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Optimal Daily Methadone Dosage to Treat Opioid Dependence
Am Fam Physician. 1999 Sep ;60(3):989-990.
While studies suggest that a low dosage (20 to 35 mg per day) of methadone is less effective than a moderate dosage (50 to 80 mg per day), little data exist on the efficacy of a high dosage (greater than 80 mg per day). Strain and colleagues compared the effectiveness of moderate- and high-dose methadone in patients who sought treatment for opioid dependence.
The study enrolled 192 adults who entered a 40-week methadone treatment program for opioid dependence. Patients reported using illicit opioids an average of 24 times per week. Patients were excluded if they had any chronic medical conditions or major mental illness. Pregnant women were also excluded.
Patients were randomly assigned to receive methadone in a moderate or a high dose. During the first week of treatment, methadone was initiated in a dosage of 30 mg per day in both the moderate- and high-dose groups. The dosage was increased during the next five weeks, with patients in the moderate-dose group receiving increases of 2 mg per week and those in the high-dose group receiving increases of 10 mg per week. By the sixth week, the dosage was 40 mg per day in the moderate-dose group and 80 mg per day in the high-dose group.
During the next 22 weeks, increases in the methadone dosages were allowed; patients in the moderate-dose group could have an increase of 5 mg twice, for a maximum daily dosage of 50 mg, and patients in the high-dose group could have an increase of 10 mg twice, for a maximum daily dosage of 100 mg. During the final 10 weeks of the study, the methadone dosage was decreased at a rate of 10 percent per week. The goal was that at the end of the 40-week study period all patients would be detoxified. The main outcome measures were self-reported opioid use, the results of urine toxicology testing and the patient's continued presence in treatment.
In the moderate-dose group, self-reported opioid use decreased from the average of 24 times per week before treatment to two or three times per week. In the high-dose group, self-reported opioid use decreased to no more than one time per week. In concert with the self-reported findings, 53.0 percent of the urine samples in the high-dose group were positive for opioids, compared with 69.9 percent of the urine samples in the moderate-dose group. Both groups had similar rates of retention in the study (159 days in the high-dose group and 157 days in the moderate-dose group). The average daily dosage of methadone was 45.8 mg in the moderate-dose group and 89.5 mg in the high-dose group.
The authors conclude that high-dose methadone leads to a significantly greater decline in opioid use. The decrease in opioid use in both groups was clinically significant, however. The authors note that daily dosages of more than 100 mg may be required for optimal benefit in some patients, but current federal regulations discourage such a high dosage.
Strain EC, et al. Moderate- vs high-dose methadone in the treatment of opioid dependence. A randomized trial. JAMA. March 17, 1999;281:1000–5.
Copyright © 1999 by the American Academy of Family Physicians.
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