MODERATE-VS HIGH-DOSE METHADONE IN THE TREATMENT OF OPIOID
DEPENDENCE

A Randomized Trial

Eric C. Strain, MD
George E. Bigelow, PhD
Ira A. Liebson, MD
Maxine L. Stitzer, PhD

Context: Methadone hydrochloride treatment is the most common
pharmacological intervention for opioid dependence, and recent interest has
focused on expanding methadone treatment availability beyond traditional
specially licensed clinics. However, despite recommendations regarding
effective dosing of methadone, controlled clinical trials of higher-dose
methadone have not been conducted.

Objective: To compare the relative clinical efficacy of moderate-vs
high-dose methadone in the treatment of opioid dependence. Design A 40-week
randomized, double-blind clinical trial starting in June 1992 and ending in
October 1995.

Setting: Outpatient substance abuse treatment research clinic at the Johns
Hopkins University Bayview Campus, Baltimore, Md.

Participants: One hundred ninety-two eligible clinic patients.

Intervention: Daily oral methadone hydrochloride in the dose range of 40 to
50 mg (n3D97) or 80 to 100 mg (n3D95), with concurrent substance abuse
counseling.

Main Outcome: Measures Opioid-positive urinalysis results and retention in
treatment.

Results: By intent-to-treat analysis, through week 30 patients in the
high-dose group had significantly lower rates of opioid-positive urine
samples compared with patients in the moderate-dose group (53.0% [95%
confidence interval {CI}, 46.9%-59.2%] vs 61.9% [95% CI, 55.9%-68.0%];
P3D.047). These differences persisted during withdrawal from methadone.
Through day 210 no significant difference was evident between dose groups in
treatment retention (high-dose group mean retention, 159 days; moderate-dose
group mean retention, 157 days). Nineteen (33%) of 57 patients in the
high-dose group and 11 (20%) of 54 patients in the moderate-dose group
completed detoxification.

Conclusions: Both moderate- and high-dose methadone treatment resulted in
decreased illicit opioid use during methadone maintenance and
detoxification. The high-dose group had significantly greater decreases in
illicit opiod use.

JAMA. 1999;281:1000-1005