What happens when people discontinue taking medications? Lessons from COMBINE

Aims: We use intensive longitudinal data methods to illuminate processes affecting patients' drinking in relation to the discontinuation of medications within an alcohol treatment study. Although previous work has focused on broad measures of medication adherence, we focus on dynamic changes in drinking both before and after patients discontinue. Design: We conducted secondary data analyses using the COMBINE (Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence) study, focused on participants who discontinued medications prior to the planned end of treatment. Using an interrupted time-series analysis, we analysed drinking in the weeks before and after discontinuation and also studied outcomes at the end of the COMBINE follow-up. Setting: Unites States of America. Participants: We describe the subsample of COMBINE participants who discontinued medications (n=450), and compare them with those who were medication-adherent (n=559) and with those who discontinued but had substantial missing data (n=217). Measurements: The primary outcomes were percentage of days abstinent (PDA) and percentage of heavy drinking days (PHDD). Medication adherence data were used to approximate the date of discontinuation. Findings: For many patients, an increase in drinking began weeks before discontinuation (PDA: F_(1,4803)=19.07, P<0.001; PHDD: F_(1,4804)=8.58, P=0.003) then escalated at discontinuation (PDA: F_(1,446)=5.05, P=0.025; PHDD: F_(1,446)=4.52, P=0.034). Among other effects, the amount of change was moderated by the reason for discontinuation (e.g. adverse event; PDA: F_(2,4803)=3.85, P=0.021; PHDD: F_(2,4804)=5.36, P=0.005) and also whether it occurred in the first or second half of treatment (PDA: F_(1,4803)=5.23, P=0.022; PHDD: F_(1,4804)=8.79, P=0.003). Conclusions: A patient's decision to stop taking medications during alcohol treatment appears to take place during a weeks-long process of disengagement from treatment. Patients who discontinue medications early in treatment or without medical consultation appear to drink more frequently and more heavily.