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Highlights & Basics
- Opioid use disorder is a significant and rapidly evolving public health concern worldwide, with increasing use of synthetic opioids such as fentanyl driving increases in opioid use disorder and in overdose deaths.
- Opioid use disorder is a problematic pattern of opioid use leading to clinically significant impairment or distress.
- It is important to assess comorbid medical and psychiatric illnesses, as well as other substance use disorders.
- Physicians should be aware of methods for screening and detection of opioid use in clinical settings.
- Opioid use disorder is a treatable, chronic disease. Evidence-based treatments include medically supervised withdrawal, maintenance therapy with relapse prevention pharmacotherapy, and psychosocial treatment.
Quick Reference
History & Exam
Key Factors
Other Factors
Diagnostics Tests
Treatment Options
Definition
Epidemiology
Etiology
Pathophysiology
Citations
American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed, text revision (DSM-5-TR). Washington, DC: American Psychiatric Association; 2022.[Full Text]
World Health Organization. WHO releases 2025 update to the International Classification of Diseases (ICD-11). Feb 2025 [Internet publication].[Full Text]
American Society of Addiction Medicine. The ASAM national practice guideline for the treatment of opioid use disorder: 2020 focused update. 2020 Mar/Apr;14(2S suppl 1):1-91.[Abstract][Full Text]
Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].[Full Text]
National Institute for Health and Care Excellence. Drug misuse in over 16s: opioid detoxification. Jul 2007 (reaffirmed 2019) [internet publication].[Full Text]
1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed, text revision (DSM-5-TR). Washington, DC: American Psychiatric Association; 2022.[Full Text]
2. World Health Organization. WHO releases 2025 update to the International Classification of Diseases (ICD-11). Feb 2025 [Internet publication].[Full Text]
3. National Institute on Drug Abuse. Commonly used drugs charts. Aug 2020 [internet publication].[Full Text]
4. United Nations Office on Drugs and Crime. World drug report 2024. 2024 [internet publication].[Full Text]
5. DeWeerdt S. Tracing the US opioid crisis to its roots. Nature. 2019 Sep;573(7773):S10-2.[Abstract][Full Text]
6. Humphreys K, Shover CL, Andrews CM, et al. Responding to the opioid crisis in North America and beyond: recommendations of the Stanford-Lancet Commission. Lancet. 2022 Feb 5;399(10324):555-604.[Abstract]
7. Keyes KM, Rutherford C, Hamilton A, et al. What is the prevalence of and trend in opioid use disorder in the United States from 2010 to 2019? Using multiplier approaches to estimate prevalence for an unknown population size. Drug Alcohol Depend Rep. 2022 Jun:3:100052.[Abstract][Full Text]
8. Dowell D, Brown S, Gyawali S, et al. Treatment for opioid use disorder: population estimates - United States, 2022. MMWR Morb Mortal Wkly Rep. 2024 Jun 27;73(25):567-74.[Abstract][Full Text]
9. United Nations Office on Drugs and Crime. Key findings and conclusions. Jun 2024 [internet publication].[Full Text]
10. National Institute on Drug Abuse. Drug overdose deaths: facts and figures. Aug 2024 [internet publication].[Full Text]
11. Wilson N, Kariisa M, Seth P, et al. Drug and opioid-involved overdose deaths - United States, 2017-2018. MMWR Morb Mortal Wkly Rep. 2020 Mar 20;69(11):290-7.[Abstract][Full Text]
12. Park TW, Saitz R, Ganoczy D, et al. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ. 2015 Jun 10;350:h2698.[Abstract][Full Text]
13. Sun EC, Dixit A, Humphreys K, et al. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. BMJ. 2017 Mar 14;356:j760.[Abstract][Full Text]
14. Jeffery MM, Hooten WM, Jena AB, et al. Rates of physician coprescribing of opioids and benzodiazepines after the release of the Centers for Disease Control and Prevention guidelines in 2016. JAMA Netw Open. 2019 Aug 2;2(8):e198325.[Abstract][Full Text]
15. Zhu DT, Cano M. Fentanyl-xylazine overdose deaths in the USA, 2018-2023. Inj Prev. 2025 Apr 2:ip-2024-045596.[Abstract][Full Text]
16. Palamar JJ, Krotulski AJ. Medetomidine infiltrates the US illicit opioid market. JAMA. 2024 Nov 5;332(17):1425-6.
17. Zhu DT, Palamar JJ. Responding to medetomidine: clinical and public health needs. Lancet Reg Health Am. 2025 Apr;44:101053.[Full Text]
18. European Union Drugs Agency. Heroin and other opioids - the current situation in Europe (European Drug Report 2024). Jun 2024 [internet publication].[Full Text]
19. Blanco C, Volkow ND. Management of opioid use disorder in the USA: present status and future directions. Lancet. 2019 Apr 27;393(10182):1760-72.[Abstract]
20. Nechuta S, Mukhopadhyay S, Golladay M, et al. Trends, patterns, and maternal characteristics of opioid prescribing during pregnancy in a large population-based cohort study. Drug Alcohol Depend. 2022 Apr 1;233:109331.[Abstract][Full Text]
21. Ko JY, D'Angelo DV, Haight SC, et al. Vital signs: prescription opioid pain reliever use during pregnancy - 34 U.S. jurisdictions, 2019. MMWR Morb Mortal Wkly Rep. 2020 Jul 17;69(28):897-903.[Abstract][Full Text]
22. Bateman BT, Hernandez-Diaz S, Straub L, et al. Association of first trimester prescription opioid use with congenital malformations in the offspring: population based cohort study. BMJ. 2021 Feb 10;372:n102.[Abstract][Full Text]
23. Degenhardt L, Peacock A, Colledge S, et al. Global prevalence of injecting drug use and sociodemographic characteristics and prevalence of HIV, HBV, and HCV in people who inject drugs: a multistage systematic review. Lancet Glob Health. 2017 Dec;5(12):e1192-207.[Abstract][Full Text]
24. Neaigus A, Miller M, Friedman SR, et al. Potential risk factors for the transition to injecting among non-injecting heroin users: a comparison of former injectors and never injectors. Addiction. 2001 Jun;96(6):847-60.[Abstract]
25. Santo T Jr, Campbell G, Gisev N, et al. Exposure to childhood trauma increases risk of opioid use disorder among people prescribed opioids for chronic non-cancer pain. Drug Alcohol Depend. 2022 Jan 1;230:109199.[Abstract]
26. Fortson K, Rajbhandari-Thapa J, Ingels J, et al. Adverse childhood experiences, risk of opioid misuse and its pathway among students at a public university. J Am Coll Health. 2021 Nov 17:1-10.[Abstract]
27. Guarino H, Mateu-Gelabert P, Quinn K, et al. Adverse childhood experiences predict early initiation of opioid use behaviors. Front Sociol. 2021 May 13;6:620395.[Abstract][Full Text]
28. Barry R, Anderson J, Tran L, et al. Prevalence of mental health disorders among individuals experiencing homelessness: a systematic review and meta-analysis. JAMA Psychiatry. 2024 Jul 1;81(7):691-9.[Abstract]
29. Manhapra A, Stefanovics E, Rosenheck R. The association of opioid use disorder and homelessness nationally in the veterans health administration. Drug Alcohol Depend. 2021 Jun 1;223:108714.[Abstract]
30. Doran KM, Rahai N, McCormack RP, et al. Substance use and homelessness among emergency department patients. Drug Alcohol Depend. 2018 Jul 1;188:328-33.[Abstract][Full Text]
31. Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse: results from the Epidemiologic Catchment Area (ECA) study. JAMA. 1990 Nov 21;264(19):2511-8.[Abstract]
32. Klimas J, Gorfinkel L, Fairbairn N, et al. Strategies to identify patient risks of prescription opioid addiction when initiating opioids for pain: a systematic review. JAMA Netw Open. 2019 May 3;2(5):e193365.[Abstract][Full Text]
33. Santo T Jr, Campbell G, Gisev N, et al. Prevalence of mental disorders among people with opioid use disorder: a systematic review and meta-analysis. Drug Alcohol Depend. 2022 Sep 1;238:109551.[Abstract]
34. Buresh M, Stern R, Rastegar D. Treatment of opioid use disorder in primary care. BMJ. 2021 May 19;373:n784.[Abstract]
35. Crist RC, Reiner BC, Berrettini WH. A review of opioid addiction genetics. Curr Opin Psychol. 2019 Jun;27:31-5.[Abstract][Full Text]
36. Cox BM, Christie MJ, Devi L, et al. Challenges for opioid receptor nomenclature: IUPHAR Review 9. Br J Pharmacol. 2015 Jan;172(2):317-23.[Abstract][Full Text]
37. Donica CL, Awwad HO, Thakker DR, et al. Cellular mechanisms of nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor regulation and heterologous regulation by N/OFQ. Mol Pharmacol. 2013 May;83(5):907-18.[Abstract][Full Text]
38. Valentino RJ, Volkow ND. Untangling the complexity of opioid receptor function. Neuropsychopharmacology. 2018 Dec;43(13):2514-20.[Abstract][Full Text]
39. Morrone LA, Scuteri D, Rombolà L, et al. Opioids resistance in chronic pain management. Curr Neuropharmacol. 2017 Apr;15(3):444-56.[Abstract][Full Text]
40. Kosten TR, George TP. The neurobiology of opioid dependence: implications for treatment. Sci Pract Perspect. 2002 Jul;1(1):13-20.[Abstract][Full Text]
41. Koob GF, Le Moal M. Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology. 2001 Feb;24(2):97-129.[Abstract][Full Text]
42. Dawe S, Gray JA. Craving and drug reward: a comparison of methadone and clonidine in detoxifying opiate addicts. Drug Alcohol Depend. 1995 Oct;39(3):207-12.[Abstract]
43. Campbell G, Noghrehchi F, Nielsen S, et al. Risk factors for indicators of opioid-related harms amongst people living with chronic non-cancer pain: findings from a 5-year prospective cohort study. EClinicalMedicine. 2020 Nov;28:100592.[Abstract][Full Text]
44. Shanahan L, Hill SN, Bechtiger L, et al. Prevalence and childhood precursors of opioid use in the early decades of life. JAMA Pediatr. 2021 Mar 1;175(3):276-85.[Abstract][Full Text]
45. Wilton J, Abdia Y, Chong M, et al. Prescription opioid treatment for non-cancer pain and initiation of injection drug use: large retrospective cohort study. BMJ. 2021 Nov 18;375:e066965.[Abstract][Full Text]
46. Davis MA, Lin LA, Liu H, et al. Prescription opioid use among adults with mental health disorders in the United States. J Am Board Fam Med. 2017 Jul-Aug;30(4):407-17.[Abstract][Full Text]
47. Edlund MJ, Steffick D, Hudson T, et al. Risk factors for clinically recognized opioid abuse and dependence among veterans using opioids for chronic non-cancer pain. Pain. 2007 Jun;129(3):355-62.[Abstract]
48. Griesler PC, Hu MC, Wall MM, et al. Assessment of prescription opioid medical use and misuse among parents and their adolescent offspring in the US. JAMA Netw Open. 2021 Jan 4;4(1):e2031073.[Abstract][Full Text]
49. Birnbaum HG, White AG, Schiller M, et al. Societal costs of prescription opioid abuse, dependence, and misuse in the United States. Pain Med. 2011 Apr;12(4):657-67.[Abstract][Full Text]
50. Håkansson A, Berglund M. Risk factors for criminal recidivism - a prospective follow-up study in prisoners with substance abuse. BMC Psychiatry. 2012 Aug 15;12:111.[Abstract][Full Text]
51. Molero Y, Zetterqvist J, Binswanger IA, et al. Medications for alcohol and opioid use disorders and risk of suicidal behavior, accidental overdoses, and crime. Am J Psychiatry. 2018 Oct 1;175(10):970-8.[Abstract][Full Text]
52. Dowell D, Ragan KR, Jones CM, et al. CDC clinical practice guideline for prescribing opioids for pain - United States, 2022. MMWR Recomm Rep. 2022 Nov 4;71(3):1-95.[Abstract][Full Text]
53. Paice JA, Bohlke K, Barton D, et al. Use of opioids for adults with pain from cancer or cancer treatment: ASCO Guideline. J Clin Oncol. 5 Dec 2022 [Epub ahead of print].[Abstract][Full Text]
54. Najib U, Cheng EM, Halker Singh RB, et al. AAN position: opioids. Neurology. 2025 May 13;104(9).[Full Text]
55. U.S. Food and Drug Administration. FDA updates prescribing information for all opioid pain medicines to provide additional guidance for safe use. Apr 2023 [internet publication].[Full Text]
56. U.S. Food and Drug Administration. FDA is requiring opioid pain medicine manufacturers to update prescribing information regarding long-term use. Jul 2025 [internet publication].[Full Text]
57. Hadland SE, Agarwal R, Raman SR, et al. Opioid prescribing for acute pain management in children and adolescents in outpatient settings: clinical practice guideline. Pediatrics. 2024 Sep 30:e2024068752.[Abstract][Full Text]
58. US Preventive Services Task Force, Krist AH, Davidson KW, et al. Primary care-based interventions to prevent illicit drug use in children, adolescents, and young adults: US Preventive Services Task Force recommendation statement. JAMA. 2020 May 26;323(20):2060-6.[Abstract]
59. Chadi N, Walker-Harding L, Committee on Substance Use and Prevention. Nonmedical use of controlled medications by adolescents and young adults: clinical report. Pediatrics. 2024 Dec 1;154(6):e2024069298.[Abstract][Full Text]
60. Pantin H, Coatsworth JD, Feaster DJ, et al. Familias Unidas: the efficacy of an intervention to promote parental investment in Hispanic immigrant families. Prev Sci. 2003 Sep;4(3):189-201.[Abstract]
61. de Graaf I, Speetjens P, Smit F, et al. Effectiveness of the Triple P Positive Parenting Program on behavioral problems in children: a meta-analysis. Behav Modif. 2008 Sep;32(5):714-35.[Abstract]
62. Spoth R, Lopez Reyes M, Redmond C, et al. Assessing a public health approach to delay onset and progression of adolescent substance use: latent transition and log-linear analyses of longitudinal family preventive intervention outcomes. J Consult Clin Psychol. 1999 Oct;67(5):619-30.[Abstract]
63. Compton WM, Jones CM, Baldwin GT, et al. Targeting youth to prevent later substance use disorder: an underutilized response to the US opioid crisis. Am J Public Health. 2019 Jun;109(s3):S185-9.[Abstract][Full Text]
64. Sandhu HK, Booth K, Furlan AD, et al. Reducing opioid use for chronic pain with a group-based intervention: a randomized clinical trial. JAMA. 2023 May 23;329(20):1745-56.[Abstract][Full Text]
65. American Society of Addiction Medicine. The ASAM national practice guideline for the treatment of opioid use disorder: 2020 focused update. 2020 Mar/Apr;14(2S suppl 1):1-91.[Abstract][Full Text]
66. Mitchell C, Dolan N, Dürsteler KM. Management of dependent use of illicit opioids. BMJ. 2020 Mar 9;368:m710.[Abstract]
67. Srivastava AB, Mariani JJ, Levin FR. New directions in the treatment of opioid withdrawal. Lancet. 2020 Jun 20;395(10241):1938-48.[Abstract][Full Text]
68. Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].[Full Text]
69. McLellan AT, Luborsky L, Woody GE, et al. An improved diagnostic evaluation instrument for substance abuse patients. The Addiction Severity Index. J Nerv Ment Dis. 1980 Jan;168(1):26-33.[Abstract]
70. Substance Abuse and Mental Health Services Administration. Clinical drug testing in primary care: technical assistance publication series TAP 32. 2012 [internet publication].[Full Text]
71. Moeller KE, Lee KC, Kissack JC. Urine drug screening: practical guide for clinicians. Mayo Clin Proc. 2008 Jan;83(1):66-76.[Abstract][Full Text]
72. Mayo Clinic Laboratories. Methadone [internet publication].[Full Text]
73. Wesson DR, Ling W. The clinical opiate withdrawal scale (COWS). J Psychoactive Drugs. 2003 Apr-Jun;35(2):253-9.[Abstract]
74. US Preventive Services Task Force. Unhealthy drug use: screening. Jun 2020 [internet publication].[Full Text]
75. American Academy of Family Physicians. Clinical preventive service recommendation on opioid use disorder (OUD): screening. 2025 [internet publication].[Full Text]
76. Hickman M, Lingford-Hughes A, Bailey C, et al. Does alcohol increase the risk of overdose death: the need for a translational approach. Addiction. 2008 Jul;103(7):1060-2.[Abstract]
77. Zacny JP, Lichtor SA. Nonmedical use of prescription opioids: motive and ubiquity issues. J Pain. 2008 Jun;9(6):473-86.[Abstract][Full Text]
78. Starrels JL, Becker WC, Alford DP, et al. Systematic review: treatment agreements and urine drug testing to reduce opioid misuse in patients with chronic pain. Ann Internal Med. 2010 Jun 1;152(11):712-20.[Abstract]
79. American College of Surgeons. Best practices guidelines: screening and intervention for mental health disorders and substance use and misuse in the acute trauma patient. Dec 2022 [internet publication].[Full Text]
80. American College of Obstetricians and Gynecologists. Opioid use and opioid use disorder in pregnancy. Committee Opinion No 711. Aug 2017 (reaffirmed 2021) [internet publication].[Full Text]
81. Ecker J, Abuhamad A, Hill W, et al. Substance use disorders in pregnancy: clinical, ethical, and research imperatives of the opioid epidemic: a report of a joint workshop of the Society for Maternal-Fetal Medicine, American College of Obstetricians and Gynecologists, and American Society of Addiction Medicine. Am J Obstet Gynecol. 2019 Jul;221(1):B5-28.[Abstract][Full Text]
82. Edlund MJ, Martin BC, Russo JE, et al. The role of opioid prescription in incident opioid abuse and dependence among individuals with chronic noncancer pain: the role of opioid prescription. Clin J Pain. 2014 Jul;30(7):557-64.[Abstract][Full Text]
83. Sheehan DV, Lecrubier Y, Sheehan KH, et al. The mini-international neuropsychiatric Interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 (20 suppl):22-33;quiz 34-57.[Abstract]
84. Yudko E, Lozhkina O, Fouts A. A comprehensive review of the psychometric properties of the Drug Abuse Screening Test. J Subst Abuse Treat. 2007 Mar;32(2):189-98.[Abstract]
85. Rosenberg SD, Drake RE, Wolford GL, et al. Dartmouth Assessment of Lifestyle Instrument (DALI): a substance use disorder screen for people with severe mental illness. Am J Psychiatry. 1998 Feb;155(2):232-8.[Abstract]
86. Wickersham JA, Azar MM, Cannon CM, et al. Validation of a brief measure of opioid dependence: the rapid opioid dependence screen (RODS). J Correct Health Care. 2015 Jan;21(1):12-26.[Abstract][Full Text]
87. Rieb LM, Samaan Z, Furlan AD, et al. Canadian guidelines on opioid use disorder among older adults. Can Geriatr J. 2020 Mar;23(1):123-34.[Abstract][Full Text]
88. Jarvis M, Williams J, Hurford M, et al. Appropriate use of drug testing in clinical addiction medicine. J Addict Med. 2017 May/Jun;11(3):163-73.[Abstract][Full Text]
89. World Health Organization. Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence. Jan 2009 [internet publication].[Full Text]
90. Mattick RP, Breen C, Kimber J, et al. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014 Feb 6;(2):CD002207.[Abstract][Full Text]
91. Krupitsky E, Nunes EV, Ling W, et al. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. Lancet. 2011 Apr 30;377(9776):1506-13.[Abstract][Full Text]
92. Mattick RP, Breen C, Kimber J, et al. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database Syst Rev. 2009 Jul 8;2009(3):CD002209.[Abstract][Full Text]
93. Lowry N, Najia C, Kelleher M, et al. Patient experience of opioid use disorder treatment medications: a systematic review of contemporary qualitative research. BMJ Open. 2024 Dec 4;14(12):e088617.[Abstract][Full Text]
94. American Society of Addiction Medicine. Engagement and retention of nonabstinent patients in substance use treatment: clinical consideration for addiction treatment providers. Oct 2024 [internet publication].[Full Text]
95. Saber-Tehrani AS, Bruce RD, Altice FL. Pharmacokinetic drug interactions and adverse consequences between psychotropic medications and pharmacotherapy for the treatment of opioid dependence. Am J Drug Alcohol Abuse. 2011 Jan;37(1):1-11.[Abstract]
96. Mee-Lee D, Shulman GD, Fishman MJ, et al., (eds). The ASAM Criteria: treatment criteria for addictive, substance-related, and co-occurring conditions. 3rd ed. Carson City, NY: The Change Companies; 2013.
97. National Institute for Health and Care Excellence. Drug misuse in over 16s: opioid detoxification. Jul 2007 (reaffirmed 2019) [internet publication].[Full Text]
98. Galanter M, Kleber HD, eds. The American Psychiatric Publishing textbook of substance abuse treatment. Washington, DC: American Psychiatric Publishing; 2008.
99. Gowing L, Farrell M, Ali R, et al. Alpha₂-adrenergic agonists for the management of opioid withdrawal. Cochrane Database Syst Rev. 2016 May 3;2016(5):CD002024.[Abstract][Full Text]
100. American College of Emergency Physicians Clinical Policies Subcommittee (writing committee) on opioids; Hatten BW, Cantrill SV, et al. Clinical policy: critical issues related to opioids in adult patients presenting to the emergency department. Ann Emerg Med. 2020 Sep;76(3):e13-39.[Abstract][Full Text]
101. US Department of Veterans Affairs; Department of Defense. VA/DoD clinical practice guideline for the management of substance use disorders. Aug 2021 [internet publication].[Full Text]
102. Blazes CK, Morrow JD. Reconsidering the usefulness of adding naloxone to buprenorphine. Front Psychiatry. 2020 Sep 11;11:549272.[Abstract][Full Text]
103. Gowing L, Ali R, White JM, et al. Buprenorphine for managing opioid withdrawal. Cochrane Database Syst Rev. 2017 Feb 21;2(2):CD002025.[Abstract][Full Text]
104. Johnson RE, Fudala PJ, Jaffe JH. Outpatient comparison of buprenorphine and methadone maintenance. I. Effects on opiate use and self-reported adverse effects and withdrawal symptomatology. NIDA Res Monogr. 1990;105:585-6.[Abstract]
105. Fudala PJ, Johnson RE, Jaffe JH. Outpatient comparison of buprenorphine and methadone maintenance. II. Effects on cocaine usage, retention time in study and missed clinic visits. NIDA Res Monogr. 1990;105:587-8.[Abstract]
106. Johnson RE, McCagh JC. Buprenorphine and naloxone for heroin dependence. Curr Psychiatry Rep. 2000 Dec;2(6):519-26.[Abstract]
107. Meader N. A comparison of methadone, buprenorphine and alpha(2) adrenergic agonists for opioid detoxification: a mixed treatment comparison meta-analysis. Drug Alcohol Depend. 2010 Apr 1;108(1-2):110-4.[Abstract]
108. Amato L, Davoli M, Minozzi S, et al. Methadone at tapered doses for the management of opioid withdrawal. Cochrane Database Syst Rev. 2013 Feb 28;2013(2):CD003409.[Abstract][Full Text]
109. Kleber HD, Topazian M, Gaspari J, et al. Clonidine and naltrexone in the outpatient treatment of heroin withdrawal. Am J Drug Alcohol Abuse. 1987;13(1-2):1-17.[Abstract]
110. Vining E, Kosten TR, Kleber HD. Clinical utility of rapid clonidine-naltrexone detoxification for opioid abusers. Br J Addict. 1988 May;83(5):567-75.[Abstract]
111. Amato L, Minozzi S, Davoli M, et al. Psychosocial and pharmacological treatments versus pharmacological treatments for opioid detoxification. Cochrane Database Syst Rev. 2011 Sep 7;(9):CD005031.[Abstract][Full Text]
112. Bolívar HA, Klemperer EM, Coleman SRM, et al. Contingency management for patients receiving medication for opioid use disorder: a systematic review and meta-analysis. JAMA Psychiatry. 2021 Oct 1;78(10):1092-102.[Abstract][Full Text]
113. Broome KM, Joe GW, Simpson DD. HIV risk reduction in outpatient drug abuse treatment: individual and geographic differences. AIDS Educ Prev. 1999 Aug;11(4):293-306.[Abstract]
114. Longshore D, Hsieh S. Drug abuse treatment and risky sex: evidence for a cumulative treatment effect? Am J Drug Alcohol Abuse. 1998 Aug;24(3):439-51.[Abstract]
115. Santo T Jr, Clark B, Hickman M, et al. Association of opioid agonist treatment with all-cause mortality and specific causes of death among people with opioid dependence: a systematic review and meta-analysis. JAMA Psychiatry. 2021 Sep 1;78(9):979-93.[Abstract][Full Text]
116. Nielsen S, Tse WC, Larance B. Opioid agonist treatment for people who are dependent on pharmaceutical opioids. Cochrane Database Syst Rev. 2022 Sep 5;9(9):CD011117.[Abstract][Full Text]
117. Sordo L, Barrio G, Bravo MJ, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017 Apr 26;357:j1550.[Abstract][Full Text]
118. National Institute for Health and Care Excellence. Methadone and buprenorphine for the management of opioid dependence. Jan 2007 (reaffirmed Feb 2016) [internet publication].[Full Text]
119. Bruneau J, Ahamad K, Goyer MÈ, et al. Management of opioid use disorders: a national clinical practice guideline. CMAJ. 2018 Mar 5;190(9):E247-57.[Abstract][Full Text]
120. Zhang P, Tossone K, Ashmead R, et al. Examining differences in retention on medication for opioid use disorder: an analysis of Ohio Medicaid data. J Subst Abuse Treat. 2022 May;136:108686.[Abstract]
121. Degenhardt L, Clark B, Macpherson G, et al. Buprenorphine versus methadone for the treatment of opioid dependence: a systematic review and meta-analysis of randomised and observational studies. Lancet Psychiatry. 2023 Jun;10(6):386-402.[Abstract]
122. Department of Health and Social Care. Guidance on drug misuse and dependence: UK guidelines on clinical management. Dec 2017 [internet publication].[Full Text]
123. Brunner E, Chen CA, Klein T, et al. Joint cinical practice guideline on benzodiazepine tapering: considerations when risks outweigh benefits. J Gen Intern Med. 2025 Jun 17.[Abstract][Full Text]
124. Fudala PJ, Bridge TP, Herbert S, et al. Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone. N Engl J Med. 2003 Sep 4;349(10):949-58.[Abstract][Full Text]
125. Kornør H, Lobmaier PPK, Kunøe N. Sustained-release naltrexone for opioid dependence. Cochrane Database Syst Rev. 2025 May 9;5(5):CD006140.[Abstract][Full Text]
126. Tanum L, Solli KK, Latif ZE, et al. Effectiveness of injectable extended-release naltrexone vs daily buprenorphine-naloxone for opioid dependence: a randomized clinical noninferiority trial. JAMA Psychiatry. 2017 Dec 1;74(12):1197-205.[Abstract][Full Text]
127. Lee JD, Nunes EV Jr, 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 Jan 27;391(10118):309-18.[Abstract][Full Text]
128. Syed YY, Keating GM. Extended-release intramuscular naltrexone (VIVITROL®): a review of its use in the prevention of relapse to opioid dependence in detoxified patients. CNS Drugs. 2013 Oct;27(10):851-61.[Abstract]
129. Lee JD, Friedmann PD, Kinlock TW, et al. Extended-release naltrexone to prevent opioid relapse in criminal justice offenders. N Engl J Med. 2016 Mar 31;374(13):1232-42.[Abstract][Full Text]
130. 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 Nov;73(6):991-7.[Abstract]
131. Washton AM, Pottash AC, Gold MS. Naltrexone in addicted business executives and physicians. J Clin Psychiatry. 1984 Sep;45(9 Pt 2):39-41.[Abstract]
132. Washton AM, Gold MS, Pottash AC. Successful use of naltrexone in addicted physicians and business executives. Adv Alcohol Subst Abuse. 1984 Winter;4(2):89-96.[Abstract]
133. Roth A, Hogan I, Farren C. Naltrexone plus group therapy for the treatment of opiate-abusing health-care professionals. J Subst Abuse Treat. 1997 Jan-Feb;14(1):19-22.[Abstract]
134. Brahen LS, Henderson RK, Capone T, et al. Naltrexone treatment in a jail work-release program. J Clin Psychiatry. 1984 Sep;45(9 pt 2):49-52.[Abstract]
135. Minozzi S, Amato L, Vecchi S, et al. Oral naltrexone maintenance treatment for opioid dependence. Cochrane Database Syst Rev. 2011 Apr 13;2011(4):CD001333.[Abstract][Full Text]
136. Woody GE, McLellan AT, Luborsky L, et al. Psychotherapy in community methadone programs: a validation study. Am J Psychiatry. 1995 Sep;152(9):1302-8.[Abstract]
137. Dugosh K, Abraham A, Seymour B, et al. A systematic review on the use of psychosocial interventions in conjunction with medications for the treatment of opioid addiction. J Addict Med. 2016 Mar-Apr;10(2):93-103.[Abstract][Full Text]
138. Schwenker R, Dietrich CE, Hirpa S, et al. Motivational interviewing for substance use reduction. Cochrane Database Syst Rev. 2023 Dec 12;12(12):CD008063.[Abstract][Full Text]
139. Hruschak V, Cochran G, Wasan AD. Psychosocial interventions for chronic pain and comorbid prescription opioid use disorders: a narrative review of the literature. J Opioid Manag. 2018 Sep/Oct;14(5):345-58.[Abstract]
140. Avery N, McNeilage AG, Stanaway F, et al. Efficacy of interventions to reduce long term opioid treatment for chronic non-cancer pain: systematic review and meta-analysis. BMJ. 2022 Apr 4;377:e066375.[Abstract][Full Text]
141. Garland EL, Hanley AW, Nakamura Y, et al. Mindfulness-oriented recovery enhancement vs supportive group therapy for co-occurring opioid misuse and chronic pain in primary care: a randomized clinical trial. JAMA Intern Med. 2022 Apr 1;182(4):407-17.[Abstract][Full Text]
142. McGovern R, Newham JJ, Addison MT, et al. Effectiveness of psychosocial interventions for reducing parental substance misuse. Cochrane Database Syst Rev. 2021 Mar 16;3(3):CD012823.[Abstract][Full Text]
143. Marsch LA, Bickel WK, Badger GJ, et al. Comparison of pharmacological treatments for opioid-dependent adolescents: a randomized controlled trial. Arch Gen Psychiatry. 2005 Oct;62(10):1157-64.[Abstract][Full Text]
144. Woody GE, Poole SA, Subramaniam G, et al. Extended vs. short-term buprenorphine-naloxone for treatment of opioid-addicted youth: a randomized trial. JAMA. 2008 Nov 5;300(17):2003-11.[Abstract][Full Text]
145. Feillin DA. Treatment of adolescent opioid dependence: no quick fix. JAMA. 2008 Nov 5;300(17):2057-9.[Abstract]
146. Hopfer CJ, Khuri E, Crowley TJ, et al. Adolescent heroin use: a review of the descriptive and treatment literature. J Subst Abuse Treat. 2002 Oct;23(3):231-37.[Abstract]
147. Marsch LA. Treatment of adolescents. In: Strain EC, Stitzer ML, eds. The treatment of opioid dependence. Baltimore, MD: Johns Hopkins University Press; 2005:497-507.
148. Dattel BJ. Substance abuse in pregnancy. Semin Perinatol. 1990 Apr;14(2):179-87.[Abstract]
149. World Health Organization. Guidelines for identification and management of substance use and substance use disorders in pregnancy. 2014 [internet publication].[Full Text]
150. Terplan M, Laird HJ, Hand DJ, et al. Opioid detoxification during pregnancy: a systematic review. Obstet Gynecol. 2018 May;131(5):803-14.[Abstract][Full Text]
151. Substance Abuse and Mental Health Services Administration. Evidence-based, whole-person care for pregnant people who have opioid use disorder. Mar 2024 [internet publication].[Full Text]
152. Suarez EA, Huybrechts KF, Straub L, et al. Buprenorphine versus methadone for opioid use disorder in pregnancy. N Engl J Med. 2022 Dec 1;387(22):2033-44.[Abstract]
153. Atluru S, Bruehlman AK, Vaughn P, et al. Naltrexone compared with buprenorphine or methadone in pregnancy: a systematic review. Obstet Gynecol. 2024 Mar 1;143(3):403-10.[Abstract]
154. Wurst KE, Zedler BK, Joyce AR, et al. A Swedish population-based study of adverse birth outcomes among pregnant women treated with buprenorphine or methadone: preliminary findings. Subst Abuse. 2016 Sep 15:10:89-97.[Abstract][Full Text]
155. Lejeune C, Simmat-Durand L, Gourarier L, et al. Prospective multicenter observational study of 260 infants borne to 259 opiate-dependent mothers on methadone or high-dose buprenophine substitution. Drug Alcohol Depend. 2006 May 20;82(3):250-7.[Abstract]
156. Schindler SD, Eder H, Ortner R, et al. Neonatal outcome following buprenorphine maintenance during conception and throughout pregnancy. Addiction. 2003 Jan;98(1):103-10.[Abstract]
157. Hytinantti T, Kahila H, Renlund M, et al. Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero. Acta Pediatr. 2008 Aug;97(8):1040-4.[Abstract]
158. Kakko J, Heilig M, Sarman I. Buprenorphine and methadone treatment of opiate dependence during pregnancy: comparison of fetal growth and neonatal outcomes in two consecutive case series. Drug Alcohol Depend. 2008 Jul 1;96(1-2):69-78.[Abstract]
159. Harris M, Schiff DM, Saia K, et al. Academy of breastfeeding medicine clinical protocol #21: breastfeeding in the setting of substance use and substance use disorder (revised 2023). Breastfeed Med. 2023 Oct;18(10):715-33.[Abstract][Full Text]
160. Link HM, Jones H, Miller L, et al. Buprenorphine-naloxone use in pregnancy: a systematic review and metaanalysis. Am J Obstet Gynecol MFM. 2020 Aug;2(3):100179.[Abstract]
161. Minozzi S, Amato L, Jahanfar S, et al. Maintenance agonist treatments for opiate-dependent pregnant women. Cochrane Database Syst Rev. 2020 Nov 9;11(11):CD006318.[Abstract][Full Text]
162. Huybrechts KF, Hernández-Díaz S, Straub L, et al. Association of maternal first-trimester ondansetron use with cardiac malformations and oral clefts in offspring. JAMA. 2018 Dec 18;320(23):2429-37.[Abstract][Full Text]
163. Royal College of Obstetricians and Gynaecologists. Management of nausea and vomiting of pregnancy and hyperemesis gravidarum: green-top guideline no. 69. Jun 2016 [internet publication].[Full Text]
164. Medicines and Healthcare products Regulatory Agency. Ondansetron: small increased risk of oral clefts following use in the first 12 weeks of pregnancy. Jan 2020 [internet publication].[Full Text]
165. Sees KL, Delucchi KL, Masson C, et al. Methadone maintenance vs 180-day psychosocially enriched detoxification for treatment of opioid dependence: a randomized controlled trial. JAMA. 2000 Mar 8;283(10):1303-10.[Abstract][Full Text]
166. Nosyk B, Sun H, Evans E, et al. Defining dosing pattern characteristics of successful tapers following methadone maintenance treatment: results from a population-based retrospective cohort study. Addiction. 2012 Sep;107(9):1621-9.[Abstract][Full Text]
167. Eklund C, Hiltunen AJ, Melin L, et al. Factors associated with successful withdrawal from methadone maintenance treatment in Sweden. Int J Addict. 1995 Aug;30(10):1335-53.[Abstract]
168. Lu Q, Zou X, Liu Y, et al. Dose tapering strategy for heroin abstinence among methadone maintenance treatment participants: evidence from a retrospective study in Guangdong, China. Int J Environ Res Public Health. 2019 Aug 6;16(15):2800.[Abstract][Full Text]
169. Amass L, Bickel WK, Higgins ST, et al. A preliminary investigation of outcome following gradual or rapid buprenorphine detoxification. J Addict Dis. 1994;13(3):33-45.[Abstract]
170. Ling W, Amass L, Shoptaw S, et al. A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network. Addiction. 2005 Aug;100(8):1090-100.[Abstract][Full Text]
171. Novick DM, Kreek MJ, Fanizza AM, et al. Methadone disposition in patients with chronic liver disease. Clin Pharmacol Ther. 1981 Sep;30(3):353-62.[Abstract]
172. Kreek MJ, Schecter AJ, Gutjahr CL, et al. Methadone use in patients with chronic renal disease. Drug Alcohol Depend. 1980 Mar;5(3):197-205.[Abstract]
173. Dashe JS, Jackson GL, Olscher DA, et al. Opioid detoxification in pregnancy. Obstet Gynecol. 1998 Nov;92(5):854-8.[Abstract]
174. McCarthy JJ, Leamon MH, Stenson G, et al. Outcomes of neonates conceived on methadone maintenance therapy. J Subst Abuse Treat. 2008 Sep;35(2):202-6.[Abstract]
175. Fareed A, Casarella J, Amar R, et al. Methadone maintenance dosing guideline for opioid dependence, a literature review. J Addict Dis. 2010 Jan;29(1):1-14.[Abstract]
176. Fareed A, Vayalapalli S, Stout S, et al. Effect of methadone maintenance treatment on heroin craving, a literature review. J Addict Dis. 2011 Jan;30(1):27-38.[Abstract]
177. Flynn PM, Joe GW, Broome KM, et al. Recovery from opioid addiction in DATOS. J Subst Abuse Treat. 2003 Oct;25(3):177-86.[Abstract]
178. McLellan AT, Arndt IO, Metzger DS, et al. The effects of psychosocial services in substance abuse treatment. JAMA. 1993 Apr 21;269(15):1953-9.[Abstract]
179. Fiellin DA, Pantalon MV, Chawarski MC, et al. Counseling plus buprenorphine-naloxone maintenance therapy for opioid dependence. N Engl J Med. 2006 Jul 27;355(4):365-74.[Abstract][Full Text]
180. Robertson JR, Raab GM, Bruce M, et al. Addressing the efficacy of dihydrocodeine versus methadone as an alternative maintenance treatment for opiate dependence: a randomized controlled trial. Addiction. 2006 Dec;101(12):1752-9.[Abstract]
181. Carney T, Van Hout MC, Norman I, et al. Dihydrocodeine for detoxification and maintenance treatment in individuals with opiate use disorders. Cochrane Database Syst Rev. 2020 Feb 18;2(2):CD012254.[Abstract][Full Text]
182. Oviedo-Joekes E, March JC, Romero M, et al. The Andalusian trial on heroin-assisted treatment: a 2 year follow-up. Drug Alcohol Rev. 2010 Jan;29(1):75-80.[Abstract]
183. Oviedo-Joekes E, Guh D, Brissette S, et al. Effectiveness of diacetylmorphine versus methadone for the treatment of opioid dependence in women. Drug Alcohol Depend. 2010 Sep 1;111(1-2):50-7.[Abstract]
184. Karow A, Reimer J, Schäfer I, et al. Quality of life under maintenance treatment with heroin versus methadone in patients with opioid dependence. Drug Alcohol Depend. 2010 Dec 1;112(3):209-15.[Abstract]
185. Ferri M, Davoli M, Perucci CA. Heroin maintenance for chronic heroin-dependent individuals. Cochrane Database Syst Rev. 2011 Dec 7;2011(12):CD003410.[Abstract][Full Text]
186. Canadian Research Initiative in Substance Misuse. National injectable opioid agonist treatment for opioid use disorder clinical guideline. Sep 2019 [internet publication].[Full Text]
187. Miranda A, Taca A. Neuromodulation with percutaneous electrical nerve field stimulation is associated with reduction in signs and symptoms of opioid withdrawal: a multisite, retrospective assessment. Am J Drug Alcohol Abuse. 2018;44(1):56-63.[Abstract][Full Text]
188. Beck T, Haasen C, Verthein U, et al. Maintenance treatment for opioid dependence with slow-release oral morphine: a randomized cross-over, non-inferiority study versus methadone. Addiction. 2014 Apr;109(4):617-26.[Abstract][Full Text]
189. Hämmig R, Köhler W, Bonorden-Kleij K, et al. Safety and tolerability of slow-release oral morphine versus methadone in the treatment of opioid dependence. J Subst Abuse Treat. 2014 Oct;47(4):275-81.[Abstract]
190. Klimas J, Gorfinkel L, Giacomuzzi SM, et al. Slow release oral morphine versus methadone for the treatment of opioid use disorder. BMJ Open. 2019 Apr 2;9(4):e025799.[Abstract][Full Text]
191. Lehmann K, Kuhn S, Baschirotto C, et al. Substitution treatment for opioid dependence with slow-release oral morphine: retention rate, health status, and substance use after switching to morphine. J Subst Abuse Treat. 2021 Aug;127:108350.[Abstract]
192. Dunn KE, Tompkins DA, Bigelow GE, et al. Efficacy of tramadol extended-release for opioid withdrawal: a randomized clinical trial. JAMA Psychiatry. 2017 Sep 1;74(9):885-93.[Abstract][Full Text]
193. Powell VD, Rosenberg JM, Yaganti A, et al. Evaluation of buprenorphine rotation in patients receiving long-term opioids for chronic pain: a systematic review. JAMA Netw Open. 2021 Sep 1;4(9):e2124152.[Abstract][Full Text]
194. Yakovenko I, Mukaneza Y, Germé K, et al. Management of opioid use disorder: 2024 update to the national clinical practice guideline. CMAJ. 2024 Nov 11;196(38):E1280-90.[Abstract][Full Text]
195. Manchikanti L, Kaye AM, Knezevic NN, et al. Comprehensive, evidence-based, consensus guidelines for prescription of opioids for chronic non-cancer pain from the American Society of Interventional Pain Physicians (ASIPP). Pain Physician. 2023 Dec;26(7s):S7-126.[Abstract][Full Text]
196. Fairbairn N, Ross J, Trew M, et al. Injectable opioid agonist treatment for opioid use disorder: a national clinical guideline. CMAJ. 2019 Sep 23;191(38):E1049-56.[Abstract][Full Text]
197. Larney S, Tran LT, Leung J, et al. All-cause and cause-specific mortality among people using extramedical opioids: a systematic review and meta-analysis. JAMA Psychiatry. 2020 May 1;77(5):493-502.[Abstract][Full Text]
198. McLellan AT, Luborsky L, Woody GE, et al. Predicting response to alcohol and drug abuse treatments: role of psychiatric severity. Arch Gen Psychiatry. 1983 Jun;40(6):620-5.[Abstract]
199. McLellan AT, Lewis DC, O'Brien CP, et al. Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation. JAMA. 2000 Oct 4;284(13):1689-95.[Abstract]
200. Keen C, Kinner SA, Young JT, et al. Periods of altered risk for non-fatal drug overdose: a self-controlled case series. Lancet Public Health. 2021 Apr;6(4):e249-59.[Abstract][Full Text]
201. Kariisa M, Patel P, Smith H, et al. Notes from the field: xylazine detection and involvement in drug overdose deaths - United States, 2019. MMWR Morb Mortal Wkly Rep. 2021 Sep 17;70(37):1300-2.[Abstract][Full Text]
202. Boyer EW. Management of opioid analgesic overdose. N Engl J Med. 2012 Jul 12;367(2):146-55.[Full Text]
203. Osterwalder JJ. Naloxone - for intoxications with intravenous heroin and heroin mixtures - harmless or hazardous? A prospective clinical study. J Toxicol Clin Toxicol. 1996;34(4):409-16.[Abstract]
204. Berlot G, Gullo A, Romano E, et al. Naloxone in cardiorespiratory arrest. Anaesthesia. 1985 Aug;40(8):819.[Abstract]
205. Mills CA, Flacke JW, Flacke WE, et al. Narcotic reversal in hypercapnic dogs: comparison of naloxone and nalbuphine. Can J Anaesth. 1990 Mar;37(2):238-44.[Abstract]
206. Surgeon General. Surgeon General's advisory on naloxone and opioid overdose. Apr 2022 [internet publication].[Full Text]
207. Centers for Disease Control and Prevention; US Public Health Service. Preexposure prophylaxis for the prevention of HIV infection in the United States - 2021 update: a clinical practice guideline. 2021 [internet publication].[Full Text]
208. Voelker R. Harm reduction strategies for people who use drugs. JAMA. 2025 Feb 19.
209. Tanner MR, O'Shea JG, Byrd KM, et al. Antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV - CDC recommendations, United States, 2025. MMWR Recomm Rep. 2025 May 8;74(1):1-56.[Abstract][Full Text]
210. Centers for Disease Control and Prevention. Vaccines & immunizations: adult immunization schedule by age: recommendations for ages 19 years or older, United States, 2025. Jul 2025 [internet publication].[Full Text]
211. American Academy of Pediatrics Committee on Drugs. Neonatal drug withdrawal. Pediatrics. 1998 Jun;101(6):1079-88.[Abstract]
212. Finnegan LP, Connaughton JF Jr, Kron RE, et al. Neonatal abstinence syndrome: assessment and management. Addict Dis. 1975;2(1-2):141-58.[Abstract]
213. Young LW, Ounpraseuth ST, Merhar SL, et al. Eat, sleep, console approach or usual care for neonatal opioid withdrawal. N Engl J Med. 2023 Jun 22;388(25):2326-37.[Abstract][Full Text]
214. Patrick SW, Barfield WD, Poindexter BB, et al. Neonatal opioid withdrawal syndrome. Pediatrics. 2020 Nov;146(5):e2020029074.[Abstract][Full Text]
215. Zankl A, Martin J, Davey JG, et al. Sedatives for opioid withdrawal in newborn infants. Cochrane Database Syst Rev. 2021 May 18;5:CD002053.[Abstract][Full Text]
216. Zankl A, Martin J, Davey JG, et al. Opioid treatment for opioid withdrawal in newborn infants. Cochrane Database Syst Rev. 2021 Jul 7;7(7):CD002059.[Abstract][Full Text]
217. Kraft WK, Gibson E, Dysart K, et al. Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial. Pediatrics. 2008 Sep;122(3):e601-7.[Abstract]
218. Kraft WK, Adeniyi-Jones SC, Chervoneva I, et al. Buprenorphine for the treatment of the neonatal abstinence syndrome. N Engl J Med. 2017 Jun 15;376(24):2341-8.[Abstract][Full Text]
219. de Vries F, Bruin M, Lobatto DJ, et al. Opioids and their endocrine effects: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2020 Mar 1;105(3):1020-9.[Abstract][Full Text]
220. Karavitaki N, Bettinger JJ, Biermasz N, et al. Exogenous opioids and the human endocrine system: an Endocrine Society scientific statement. Endocr Rev. 2024 Nov 22;45(6):773-94.[Abstract][Full Text]
