Naltrexone and combined behavioral intervention effects on trajectories of drinking in the COMBINE study

Gueorguieva, Ralitza; Wu, Ran; Donovan, Dennis; Rounsaville, Bruce J.; Couper, David; Krystal, John H.; O’Malley, Stephanie S.

doi:10.1016/j.drugalcdep.2009.10.017

« Previous Next »Drug and Alcohol Dependence
Volume 107, Issue 2 , Pages 221-229, 1 March 2010

Naltrexone and combined behavioral intervention effects on trajectories of drinking in the COMBINE study

Ralitza Gueorguieva
- Yale University School of Public Health and School of Medicine, New Haven, CT 06520, USA
- Corresponding author at: 60 College St., Room 215B, New Haven, CT 06520-8034, USA. Tel.: +1 203 974 7529; fax: +1 203 974 7662.
Ran Wu
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA
Dennis Donovan
- Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Washington, Seattle, WA 98105, USA
Bruce J. Rounsaville
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA
David Couper
- Department of Biostatistics, The University of North Carolina at Chapel Hill, NC 27514, USA
John H. Krystal
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA
- VA Connecticut Healthcare System, West Haven, CT 06516, USA
Stephanie S. O’Malley
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA

Received 14 August 2009; received in revised form 28 October 2009; accepted 28 October 2009.

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.

Conclusion

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.

Keywords: Alcohol research, Naltrexone, Acamprosate, Combined behavioral intervention, Clinical trial, Trajectory-based analysis