Buprenorphine and methadone are the two main opioid agonist treatments approved for opioid use disorder. Buprenorphine is a partial agonist of the mu opioid receptors, which has been merely available through sublingual form until now. In practice, the use of buprenorphine is smoother than that of methadone, and it induces reduced risks of overdose. However, sublingual buprenorphine also exposes to risks (e.g., withdrawal, misuse) and constraints (e.g., daily intake). Three new galenic formulations of prolonged-release buprenorphine (PRB) are being commercialized and should allow some improvements in patients' comfort and safety. This narrative review aims to describe the main technical features and efficacy and safety data of these PRBs, as well as patients' and professionals' expectancies and concerns, using data of the scientific literature and the regulatory texts. PRBs consist of one subcutaneous implant and two subcutaneous injection depots. Sixmo®/Probuphine® is a six-month-long implant which needs to be surgically placed and removed and is approved for subjects previously treated with a maximum daily dose of 8mg of sublingual buprenorphine, and can be used only for two successive periods of six months before the subject needs to be switched back to sublingual form. Sublocade® is a one-month-long depot formulation that is indicated in switch from sublingual buprenorphine, and which proposes only two dose schemes, i.e., 100 and 300mg monthly. Buvidal®/Brixadi® is a one-week- or one-month-long depot formulation with multiple dosages, which can be used in initiation or in switched from sublingual formulations. While opioid users report some concerns with a risk of coercive use of long-acting forms of buprenorphine, both users and professionals deem that these new specialties could be particularly appreciated in stabilized patients bothered with the daily intake of the treatments, or specific situations at risk of treatment dropout (e.g., following hospital discharge or prison release).

[Prolonged-release buprenorphine formulations: Perspectives for clinical practice].

BACKGROUND AND AIMS: Opioid agonist treatment is effective but resource intensive to administer safely in custodial settings, leading to significant under-treatment of opioid dependence in these settings world-wide. This study assessed the safety of subcutaneous slow-release depot buprenorphine in custody.

SETTING: This is an open-label, non-randomized trial conducted in correctional centres in New South Wales, Australia. Sixty-seven men and women, aged ≥ 18 years of various security classifications with a diagnosis of moderate to severe DSM-5 opioid use disorder currently serving a custodial sentence of ≥ 6 months were recruited between November 2018 and July 2019. Patients not in opioid agonist treatment at recruitment commenced depot buprenorphine; patients already stable on oral methadone treatment were recruited to the comparison arm.

INTERVENTION AND COMPARATOR: Depot buprenorphine (CAM2038 weekly for 4 weeks then monthly) and daily oral methadone. Safety was assessed by adverse event (AE) monitoring and physical examinations at every visit. Participants were administered a survey assessing self-reported diversion and substance use at baseline and weeks 4 and 16.

FINDINGS: Retention in depot buprenorphine treatment was 92.3%. Ninety-four per cent of patients reported at least one adverse event, typically mild and transient. No diversion was identified. The prevalence of self-reported non-prescribed opioid use among depot buprenorphine patients decreased significantly between baseline (97%) and week 16 (12%, odds ratio = 0.0035, 95% confidence interval = 0.0007-0.018, P < 0.0001).

CONCLUSIONS: This first study of depot buprenorphine in custodial settings showed treatment retention and outcomes comparable to those observed in community settings and for other opioid agonist treatment used in custodial settings, without increased risk of diversion.

Treatment of opioid dependence with depot buprenorphine (CAM2038) in custodial settings.

Opioid maintenance treatment with oral methadone or sublingual buprenorphine is
 the first-line treatment in opioid dependence. Three novel long-acting
 buprenorphine formulations have been approved or will be available soon: for
 subcutaneous weekly and monthly application, the depot formulations CAM 2038
 (Buvidal®), the monthly depot formulation RBP-6000
 (Sublocade™), and a 6-month buprenorphine implant (Probuphine™).
 Clinical data available so far on the efficacy of these 3 medications are given,
 and possible clinical implications are discussed.

Novel Long-Acting Buprenorphine Medications for Opioid Dependence: Current Update.

http://www.journalofsubstanceabusetreatment.com/article/S0740547222000630/pdf

Long-acting depot buprenorphine in people who are homeless: Views and experiences.

Determinants of interest in extended-released buprenorphine: A survey among 366 French patients treated with buprenorphine or methadone.

Introduction: Since the 1990s, opioid maintenance treatments (OMTs), i.e. mostly methadone and buprenorphine, have represented the therapeutic cornerstone of opioid dependence. In France, the public health strategy on opioid dependence, identified here as the 'French model', has consisted of offering a facilitated access to buprenorphine, to reach a large treatment coverage and reduce opioid-related mortality. Areas covered: Recently, a new formulation of subcutaneous buprenorphine depot (Buvidal®) has been approved in Europe for treatment of opioid dependence. The place of Buvidal® among the pre-existing arsenal of OMTs is discussed in the light of the pharmacological specificities of this new formulation, and with the particular standpoint of the French model on opioid dependence. Expert opinion: Buvidal® could constitute a promising treatment option mainly in case of: 1) OMT initiation, including in non-specialized addiction medicine care; 2) Discharge from prison or hospital; Diversion/misuse of 3) buprenorphine or 4) methadone; 5) Clinically stabilized patients wishing to avoid daily oral taking of the medication. As such, this new formulation should be highly accessible, which will require specific pathways through care as the product is intended to be administered by a healthcare professional.

https://www.tandfonline.com/doi/pdf/10.1080/17425247.2019.1649252

What place for prolonged-release buprenorphine depot-formulation Buvidal® in the treatment arsenal of opioid dependence? Insights from the French experience on buprenorphine.

Purpose: Extended-release buprenorphine (XR-BUP) covers a range of formulations of buprenorphine-based treatments for opioid use disorder (OUD) that release the medication over a period of one week, one month, or six months. OUD is particularly prevalent among incarcerated populations, and previous findings have shown that incarcerated subjects were not less interested in XR-BUP than non-incarcerated subjects. However, no study has ever investigated whether the factors of interest in XR-BUP were similar in incarcerated and non-incarcerated populations.

Patients and methods: We carried out post-hoc analyses using data from the "AMBRE" survey, which was conducted among 366 individuals with OUD, that were recruited in 68 French addiction settings, including six prison medical centers. The reasons for interest in XR-BUP were compared between incarcerated and non-incarcerated interviewees, using logistic regressions models, which provided raw and adjusted odds ratios (aORs) and 95% confidence intervals (95% CI). Adjustment variables were gender, age category, level of education, and type of current medication for OUD, respectively.

Results: Data from 317 participants (ie, 221 non-incarcerated, and 96 incarcerated individuals) were included in the analyses. Adjusted comparisons found that "no longer taking a daily treatment" (aOR= 2.91; 95% CI= 1.21-6.98) and "having a more discreet medication" (aOR= 1.76; 95% CI= 1.01-3.10) were reasons that appealed more to incarcerated participants than to non-incarcerated ones. On the other hand, the potential reduction of withdrawal symptoms (aOR= 0.54; 95% CI= 0.29-0.99) or the risk of misuse (aOR= 0.56; 95% CI= 0.34-0.94) associated with XR-BUP treatment were considered more important by non-incarcerated individuals than by incarcerated ones.

Conclusion: Incarcerated interviewees were interested in XR-BUP for different reasons than those outside prison. In particular, incarcerated patients were more interested in practicability and discretion features, and less in improving recovery or reducing misuse than non-incarcerated patients.

/pdf/factors-of-interest-in-extended-release-buprenorphine-1il5eioze5.pdf

Margaux Kosim

Papers

What place for prolonged-release buprenorphine depot-formulation Buvidal® in the treatment arsenal of opioid dependence? Insights from the French experience on buprenorphine.

Determinants of interest in extended-released buprenorphine: A survey among 366 French patients treated with buprenorphine or methadone.

Factors of Interest in Extended-Release Buprenorphine: Comparisons Between Incarcerated and Non-Incarcerated Patients with Opioid Use Disorder.