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 (n = 97) or 80 to 100 mg (n = 95), 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%]; P = .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 opioid use.