Download PDF
Semin Neurol 2024; 44(04): 441-451
DOI: 10.1055/s-0044-1787571
Review Article

Opioid Maintenance Therapy: A Review of Methadone, Buprenorphine, and Naltrexone Treatments for Opioid Use Disorder

David C. Fipps 
1   Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota
,
Tyler S. Oesterle
1   Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota
,
Bhanu P. Kolla
1   Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota
› Author Affiliations
› Further Information
    Permissions and Reprints

Abstract

The rates of opioid use and opioid related deaths are escalating in the United States. Despite this, evidence-based treatments for Opioid Use Disorder are underutilized. There are three medications FDA approved for treatment of Opioid Use Disorder: Methadone, Buprenorphine, and Naltrexone. This article reviews the history, criteria, and mechanisms associated with Opioid Use Disorder. Pertinent pharmacology considerations, treatment strategies, efficacy, safety, and challenges of Methadone, Buprenorphine, and Naltrexone are outlined. Lastly, a practical decision making algorithm is discussed to address pertinent psychiatric and medical comorbidities when prescribing pharmacology for Opioid Use Disorder.

Keywords

Opioid Crisis - Opioid Maintenance Therapy - Opioid Use Disorder - Methadone - Buprenorphine - Naltrexone


Publication History

Article published online:
07 June 2024

© 2024. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Oesterle TS, Kolla BP, Rummans TA, Gold MS. Medication-assisted therapies for opioid use disorders in patients with chronic pain. J Neurol Sci 2020; 411: 116728
    CrossrefPubMedGoogle Scholar
  • 2 Brook K, Bennett J, Desai SP. The chemical history of morphine: an 8000-year journey, from resin to de-novo synthesis. J Anesth Hist 2017; 3 (02) 50-55
    CrossrefPubMedGoogle Scholar
  • 3 Brownstein MJ. A brief history of opiates, opioid peptides, and opioid receptors. Proc Natl Acad Sci U S A 1993; 90 (12) 5391-5393
    CrossrefPubMedGoogle Scholar
  • 4 Sabatowski R, Schäfer D, Kasper SM, Brunsch H, Radbruch L. Pain treatment: a historical overview. Curr Pharm Des 2004; 10 (07) 701-716
    CrossrefPubMedGoogle Scholar
  • 5 Kolodny A, Courtwright DT, Hwang CS. et al. The prescription opioid and heroin crisis: a public health approach to an epidemic of addiction. Annu Rev Public Health 2015; 36: 559-574
    CrossrefPubMedGoogle Scholar
  • 6 Puntillo K, Neighbor M, O'Neil N, Nixon R. Accuracy of emergency nurses in assessment of patients' pain. Pain Manag Nurs 2003; 4 (04) 171-175
    CrossrefPubMedGoogle Scholar
  • 7 Max MB. Improving outcomes of analgesic treatment: is education enough?. Ann Intern Med 1990; 113 (11) 885-889
    CrossrefPubMedGoogle Scholar
  • 8 Scholl L, Seth P, Kariisa M, Wilson N, Baldwin G. Drug and opioid-involved overdose deaths - United States, 2013-2017. MMWR Morb Mortal Wkly Rep 2018; 67 (5152): 1419-1427
    CrossrefPubMedGoogle Scholar
  • 9 National Survey on Drug Use and Health. 2020 National Survey on Drug Use and Health Detailed Tables. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2021. Accessed November 22, 2022 at: https://www.samhsa.gov/data/report/2020-nsduh-detailed-tables
    PubMed
  • 10 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR). Washington, DC: American Psychiatric Association; 2022
    CrossrefGoogle Scholar
  • 11 Jalabert M, Bourdy R, Courtin J. et al. Neuronal circuits underlying acute morphine action on dopamine neurons. Proc Natl Acad Sci U S A 2011; 108 (39) 16446-16450
    CrossrefPubMedGoogle Scholar
  • 12 Jones JD, Levin CJ, Mumtaz M, Comer SD. Neurobiology of opioids. In: Brady KT, Levin FR, Marc Galanter, Kleber HD. eds. The American Psychiatric Association Publishing Textbook of Substance Use Disorder Treatment. 6th ed.. American Psychiatric Association Publishing; 2021
    Google Scholar
  • 13 Bergeria CL, Strain EC. Opioid use disorder: pernicious and persistent. Am J Psychiatry 2022; 179 (10) 708-714
    CrossrefPubMedGoogle Scholar
  • 14 Burma NE, Kwok CH, Trang T. Therapies and mechanisms of opioid withdrawal. Pain Manag (Lond) 2017; 7 (06) 455-459
    CrossrefPubMedGoogle Scholar
  • 15 Feltenstein MW, See RE. The neurocircuitry of addiction: an overview. Br J Pharmacol 2008; 154 (02) 261-274
    CrossrefPubMedGoogle Scholar
  • 16 Baler RD, Volkow ND. Drug addiction: the neurobiology of disrupted self-control. Trends Mol Med 2006; 12 (12) 559-566
    CrossrefPubMedGoogle Scholar
  • 17 Kalivas PW, Volkow ND. The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 2005; 162 (08) 1403-1413
    CrossrefPubMedGoogle Scholar
  • 18 Trang T, Al-Hasani R, Salvemini D, Salter MW, Gutstein H, Cahill CM. Pain and poppies: the good, the bad, and the ugly of opioid analgesics. J Neurosci 2015; 35 (41) 13879-13888
    CrossrefPubMedGoogle Scholar
  • 19 Corder G, Castro DC, Bruchas MR, Scherrer G. Endogenous and exogenous opioids in pain. Annu Rev Neurosci 2018; 41: 453-473
    CrossrefPubMedGoogle Scholar
  • 20 Der-Avakian A, Markou A. The neurobiology of anhedonia and other reward-related deficits. Trends Neurosci 2012; 35 (01) 68-77
    CrossrefPubMedGoogle Scholar
  • 21 Le Merrer J, Plaza-Zabala A, Del Boca C, Matifas A, Maldonado R, Kieffer BL. Deletion of the δ opioid receptor gene impairs place conditioning but preserves morphine reinforcement. Biol Psychiatry 2011; 69 (07) 700-703
    CrossrefPubMedGoogle Scholar
  • 22 Valentino RJ, Volkow ND. Untangling the complexity of opioid receptor function. Neuropsychopharmacology 2018; 43 (13) 2514-2520
    CrossrefPubMedGoogle Scholar
  • 23 Badal S, Turfus S, Rajnarayanan R, Wilson-Clarke C, Sandiford SL. Analysis of natural product regulation of opioid receptors in the treatment of human disease. Pharmacol Ther 2018; 184: 51-80
    CrossrefPubMedGoogle Scholar
  • 24 Al-Hasani R, Bruchas MR. Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiology 2011; 115 (06) 1363-1381
    CrossrefPubMedGoogle Scholar
  • 25 Williams J. Basic opioid pharmacology. Rev Pain 2008; 1 (02) 2-5
    CrossrefPubMedGoogle Scholar
  • 26 Schmid CL, Kennedy NM, Ross NC. et al. Bias factor and therapeutic window correlate to predict safer opioid analgesics. Cell 2017; 171 (05) 1165-1175.e13
    CrossrefPubMedGoogle Scholar
  • 27 Raehal KM, Bohn LM. β-arrestins: regulatory role and therapeutic potential in opioid and cannabinoid receptor-mediated analgesia. Handb Exp Pharmacol 2014; 219: 427-443
    CrossrefPubMedGoogle Scholar
  • 28 Kroenke K, Alford DP, Argoff C. et al. Challenges with implementing the Centers for Disease Control and Prevention opioid guideline: a consensus panel report. Pain Med 2019; 20 (04) 724-735
    CrossrefPubMedGoogle Scholar
  • 29 Chang DC, Klimas J, Wood E, Fairbairn N. A case of opioid overdose and subsequent death after medically supervised withdrawal: the problematic role of rapid tapers for opioid use disorder. J Addict Med 2018; 12 (01) 80-83
    CrossrefPubMedGoogle Scholar
  • 30 Volkow ND, Frieden TR, Hyde PS, Cha SS. Medication-assisted therapies–tackling the opioid-overdose epidemic. N Engl J Med 2014; 370 (22) 2063-2066
    CrossrefPubMedGoogle Scholar
  • 31 Oesterle TS, Thusius NJ, Rummans TA, Gold MS. Medication-assisted treatment for opioid-use disorder. Mayo Clin Proc 2019; 94 (10) 2072-2086
    CrossrefPubMedGoogle Scholar
  • 32 Strain EC, Stoller KB. Methadone and buprenorphine maintenance treatment of opioid-related disorders. In: Brady KT, Levin FR, Galanter M, Kleber HD. eds. The American Psychiatric Association Publishing Textbook of Substance Use Disorder Treatment. 6th ed.. American Psychiatric Association Publishing; 2021
    Google Scholar
  • 33 Eap CB, Buclin T, Baumann P. Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Clin Pharmacokinet 2002; 41 (14) 1153-1193
    CrossrefPubMedGoogle Scholar
  • 34 Walsh SL, Strain ED. Pharmacology of Methadone in the Treatment of Opioid Dependence. Baltimore, MD: Hopkins Press; 2005
    Google Scholar
  • 35 Kristensen K, Christensen CB, Christrup LL. The mu1, mu2, delta, kappa opioid receptor binding profiles of methadone stereoisomers and morphine. Life Sci 1995; 56 (02) PL45-PL50
    CrossrefPubMedGoogle Scholar
  • 36 Haroutiunian S, McNicol ED, Lipman AG. Methadone for chronic non-cancer pain in adults. Cochrane Database Syst Rev 2012; 11 (11) CD008025
    PubMedGoogle Scholar
  • 37 Dole VP, Nyswander ME, Kreek MJ. Narcotic blockade. Arch Intern Med 1966; 118 (04) 304-309
    CrossrefPubMedGoogle Scholar
  • 38 Joseph H, Stancliff S, Langrod J. Methadone maintenance treatment (MMT): a review of historical and clinical issues. Mt Sinai J Med 2000; 67 (5-6): 347-364
    PubMedGoogle Scholar
  • 39 Ball J, Ross A. The Effectiveness of Methadone Maintenance Treatment. New York, NY: Springer New York, NY; 2012
    Google Scholar
  • 40 Chou R, Cruciani RA, Fiellin DA. et al; American Pain Society, Heart Rhythm Society. Methadone safety: a clinical practice guideline from the American Pain Society and College on problems of drug dependence, in collaboration with the Heart Rhythm Society. J Pain 2014; 15 (04) 321-337
    CrossrefPubMedGoogle Scholar
  • 41 Wakeman SE, Larochelle MR, Ameli O. et al. Comparative effectiveness of different treatment pathways for opioid use disorder. JAMA Netw Open 2020; 3 (02) e1920622
    CrossrefPubMedGoogle Scholar
  • 42 Farrell M, Ward J, Mattick R. et al. Methadone maintenance treatment in opiate dependence: a review. BMJ 1994; 309 (6960): 997-1001
    CrossrefPubMedGoogle Scholar
  • 43 Mattick RP, Breen C, Kimber J, Davoli M. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database Syst Rev 2009; 2009 (03) CD002209
    PubMedGoogle Scholar
  • 44 Larochelle MR, Bernson D, Land T. et al. Medication for opioid use disorder after nonfatal opioid overdose and association with mortality: a cohort study. Ann Intern Med 2018; 169 (03) 137-145
    CrossrefPubMedGoogle Scholar
  • 45 Molero Y, Zetterqvist J, Binswanger IA, Hellner C, Larsson H, Fazel S. Medications for alcohol and opioid use disorders and risk of suicidal behavior, accidental overdoses, and crime. Am J Psychiatry 2018; 175 (10) 970-978
    CrossrefPubMedGoogle Scholar
  • 46 Carley JA, Oesterle T. Therapeutic approaches to opioid use disorder: what is the current standard of care?. Int J Gen Med 2021; 14: 2305-2311
    CrossrefPubMedGoogle Scholar
  • 47 Chou R, Weimer MB, Dana T. Methadone overdose and cardiac arrhythmia potential: findings from a review of the evidence for an American Pain Society and College on problems of drug dependence clinical practice guideline. J Pain 2014; 15 (04) 338-365
    CrossrefPubMedGoogle Scholar
  • 48 Stallvik M, Nordstrand B, Kristensen Ø, Bathen J, Skogvoll E, Spigset O. Corrected QT interval during treatment with methadone and buprenorphine–relation to doses and serum concentrations. Drug Alcohol Depend 2013; 129 (1-2): 88-93
    CrossrefPubMedGoogle Scholar
  • 49 Committee Opinion No. Committee opinion no. 711: opioid use and opioid use disorder in pregnancy. Obstet Gynecol 2017; 130 (02) e81-e94
    CrossrefPubMedGoogle Scholar
  • 50 Dashe JS, Jackson GL, Olscher DA, Zane EH, Wendel Jr GD. Opioid detoxification in pregnancy. Obstet Gynecol 1998; 92 (05) 854-858
    PubMedGoogle Scholar
  • 51 Stewart RD, Nelson DB, Adhikari EH. et al. The obstetrical and neonatal impact of maternal opioid detoxification in pregnancy. Am J Obstet Gynecol 2013; 209 (03) 267.e1-267.e5
    CrossrefPubMedGoogle Scholar
  • 52 Tran TH, Griffin BL, Stone RH, Vest KM, Todd TJ. Methadone, buprenorphine, and naltrexone for the treatment of opioid use disorder in pregnant women. Pharmacotherapy 2017; 37 (07) 824-839
    CrossrefPubMedGoogle Scholar
  • 53 U.S. Food and Drug Administration. Highlights of prescribing information: dolophine (methadone hydrochloride). Silver Spring, MD: U.S. Food and Drug Administration; 2014. Accessed November 22, 2022 at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/006134s038lbl.pdf
    Google Scholar
  • 54 Sachs HC. Committee On Drugs. The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics 2013; 132 (03) e796-e809
    CrossrefPubMedGoogle Scholar
  • 55 Capata M, Hartwell K. Opioid antagonist treatment of opioid-related disorders. In: Brady K, Levin F, Galanter M, Kleber H. eds. The American Psychiatric Association Publishing Textbook of Substance Use Disorder Treatment. 6th ed.. American Psychiatric Association Publishing; 2021
    Google Scholar
  • 56 Brunström M, Carlberg B. Association of blood pressure lowering with mortality and cardiovascular disease across blood pressure levels: a systematic review and meta-analysis. JAMA Intern Med 2018; 178 (01) 28-36
    CrossrefPubMedGoogle Scholar
  • 57 Lev R, Petro S, Lee A. et al. Methadone related deaths compared to all prescription related deaths. Forensic Sci Int 2015; 257: 347-352
    CrossrefPubMedGoogle Scholar
  • 58 Dasgupta N, Freifeld C, Brownstein JS. et al. Crowdsourcing black market prices for prescription opioids. J Med Internet Res 2013; 15 (08) e178
    CrossrefPubMedGoogle Scholar
  • 59 Madden ME, Shapiro SL. The methadone epidemic: methadone-related deaths on the rise in Vermont. Am J Forensic Med Pathol 2011; 32 (02) 131-135
    CrossrefPubMedGoogle Scholar
  • 60 Gudin J, Fudin J. A narrative pharmacological review of buprenorphine: a unique opioid for the treatment of chronic pain. Pain Ther 2020; 9 (01) 41-54
    CrossrefPubMedGoogle Scholar
  • 61 Weinstein ZM, Gryczynski G, Cheng DM. et al. Tapering off and returning to buprenorphine maintenance in a primary care Office Based Addiction Treatment (OBAT) program. Drug Alcohol Depend 2018; 189: 166-171
    CrossrefPubMedGoogle Scholar
  • 62 Johnson RE, Strain EC, Amass L. Buprenorphine: how to use it right. Drug Alcohol Depend 2003; 70 (2, suppl): S59-S77
    CrossrefPubMedGoogle Scholar
  • 63 Walsh SL, Eissenberg T. The clinical pharmacology of buprenorphine: extrapolating from the laboratory to the clinic. Drug Alcohol Depend 2003; 70 (2, suppl): S13-S27
    CrossrefPubMedGoogle Scholar
  • 64 Preston KL, Bigelow GE, Liebson IA. Effects of sublingually given naloxone in opioid-dependent human volunteers. Drug Alcohol Depend 1990; 25 (01) 27-34
    CrossrefPubMedGoogle Scholar
  • 65 Brixadi, Sublocade competitor, resubmits application to FDA. Alcohol Drug Abuse Wkly 2021; 33 (25) 8
    CrossrefPubMedGoogle Scholar
  • 66 Lewis JW. Buprenorphine. Drug Alcohol Depend 1985; 14 (3-4): 363-372
    CrossrefPubMedGoogle Scholar
  • 67 Jasinski DR, Pevnick JS, Griffith JD. Human pharmacology and abuse potential of the analgesic buprenorphine: a potential agent for treating narcotic addiction. Arch Gen Psychiatry 1978; 35 (04) 501-516
    CrossrefPubMedGoogle Scholar
  • 68 Public Law 115-271 - Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act or the SUPPORT for Patients and Communities Act. Accessed May 22, 2024 at: https://www.govinfo.gov/app/details/PLAW-115publ2712018
    PubMedGoogle Scholar
  • 69 Substance Abuse and Mental Health Services Administration. Statutes, Regulations, and Guidelines. Accessed August 29, 2020 at: https://www.samhsa.gov/medications-substance-use-disorders/statutes-regulations-guidelines
    PubMed
  • 70 U.S. Department of Health & Human Services. Removal of DATA Waiver (X-Waiver) Requirement. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2023. Accessed February 7, 2023 at: https://www.samhsa.gov/medications-substance-use-disorders/removal-data-waiver-requirement
    Google Scholar
  • 71 Oesterle TS, Kolla B, Risma CJ. et al. Substance use disorders and telehealth in the COVID-19 pandemic era: a new outlook. Mayo Clin Proc 2020; 95 (12) 2709-2718
    CrossrefPubMedGoogle Scholar
  • 72 Antoine D, Huhn AS, Strain EC. et al. Method for successfully inducting individuals who use illicit fentanyl onto buprenorphine/naloxone. Am J Addict 2021; 30 (01) 83-87
    CrossrefPubMedGoogle Scholar
  • 73 Greenwald MK, Herring AA, Perrone J, Nelson LS, Azar P. A neuropharmacological model to explain buprenorphine induction challenges. Ann Emerg Med 2022; 80 (06) 509-524
    CrossrefPubMedGoogle Scholar
  • 74 Center for Substance Abuse Treatment. Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2004
    Google Scholar
  • 75 Lizasoain I, Leza JC, Lorenzo P. Buprenorphine: bell-shaped dose-response curve for its antagonist effects. Gen Pharmacol 1991; 22 (02) 297-300
    CrossrefPubMedGoogle Scholar
  • 76 Jakubowski A, Fox A. Defining low-threshold buprenorphine treatment. J Addict Med 2020; 14 (02) 95-98
    CrossrefPubMedGoogle Scholar
  • 77 TIP 63: Medications for Opioid Use Disorder - Full Document | SAMHSA publications and digital products. Accessed May 22, 2024 at: https://store.samhsa.gov/product/TIP-63-Medications-for-Opioid-Use-Disorder-Full-Document/PEP21-02-01-0022021
    PubMed
  • 78 Samples H, Williams AR, Crystal S, Olfson M. Impact of long-term buprenorphine treatment on adverse health care outcomes in Medicaid. Health Aff (Millwood) 2020; 39 (05) 747-755
    CrossrefPubMedGoogle Scholar
  • 79 Dalsbo TK, Steiro A, Stromme H, Reinar LM. Effectiveness of Tapering from Methadone or Buprenorphine Maintenance Treatment Compared to Traditional Maintenance Treatment for People with Opiate Addiction: Systematic Review. Oslo: Norway; 2017
    Google Scholar
  • 80 Li X, Shorter D, Kosten TR. Buprenorphine in the treatment of opioid addiction: opportunities, challenges and strategies. Expert Opin Pharmacother 2014; 15 (15) 2263-2275
    CrossrefPubMedGoogle Scholar
  • 81 Kampman K, Jarvis M. American Society of Addiction Medicine (ASAM) National Practice guideline for the use of medications in the treatment of addiction involving opioid use. J Addict Med 2015; 9 (05) 358-367
    CrossrefPubMedGoogle Scholar
  • 82 Nielsen S, Larance B, Degenhardt L, Gowing L, Kehler C, Lintzeris N. Opioid agonist treatment for pharmaceutical opioid dependent people. Cochrane Database Syst Rev 2016; (05) CD011117
    PubMedGoogle Scholar
  • 83 Blum K, Han D, Modestino EJ. et al. A systematic, intensive statistical investigation of data from the comprehensive analysis of reported drugs (CARD) for compliance and illicit opioid abstinence in substance addiction treatment with buprenorphine/naloxone. Subst Use Misuse 2018; 53 (02) 220-229
    CrossrefPubMedGoogle Scholar
  • 84 Ling W, Charuvastra C, Collins JF. et al. Buprenorphine maintenance treatment of opiate dependence: a multicenter, randomized clinical trial. Addiction 1998; 93 (04) 475-486
    CrossrefPubMedGoogle Scholar
  • 85 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 (01) 79-87
    CrossrefPubMedGoogle Scholar
  • 86 Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2014; 2014 (02) CD002207
    PubMedGoogle Scholar
  • 87 Isbister GK, Brown AL, Gill A, Scott AJ, Calver L, Dunlop AJ. QT interval prolongation in opioid agonist treatment: analysis of continuous 12-lead electrocardiogram recordings. Br J Clin Pharmacol 2017; 83 (10) 2274-2282
    CrossrefPubMedGoogle Scholar
  • 88 Petry NM, Bickel WK, Piasecki D, Marsch LA, Badger GJ. Elevated liver enzyme levels in opioid-dependent patients with hepatitis treated with buprenorphine. Am J Addict 2000; 9 (03) 265-269
    CrossrefPubMedGoogle Scholar
  • 89 Saxon AJ, Ling W, Hillhouse M. et al. Buprenorphine/naloxone and methadone effects on laboratory indices of liver health: a randomized trial. Drug Alcohol Depend 2013; 128 (1-2): 71-76
    CrossrefPubMedGoogle Scholar
  • 90 Johnson H, Paulozzi L, Porucznik C, Mack K, Herter B. Hal Johnson Consulting and Division of Disease Control and Health Promotion, Florida Department of Health. Decline in drug overdose deaths after state policy changes - Florida, 2010-2012. MMWR Morb Mortal Wkly Rep 2014; 63 (26) 569-574
    PubMedGoogle Scholar
  • 91 Schuman-Olivier Z, Hoeppner BB, Weiss RD, Borodovsky J, Shaffer HJ, Albanese MJ. Benzodiazepine use during buprenorphine treatment for opioid dependence: clinical and safety outcomes. Drug Alcohol Depend 2013; 132 (03) 580-586
    CrossrefPubMedGoogle Scholar
  • 92 Reynaud M, Tracqui A, Petit G, Potard D, Courty P. Six deaths linked to misuse of buprenorphine-benzodiazepine combinations. Am J Psychiatry 1998; 155 (03) 448-449
    CrossrefPubMedGoogle Scholar
  • 93 Debelak K, Morrone WR, O'Grady KE, Jones HE. Buprenorphine + naloxone in the treatment of opioid dependence during pregnancy-initial patient care and outcome data. Am J Addict 2013; 22 (03) 252-254
    CrossrefPubMedGoogle Scholar
  • 94 Wiegand SL, Stringer EM, Stuebe AM, Jones H, Seashore C, Thorp J. Buprenorphine and naloxone compared with methadone treatment in pregnancy. Obstet Gynecol 2015; 125 (02) 363-368
    CrossrefPubMedGoogle Scholar
  • 95 Reckitt Benckiser Healthcare (UK) Ltd. Highlights of prescribing information: Subutex (buprenorphine). Richmond, VA: Reckitt Benckiser Pharmaceuticals Inc.; 2002. . Accessed November 22, 2022 at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020732s006s007lbl.pdf
    Google Scholar
  • 96 Langabeer JR, Stotts AL, Cortez A, Tortolero G, Champagne-Langabeer T. Geographic proximity to buprenorphine treatment providers in the U.S. Drug Alcohol Depend 2020; 213: 108131
    CrossrefPubMedGoogle Scholar
  • 97 Yokell MA, Zaller ND, Green TC, Rich JD. Buprenorphine and buprenorphine/naloxone diversion, misuse, and illicit use: an international review. Curr Drug Abuse Rev 2011; 4 (01) 28-41
    CrossrefPubMedGoogle Scholar
  • 98 Cicero TJ, Ellis MS, Chilcoat HD. Understanding the use of diverted buprenorphine. Drug Alcohol Depend 2018; 193: 117-123
    CrossrefPubMedGoogle Scholar
  • 99 Meyer MC, Straughn AB, Lo MW, Schary WL, Whitney CC. Bioequivalence, dose-proportionality, and pharmacokinetics of naltrexone after oral administration. J Clin Psychiatry 1984; 45 (9 Pt 2): 15-19
    PubMedGoogle Scholar
  • 100 Verebey K. The clinical pharmacology of naltrexone: pharmacology and pharmacodynamics. NIDA Res Monogr 1981; 28: 147-158
    PubMedGoogle Scholar
  • 101 Minozzi S, Amato L, Vecchi S, Davoli M, Kirchmayer U, Verster A. Oral naltrexone maintenance treatment for opioid dependence. Cochrane Database Syst Rev 2011; 2011 (04) CD001333
    PubMedGoogle Scholar
  • 102 Lee JD, Nunes Jr EV, Novo P. et al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet 2018; 391 (10118): 309-318
    CrossrefPubMedGoogle Scholar
  • 103 Kleber HD. Naltrexone. J Subst Abuse Treat 1985; 2 (02) 117-122
    CrossrefPubMedGoogle Scholar
  • 104 Bigelow GE, Preston KL, Schmittner J, Dong Q, Gastfriend DR. Opioid challenge evaluation of blockade by extended-release naltrexone in opioid-abusing adults: dose-effects and time-course. Drug Alcohol Depend 2012; 123 (1-3): 57-65
    CrossrefPubMedGoogle Scholar
  • 105 Blumberg H, Dayton HB. Naloxone, naltrexone, and related noroxymorphones. Adv Biochem Psychopharmacol 1973; 8 (00) 33-43
    PubMedGoogle Scholar
  • 106 Bisaga A, Mannelli P, Sullivan MA. et al. Antagonists in the medical management of opioid use disorders: historical and existing treatment strategies. Am J Addict 2018; 27 (03) 177-187
    CrossrefPubMedGoogle Scholar
  • 107 Sigmon SC, Bisaga A, Nunes EV, O'Connor PG, Kosten T, Woody G. Opioid detoxification and naltrexone induction strategies: recommendations for clinical practice. Am J Drug Alcohol Abuse 2012; 38 (03) 187-199
    CrossrefPubMedGoogle Scholar
  • 108 Sullivan M, Bisaga A, Pavlicova M. et al. Long-acting injectable naltrexone induction: a randomized trial of outpatient opioid detoxification with naltrexone versus buprenorphine. Am J Psychiatry 2017; 174 (05) 459-467
    CrossrefPubMedGoogle Scholar
  • 109 Bisaga A, Mannelli P, Yu M. et al. Outpatient transition to extended-release injectable naltrexone for patients with opioid use disorder: a phase 3 randomized trial. Drug Alcohol Depend 2018; 187: 171-178
    CrossrefPubMedGoogle Scholar
  • 110 Johansson BA, Berglund M, Lindgren A. Efficacy of maintenance treatment with naltrexone for opioid dependence: a meta-analytical review. Addiction 2006; 101 (04) 491-503
    CrossrefPubMedGoogle Scholar
  • 111 Gold MS, Dackis CA, Washton AM. The sequential use of clonidine and naltrexone in the treatment of opiate addicts. Adv Alcohol Subst Abuse 1984; 3 (03) 19-39
    CrossrefPubMedGoogle Scholar
  • 112 Comer SD, Collins ED, Kleber HD, Nuwayser ES, Kerrigan JH, Fischman MW. Depot naltrexone: long-lasting antagonism of the effects of heroin in humans. Psychopharmacology (Berl) 2002; 159 (04) 351-360
    CrossrefPubMedGoogle Scholar
  • 113 Sullivan MA, Bisaga A, Pavlicova M. et al. A randomized trial comparing extended-release injectable suspension and oral naltrexone, both combined with behavioral therapy, for the treatment of opioid use disorder. Am J Psychiatry 2019; 176 (02) 129-137
    CrossrefPubMedGoogle Scholar
  • 114 Brewer C, Streel E. Long-acting naltrexone has long-acting benefits and 100% induction rates are not difficult to achieve. Addiction 2019; 114 (01) 188-189
    CrossrefPubMedGoogle Scholar
  • 115 Garbutt JC, Kranzler HR, O'Malley SS. et al; Vivitrex Study Group. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. JAMA 2005; 293 (13) 1617-1625
    CrossrefPubMedGoogle Scholar
  • 116 Darpo B, Zhou M, Bai SA, Ferber G, Xiang Q, Finn A. Differentiating the effect of an opioid agonist on cardiac repolarization from µ-receptor-mediated, indirect effects on the QT interval: a randomized, 3-way crossover study in healthy subjects. Clin Ther 2016; 38 (02) 315-326
    CrossrefPubMedGoogle Scholar
  • 117 Tetrault JM, Tate JP, McGinnis KA. et al; Veterans Aging Cohort Study Team. Hepatic safety and antiretroviral effectiveness in HIV-infected patients receiving naltrexone. Alcohol Clin Exp Res 2012; 36 (02) 318-324
    CrossrefPubMedGoogle Scholar
  • 118 Mitchell MC, Memisoglu A, Silverman BL. Hepatic safety of injectable extended-release naltrexone in patients with chronic hepatitis C and HIV infection. J Stud Alcohol Drugs 2012; 73 (06) 991-997
    CrossrefPubMedGoogle Scholar
  • 119 Jones CW, Terplan M. Pregnancy and naltrexone pharmacotherapy. Obstet Gynecol 2018; 132 (04) 923-925
    CrossrefPubMedGoogle Scholar
  • 120 Chan CF, Page-Sharp M, Kristensen JH, O'Neil G, Ilett KF. Transfer of naltrexone and its metabolite 6,beta-naltrexol into human milk. J Hum Lact 2004; 20 (03) 322-326
    CrossrefPubMedGoogle Scholar
  • 121 Duramed Pharmaceuticals Inc. REVIA®. Cincinnati, OH: Duramed Pharmaceuticals, Inc.; 2013. . Accessed November 22, 2022 at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/018932s017lbl.pdf
    Google Scholar
  • 122 Harrison TK, Kornfeld H, Aggarwal AK, Lembke A. Perioperative considerations for the patient with opioid use disorder on buprenorphine, methadone, or naltrexone maintenance therapy. Anesthesiol Clin 2018; 36 (03) 345-359
    CrossrefPubMedGoogle Scholar
  • 123 Anderson TA, Quaye ANA, Ward EN, Wilens TE, Hilliard PE, Brummett CM. To stop or not, that is the question: acute pain management for the patient on chronic buprenorphine. Anesthesiology 2017; 126 (06) 1180-1186
    CrossrefPubMedGoogle Scholar