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.

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.

Figure 1

Three trajectories of any drinking. Solid lines with symbols represent sample-based probabilities of drinking based on all subjects weighted by the posterior probability of trajectory membership. Solid lines without symbols represent model-based probabilities of drinking over time for each trajectory group.

Figure 2

Three trajectories of heavy drinking. Solid lines with symbols represent sample-based probabilities of drinking based on all subjects weighted by the posterior probability of trajectory membership. Solid lines without symbols represent model-based probabilities of drinking over time for each trajectory group.

Figure 3

Probabilities of trajectory membership in any drinking model with three trajectories.

Figure 4

Probabilities of trajectory membership in heavy drinking model with three trajectories.

Figure 5

Six trajectories of any drinking. Note: Solid lines with symbols represent sample-based probabilities of drinking based on all subjects weighted by the posterior probability of trajectory membership. Solid lines without symbols represent model-based probabilities of drinking over time for each trajectory group.

Figure 6

Probabilities of trajectory membership in any drinking model with six trajectories.