Buprenorphine implants for treatment of opioid dependence: Randomized comparison to placebo and sublingual buprenorphine/naloxone

Aims: To evaluate the safety and efficacy of buprenorphine implants (BI) versus placebo implants (PI) for the treatment of opioid dependence. A secondary aim compared BI to open-label sublingual buprenorphine/naloxone tablets (BNX). Design: Randomized, double-blind, placebo-controlled trial. Subjects received either four buprenorphine implants (80mg/implant) (n=114), four placebo implants (n=54) or open-label BNX (12-16mg/day) (n=119). Setting: Twenty addiction treatment centers. Participants: Adult out-patients (ages 18-65) with DSM-IV-TR opioid dependence. Measurements: The primary efficacy end-point was the percentage of urine samples negative for opioids collected from weeks 1 to 24, examined as a cumulative distribution function (CDF). Findings: The BI CDF was significantly different from placebo (P<0.0001). Mean [95% confidence interval (CI)] proportions of urines negative for opioids were: BI=31.2% (25.3, 37.1) and PI=13.4% (8.3, 18.6). BI subjects had a higher study completion rate relative to placebo (64 versus 26%, P<0.0001), lower clinician-rated (P<0.0001) and patient-rated (P<0.0001) withdrawal, lower patient-ratings of craving (P<0.0001) and better subjects' (P=0.031) and clinicians' (P=0.022) global ratings of improvement. BI also resulted in significantly lower cocaine use (P=0.0016). Minor implant-site reactions were comparable in the buprenorphine [27.2% (31 of 114)] and placebo groups [25.9% (14 of 54)]. BI were non-inferior to BNX on percentage of urines negative for opioids [mean (95% CI)=33.5 (27.3, 39.6); 95% CI for the difference of proportions=(-10.7, 6.2)]. Conclusions: Compared with placebo, buprenorphine implants result in significantly less frequent opioid use and are non-inferior to sublingual buprenorphine/naloxone tablets.