Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial. Efficacy of methadone versus methadone and guanfacine in the detoxification of heroin-addicted patients. Controlled trial of prescribed heroin in the treatment of opioid addiction.
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.
                To compare the relative clinical efficacy of moderate- vs high-dose methadone in the treatment of opioid dependence.
                A 40-week randomized, double-blind clinical trial starting in June 1992 and ending in October 1995.
                Outpatient substance abuse treatment research clinic at the Johns Hopkins University Bayview Campus, Baltimore, Md.
                One hundred ninety-two eligible clinic patients.
                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.
                Opioid-positive urinalysis results and retention in treatment.
                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.
                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. In a randomized double-blind study, the clinical efficacy of methadone vs. methadone and guanfacine was assessed in terms of evolution of opioid withdrawal symptoms during inpatient detoxification. A total of 144 patients were included and randomly allocated to three different treatment groups: methadone alone, and two combined treatment schedules (methadone plus 3 or 4 mg of guanfacine). No differences were observed among the three groups with regard to retention rate throughout the study period. Both therapies, methadone and methadone plus guanfacine, determined a slight increase in withdrawal scores when methadone was discontinued. However, guanfacine was unable to effectively control methadone-associated withdrawal symptoms. These results indicate that guanfacine does not effectively reduce the opioid withdrawal symptoms. This study aimed to assess the efficacy of the prescription of intravenous diacetylmorphine (DAM) versus oral methadone with medical and psychosocial support, with a view of improving physical and mental health as well as social integration among socially excluded, opioid-dependent individuals for whom standard treatments have failed.
                This study used an open, randomized controlled trial.
                This study took place in Granada, Spain.
                Sixty-two opioid-dependent participants were randomized, 31 in each treatment group, and 50 of them were analyzed. The participants were recruited directly from the streets, through peer outreach, in well-known meeting places for drug-addicted individuals.
                Participants in the experimental group received injected DAM, twice a day, plus oral methadone, once a day, for 9 months. The control group received only oral methadone, once a day. The two groups received an equivalent opioid dosage. The average DAM dosage was 274.5 mg/day (range: 15-600 mg), and an average methadone dosage was 42.6 mg/day (range: 18-124 mg). The daily methadone dosage in the control group was 105 mg/day (range: 40-180 mg). Comprehensive clinical, psychological, social, and legal support was given to both groups.
                The following were measured in this study: general health, quality of life, drug-addiction-related problems, nonmedical use of heroin, risk behavior for HIV and HCV, and psychological, family, and social status.
                Both groups improved with respect to the total domain assessed. Those in the experimental group showed greater improvement in terms of physical health (the improvement was 2.5 times higher; p = .034) and risk behavior for HIV infection (the improvement was 1.6 times higher; p = .012). In addition, this group decreased its street heroin use from 25 days/month to 8 days/month as seen on the Addiction Severity Index (p = .020), as well as the number of days free from drug-related problems (the improvement was 2.1 times higher; p = .004) or involvement in crime (from 11 days/month to <1 day/month; p = .096 between groups).
                These findings support the hypothesis that, under the same conditions, DAM could be safely delivered, in our context. Also, in physical health, HIV risk behavior, street heroin use, and days involved in crime, DAM plus methadone was more efficacious than methadone alone. This implies that this treatment could provide an effective alternative for the treatment of socially excluded, opioid-dependent patients with severe physical and mental health problems because of drug addiction, when all available previous treatments have failed.
The three studies provide very limited evidence of the efficacy of methadone for CNCP, and there were too few data for pooled analysis of efficacy or harm, or to have confidence in the results of the individual studies. No conclusions can be made regarding differences in efficacy or safety between methadone and placebo, other opioids, or other treatments.