Baseline trajectories of drinking moderate acamprosate and naltrexone effects in the COMBINE study

The COMBINE study evaluated the effects of acamprosate, naltrexone, and the Combined Behavioral Intervention (CBI). In secondary analyses, our goals were to identify trajectories of any drinking prior to randomization, to characterize subjects in these trajectories, and to assess whether prerandomization trajectories predict drinking outcomes and moderate treatment response.

We analyzed daily indicators of any drinking in 90 days prior to randomization using a trajectory-based approach. General linear models and generalized logistic regression assessed main and interactive effects of prerandomization drinking trajectories and treatment on summary drinking measures during active treatment.

We identified five trajectories of any drinking prior to randomization: "T1: frequent drinkers", "T2: very frequent drinkers", "T3: nearly daily drinkers", "T4: consistent daily drinkers", and "T5: daily drinkers stopping early". During treatment, "T3: nearly daily drinkers" and "T4: consistent daily drinkers" had significantly worse drinking outcomes than "T1: frequent drinkers", while "T5: daily drinkers stopping early" had comparable drinking outcomes to "T1: frequent drinkers". Acamprosate significantly increased the chance of abstinence from heavy drinking for the "T2: very frequent drinking" trajectory but decreased the chance of abstinence from heavy drinking for "T5: daily drinkers stopping early". Naltrexone differentially improved rates of continuous abstinence for very frequent drinkers.

Acamprosate benefited very frequent drinkers and contrary to expectations was associated with poorer response compared to placebo for consistent daily drinkers who had longer durations of pretreatment abstinence (e.g., ≥14 days). Baseline drinking trajectories also moderated naltrexone effects. These findings may help clinicians identify patients for whom acamprosate and naltrexone may be most beneficial.