Methadone has been used effectively for more than 30 years as a
treatment for heroin addiction. The medication blocks heroin's narcotic
effects without creating a drug "high," eliminates withdrawal symptoms,
and relieves the craving associated with addiction. Methadone is
administered orally in licensed clinics and its effects typically last 24
to 36 hours.
Although methadone has been used for decades, no clinical consensus has
been reached about the most effective daily dose. Many clinics do not
adjust dosages according to the needs of individual patients. Instead,
they administer fixed doses. One clinic might use doses of 25 milligrams
(mg) per day for all patients; others may administer daily doses of 60 mg.
"Federal regulations require that a clinic receive a special exemption in
order to provide patients with doses greater than 100 mg per day, but no
contemporary studies have examined the effectiveness of daily doses
greater than 80 mg," says Dr. Eric Strain, a NIDA-supported researcher at
The Johns Hopkins University Medical Center in Baltimore.
Following a 1-week orientation period, patients receiving
high-dose (80-100 mg) methadone treatment had less self-reported
heroin use and lower rates of drug-positive urine samples than
patients on moderate-dose (40-50 mg) treatment. Urine results are
shown as 3-week averages of twice-weekly
Dr. Strain and his colleagues investigated the effectiveness of
high-dose -80 to 100 mg per day-methadone treatment and found this dosage
to be more effective in reducing heroin use than treatment with a moderate
dose of 40 to 50 mg per day. The study involved 192 patients. Sixty-five
percent of participants were male; pregnant women were excluded from the
During the first week of treatment all patients received 30-mg daily
methadone doses. Daily doses were increased until, by the 8th week, half
the patients were receiving a moderate dose of 40 to 50 mg per day and the
other half were receiving a high dose of 80-to-100 mg per day. These doses
were maintained through the study's 30th week. Dosages were then decreased
by 10 percent each week during the final 10 weeks of the program. Patients
were encouraged to enroll in long-term community-based treatment programs
following completion of the 40-week study.
Dr. Strain and his colleagues evaluated the effectiveness of treatment
through analysis of twice-weekly observed urine testing, weekly patient
reports of heroin use, and the length of time patients remained in
treatment. "The high-dose group used opiates significantly less during
treatment than did the moderate-dose group on average," Dr. Strain says.
"Patients in the high-dose group reported using opiates no more than once
a week. The moderate-dose group reported using drugs two to three times
per week on average." Among patients who completed the 30-week active
phase, 33 percent of high-dose patients remained in treatment throughout a
10-week methadone phase-out, compared with 20 percent of moderate-dose
patients. There were no gender-related differences in outcome for high- or
moderate-dose groups, and no difference was reported between the high- and
moderate-dose patients for side effects such as grogginess or
In an earlier study, the researchers found that moderate-dose treatment
of 50 mg per day was more effective than low-dose treatment of 20 mg per
day. "The current study provides strong evidence that we can achieve much
better outcomes at dose rates much higher than 50 mg per day," Dr. Strain
Dosages exceeding the currently regulated ceiling of 100 mg per day may
provide the best result for some patients, Dr. Strain says, but he notes
that clinical trials would be needed to support changing this regulation.
"The most important aspect of our research from a therapeutic and public
health perspective is that methadone treatment over a broad range of doses
results in significant clinical improvement for opioid-addicted patients,"
Strain, E.C.; Bigelow, G.E.; Liebson, I.A.; and Stitzer, M.L. Moderate-
vs high-dose methadone in the treatment of opioid dependence: A randomized
trial. Journal of the American Medical Association
Strain, E.C.; Stitzer, M.L.; Liebson, I.A.; and Bigelow, G.E.
Dose-response effects of methadone in the treatment of opioid dependence.
Annals of Internal Medicine 119:23-27,