Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: a 2-phase randomized controlled trial

Abstract

Context: No randomized trials have examined treatments for prescription opioid dependence, despite its increasing prevalence.

Objective: To evaluate the efficacy of brief and extended buprenorphine hydrochloride-naloxone hydrochloride treatment, with different counseling intensities, for patients dependent on prescription opioids.

Design: Multisite, randomized clinical trial using a 2-phase adaptive treatment research design. Brief treatment (phase 1) included 2-week buprenorphine-naloxone stabilization, 2-week taper, and 8-week postmedication follow-up. Patients with successful opioid use outcomes exited the study; unsuccessful patients entered phase 2: extended (12-week) buprenorphine-naloxone treatment, 4-week taper, and 8-week postmedication follow-up.

Setting: Ten US sites. Patients A total of 653 treatment-seeking outpatients dependent on prescription opioids.

Interventions: In both phases, patients were randomized to standard medical management (SMM) or SMM plus opioid dependence counseling; all received buprenorphine-naloxone.

Main outcome measures: Predefined "successful outcome" in each phase: composite measures indicating minimal or no opioid use based on urine test-confirmed self-reports.

Results: During phase 1, only 6.6% (43 of 653) of patients had successful outcomes, with no difference between SMM and SMM plus opioid dependence counseling. In contrast, 49.2% (177 of 360) attained successful outcomes in phase 2 during extended buprenorphine-naloxone treatment (week 12), with no difference between counseling conditions. Success rates 8 weeks after completing the buprenorphine-naloxone taper (phase 2, week 24) dropped to 8.6% (31 of 360), again with no counseling difference. In secondary analyses, successful phase 2 outcomes were more common while taking buprenorphine-naloxone than 8 weeks after taper (49.2% [177 of 360] vs 8.6% [31 of 360], P < .001). Chronic pain did not affect opioid use outcomes; a history of ever using heroin was associated with lower phase 2 success rates while taking buprenorphine-naloxone.

Conclusions: Prescription opioid-dependent patients are most likely to reduce opioid use during buprenorphine-naloxone treatment; if tapered off buprenorphine-naloxone, even after 12 weeks of treatment, the likelihood of an unsuccessful outcome is high, even in patients receiving counseling in addition to SMM.

Trial registration: ClinicalTrials.gov NCT00316277.

Figure 1

Study Design ¹Stratified by presence or absence of a history of heroin use and current chronic pain ²Standard Medical Management; phase 1, week 1: 2 visits; weeks 2 to 4: 1 visit/wk; and weeks 5 to 8: biweekly visits ³Opioid dependence counseling (ODC); phase 1, Weeks 1 to 4: 2 visits/wk: Weeks 5 to 8: biweekly visits ⁴Buprenorphine-naloxone (bup/nx) dose; 8 to 32 mg/d ⁵Phase 1 primary endpoint: completion of week 12 with self-reported opioid use on no more than 4 days in a month; absence of 2 consecutive opioid-positive urine test results; no additional substance use disorder treatment (other than self-help); and no more than 1 missing urine sample ⁶Stratified by phase 1 counseling condition, that is, SMM or SMM+ODC ⁷SMM; phase 2. week 1: 2 visits; and weeks 2 to 16: 1 visit/wk ⁸ODC; phase 2, Weeks 1 to 6; 2 visits/wk; and weeks 7 to 12: 1 visit/wk ⁹Phase 2 primary endpoint: abstinent from opioids during week 12 (the final week of bu/nx stabilization) and during at least 2 of the previous 3 weeks (weeks 9–11) ¹⁰Phase 2 secondary endpoint: abstinent from opioids during week 24 and during at least 2 of the previous 3 weeks (weeks 21–23)

Figure 2

Randomization, Treatment, and Follow-up of Study Patients ^*Reasons (n = 315) for not meeting Inclusion/Exclusion Criteria: not physically dependent on opioids (n = 47); unable to meet study requirements (n = 39); psychotic or psychiatrically unstable (n = 34); not in good general health (n = 32); did not meet DSM-IV criteria for current opioid dependence (n = 32); medical condition made participation medically hazardous (n = 25); no medical clearance from treating physician prescribing opioids (n = 23); traumatic or major pain event (n = 18); heroin use more than 4 days in the past 30 days (n = 18); history of opioid use as a result of heroin use (n = 17); (10) dependent on alcohol, sedative-hypnotics or stimulants (n = 10); required ongoing pain management (n = 10); participated in methadone treatment/methadone dose greater than 40 mg (n = 4); pending surgery (n = 3); and liver function test results 5 times the upper limit of normal (n = 3). A participant could be represented in more than one category of the reasons for non-eligibility; 5 patients who did not meet all inclusion criteria were randomized. ODC indicates opioid dependence counseling; and SMM, standard medical management.