Characterizing opioid withdrawal during double-blind buprenorphine detoxification

Abstract

Background: Prescription opioid (PO) abuse has become an urgent public health issue in the United States. Detoxification is one important treatment option, yet relatively little is known about the time course and severity of opioid withdrawal during buprenorphine detoxification.

Methods: This is a secondary analysis of data from a randomized, placebo-controlled, double-blind evaluation of 1, 2, and 4-week outpatient buprenorphine tapers among primary prescription opioid (PO) abusers. The aim is to characterize the time course and severity of buprenorphine withdrawal under rigorous, double-blind conditions, across multiple taper durations, and using multiple withdrawal-related measures (i.e., self-report and observer ratings, pupil diameter, ancillary medication utilization). Participants were PO-dependent adults undergoing buprenorphine detoxification and biochemically-verified to be continuously abstinent from opioids during their taper (N = 28).

Results: Participants randomly assigned to the 4-week taper regimen experienced a relatively mild and stable course of withdrawal, with few peaks in severity. In contrast, the 1- and 2-week taper groups experienced stark increases in withdrawal severity during the week following the last buprenorphine dose, followed by declines in withdrawal severity thereafter. The 4-week taper group also reported significantly fewer disruptions in sleep compared to the other experimental groups. When predictors of withdrawal were examined, baseline ratings of "Expected Withdrawal Severity" was the most robust predictor of withdrawal experienced during the taper.

Conclusion: Data from this trial may inform clinicians about the expected time course, magnitude, and pattern of buprenorphine withdrawal and aid efforts to identify patients who may need additional clinical support during outpatient buprenorphine detoxification.

Keywords: Buprenorphine; Detoxification; Prescription opioid; Taper; Withdrawal.

Figure 1. Mean Withdrawal Scores During Buprenorphine Taper

Withdrawal outcomes presented as a function of study day for the 1, 2, and 4-week taper groups, with participants’ mean buprenorphine dose (mg; grey bars) also shown to aid interpretation. Mean CINA Total Severity score (square symbols) and mean VAS ratings of Withdrawal (circle symbols) are shown for the 1-week (top panel), 2-week (middle panel), and 4-week (bottom panel) taper groups. Filled symbols represent the days on which participants received an active buprenorphine dose; open symbols represent days on which they received color-matched placebo. Error bars represent SEM.

Figure 2. Mean Peak CINA Scores

Mean peak CINA total and individual item scores are presented across study week for the 1-week (circle), 2-week (triangle), and 4-week (square) taper groups. Filled symbols represent weeks in which participants received buprenorphine; open symbols represent weeks in which they received placebo. Error bars represent SEM. Only items with significant effects are presented. No taper group x study week posthoc test results reached significance.

Figure 3. Mean Peak Self-Report Ratings and Ancillary Medication Utilization

Mean peak self-report ratings of VAS items, Sleep Quantity, and ancillary medication utilization are presented across study week for the 1-week (circle), 2-week (triangle), and 4-week (square) taper groups. Filled symbols represent weeks in which participants received buprenorphine; open symbols represent weeks in which they received placebo. Error bars represent SEM. Only items with significant effects are presented. No taper group x study week posthoc test results reached significance.