Dose-response effects of methadone in the treatment of opioid dependence

Ann Intern Med. 1993 Jul 1;119(1):23-7. doi: 10.7326/0003-4819-119-1-199307010-00004.


Objective: To compare the dose effectiveness of low to moderate doses of methadone in a sample of a contemporary population of opioid abusers, because the optimal dosing of methadone in the treatment of opioid dependence remains an issue.

Design: A randomized, double-blind, placebo-controlled study.

Setting: A methadone treatment research clinic.

Patients: Participants (n = 247) were opioid-dependent patients with a high rate of cocaine use.

Intervention: All participants were initially treated with active methadone for a minimum of 5 weeks and then received 15 weeks of stable dosing at 50, 20, or 0 mg per day. Individual counseling and group therapy were included.

Measurements: Treatment retention and illicit drug use as determined by intensive urine monitoring.

Results: Retention was better for patients who remained on active medication. By treatment week 20, retention was 52.4% for the 50-mg, 41.5% for the 20-mg, and 21.0% for the 0-mg group (50 versus 0 and 20 versus 0, P < 0.05; 50 versus 20, P > 0.05). Only the 50-mg treatment group had a reduced rate of opioid-positive urine samples (56.4% versus 67.6% and 73.6% for the 20-mg and 0-mg groups, respectively; P < 0.05) and cocaine-positive urine samples (52.6% versus 62.4% and 67.1% for the 20- and 0-mg groups, respectively; P < 0.05).

Conclusions: There is a dose-response effect for methadone treatment. Doses as low as 20 mg may improve retention but are inadequate for suppressing illicit drug use.

Publication types

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

MeSH terms

  • Adult
  • Cocaine / urine
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Methadone / administration & dosage*
  • Narcotics / urine
  • Opioid-Related Disorders / complications
  • Opioid-Related Disorders / rehabilitation*
  • Opioid-Related Disorders / urine
  • Patient Compliance
  • Patient Dropouts
  • Substance-Related Disorders / complications
  • Survival Analysis


  • Narcotics
  • Cocaine
  • Methadone