221.
3. Mao J. Opioid-induced abnormal pain sensitivity. Curr Pain Headache Rep. 2006;10:67-70.
4. Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J Med. 2003;349:1943-1953.
5. Michna E, Ross EL, Hynes WL, et al. Predicting aberrant drug behavior in patients treated for chronic pain: importance of abuse history. J Pain Symptom Manage. 2004;28:250-258.

EDGAR L. ROSS, MD,
CAROLINE HOLCOMB, and
ROBERT N. JAMISON, PhDPain Management Center, Brigham & Women's Hospital, Boston.