Relationship Between Medication Adherence and Treatment Outcomes: The COMBINE Study

BACKGROUND: Within the alcoholism field, there is mounting evidence supporting an important relationship between medication adherence and drinking outcomes. Little is known however, about the complex relationships between medication and treatment variables and drinking outcomes. The present paper reports on the differential impact of medication adherence and treatment factors on drinking outcomes. Data derived from the COMBINE Study was used to investigate the interrelationships between medication adherence, combination treatments and drinking outcomes. METHODS: Twelve hundred and twenty-six patients were randomized to 1 of 8 different combination treatments involving 2 medications--naltrexone and acamprosate and placebo, and 2 behavioral treatments--medical management (MM) and combined behavioral intervention (CBI). Two primary drinking outcomes were percent days abstinent (PDA) and time to first heavy drinking day. Medication adherence was defined as a proportion that reflects the number of pills taken by the maximum number of pills expected to be taken over the course of the trial. A generalized linear mixed model was used to estimate the effects of adherence on PDA while proportional hazards model was used to examine similar co-variate effects on time to first heavy drinking day. RESULTS: Concerning time to first heavy drinking day, a significant three-way interaction was found between medication adherence, CBI and naltrexone (p = 0.0160). Within the MM only plus placebo group (no CBI), significant differences were found in "recovery" (i.e., no heavy drinking days) rates between adherers and nonadherers (40% vs. 10%, p < 0.0001). Such differences became nonsignificant (p = 0.12) when CBI was introduced into the relationship. CBI did not add any such advantage to naltrexone-treated patients. CONCLUSIONS: CBI might serve a protective function for nonadherers in the placebo group; the median relapse time was reduced when these nonadherers were exposed to the alcohol specialty intervention. CBI offered little additional benefit to nonadherers in the naltrexone group. Among nonadherers in the naltrexone group, relapse rates appear to be more a function of inadequate exposure to the active medication and less influenced by CBI.