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Dose-Response Effects of Methadone in the Treatment of Opioid Dependence

Eric C. Strain, MD; Maxine L. Stitzer, PhD; Ira A. Liebson, MD; and George E. Bigelow, PhD
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From Johns Hopkins University School of Medicine, Baltimore, Maryland. Requests for Reprints: Eric C. Strain, MD, The Department of Psychiatry, Johns Hopkins University School of Medicine, Francis Scott Key Medical Center, 4940 Eastern Avenue, Baltimore, MD 21224. Acknowledgments: The authors thank the clinic and research staff for their assistance in the execution of this study. Grant Support: By USPHS grant R01-DA05792.

Copyright 2004 by the American College of Physicians

Ann Intern Med. 1993;119(1):23-27. doi:10.7326/0003-4819-119-1-199307010-00004
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Objective: To compare the dose effectiveness of low to moderate doses of methadone in a sample of a contemporary population of opioid abusers, because the optimal dosing of methadone in the treatment of opioid dependence remains an issue.

Design: A randomized, double-blind, placebo-controlled study.

Setting: A methadone treatment research clinic.

Patients: Participants (n = 247) were opioid-dependent patients with a high rate of cocaine use.

Intervention: All participants were initially treated with active methadone for a minimum of 5 weeks and then received 15 weeks of stable dosing at 50, 20, or 0 mg per day. Individual counseling and group therapy were included.

Measurements: Treatment retention and illicit drug use as determined by intensive urine monitoring.

Results: Retention was better for patients who remained on active medication. By treatment week 20, retention was 52.4% for the 50-mg, 41.5% for the 20-mg, and 21.0% for the 0-mg group (50 versus 0 and 20 versus 0, P < 0.05; 50 versus 20, P > 0.05). Only the 50-mg treatment group had a reduced rate of opioid-positive urine samples (56.4% versus 67.6% and 73.6% for the 20-mg and 0-mg groups, respectively; P < 0.05) and cocaine-positive urine samples (52.6% versus 62.4% and 67.1% for the 20- and 0-mg groups, respectively; P < 0.05).

Conclusions: There is a dose-response effect for methadone treatment. Doses as low as 20 mg may improve retention but are inadequate for suppressing illicit drug use.


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Figure 1.
Dosing schedule.

Patients were randomly assigned to a fixed dose schedule at admission. All patients received 25 mg of methadone the first week, and dose changes were implemented from weeks 2 through 5. Patients were stabilized on 50, 20, or 0 mg of methadone by week 6 of treatment.

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Figure 2.
Retention in treatment.n

The percentage of patients who remained in treatment at each week while on one of three methadone dosing regimens ( = 247). Symbols have been displaced horizontally to improve clarity.

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