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 (80 mg/implant) ( n  = 114), four placebo implants ( n  = 54) or open‐label BNX (12–16 mg/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.