Correspondence
Treating Opioid Dependence
N Engl J Med 2001; 344:530-531February 15, 2001
- Article
To the Editor:
The article by Johnson et al. on the treatment of opioid dependence (Nov. 2 issue)1 and the accompanying editorial by O'Connor2 serve an important purpose in making physicians and, one hopes, the public more aware of the effectiveness of methadone maintenance for heroin dependence. It is discouraging, however, that the ineffectiveness of low-dose methadone therapy still has to be demonstrated. The effectiveness of methadone, at an average dose of 100 mg per day, was shown by Dole et al.3 more than 30 years ago and has been repeatedly confirmed since then, with some patients needing a dose higher than 100 mg per day.4 If the high-dose group in the study by Johnson et al. had actually received a high dose of methadone (i.e., higher than 100 mg per day), its effectiveness might have been even more impressive. The low-dose group received a daily dose of 20 mg of methadone, which would not even be an analgesic dose if used for chronic pain. Unfortunately, most programs are using inadequate doses of methadone with, not surprisingly, poor results.
Buprenorphine has been shown to be effective as maintenance therapy for heroin dependence; however, the authors do not mention its high potential for abuse. It is one of the most frequently abused drugs in Australia and Scotland.5 It would have been helpful if Johnson et al. and O'Connor had mentioned the risk of addiction with buprenorphine as well as its effectiveness as maintenance therapy.
5 ReferencesBarry Stimmel, M.D.
Mount Sinai School of Medicine, New York, NY 10029-65741
Johnson RE ,Chutuape MA ,Strain EC ,Walsh SL ,Stitzer ML ,Bigelow GE . A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. N Engl J Med 2000;343:1290-1297
Full Text | Web of Science | Medline2
O'Connor PG . Treating opioid dependence -- new data and new opportunities. N Engl J Med 2000;343:1332-1334
Full Text | Web of Science | Medline3
Dole VP ,Nyswander ME ,Kreek MJ . Narcotic blockade. Am J Intern Med 1966;188:304-309
CrossRef | Web of Science4
Barnett PG ,Hui SS . The cost-effectiveness of methadone maintenance. Mt Sinai J Med 2000;67:365-374
Web of Science | Medline5
Lavelle TL ,Hammersley R ,Forsyth A ,Bain D . The use of buprenorphine and temazepam by drug injectors. J Addict Dis 1991;10:5-14
CrossRef | Medline
To the Editor:
A maintenance dose of 20 mg of methadone per day is homeopathic. A dose of 60 to 100 mg per day is not high; it is a standard dose. Daily doses above 110 mg are high. The state of California permits a dose of up to 180 mg per day.
A policy of allowing private physicians to prescribe methadone to addicts has both positive and negative aspects. It assists addicts who live in states that do not have methadone treatment programs, and it is appealing because of the dosing schedule and privacy. But how many private physicians want patients with opioid dependence in their waiting rooms or want to assume the responsibility for their primary care?
As methadone maintenance has evolved, we now realize that opioid dependence is a complex problem and needs more attention. It is not enough to give an addict methadone every day. There are other, large problems associated with opioid dependence. Most heroin addicts did not graduate from high school, are functionally illiterate, do not have job skills, and have serious emotional problems, and at least a third of them abuse alcohol. (This last fact is not mentioned in the article or editorial, nor is the fact that most heroin addicts are positive for hepatitis C virus.) Few medical offices are equipped to address these problems. Addicts need help in learning the coping skills required for living in the community. In the past decade, treatment centers began seeing the addict as a whole person, not just a needle user. The problems associated with opioid dependence are addressed in many of the large clinics, with even dietary counseling provided.
Thomas V. Reese, Sr., M.D.
3120 Nahenahe Pl., Kihei, HI 96753Author/Editor Response
The authors reply:
To the Editor: Both Stimmel and Reese object to the term “high dose” for a dose of 60 to 100 mg of methadone per day. We used the term in its relative, not absolute, sense, and we agree that for some patients, even higher doses may be necessary and appropriate.
Both Stimmel and Reese also criticize our use of a lower-dose control treatment. However, inclusion of this treatment was critical for documenting the effectiveness of the other study treatments, and our rescue procedure made it ethically acceptable. We agree that higher doses should be considered, and our findings support their use. It is our hope that well-controlled clinical trials1,2 will help accomplish what 35 years of uncontrolled clinical experience has not.
Stimmel and Reese err in suggesting that a 20-mg dose of methadone is ineffective or homeopathic. In the group of patients who received this dose, there was a large reported reduction in heroin use, and in an earlier study, patients who received this dose reported substantial improvements in both symptoms and drug use.3 The effectiveness of low methadone doses in suppressing opioid withdrawal probably contributes to the frequent failure of physicians to increase doses to a level that optimally reduces heroin use.
Stimmel suggests that buprenorphine may have a high potential for abuse. It does have a potential for abuse, but it is probably less than that of methadone or heroin. Buprenorphine has typically been abused in circumstances of limited regulation, limited availability of other opioids, or both. Once it has been approved by the Food and Drug Administration (FDA), the primary formulation for the treatment of heroin dependence will be a combination product containing the antagonist naloxone, which dramatically reduces the potential for abuse through injection by opioid-dependent persons.4
Reese notes that many heroin-dependent patients have serious behavioral and medical problems. We certainly concur. Increasing the array of treatment options should result in a larger proportion of patients who receive some form of treatment and should enhance opportunities to address these problems.
4 ReferencesRolley E. Johnson, Pharm.D.
Eric C. Strain, M.D.
George E. Bigelow, Ph.D.
Johns Hopkins University School of Medicine, Baltimore, MD 212241
Strain EC ,Bigelow GE ,Liebson IA ,Stitzer ML . Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial. JAMA 1999;281:1000-1005
CrossRef | Web of Science | Medline2
Eissenberg T ,Bigelow GE ,Strain EC , et al. Dose-related efficacy of levomethadyl acetate for treatment of opioid dependence: a randomized clinical trial. JAMA 1997;277:1945-1951
CrossRef | Web of Science | Medline3
Strain EC ,Stitzer ML ,Liebson IA ,Bigelow GE . Methadone dose and treatment outcome. Drug Alcohol Depend 1993;33:105-117
CrossRef | Web of Science | Medline4
Mendelson J ,Jones RT ,Welm S , et al. Buprenorphine and naloxone combinations: the effects of three dose ratios in morphine-stabilized, opiate-dependent volunteers. Psychopharmacology (Berl) 1999;141:37-46
CrossRef | Web of Science | Medline
Author/Editor Response
The editorialist replies:
To the Editor: As Stimmel and Reese point out, the dose of methadone is clearly related to its effectiveness in treating opioid dependence.1 For example, one study found that a “high” dose, in the range of 80 to 100 mg per day, was superior to a “moderate” dose, in the range of 40 to 50 mg per day, in reducing illicit opioid use.2 Even higher doses (more than 100 mg per day) may be necessary for some patients.
Like other opioids, buprenorphine has a potential for abuse, although as a partial opioid agonist, buprenorphine may have less potential for abuse than pure opioid agonists such as methadone. A preparation that is likely to be approved in the United States is a combination of buprenorphine and naloxone, which may further decrease (but not eliminate) the potential for abuse, especially among opioid-dependent injection-drug users.3
Office-based maintenance therapy for opioid dependence has the potential to provide greatly increased access to treatment. Although I agree with Reese that this approach may be especially useful in areas that do not have maintenance programs, it will also be useful in areas where programs exist but access to them is limited because of an insufficient number of treatment slots or other barriers. Studies of office-based methadone maintenance in Connecticut and elsewhere suggest that finding private physicians who are willing and able to provide such treatment and primary care for stabilized patients may not be difficult. I agree that the simple act of dispensing a medication is generally not sufficient and that counseling and other services are critical elements of treatment for opioid dependence and other medical disorders. However, studies of office-based methadone maintenance suggest that selected patients can do well in the office setting.1,4 Nonetheless, it is unlikely that office-based methadone maintenance will be broadly available in the near future.
In 2000, President Bill Clinton signed legislation (Public Law 106-310) that authorizes appropriately trained physicians to prescribe Schedule III, IV, and V controlled substances that have been approved for the treatment of opioid dependence. Although as of this writing the FDA has yet to approve such medications, it is likely that buprenorphine will eventually be approved for this purpose.5 Critical issues remain to be addressed. These include the training of physicians, the selection of patients, the appropriate level of counseling, the effectiveness and safety of office-based treatment, satisfaction on the part of patients and physicians, and links with substance-abuse programs.
5 ReferencesPatrick G. O'Connor, M.D., M.P.H.
Yale University School of Medicine, New Haven, CT 06520-80251
O'Connor PG ,Fiellin DA . Pharmacologic treatment of heroin-dependent patients. Ann Intern Med 2000;133:40-54
Web of Science | Medline2
Strain EC ,Bigelow GE ,Liebson IA ,Stitzer ML . Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial. JAMA 1999;281:1000-1005
CrossRef | Web of Science | Medline3
Robinson GM ,Dukes PD ,Robinson BJ ,Cooke RR ,Mahoney GN . The misuse of buprenorphine and a buprenorphine-naloxone combination in Wellington, New Zealand. Drug Alcohol Depend 1993;33:81-86
CrossRef | Web of Science | Medline4
Novick DM ,Joseph H ,Salsitz EA , et al. Outcomes of treatment of socially rehabilitated methadone maintenance patients in physicians' offices (medical maintenance): follow-up at three and a half to nine and a fourth years. J Gen Intern Med 1994;9:127-130
CrossRef | Web of Science | Medline5
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- Citing Articles (1)
Citing Articles
1
Christoph Ostgathe, Jan Gaertner, Friedemann Nauck, Raymond Voltz. (2008) High Dose Levo-Methadone Treatment for Cancer Pain in a Patient with a History of Drug Addiction. Journal of Pain and Symptom Management 35:3, 229-231
CrossRef
