A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence

N Engl J Med. 2000 Nov 2;343(18):1290-7. doi: 10.1056/NEJM200011023431802.


Background: Opioid dependence is a chronic, relapsing disorder with important public health implications.

Methods: In a 17-week randomized study of 220 patients, we compared levomethadyl acetate (75 to 115 mg), buprenorphine (16 to 32 mg), and high-dose (60 to 100 mg) and low-dose (20 mg) methadone as treatments for opioid dependence. Levomethadyl acetate and buprenorphine were administered three times a week. Methadone was administered daily. Doses were individualized except in the group assigned to low-dose methadone. Patients with poor responses to treatment were switched to methadone.

Results: There were 55 patients in each group; 51 percent completed the trial. The mean (+/-SE) number of days that a patient remained in the study was significantly higher for those receiving levomethadyl acetate (89+/-6), buprenorphine (96+/-4), and high-dose methadone (105+/-4) than for those receiving low-dose methadone (70+/-4, P<0.001). Continued participation was also significantly more frequent among patients receiving high-dose methadone than among those receiving levomethadyl acetate (P=0.02). The percentage of patients with 12 or more consecutive opioid-negative urine specimens was 36 percent in the levomethadyl acetate group, 26 percent in the buprenorphine group, 28 percent in the high-dose methadone group, and 8 percent in the low-dose methadone group (P=0.005). At the time of their last report, patients reported on a scale of 0 to 100 that their drug problem had a mean severity of 35 with levomethadyl acetate, 34 with buprenorphine, 38 with high-dose methadone, and 53 with low-dose methadone (P=0.002).

Conclusions: As compared with low-dose methadone, levomethadyl acetate, buprenorphine, and high-dose methadone substantially reduce the use of illicit opioids.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use*
  • Buprenorphine / adverse effects
  • Buprenorphine / therapeutic use*
  • Cocaine-Related Disorders / complications
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Methadone / administration & dosage
  • Methadone / adverse effects
  • Methadone / therapeutic use*
  • Methadyl Acetate / adverse effects
  • Methadyl Acetate / therapeutic use*
  • Middle Aged
  • Narcotics / urine
  • Opioid-Related Disorders / complications
  • Opioid-Related Disorders / drug therapy*
  • Treatment Outcome


  • Analgesics, Opioid
  • Narcotics
  • Buprenorphine
  • Methadyl Acetate
  • Methadone