Download PDF
Pharmacopsychiatry 2021; 54(01): 18-22
DOI: 10.1055/a-1298-4508
Review

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

Michael Soyka
› Further Information
Also available at
   Permissions and Reprints

Abstract

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.

Key words

opioid dependence - maintainance treatment - buprenorphine - depot - implant


Publication History

Received: 26 March 2020
Received: 17 October 2020

Accepted: 21 October 2020

Article published online:
19 November 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Degenhardt L, Charlson F, Mathers B. et al. The global epidemiology and burden of opioid dependence: results from the global burden of disease 2010 study. Addiction 2014; 109: 1320-1333
    CrossrefPubMedSearch in Google Scholar
  • 2 Schuckit MA. Treatment of opioid-use disorders. N Engl J Med 2016; 375: 1596-1597
    CrossrefPubMedSearch in Google Scholar
  • 3 Atzendorf J, Rauschert L, Seitz NN. et al. Gebrauch von Alkohol, Tabak, illegalen Drogen und Medikamenten. Dtsch Ärzteblatt 2019; 116: 577-584
    PubMedSearch in Google Scholar
  • 4 Center for Behavioral Health Statistics and Quality (CBHSQ). National survey on drug use and health: Detailed tables. Substance Abuse and Mental Health Services Administrations, Rockville, MD 2016
    PubMed
  • 5 Bell J, Strang J. Medication treatment of opioid use disorder. Biol Psychiatry 2020; 87: 82-88
    CrossrefPubMedSearch in Google Scholar
  • 6 McLellan AT, McKay JR, Forman R. et al. Reconsidering the evaluation of addiction treatment: from retrospective follow-up to concurrent recovery monitoring. Addiction 2005; 100: 447-458
    CrossrefPubMedSearch in Google Scholar
  • 7 Russolillo A, Moniruzzaman A, McCandless LC. et al. Associations between methadone maintenance treatment and crime: A 17-year longitudinal cohort study of Canadian provincial offenders. Addiction 2018; 113: 656-667
    CrossrefPubMedSearch in Google Scholar
  • 8 Dennis ML, Scott CK, Funk R. et al. The duration and correlates of addiction and treatment careers. J Subst Abuse Treat 2005; 28: 51-62
    CrossrefPubMedSearch in Google Scholar
  • 9 Gossop M, Marsden J, Stewart D. et al. Outcomes after methadone maintenance and methadone reduction treatments: Two-year follow-up results from the National Treatment Outcome Research Study. Drug Alcohol Depend 2001; 62: 255-264
    CrossrefPubMedSearch in Google Scholar
  • 10 Bell J. Pharmacological maintenance treatments of opiate addiction. Br J Clin Pharmacol 2014; 77: 253-263
    CrossrefPubMedSearch in Google Scholar
  • 11 Amato L, Minozzi S, Davoli M. et al. Psychosocial combined with agonist maintenance treatments versus agonist maintenance treatments alone for treatment of opioid dependence. Cochrane Database Syst Rev 2011; 10: CD004147
    CrossrefPubMedSearch in Google Scholar
  • 12 Mattick RP, Breen C, Kimber J. et al. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2014; CD002207
    CrossrefPubMedSearch in Google Scholar
  • 13 Soyka M, Strehle J, Rehm J. et al. Six-year outcome of opioid maintenance treatment in heroin-dependent patients: Results from a naturalistic study in a nationally representative sample. Eur Addict Res 2017; 23: 97-105
    CrossrefPubMedSearch in Google Scholar
  • 14 Walter M, Soyka M. Opioide. In: Soyka M, Batra A, Heinz A, Moggi F, Walter M. Suchtmedizin. München: Elsevier; 2019: 177-202
    Search in Google Scholar
  • 15 Volkow ND, Frieden TR, Hyde PS. et al. Medication-assisted therapies: Tackling the opioid-overdose epidemic. N Engl J Med 2014; 370: 2063-2066
    CrossrefPubMedSearch in Google Scholar
  • 16 Rehm J, Gschwend P, Steffen T. et al. Feasibility, safety, and efficacy of injectable heroin prescription for refractory opioid addicts: A follow-up study. Lancet 2001; 358: 1417-1423
    CrossrefPubMedSearch in Google Scholar
  • 17 Strang J, Groshkova T. Uchtenhagen. et al. Heroin on trial: Systematic review and meta-analysis of randomised trials of diamorphine prescribing as treatment for refractory heroin addiction. Br J Psychiatry 2015; 207: 5-14
    CrossrefPubMedSearch in Google Scholar
  • 18 Teesson M, Mills K, Ross J. et al. The impact of treatment on 3 years’ outcome for heroin dependence: findings from the Australian Treatment Outcome Study (ATOS). Addiction 2007; 103: 80-88
    CrossrefPubMedSearch in Google Scholar
  • 19 Kimber J, Larney S, Hickman M. et al. Mortality risk of opioid substitution therapy with methadone versus buprenorphine: A retrospective cohort study. Lancet Psychiat 2015; 2: 901-908
    CrossrefPubMedSearch in Google Scholar
  • 20 Bundesärztekammer. Richtlinie der Bundesärztekammer zur Durchführung der substitutionsgestützten Behandlung Opioidabhängiger 2017; Im Internet: www.bundesaerztekammer.de/fileadmin/user_upload/ downloads/pdf-Ordner/RL/Substitution.pdf; Stand: 18.11.2019
    PubMed
  • 21 Bell J, Burrell T, Indig D. et al. Cycling in and out of treatment; participation in methadone treatment in NSW, 1990–2002. Drug Alcohol Depend 2006; 81: 55-61
    CrossrefPubMedSearch in Google Scholar
  • 22 Zhang L, Zou X, Zhang D. et al. Investigation of repeat client drop-out and re-enrolment cycles in fourteen methadone maintenance treatment clinics in Guangdong, China. PLoS One 2015; 10: e0139942
    CrossrefPubMedSearch in Google Scholar
  • 23 Bell J. The global diversion of pharmaceutical drugs: opiate treatment and the diversion of pharmaceutical opiates: a clinician’s perspective. Addiction 2010; 105: 1531-1537
    CrossrefPubMedSearch in Google Scholar
  • 24 Timko C, Schultz NR, Cucciare MA. et al. Retention in medication-assisted treatment for opiate dependence: A systematic review. J Addict Dis 2016; 35: 22-35
    CrossrefPubMedSearch in Google Scholar
  • 25 Fareed A, Vayalapalli S, Casarella J. et al. Effect of buprenorphine dose on treatment outcome. J Addict Dis 2012; 31: 8-18
    CrossrefPubMedSearch in Google Scholar
  • 26 Greenwald MK, Comer SD, Fiellin DA. Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: Implications for clinical use and policy. Drug Alcohol Depend 2014; 144: 1-11
    CrossrefPubMedSearch in Google Scholar
  • 27 Greenwald MK, Johanson CE, Moody DE. et al. Effects of buprenorphine maintenance dose on mu-opioid receptor availability, plasma concentrations, and antagonist blockade in heroin-dependent volunteers. Neuropsychopharmacol 2003; 28: 2000-2009
    CrossrefPubMedSearch in Google Scholar
  • 28 Kuhlman JJ, Levine B, Johnson RE. et al. Relationship of plasma buprenorphine and norbuprenorphine to withdrawal symptoms during dose induction, maintenance and withdrawal from sublingual buprenorphine. Addiction 1998; 93: 549-559
    CrossrefPubMedSearch in Google Scholar
  • 29 Hser YI, Evans E, Huang D. et al. Long-term outcomes after randomization to buprenorphine/naloxone versus methadone in a multi-site trial. Addiction 2016; 111: 695-705
    CrossrefPubMedSearch in Google Scholar
  • 30 Hser YI, Saxon AJ, Huang D. et al. Treatment retention among patients randomized to buprenorphine/naloxone compared to methadone in a multi-site trial. Addiction 2014; 109: 8-18
    PubMedSearch in Google Scholar
  • 31 Bell J, Butler B, Lawrance A. et al. Comparing overdose mortality associated with methadone and buprenorphine treatment. Drug Alcohol Depend 2009; 104: 73-77
    CrossrefPubMedSearch in Google Scholar
  • 32 Bell J, Trinh L, Butler B. et al. Comparing retention in treatment and mortality in people after initial entry to methadone and buprenorphine treatment. Addiction 2009; 104: 1193-1200
    CrossrefPubMedSearch in Google Scholar
  • 33 Deamer RL, Wilson DR, Clark DS. et al. Torsades de pointes associated with high dose levomethadyl acetate (ORLAAM). J Addict Dis 2001; 20: 7-14
    CrossrefPubMedSearch in Google Scholar
  • 34 European Agency for the Evaluation of Medical Products. EMEA public statement to suspend the marketing authorization for Orlaam (levoacetylmethadol) in the European Union. 2001; EMEA/8776/01
    PubMed
  • 35 Wieneke H, Conrads H, Wolstein J. et al. Levo-alpha-acetylmethadol (LAAM) induced QTc-prolongation-results from a controlled clinical trial. Eur J Med Res 2009; 14: 7-12
    CrossrefPubMedSearch in Google Scholar
  • 36 Ling W, Shoptaw S. Goodman-Meza. Depot buprenorphine in the management of opioid use disorder. From development to implementation. Subst Abuse Rehabil 2019; 10: 69-78
    PubMedSearch in Google Scholar
  • 37 Coe MA, Lofwall MR, Walsh SL. Buprenorphine pharmacology review: update on transmucosal and long-acting formulations. J Addict Med 2019; 13: 93-193
    CrossrefPubMedSearch in Google Scholar
  • 38 Walsh SL, Comer SD, Lofwall MR. et al. Effect of buprenorphine weekly depot (CAM 2038) and hydromorphone blockade in individuals with opioid use disorder: a randomised clinical trial. JAMA Psychiatry 2017; 74: 894-902
    CrossrefPubMedSearch in Google Scholar
  • 39 Albayaty M, Linden M, Olsson H. et al. Pharmacokinetic evaluation of one-weekly and once-monthly buprenorphine subcutaneous injection depots (CAM 2038) versus intravenous and sublingual buprenorphine in healthy volunteers under naltrexone blockade: An open-label phase 1 study. Adv Ther 2017; 34: 560-575
    CrossrefPubMedSearch in Google Scholar
  • 40 Haasen C, Linden M, Tiberg F. Pharmacokinetics and pharmacodynamics of a buprenorphine subcutaneous depot formulation (CAM2038) for once-weekly dosing in patients with opioid disorder. J Subst Abuse Treat 2017; 78: 22-29
    CrossrefPubMedSearch in Google Scholar
  • 41 Lofwall MR, Walsh SL, Nunes EV. et al. Weekly and monthly subcutaneous buprenorhpine depot formulations vs daily sublingual burpenorphine with naloxone for treatment of opioid use disorder: a randomized clinical Trial. JAMA Intern Med 2018; 178: 764-773
    CrossrefPubMedSearch in Google Scholar
  • 42 Frost M, Bailey GL, Lintzeris L. et al. Longtime safety of weekly and monthly subcutaneous Buprenorphindepot (CAM 2038) in the treatment of adult out-patients with opiod use disorders. Addiction 2019; 114: 1416-1426
    CrossrefPubMedSearch in Google Scholar
  • 43 Laffont CM, Gomeni R, Heidbreder C. et al. Population pharmacokinetic modeling after repeated administrations of RBP-6000, a new, subcutaneously injectable, long-acting, sustained-release formulation of buprenorphine, for the treatment of opioid use disorder. J Clin Pharmacol 2016; 56: 806-815
    CrossrefPubMedSearch in Google Scholar
  • 44 Nasser AF, Heidbreder C, Gomeni R. et al. A population pharmacokinetic and pharmacodynamic modelling approach to support the clinical development of RBP-6000, a new, subcutaneously injectable, long-acting, sustained-release formulation of buprenorphine, for the treatment of opioid dependence. Clin Pharmacokinet 2014; 53: 813-824
    CrossrefPubMedSearch in Google Scholar
  • 45 Haight BR, Learned SM, Laffont CM. Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2019; 393: 778-790
    CrossrefPubMedSearch in Google Scholar
  • 46 Ling W, Nadipelli VR, Solem CT. et al. Patient-centered outcomes in participants of a buprenorphine monthly depot (bup-xr) double-blind, placebo-controlled, multicenter, phase study. J Addict Med 2019; 13: 442-449
    CrossrefPubMedSearch in Google Scholar
  • 47 Barnwal P, Das S, Mondal S. et al. Probuphine® (buprenorphine implant): a promising candidate in opioid dependence. Ther Adv Psychopharmacol 2017; 7: 119-134
    CrossrefPubMedSearch in Google Scholar
  • 48 Itzoe M, Guarnieri M. New developments in managing opioid addiction: impact of a subdermal buprenorphine implant. Drug Des Devel Ther 2017; 11: 1429-1437 doi: 10.2147/DDDT.S109331
    CrossrefPubMedSearch in Google Scholar
  • 49 White J, Bell J, Saunders JB. et al. Open-label dose-finding trial of buprenorphine implants (Probuphine) for treatment of heroin dependence. Drug Alcohol Depend 2009; 103: 37-43.
    CrossrefPubMedSearch in Google Scholar
  • 50 Ling W, Casadonte P, Bigelow G. et al. Buprenorphine implants for treatment of opioid dependence: A randomized controlled trial. JAMA 2010; 304: 1576-1583
    CrossrefPubMedSearch in Google Scholar
  • 51 Rosenthal RN, Ling W, Casadonte P. et al. Buprenorphine implants for treatment of opioid dependence: randomized comparison to placebo and sublingual buprenorphine/naloxone. Addiction 2013; 108: 2141-2149
    CrossrefPubMedSearch in Google Scholar
  • 52 Rosenthal RN, Lofwall MR, Kim S. et al. Effect of buprenorphine implants on illicit opioid use among abstinent adults with opioid dependence treated with sublingual buprenorphine: A randomized clinical trial. JAMA 2016; 316: 282-290
    CrossrefPubMedSearch in Google Scholar
  • 53 Pendergrass SA, Crist RC, Jones LK. et al. The importance of buprenorphine research in the opioid crisis. Mol Psychiatry 2019; 24: 626-632
    CrossrefPubMedSearch in Google Scholar
  • 54 Kelty E, Cumming C, Troeung L. et al. Buprenorphine alone or with naloxone: Which is safer?. J Psychopharmacol 2018; 32: 344-352
    CrossrefPubMedSearch in Google Scholar
  • 55 Allikmets S, Vink JP. Clinical applications of burprenorphine depot injection for opioid use disorder. Addiction 2020; 115 : doi:10.1111/add.14818
    PubMedSearch in Google Scholar
  • 56 Kenney SR, Anderson BJ, Bailey GL. et al. Buprenorphine treatment formulations: Preferences among persons in opioid withdrawal management. J Subst Abuse Treat 2018; 94: 55-59.
    CrossrefPubMedSearch in Google Scholar
  • 57 Tompkins CNE, Neale J, Strang J. Opioid users willingness to receive prolonged-release buprenorphine depot injections for opioid use disorder. J Subst Abuse Treatment 2019; 104: 64-71
    CrossrefPubMedSearch in Google Scholar
  • 58 Neale J, Tompkins CNE, Strang J. Prolonged-release opioid agonist therapy: qualitative study exploring patients views of 1-week. 1-month and 6-month buprenorphine formulations. Harm Reduct J 2019; 16: 25 doi: 10.1186/s12954-019-0296-4
    CrossrefPubMedSearch in Google Scholar
  • 59 Gilman M, Li L, Hudson K. et al. Current and future options for opioid use disorder: a survey assessing real-world opinion of service users on novel therapies including depot formulations of buprenorphine. Patient Prefer Adherence 2018; 12: 2123-2129
    CrossrefPubMedSearch in Google Scholar
  • 60 Ling W, Shoptaw S, Goodman-Meza D. Depot buprenorphine injection in the management of opioid use disorder: from development to implementation. Subst Abuse Rehabil 2019; 10: 69-78
    CrossrefPubMedSearch in Google Scholar
  • 61 Soyka M. Covid-19 and substitution. Suchtmed 2020; 22: 119-121
    PubMedSearch in Google Scholar
  • 62 Vorspan F, Hjelström P, Simon N. et al. What place for prolonged-release buprenorphine depot-formulation buvidal in the treatment arsenal if opioid dependence? Insights from the French experience on buprenorphine. Expert Opin Drug Deliv 2019; 16: 907-914
    CrossrefPubMedSearch in Google Scholar
  • 63 Larance B, Degenhardt L, Grebely J. et al. Perceptions of extended-release buprenorphine injections for opioid use disorder among people who regularly use opioids in Australia. Addiction 2019; 115: 1295-1305
    CrossrefPubMedSearch in Google Scholar
  • 64 Shover CL, Humphreys K. Predictors of availability of long-acting medication for opioid use disorder. Drug Alcohol Depend 2019; doi.
    CrossrefPubMedSearch in Google Scholar
  • 65 Hjelström P, Nordbeck EB, Tiberg F. Optimal dose of buprenorphine in opioid use disorder treatment: A review of pharmacodynamic and efficacy data. Drug Dev Ind Pharm 2020; doi.
    CrossrefPubMedSearch in Google Scholar
  • 66 McCance-Katz EF, Sullivan LE, Nallani S. Drug interactions of clinical importance among the opioids, methadone and buprenorphine, and other frequently prescribed medications: A review. Am J Addict 2010; 19: 4-16
    CrossrefPubMedSearch in Google Scholar
  • 67 Liu T, Gobburu VS. A physiologically based pharmacokinetic modeling approach to predict drug-drug interactions of buprenorphine after subcutaneous administration of CAM2038 with perpetrators of CYP3A4. J Pharm Sci 2018; 107: 942-948
    CrossrefPubMedSearch in Google Scholar