Predictors of outcome for short-term medically supervised opioid withdrawal during a randomized, multicenter trial of buprenorphine-naloxone and clonidine in the NIDA clinical trials network drug and alcohol dependence

Abstract

Few studies in community settings have evaluated predictors, mediators, and moderators of treatment success for medically supervised opioid withdrawal treatment. This report presents new findings about these factors from a study of 344 opioid-dependent men and women prospectively randomized to either buprenorphine-naloxone or clonidine in an open-label 13-day medically supervised withdrawal study. Subjects were either inpatient or outpatient in community treatment settings; however not randomized by treatment setting. Medication type (buprenorphine-naloxone versus clonidine) was the single best predictor of treatment retention and treatment success, regardless of treatment setting. Compared to the outpatient setting, the inpatient setting was associated with higher abstinence rates but similar retention rates when adjusting for medication type. Early opioid withdrawal severity mediated the relationship between medication type and treatment outcome with buprenorphine-naloxone being superior to clonidine at relieving early withdrawal symptoms. Inpatient subjects on clonidine with lower withdrawal scores at baseline did better than those with higher withdrawal scores; inpatient subjects receiving buprenorphine-naloxone did better with higher withdrawal scores at baseline than those with lower withdrawal scores. No relationship was found between treatment outcome and age, gender, race, education, employment, marital status, legal problems, baseline depression, or length/severity of drug use. Tobacco use was associated with worse opioid treatment outcomes. Severe baseline anxiety symptoms doubled treatment success. Medication type (buprenorphine-naloxone) was the most important predictor of positive outcome; however the paper also considers other clinical and policy implications of other results, including that inpatient setting predicted better outcomes and moderated medication outcomes.

Figure 1. Interaction between Medication Type, Withdrawal Severity, and Attendance Outcome

Interaction between medication type and withdrawal symptoms. Compared to clonidine, subjects on buprenorphine-naloxone had more days of treatment abstinence regardless of baseline COWS severity. For the clonidine group, individuals with low withdrawal symptoms had more days of treatment abstinence than those with high withdrawal symptoms.

Figure 2. Mediational model

Mediational Model based on Baron and Kenny. Establishing mediation requires a) medication type to affect opioid withdrawal (i.e., path a), b) opioid withdrawal to affect classification as a treatment responder (i.e., path b), and c) medication type to affect treatment response (i.e., path c). When adjusting for the proposed mediator (opioid withdrawal), the regression coefficient associated with medication type in path c should be non-significant, or substantially reduced.