A randomized, double-blind evaluation of buprenorphine taper duration in primary prescription opioid abusers

Abstract

Importance: Although abuse of prescription opioids (POs) is a significant public health problem, few experimental studies have investigated the treatment needs of this growing population.

Objective: To evaluate, following brief stabilization with a combination of buprenorphine hydrochloride and naloxone hydrochloride dihydrate, the relative efficacy of 1-, 2-, and 4-week buprenorphine tapering regimens and subsequent naltrexone hydrochloride therapy in PO-dependent outpatients.

Design, setting, and participants: A double-blind, 12-week randomized clinical trial was conducted in an outpatient research clinic. Following a brief period of buprenorphine stabilization, 70 PO-dependent adults were randomized to receive 1-, 2-, or 4-week tapers followed by naltrexone therapy.

Intervention: During phase 1 (weeks 1-5 after randomization), participants visited the clinic daily; during phase 2 (weeks 6-12), visits were reduced to thrice weekly. Participants received behavioral therapy and urine toxicology testing throughout the trial.

Main outcomes and measures: The percentage of participants negative for illicit opioid use, retention, naltrexone ingestion, and favorable treatment response (ie, retained in treatment, opioid abstinent, and receiving naltrexone at the end of the study).

Results: Opioid abstinence at the end of phase 1 was greater in the 4-week compared with the 2- and 1-week taper conditions (P = .02), with 63% (n = 14), 29% (n = 7), and 29% (n = 7) of participants abstinent in the 4-, 2-, and 1-week conditions, respectively. Abstinence at the end of phase 2 was also greater in the 4-week compared with the 2- and 1-week conditions (P = .03), with 50% (n = 11), 16% (n = 4), and 20% (n = 5) of participants abstinent in the 4-, 2-, and 1-week conditions, respectively. There were more treatment responders in the 4-week condition (P = .03), with 50% (n = 11), 17% (n = 4), and 21% (n = 5) of participants in the 4-, 2-, and 1-week groups considered responders at the end of treatment, respectively. Retention and naltrexone ingestion also were superior in the 4-week vs briefer tapers (both P = .04). Experimental condition (ie, taper duration) was the strongest predictor of treatment response, followed by buprenorphine stabilization dose.

Conclusions and relevance: This study represents a rigorous experimental evaluation of outpatient buprenorphine stabilization, brief taper, and naltrexone maintenance for treatment of PO dependence. Results suggest that a meaningful subset of PO-dependent outpatients may respond positively to a 4-week taper plus naltrexone maintenance intervention.

Trial registration: ClinicalTrials.gov NCT00719095.

Figure 1

A Schematic of the Experimental Design, Including Stabilization, Taper, and Naltrexone Maintenance Phases Arrows represent participant randomization following stabilization into 1 of 3 experimental conditions prior to initiation of the buprenorphine (BUP) taper. MWF indicates Monday, Wednesday, and Friday.

Figure 2

Consolidated Standards for Reporting of Trials Flow Diagram of Participants A schematic of participant enrollment, randomization, and study completion.

Figure 3

Effects of Buprenorphine Taper Duration on Illicit Opioid Abstinence Achieved Data points represent the percentage of opioid-negative urine samples submitted at each consecutive urine-sample visit before and after randomization. Data are presented for the entire group of participants at intake and stabilization and for each experimental group after randomization: 1-week, 2-week, and 4-week taper conditions.

Figure 4

Effects of Buprenorphine Taper Duration on Treatment Retention and Naltrexone Ingestion at the End of Each Study Phase Data are presented for 1-week, 2-week, and 4-week taper conditions.