title: Naltrexone and combined behavioral intervention effects on trajectories of drinking in the COMBINE study.
abstract: OBJECTIVE
  COMBINE is the largest study of pharmacotherapy for alcoholism in the United States to date, designed to answer questions about the benefits of combining behavioral and pharmacological interventions. Trajectory-based analyses of daily drinking data allowed identification of distinct drinking trajectories in smaller studies and demonstrated significant naltrexone effects even when primary analyses on summary drinking measures were unsuccessful. The objective of this study was to replicate and refine trajectory estimation and to assess effects of naltrexone, acamprosate and therapy on the probabilities of following particular trajectories in COMBINE. It was hypothesized that different treatments may affect different trajectories of drinking.
  
  
  METHODS
  We conducted exploratory analyses of daily indicators of any drinking and heavy drinking using a trajectory-based approach and assessed trajectory membership probabilities and odds ratios for treatment effects.
  
  
  RESULTS
  We replicated the trajectories ("abstainer", "sporadic drinker", "consistent drinker") established previously in smaller studies. However, greater numbers of trajectories better described the heterogeneity of drinking over time. Naltrexone reduced the chance to follow a "nearly daily" trajectory and Combined Behavioral Intervention (CBI) reduced the chance to be in an "increasing to nearly daily" trajectory of any drinking. The combination of naltrexone and CBI increased the probability of membership in a trajectory in which the frequency of any drinking declined over time. Trajectory membership was associated with different patterns of treatment compliance.
  
  
  CONCLUSIONS
  The trajectory-analyses identified specific patterns of drinking that were differentially influenced by each treatment and provided support for hypotheses about the mechanisms by which these treatments work.
authors.affiliation: Yale University School of Public Health and School of Medicine, New Haven, CT 06520, USA. ralitza.gueorguieva@yale.edu
authors.forename: Ralitza
authors.initials: R
authors.lastname: Gueorguieva
authors.forename: Ran
authors.initials: R
authors.lastname: Wu
authors.forename: Dennis
authors.initials: D
authors.lastname: Donovan
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Rounsaville
authors.forename: David
authors.initials: D
authors.lastname: Couper
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: O'Malley
mesh_terms: D000077443:Acamprosate; D000328:Adult; D000427:Alcohol Deterrents / Q000627:therapeutic use; D000428:Alcohol Drinking / Q000523:psychology* / Q000628:therapy*; D001521:Behavior Therapy / Q000379:methods / Q000706:statistics & numerical data; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D013654:Taurine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome; D014481:United States
chemical_list: D000427:Alcohol Deterrents; D009292:Narcotic Antagonists; D013654:Taurine; D009271:Naltrexone; D000077443:Acamprosate