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

Abstract

Aims To evaluate 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 4 buprenorphine implants (80 mg/implant) (n=114), 4 placebo implants (n=54), or open-label BNX (12–16 mg/d) (n=119). Setting 20 addiction treatment centers. Participants Adult outpatients (ages 18 to 65) with DSM-IV-TR opioid dependence. Measurements The primary efficacy endpoint was the percent 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<.0001). Mean (95% 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% vs. 26%, P<.0001), lower clinician-rated (P<.0001) and patient-rated (P<.0001) withdrawal, lower patient-ratings of craving (P<.0001), and better subjects’ (P=.031) and clinicians’ (P=.022) global ratings of improvement. BI also resulted in significantly lower cocaine use (P=.0016). Minor implant-site reactions were comparable in the buprenorphine (27.2% [31/114]) and placebo groups (25.9% [14/54]). BI were non-inferior to BNX on percent urines negative for opioids [mean (95% CI): 33.5 (27.3, 39.6); 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.

Discontinuation of Buprenorphine Maintenance Therapy: Perspectives and Outcomes

“…In light of our early analysis here, we predict that successful retention will be associated with BMT education during residency, relaxed BMT program rules, and methods that reduce diversion without preventing treatment, e.g. buprenorphine implants (Ling et al, 2010; Rosenthal et al, 2013). …”

“…Five studies were excluded on the basis that they did not include a follow-up period of 1 month or longer. One study was excluded on the basis that it did not maintain patients for at least 14 days before taper (Rosenthal et al, 2013). Five studies of buprenorphine outcomes met all criteria (Breen et al, 2003; Ling et al, 2009; Sigmon et al, 2013; Weiss et al, 2011; Woody et al, 2008).…”

Sustained‐release subdermal buprenorphine implants: the future of opioid use disorder management?

“…Buprenorphine release is dependent on the rate of dissolution and passive diffusion through the EVA copolymer matrix . Probuphine pharmacokinetics are consistent across all human clinical trials . Maximal plasma concentrations are achieved within 24 h of administration and decline exponentially to a low, non‐fluctuating concentration from week 4 to week 24 eliminating typical peaks and troughs associated with SL administration.…”

Novel Treatment Options in Depression and Psychosis

“…The contemporary clinical use of opioid agonists as ADs in clinical practice remains highly limited because of unresolved issues of abuse and dependence. 17 To overcome the limitations of opioid agonists, a combination of a µ and κ opioid partial agonist, buprenorphine, and a mu opioid antagonist samidorphan were developed. The results of a multicenter, randomized, double-blind, placebo-controlled study have shown that the modulation of the opiate system may be a novel treatment approach for treatment-resistant depression.…”