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Opioid Therapy for Chronic Pain
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     To the Editor: Ballantyne and Mao's (Nov. 13 issue)1 recommendations for prescribing doses of short-acting opioids for chronic recurrent pain may put patients at increased risk both for undertreatment of their pain episodes and for drug tolerance. In treating occasional or recurrent pain, patients may be best advised to treat episodes early and aggressively with doses of opioids, or of nonopioids that are large enough to suppress their pain completely and for long intervals. Infrequent use of large doses of opioids is not a model for the development of drug tolerance, whereas the administration of smaller, repeated doses is.2

    The physician's key role is to determine, with the patient, an adequate month's supply of medication and the maximal doses that can be taken per episode. In our experience, when patients are given this control and when sufficient medication is available, monthly prescribed amounts tend to be modest and do not tend to increase. We believe that this is how most physicians and patients effectively use short-acting opioids in managing chronic recurrent pain, and it has been the basis for successful use of opioids in both low-risk and high-risk outpatients.3,4

    John A. Hermos, M.D.

    Veterans Affairs Boston Healthcare System

    Boston, MA 02130

    john.hermos@med.va.gov

    References

    Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J Med 2003;349:1943-1953.

    Camí J, Farré M. Drug addiction. N Engl J Med 2003;349:975-986.

    Portenoy RK, Foley KM. Chronic use of opioid analgesics in non-malignant pain: report of 38 cases. Pain 1986;25:171-186.

    Chabal C, Erjavec MK, Jacobson L, Mariano A, Chaney E. Prescription opiate abuse in chronic pain patients: clinical criteria, incidence, and predictors. Clin J Pain 1997;13:150-155.

    To the Editor: Ballantyne and Mao do not mention that the rate of addiction in the population of patients with chronic pain is no different from that in the general population — from 3.2 to 18.8 percent.1 Most physicians are unaware of this fact and remain very reluctant to prescribe opioids, even in cases of terminal illness. Unfortunately, pain management is not emphasized by the majority of physicians, to the detriment of patients' comfort and quality of life. Continuing education for physicians on this subject will, one hopes, remove the stigma associated with opioid prescribing among physicians who are properly treating patients with chronic pain.

    Milton J. Klein, D.O.

    Sewickley Valley Hospital

    Sewickley, PA 15143

    References

    Fishbain DA, Rosomoff HL, Rosomoff RS. Drug abuse, dependence, and addiction in chronic pain patients. Clin J Pain 1992;8:77-85.

    To the Editor: In response to the article by Ballantyne and Mao: I advocate the use of long-acting opioids rather than short-acting opioids. Chronic pain may last 24 hours a day, but short-acting opioids offer relief only for 3 to 4 hours. Use of long-acting opioids may result in more predictable serum levels, less abuse, less reinforcement of drug-taking behaviors, and improved sleep, as compared with short-acting opioids, and the toxicity of acetaminophen is avoided.1

    Clearly, the clinical response to the use of pain medications is key. Patients must be carefully assessed with regard to analgesic response, improvement in function, side effects, and aberrant drug-taking behaviors.2 Immunosuppression and hormonal changes require further study. Measurement of testosterone levels and replacement therapy should be considered when indicated.3 Chronic pain remains a complex biologic, psychological, social, and spiritual problem. I would therefore also like to point out that opioid therapy is only one of many possible treatments and that an interdisciplinary approach is increasingly recognized as optimal for many patients.4

    Noor Gajraj, M.D.

    University of Texas Southwestern Medical Center

    Dallas, TX 75390-9068

    noor.gajraj@utsouthwestern.edu

    References

    Caldwell JR, Rapoport RJ, Davis JC, et al. Efficacy and safety of a once-daily morphine formulation in chronic, moderate-to-severe osteoarthritis pain: results from a randomized, placebo-controlled, double-blind trial and an open-label extension trial. J Pain Symptom Manage 2002;23:278-291.

    Passik SD, Kirsh KL. The need to identify predictors of aberrant drug-related behavior and addiction in patients being treated with opioids for pain. Pain Med 2003;4:186-189.

    MacIndoe JH. The challenges of testosterone deficiency: uncovering the problem, evaluating the role of therapy. Postgrad Med 2003;114:51-62.

    Flor H, Fydrich T, Turk DC. Efficacy of multidisciplinary pain treatment centers: a meta-analytic review. Pain 1992;49:221-230.

    The authors reply: Conventional wisdom, as outlined by Dr. Gajraj, states that long-acting opioids, as compared with short-acting opioids, may result in less abuse, less reinforcement of drug-seeking behavior, and improved sleep. We certainly support the use of long-acting opioids in patients with constant or near-constant pain and in those in whom opioid-related behavioral problems are likely to arise or are suspected. However, pain may emerge only occasionally, and in this case the opioid selection and dosing regimen can be tailored to the analgesic need, so that unnecessary use of opioids is avoided. Some patients express a definite preference for this type of dosing regimen and decline around-the-clock, long-acting opioids. As-needed dosing regimens (with either short- or long-acting opioids) can work well in some patients, and (in our experience) opioid-related behavioral problems rarely develop in these patients.

    Dr. Hermos gives the impression that the effect of intermittent as compared with continuous dosing on the development of opioid tolerance has been established. In fact, the debate is far from settled, but studies in animals suggest that continuous dosing results in profound tolerance to morphine, which is similar to that resulting from repeated bolus injections.1 There is no claim to be made, therefore, that continuous dosing is preferable to intermittent dosing in terms of limiting the development of tolerance.

    The issue of drug abuse in patients with chronic pain who are treated with opioids is complex and troubling, but it is an aspect of opioid use that we do not explore in our article. Dr. Klein cites incidence data that are derived from anecdotal reports; the true incidence of addiction in patients with chronic pain who are taking opioids is unknown. He points out that fear of addiction may discourage the proper use of opioids even in terminally ill patients who are suffering from pain. This is true, yet one cannot escape the need to balance the risks, including that of addiction, against the benefit of superior pain control, recognizing that opioid therapy should be carefully controlled in some situations, whereas it is appropriate to be more liberal in other situations. In our article, we specifically address the issue of opioid treatment for chronic pain in patients who are not terminally ill, and we recommend a cautious approach in such patients.

    Jane C. Ballantyne, M.D.

    Jianren Mao, M.D., Ph.D.

    Massachusetts General Hospital

    Boston, MA 02114

    jballantyne@partners.org

    References

    Vanderah TW, Gardell LR, Burgess SE, et al. Dynorphin promotes abnormal pain and spinal opioid antinociceptive tolerance. J Neurosci 2000;20:7074-7079.