title: A randomized investigation of methadone doses at or over 100 mg/day, combined with contingency management.
abstract: BACKGROUND
  Methadone maintenance for heroin dependence reduces illicit drug use, crime, HIV risk, and death. Typical dosages have increased over the past few years, based on strong experimental and clinical evidence that dosages under 60 mg/day are inadequate and that dosages closer to 100mg/day produce better outcomes. However, there is little experimental evidence for the benefits of exceeding 100 mg/day, or for individualizing methadone dosages. We sought to provide such evidence.
  
  
  METHODS
  We combined individualized methadone dosages over 100 mg/day with voucher-based cocaine-targeted contingency management (CM) in 58 heroin- and cocaine-dependent outpatients. Participants were randomly assigned to receive a fixed dose increase from 70 mg/day to 100mg/day, or to be eligible for further dose increases (up to 190 mg/day, based on withdrawal symptoms, craving, and continued heroin use). All dosing was double-blind. The main outcome measure was simultaneous abstinence from heroin and cocaine.
  
  
  RESULTS
  We stopped the study early due to slow accrual. Cocaine-targeted CM worked as expected to reduce cocaine use. Polydrug use (effect-size h=.30) and heroin craving (effect-size d=.87) were significantly greater in the flexible/high-dose condition than in the fixed-dose condition, with no trend toward lower heroin use in the flexible/high-dose participants.
  
  
  CONCLUSIONS
  Under double-blind conditions, dosages of methadone over 100mg/day, even when prescribed based on specific signs and symptoms, were not better than 100mg/day. This counterintuitive finding requires replication, but supports the need for additional controlled studies of high-dose methadone.
authors.affiliation: Treatment Section, Clinical Pharmacology & Therapeutics Branch, Intramural Research Branch of the National Institute on Drug Abuse, 251 Bayview Blvd., Suite 200, Baltimore, MD 21224, United States.
authors.forename: Ashley P
authors.initials: AP
authors.lastname: Kennedy
authors.forename: Karran A
authors.initials: KA
authors.lastname: Phillips
authors.forename: David H
authors.initials: DH
authors.lastname: Epstein
authors.forename: David A
authors.initials: DA
authors.lastname: Reamer
authors.forename: John
authors.initials: J
authors.lastname: Schmittner
authors.forename: Kenzie L
authors.initials: KL
authors.lastname: Preston
mesh_terms: D000328:Adult; D019970:Cocaine-Related Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000652:urine*; D019468:Disease Management; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006556:Heroin Dependence / Q000175:diagnosis / Q000188:drug therapy* / Q000652:urine*; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage*; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D008691:Methadone