Treatment of opioid use disorder requires a multidisciplinary approach, is typically long term in nature (possibly lifelong), and involves modifying deeply ingrained behaviours through the use of maintenance pharmacotherapy and psychosocial treatments. There is extensive and high-quality evidence to support the combination of maintenance pharmacotherapy with psychosocial treatment for optimal management of opioid use disorders, both for suppressing illicit opioid use and for retaining people in treatment.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
[88]World Health Organization. Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence. Jan 2009 [internet publication].
https://www.who.int/publications/i/item/9789241547543
[89]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.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002207.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/24500948?tool=bestpractice.com
[90]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.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960358-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/21529928?tool=bestpractice.com
[91]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.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7097731
http://www.ncbi.nlm.nih.gov/pubmed/19588333?tool=bestpractice.com
Note that terminology on treatment for opioid use disorder varies internationally; in the US, maintenance pharmacotherapy is increasingly known as ‘medication for opioid use disorder’ (MOUD), but may also be known as medication-assisted treatment (MAT) or opioid substitution therapy (OST) in some parts of the world.
It is important to note that effective treatment is individualised based on the needs and preferences of the patient, and that there is no ‘one size fits all’ approach.[92]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.
https://bmjopen.bmj.com/content/14/12/e088617.long
http://www.ncbi.nlm.nih.gov/pubmed/39632113?tool=bestpractice.com
In spite of the strong evidence in favour of long-term pharmacological treatment, some people with opioid use disorder successfully recover using self-cessation, support groups, or treatment programmes with or without pharmacotherapy.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Assessment of patient motivation for change, and evidence of family and social support, are important while planning treatment. Engagement and retention in substance use disorder treatment can be a major clinical challenge; it is recommended that healthcare providers proactively engage people who would benefit from treatment at all stages of readiness for change, including those who are uninterested or ambivalent about receiving treatment.[93]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].
https://www.asam.org/quality-care/clinical-recommendations/asam-clinical-considerations-for-engagement-and-retention-of-non-abstinent-patients-in-treatment
Non-specialists should consult and seek supervision from a practitioner experienced in treating addiction prior to prescribing pharmacotherapies to patients with opioid use disorders, particularly in special populations such as teenagers, pregnant women, and older adults.
In older patients, it is important to assess for cognitive impairment or dementia as that can affect treatment, adherence, and aftercare. Current drug history including herbal medicines and supplements should be completely reviewed to avoid potential drug interactions.[94]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.
http://www.ncbi.nlm.nih.gov/pubmed/21247284?tool=bestpractice.com
In addition, doses of drug treatments may need to be adjusted based on a patient’s age, body mass index, renal function, liver function, and nutritional status (albumin). Safe storage of drug treatments for opioid use disorder is crucial to prevent accidental or intentional overdose, particularly if there are children in the household.
In the US, the levels of service for the treatment of opioid use disorder should follow local guidelines to determine whether a patient is appropriate for early intervention, outpatient services, intensive outpatient services, partial hospitalisation services, residential services, inpatient services, or medically managed intensive inpatient services.[95]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.
Pharmacotherapy for opioid use disorder may be utilised on a short- or long-term basis as part of medically supervised withdrawal (formerly known as detoxification) or maintenance treatment. Maintenance treatment involves:[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Induction (transition from active opioid use or early withdrawal to pharmacotherapy)
Stabilisation (dose adjustment to relieve withdrawal symptoms and cravings)
Long-term maintenance (continued treatment at a therapeutic dose)
Both approaches require safe induction and stabilisation, careful monitoring and dosing, and attention to tolerance and withdrawal symptoms. While principles of induction and stabilisation overlap, maintenance aims to stabilise patients on long-term pharmacotherapy, whereas withdrawal seeks tapering. Withdrawal alone in the absence of ongoing maintenance is not recommended due to high relapse and overdose risk from reduced tolerance (see below).[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Some key principles of timing apply to both pharmacological approaches.
Safe timing and initiation of pharmacological treatment: general principles
First-line drug treatments for both medically supervised withdrawal and maintenance treatment are buprenorphine (a partial opioid agonist) and methadone (a full opioid agonist). Naltrexone, an opioid antagonist, is a second-line option for maintenance.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Pharmacological differences among these treatments are important when planning the safe timing of induction, whether for maintenance or medically supervised withdrawal. Premature administration of buprenorphine or naltrexone in the presence of residual opioids can be dangerous, and cause precipitated withdrawal:[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Naltrexone requires complete opioid abstinence (at least 7 days after short-acting opioids and 10-14 days after long-acting opioids) to prevent precipitated withdrawal. This abstinent period is typically achieved through medically supervised withdrawal with an opioid agonist or partial agonist.
Buprenorphine does not require prior full abstinence, but it is important that induction begins only after moderate withdrawal symptoms appear in those physiologically dependent on opioids, to avoid triggering precipitated withdrawal. Some clinicians, including the authors of this topic, recommend waiting for a COWS score of 13 or higher before initiating buprenorphine, although evidence to guide the specific threshold is limited.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
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Time to onset of withdrawal symptoms is dependent on the half-life of the opioid taken. For example, heroin has a short half-life and is associated with withdrawal onset within 12 hours of last use, whereas withdrawal symptoms with methadone may manifest 24-74 hours after last use.
Methadone will not precipitate withdrawal and can be started without a prior period of abstinence, but induction must be cautious, beginning with low doses and slow titration. It is best practice to wait for signs and symptoms of withdrawal to appear before starting methadone because of lack of certainty about physical dependence from self-reported histories and subsequent risk of overdose. If treatment is initiated prior to withdrawal signs and symptoms, vital signs and respiratory status should be carefully monitored given that methadone has an additive effect to opioids that are already present.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Medically supervised withdrawal
Supervised withdrawal (formerly known as detoxification) is not recommended as a standalone treatment due to high relapse rates and increased overdose risk from reduced tolerance; ongoing maintenance treatment, in combination with psychosocial treatment, is the standard of care.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Medically supervised withdrawal can occur after stabilisation with maintenance therapy, or may be used early, with transition to maintenance therapy (e.g., buprenorphine or methadone) once withdrawal symptoms begin. It is not required before starting maintenance treatment, except for with naltrexone, which requires a period of opioid abstinence beforehand, which is in practice usually achieved with supervised withdrawal.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Supervised withdrawal is preferred over abrupt cessation of opioids, which increases risks of severe symptoms and complications.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
Ultra-rapid withdrawal (e.g., under anaesthesia) is not recommended due to serious risks.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
[96]National Institute for Health and Care Excellence. Drug misuse in over 16s: opioid detoxification. Jul 2007 (reaffirmed 2019) [internet publication].
https://www.nice.org.uk/guidance/CG52
Treatment decisions are individualised and patient-centred, using shared decision-making.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
In select, clinically stable individuals pursuing abstinence, supervised withdrawal may be acceptable within a structured plan offering ongoing support and psychosocial care.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
[96]National Institute for Health and Care Excellence. Drug misuse in over 16s: opioid detoxification. Jul 2007 (reaffirmed 2019) [internet publication].
https://www.nice.org.uk/guidance/CG52
Patients must be informed that tolerance decreases post-withdrawal, elevating overdose risk, and should be advised to re-enter treatment promptly if opioid use resumes or is considered.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Withdrawal can be performed in an outpatient or inpatient setting, depending on the severity of intoxication and withdrawal symptoms, presence of comorbid conditions, and safety issues.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
The ideal duration of medically supervised withdrawal is unclear.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Clinical trials have led to the development of semi-standardised protocols.[97]Galanter M, Kleber HD, eds. The American Psychiatric Publishing textbook of substance abuse treatment. Washington, DC: American Psychiatric Publishing; 2008. There are two evidence-based withdrawal strategies: opioid agonist (i.e., methadone, buprenorphine with or without naloxone) substitution and taper, and use of an alpha-2 adrenergic agonist (i.e., clonidine [off-label use] or lofexidine) with or without naltrexone.[96]National Institute for Health and Care Excellence. Drug misuse in over 16s: opioid detoxification. Jul 2007 (reaffirmed 2019) [internet publication].
https://www.nice.org.uk/guidance/CG52
[98]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.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002024.pub5/full
http://www.ncbi.nlm.nih.gov/pubmed/27140827?tool=bestpractice.com
[
]
How do alpha2-adrenergic agonists compare with placebo or methadone for management of opioid withdrawal?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.1609/fullShow me the answer Methadone (alone) or buprenorphine (with or without naloxone) are first-line treatments for supervised withdrawal.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
[96]National Institute for Health and Care Excellence. Drug misuse in over 16s: opioid detoxification. Jul 2007 (reaffirmed 2019) [internet publication].
https://www.nice.org.uk/guidance/CG52
[99]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.
https://www.doi.org/10.1016/j.annemergmed.2020.06.049
http://www.ncbi.nlm.nih.gov/pubmed/32828340?tool=bestpractice.com
Clonidine and lofexidine (with or without naltrexone) are considered second-line agents.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Buprenorphine (with or without naloxone)
A first-line option for medically supervised withdrawal in adults.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
[96]National Institute for Health and Care Excellence. Drug misuse in over 16s: opioid detoxification. Jul 2007 (reaffirmed 2019) [internet publication].
https://www.nice.org.uk/guidance/CG52
[99]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.
https://www.doi.org/10.1016/j.annemergmed.2020.06.049
http://www.ncbi.nlm.nih.gov/pubmed/32828340?tool=bestpractice.com
[100]US Department of Veterans Affairs; Department of Defense. VA/DoD clinical practice guideline for the management of substance use disorders. Aug 2021 [internet publication].
https://www.healthquality.va.gov/guidelines/MH/sud/VADoDSUDCPG.pdf
For patients who are currently opioid dependent, do not initiate buprenorphine until there are objective signs of mild-moderate opioid withdrawal.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
Available as a sublingual tablet containing buprenorphine only, or as a sublingual tablet or film containing buprenorphine and naloxone (a mu opioid receptor antagonist).
Buprenorphine/naloxone combination treatment was developed to deter parenteral misuse of buprenorphine.[101]Blazes CK, Morrow JD. Reconsidering the usefulness of adding naloxone to buprenorphine. Front Psychiatry. 2020 Sep 11;11:549272.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517938
http://www.ncbi.nlm.nih.gov/pubmed/33061915?tool=bestpractice.com
When taken as sublingual tablets, buprenorphine’s opioid effects dominate and block opioid withdrawal.[101]Blazes CK, Morrow JD. Reconsidering the usefulness of adding naloxone to buprenorphine. Front Psychiatry. 2020 Sep 11;11:549272.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517938
http://www.ncbi.nlm.nih.gov/pubmed/33061915?tool=bestpractice.com
If the sublingual tablets are crushed and injected, naloxone’s effects dominate and can precipitate withdrawal symptoms.[101]Blazes CK, Morrow JD. Reconsidering the usefulness of adding naloxone to buprenorphine. Front Psychiatry. 2020 Sep 11;11:549272.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517938
http://www.ncbi.nlm.nih.gov/pubmed/33061915?tool=bestpractice.com
It is unclear whether rapid reduction in the dose of buprenorphine is more effective than slow reduction and whether this depends on the context of withdrawal.[102]Gowing L, Ali R, White JM, et al. Buprenorphine for managing opioid withdrawal. Cochrane Database Syst Rev. 2017 Feb 21;2(2):CD002025.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002025.pub5/full
http://www.ncbi.nlm.nih.gov/pubmed/28220474?tool=bestpractice.com
Advantages: lower risk of lethal overdose compared to methadone, appropriate for home initiation, has a long duration of action, and withdrawal symptoms are relatively mild and less severe than those of methadone.[34]Buresh M, Stern R, Rastegar D. Treatment of opioid use disorder in primary care. BMJ. 2021 May 19;373:n784.
http://www.ncbi.nlm.nih.gov/pubmed/34011512?tool=bestpractice.com
[103]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.
http://www.ncbi.nlm.nih.gov/pubmed/1876130?tool=bestpractice.com
[104]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.
http://www.ncbi.nlm.nih.gov/pubmed/1876131?tool=bestpractice.com
[105]Johnson RE, McCagh JC. Buprenorphine and naloxone for heroin dependence. Curr Psychiatry Rep. 2000 Dec;2(6):519-26.
http://www.ncbi.nlm.nih.gov/pubmed/11123005?tool=bestpractice.com
The effectiveness of buprenorphine is probably similar to tapered doses of methadone, but it is uncertain whether withdrawal symptoms resolve more quickly with buprenorphine.[102]Gowing L, Ali R, White JM, et al. Buprenorphine for managing opioid withdrawal. Cochrane Database Syst Rev. 2017 Feb 21;2(2):CD002025.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002025.pub5/full
http://www.ncbi.nlm.nih.gov/pubmed/28220474?tool=bestpractice.com
[106]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.
http://www.ncbi.nlm.nih.gov/pubmed/20074867?tool=bestpractice.com
Buprenorphine is superior to clonidine or lofexidine and comparable to methadone in terms of completion rates and withdrawal discomfort for opioid withdrawal.[102]Gowing L, Ali R, White JM, et al. Buprenorphine for managing opioid withdrawal. Cochrane Database Syst Rev. 2017 Feb 21;2(2):CD002025.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002025.pub5/full
http://www.ncbi.nlm.nih.gov/pubmed/28220474?tool=bestpractice.com
[
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How does buprenorphine compare with methadone or adrenergic agonists in people undergoing opioid withdrawal?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.1652/fullShow me the answer
Disadvantages: potential for misuse, has been reported to cause fatal respiratory depression when combined with benzodiazepines and alcohol.[68]Srivastava AB, Mariani JJ, Levin FR. New directions in the treatment of opioid withdrawal. Lancet. 2020 Jun 20;395(10241):1938-48.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385662
http://www.ncbi.nlm.nih.gov/pubmed/32563380?tool=bestpractice.com
Methadone
An alternative first-line option for medically supervised withdrawal in adults.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
[96]National Institute for Health and Care Excellence. Drug misuse in over 16s: opioid detoxification. Jul 2007 (reaffirmed 2019) [internet publication].
https://www.nice.org.uk/guidance/CG52
[99]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.
https://www.doi.org/10.1016/j.annemergmed.2020.06.049
http://www.ncbi.nlm.nih.gov/pubmed/32828340?tool=bestpractice.com
[100]US Department of Veterans Affairs; Department of Defense. VA/DoD clinical practice guideline for the management of substance use disorders. Aug 2021 [internet publication].
https://www.healthquality.va.gov/guidelines/MH/sud/VADoDSUDCPG.pdf
Shown to be safe and effective for withdrawal if used appropriately.[107]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.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003409.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/23450540?tool=bestpractice.com
There are two types of withdrawal methods: a short-term (<30 days) method for shorter-acting opioids, and a long-term (>180 days) method for methadone-maintained patients.
Induction is the most critical phase of treatment, and involves slow and careful titration to avoid potential accidental overdose. The induction phase lasts until the patient has been on a stable dose for 5-7 days.
Advantages: smoother taper than short-acting opioids (due to its longer half-life), and withdrawal symptoms are milder but prolonged compared with those of heroin.
Disadvantages: potential for misuse, possibly a longer taper than with buprenorphine or alpha-2-adrenergic agonists, unsafe in overdose and requires closer monitoring than with buprenorphine due to longer half-life and risk for respiratory depression, and needs to be dispensed at a licensed clinic in the US.[34]Buresh M, Stern R, Rastegar D. Treatment of opioid use disorder in primary care. BMJ. 2021 May 19;373:n784.
http://www.ncbi.nlm.nih.gov/pubmed/34011512?tool=bestpractice.com
[68]Srivastava AB, Mariani JJ, Levin FR. New directions in the treatment of opioid withdrawal. Lancet. 2020 Jun 20;395(10241):1938-48.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385662
http://www.ncbi.nlm.nih.gov/pubmed/32563380?tool=bestpractice.com
Clonidine or lofexidine (with or without naltrexone)
Alpha-2-adrenergic agonists (clonidine [off-label use], lofexidine) are considered second-line agents for medically supervised withdrawal.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Clonidine is generally not recommended for medically supervised withdrawal by the National Institute for Health and Care Excellence (NICE) in the UK.[96]National Institute for Health and Care Excellence. Drug misuse in over 16s: opioid detoxification. Jul 2007 (reaffirmed 2019) [internet publication].
https://www.nice.org.uk/guidance/CG52
They reduce the sympathetic nervous system response (i.e., noradrenergic release) to opioid withdrawal, reducing autonomical withdrawal symptoms. Lofexidine is a structural analogue of clonidine and is generally associated with fewer side effects.[68]Srivastava AB, Mariani JJ, Levin FR. New directions in the treatment of opioid withdrawal. Lancet. 2020 Jun 20;395(10241):1938-48.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385662
http://www.ncbi.nlm.nih.gov/pubmed/32563380?tool=bestpractice.com
Usual doses of opioids should be given on the day prior to medically supervised withdrawal, with opioids discontinued abruptly the day clonidine or lofexidine is started.
Studies have found that addition of the opioid antagonist naltrexone to clonidine can shorten the duration of withdrawal without increasing discomfort.[108]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.
http://www.ncbi.nlm.nih.gov/pubmed/3687878?tool=bestpractice.com
[109]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.
http://www.ncbi.nlm.nih.gov/pubmed/3382815?tool=bestpractice.com
Lofexidine may not suppress withdrawal symptoms as fully as clonidine, and may therefore contribute to poorer treatment retention.[68]Srivastava AB, Mariani JJ, Levin FR. New directions in the treatment of opioid withdrawal. Lancet. 2020 Jun 20;395(10241):1938-48.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385662
http://www.ncbi.nlm.nih.gov/pubmed/32563380?tool=bestpractice.com
[98]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.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002024.pub5/full
http://www.ncbi.nlm.nih.gov/pubmed/27140827?tool=bestpractice.com
Advantages: less potential for misuse, may be used in treatment settings that prohibit use of controlled substances, shorter treatment duration, and avoidance of long-term residual withdrawal symptoms that can occur with methadone.[68]Srivastava AB, Mariani JJ, Levin FR. New directions in the treatment of opioid withdrawal. Lancet. 2020 Jun 20;395(10241):1938-48.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385662
http://www.ncbi.nlm.nih.gov/pubmed/32563380?tool=bestpractice.com
Disadvantages: more adverse effects, higher dropout rate, and greater withdrawal discomfort (particularly hypotension and sedation) compared with opioid agonists.[68]Srivastava AB, Mariani JJ, Levin FR. New directions in the treatment of opioid withdrawal. Lancet. 2020 Jun 20;395(10241):1938-48.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385662
http://www.ncbi.nlm.nih.gov/pubmed/32563380?tool=bestpractice.com
[98]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.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002024.pub5/full
http://www.ncbi.nlm.nih.gov/pubmed/27140827?tool=bestpractice.com
[106]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.
http://www.ncbi.nlm.nih.gov/pubmed/20074867?tool=bestpractice.com
Supportive therapies
While there is no evidence of any specific nutrition or diet to aid medically supervised withdrawal, adequate hydration and food intake should be ensured.
Ancillary pharmacotherapy in therapeutic doses may be required for symptomatic relief, for example:[68]Srivastava AB, Mariani JJ, Levin FR. New directions in the treatment of opioid withdrawal. Lancet. 2020 Jun 20;395(10241):1938-48.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385662
http://www.ncbi.nlm.nih.gov/pubmed/32563380?tool=bestpractice.com
Ibuprofen for muscle cramps
Bismuth subsalicylate, ondansetron, or prochlorperazine for gastrointestinal issues
Trazodone for sleep disturbances
Benzodiazepines may be given in an inpatient setting on a time-limited basis for treatment of anxiety or muscle cramps.[68]Srivastava AB, Mariani JJ, Levin FR. New directions in the treatment of opioid withdrawal. Lancet. 2020 Jun 20;395(10241):1938-48.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385662
http://www.ncbi.nlm.nih.gov/pubmed/32563380?tool=bestpractice.com
Monitoring for respiratory depression is required. Use caution if prescribing on an outpatient basis. Oxazepam and chlordiazepoxide are generally the benzodiazepines of choice in clinical practice.
Psychosocial counselling is primarily given during the maintenance phase; however, support and reassurance should be provided during medically supervised withdrawal, and it is desirable to develop adjunct psychosocial approaches that might make withdrawal more effective. For example, psychosocial treatments such as contingency management can reduce dropout rates from supervised withdrawal.[110]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.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005031.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/21901695?tool=bestpractice.com
[111]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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340014
http://www.ncbi.nlm.nih.gov/pubmed/34347030?tool=bestpractice.com
[
]
What are the effects of psychosocial treatments as an adjunct to pharmacological treatments in people undergoing opioid detoxification?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.565/fullShow me the answer
Ongoing assessment for suicidality throughout the course of supervised withdrawal is strongly advisable. See Suicide risk mitigation.
Maintenance pharmacotherapy
Goals of long-term treatment are multiple, and include abstinence from illicit drugs, relapse prevention, reduction of HIV and hepatitis C risk, reduced mortality, restoration of functionality disrupted by opioid use, and decreased criminality.[112]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.
http://www.ncbi.nlm.nih.gov/pubmed/10494354?tool=bestpractice.com
[113]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.
http://www.ncbi.nlm.nih.gov/pubmed/9741945?tool=bestpractice.com
In practice this can be achieved by drug treatment which prevents or reduces opioid withdrawal and craving, and which may also blunt and block the effects of illicit opioids.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Continuing maintenance treatment after completion of medically supervised withdrawal (if this has taken place) is strongly recommended due to the high risk of relapse.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Data from observational studies suggest that all cause mortality may be reduced by up to 50% among people with opioid dependence who are enroled in any form of opioid agonist treatment.[114]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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173472
http://www.ncbi.nlm.nih.gov/pubmed/34076676?tool=bestpractice.com
Substantial evidence indicates that pharmacotherapy-assisted treatment is essential for a majority of patients with opioid use disorder.[115]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.
https://www.doi.org/10.1002/14651858.CD011117.pub3
http://www.ncbi.nlm.nih.gov/pubmed/36063082?tool=bestpractice.com
Treatment should be continued as long as the patient continues to benefit from treatment, wishes to remain in treatment, remains at risk for relapse, and suffers no serious adverse effects.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
The choice of pharmacotherapy for maintenance treatment is determined by patient preferences, past history of response to treatment, and physician assessment of the short- and long-term effects of continued drug treatment.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Buprenorphine maintenance therapy (BMT) can reduce opioid misuse compared with placebo. However, one Cochrane review found that methadone maintenance therapy (MMT) was more effective than BMT at both medium and high doses in retaining patients in treatment.[89]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.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002207.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/24500948?tool=bestpractice.com
[
]
What are the benefits and harms of buprenorphine maintenance versus placebo or methadone maintenance in people with opioid dependence?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.538/fullShow me the answer Both methadone and buprenorphine are associated with significantly lower all-cause mortality and overdose-related mortality when participants are on versus off treatment.[116]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.
http://www.bmj.com/content/357/bmj.j1550.long
http://www.ncbi.nlm.nih.gov/pubmed/28446428?tool=bestpractice.com
Cross-sectional studies suggest that the rate of mortality with BMT may be lower than that with MMT.
Methadone
A first-line option for maintenance therapy; may be preferred if both buprenorphine and methadone are equally suitable.[89]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.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002207.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/24500948?tool=bestpractice.com
[115]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.
https://www.doi.org/10.1002/14651858.CD011117.pub3
http://www.ncbi.nlm.nih.gov/pubmed/36063082?tool=bestpractice.com
[117]National Institute for Health and Care Excellence. Methadone and buprenorphine for the management of opioid dependence. Jan 2007 (reaffirmed Feb 2016) [internet publication].
https://www.nice.org.uk/guidance/TA114
[
]
What are the benefits and harms of opioid agonist treatment for people who are dependent on pharmaceutical opioids?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.4180/fullShow me the answer Has the largest and oldest evidence base of all treatment approaches to opioid use disorder.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
High oral systemic bioavailability and a long half-life make it an effective agent for maintenance.[118]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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837873
http://www.ncbi.nlm.nih.gov/pubmed/29507156?tool=bestpractice.com
Methadone may be associated with a lower risk of discontinuation than buprenorphine.[89]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.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002207.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/24500948?tool=bestpractice.com
[119]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.
http://www.ncbi.nlm.nih.gov/pubmed/34953637?tool=bestpractice.com
[120]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.
http://www.ncbi.nlm.nih.gov/pubmed/37167985?tool=bestpractice.com
Induction should begin at a low dose and increase gradually with daily monitoring over days or weeks. The recommended approach to dosing is to ‘start low and go slow'. Dosing is highly individualised, given that the bioavailability, clearance and half-life of methadone varies considerably among patients. People with no or low opioid tolerance will need a lower than usual starting dose.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Once a stable dose is reached after induction (based on suppression of craving and elimination of withdrawal), the maintenance phase begins. Patients are typically required to come to the treatment programme daily for their methadone dosing and counselling.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
[121]Department of Health and Social Care. Guidance on drug misuse and dependence: UK guidelines on clinical management. Dec 2017 [internet publication].
https://www.gov.uk/government/publications/drug-misuse-and-dependence-uk-guidelines-on-clinical-management
Patients who do well may be permitted to take methadone home for unsupervised dosing, dependent on the relevant legislation and clinical guidance in their area.
The first 4 weeks of treatment with methadone are associated with a higher risk of death (from all causes) compared with during the rest of treatment. This increase in mortality is reduced by persistent engagement with opioid substitution treatment and increased by dropping out of treatment, indicating a need to promote engagement with treatment during this initial 'golden' month.[116]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.
http://www.bmj.com/content/357/bmj.j1550.long
http://www.ncbi.nlm.nih.gov/pubmed/28446428?tool=bestpractice.com
Concurrent use of benzodiazepines or alcohol is common in patients with opioid use disorder and increases the risk of respiratory depression. However, opioid agonist treatment should not be withheld solely due to benzodiazepine use, given the high risk associated with untreated opioid use disorder. Coordinated care between prescribers (with patient consent) is advised. Patients should be counselled on the risk of respiratory depression and overdose when combining methadone with alcohol, benzodiazepines, or other central nervous system depressants. Assess the need for medically supervised withdrawal or tapering of alcohol or benzodiazepines.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
[122]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.
https://link.springer.com/article/10.1007/s11606-025-09499-2
http://www.ncbi.nlm.nih.gov/pubmed/40526204?tool=bestpractice.com
Buprenorphine
A first-line option for maintenance therapy.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
[100]US Department of Veterans Affairs; Department of Defense. VA/DoD clinical practice guideline for the management of substance use disorders. Aug 2021 [internet publication].
https://www.healthquality.va.gov/guidelines/MH/sud/VADoDSUDCPG.pdf
[115]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.
https://www.doi.org/10.1002/14651858.CD011117.pub3
http://www.ncbi.nlm.nih.gov/pubmed/36063082?tool=bestpractice.com
[118]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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837873
http://www.ncbi.nlm.nih.gov/pubmed/29507156?tool=bestpractice.com
[123]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.
http://www.nejm.org/doi/full/10.1056/NEJMoa022164#t=article
http://www.ncbi.nlm.nih.gov/pubmed/12954743?tool=bestpractice.com
Important properties that make it a good candidate for maintenance therapy include: less physical dependence and lower severity of withdrawal symptoms compared with methadone and heroin; due to a ceiling effect on respiratory depression and poor systemic bioavailability, it has reduced potential to produce lethal overdose, unlike methadone allows for flexibility of dosing. Dosing frequency depends on the formulation used and patient-specific factors.
Available as a sublingual tablet containing buprenorphine only, or as a sublingual tablet or film containing buprenorphine and naloxone. Buprenorphine/naloxone combination treatment was developed to deter parenteral misuse of buprenorphine.[101]Blazes CK, Morrow JD. Reconsidering the usefulness of adding naloxone to buprenorphine. Front Psychiatry. 2020 Sep 11;11:549272.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517938
http://www.ncbi.nlm.nih.gov/pubmed/33061915?tool=bestpractice.com
When taken as sublingual tablets, buprenorphine’s opioid effects dominate and block opioid withdrawal.[101]Blazes CK, Morrow JD. Reconsidering the usefulness of adding naloxone to buprenorphine. Front Psychiatry. 2020 Sep 11;11:549272.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517938
http://www.ncbi.nlm.nih.gov/pubmed/33061915?tool=bestpractice.com
If the sublingual tablets are crushed and injected, naloxone’s effects dominate and can precipitate withdrawal symptoms.[101]Blazes CK, Morrow JD. Reconsidering the usefulness of adding naloxone to buprenorphine. Front Psychiatry. 2020 Sep 11;11:549272.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517938
http://www.ncbi.nlm.nih.gov/pubmed/33061915?tool=bestpractice.com
For patients who are currently opioid dependent, buprenorphine should not be initiated until there are objective signs of mild-moderate opioid withdrawal, to reduce the risk of precipitated withdrawal.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
For patients with moderate to severe opioid use disorder in need of rapid treatment, buprenorphine can be administered by subcutaneous injection. The US Food and Drug Administration (FDA) has approved both a weekly and monthly extended-release buprenorphine injection for moderate to severe opioid use disorder to eliminate the need for daily administration. The weekly formulation is suitable for patients who are initiating treatment with a single dose of transmucosal (i.e., sublingual or buccal) buprenorphine or are already receiving buprenorphine, while the monthly version is for patients who are already stabilised on buprenorphine.
Buprenorphine can also be used to detoxify patients from methadone maintenance and transition to buprenorphine maintenance or a drug-free state. Patients on lower doses of methadone generally tolerate transition to buprenorphine with relatively minimal discomfort, whereas patients on higher doses of methadone may experience significant discomfort in transitioning between drugs.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
Therefore, a careful taper of methadone is recommended before initiating buprenorphine.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Do not start buprenorphine until the patient manifests signs of opioid withdrawal.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Carefully consider the setting for initiation of buprenorphine based on individual patient factors; in the US, both office-based and home-based initiation are possible.
Parenteral naltrexone
A pure mu opioid receptor antagonist that is non-addictive and produces no euphoria. An extended-release, parenteral formulation of naltrexone is available and is considered a useful treatment option following medically supervised withdrawal due to the lack of risk of physical dependence.[100]US Department of Veterans Affairs; Department of Defense. VA/DoD clinical practice guideline for the management of substance use disorders. Aug 2021 [internet publication].
https://www.healthquality.va.gov/guidelines/MH/sud/VADoDSUDCPG.pdf
Patients must be willing to receive monthly intramuscular injections.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
For patients who wish to discontinue opioids but who are motivated to continue pharmacotherapy, maintenance treatment with naltrexone is a valuable option.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
It is also a treatment for alcohol use disorder, and so may be useful when this is a co-occurring condition.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
One Cochrane review concluded that parenteral naltrexone shows mixed and uncertain effects across outcomes for opioid dependence, with possible benefits over oral naltrexone and treatment as usual, but may increase adverse events compared to opioid agonists; significant evidence gaps remain.[124]Kornør H, Lobmaier PPK, Kunøe N. Sustained-release naltrexone for opioid dependence. Cochrane Database Syst Rev. 2025 May 9;5(5):CD006140.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006140.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/40342086?tool=bestpractice.com
[
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For adolescents and adults with opioid dependence, how does sustained‐release naltrexone compare with usual care?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.4640/fullShow me the answer
Other studies suggest that, when initiated, extended-release naltrexone is as safe and effective as oral buprenorphine plus naloxone.[125]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.
https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2657484
http://www.ncbi.nlm.nih.gov/pubmed/29049469?tool=bestpractice.com
[126]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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806119
http://www.ncbi.nlm.nih.gov/pubmed/29150198?tool=bestpractice.com
In one trial, opioid-dependent adults who had completed medically supervised withdrawal and who were voluntarily seeking treatment and received this formulation had more opioid-free days compared with those who received placebo, and it was found to be generally well-tolerated.[90]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.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960358-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/21529928?tool=bestpractice.com
Trials of extended-release injectable naltrexone show a consistent pattern of clinical efficacy for maintaining abstinence, achieving pharmacotherapy adherence, maintaining retention, protecting against re-establishment of opioid physical dependence, and possibly reducing craving for opioids for some individuals, while showing good safety and tolerability.[127]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.
http://www.ncbi.nlm.nih.gov/pubmed/24018540?tool=bestpractice.com
[128]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.
http://www.nejm.org/doi/full/10.1056/NEJMoa1505409#t=article
http://www.ncbi.nlm.nih.gov/pubmed/27028913?tool=bestpractice.com
Before initiation of any formulation of naltrexone, patients must be opioid abstinent for an adequate period of time after completing opioid withdrawal; this is usually achieved by medically supervised withdrawal.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
A naloxone challenge test could be considered prior to initiation of naltrexone maintenance therapy to verify opioid abstinence, if there is clinical uncertainty.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
The formulation can be used safely in patients with opioid use disorders, including those with underlying mild to moderate chronic hepatitis C virus and/or HIV infections, and is administered once monthly.[129]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.
http://www.ncbi.nlm.nih.gov/pubmed/23036218?tool=bestpractice.com
Oral naltrexone
Patient preference for oral naltrexone is low, because of its lack of agonist effects. This leads to reduced treatment adherence and low retention rates, which limits its use in the clinical setting. Consequently it is infrequently used, and expert guidance recommends against the use of oral naltrexone except in certain limited circumstances (e.g., for those not permitted to have opioid agonist treatment).[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Has been found effective in treating specific groups of highly motivated individuals such as nurses, physicians, and prisoners in release programmes.[130]Washton AM, Pottash AC, Gold MS. Naltrexone in addicted business executives and physicians. J Clin Psychiatry. 1984 Sep;45(9 Pt 2):39-41.
http://www.ncbi.nlm.nih.gov/pubmed/6088468?tool=bestpractice.com
[131]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.
http://www.ncbi.nlm.nih.gov/pubmed/6524509?tool=bestpractice.com
[132]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.
http://www.ncbi.nlm.nih.gov/pubmed/9218232?tool=bestpractice.com
[133]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.
http://www.ncbi.nlm.nih.gov/pubmed/6469937?tool=bestpractice.com
One systematic Cochrane review found no benefit of oral naltrexone over placebo or no treatment in retention, opioid misuse, or side effects.[134]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.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001333.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/21491383?tool=bestpractice.com
Supportive therapies
Psychosocial interventions and urine drug screen monitoring, as well as assessment and treatment of comorbid medical and psychiatric conditions (e.g., depression, anxiety disorders, and personality disorders), should occur as a part of maintenance therapy.[135]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.
http://www.ncbi.nlm.nih.gov/pubmed/7653685?tool=bestpractice.com
[136]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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795974
http://www.ncbi.nlm.nih.gov/pubmed/26808307?tool=bestpractice.com
Psychosocial interventions are categorised into 'standard' and 'enhanced' care.[67]Mitchell C, Dolan N, Dürsteler KM. Management of dependent use of illicit opioids. BMJ. 2020 Mar 9;368:m710.
http://www.ncbi.nlm.nih.gov/pubmed/32152035?tool=bestpractice.com
Standard care interventions offered by a key worker may include motivational interviewing, goal setting, recovery planning, and contingency management.[67]Mitchell C, Dolan N, Dürsteler KM. Management of dependent use of illicit opioids. BMJ. 2020 Mar 9;368:m710.
http://www.ncbi.nlm.nih.gov/pubmed/32152035?tool=bestpractice.com
[111]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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340014
http://www.ncbi.nlm.nih.gov/pubmed/34347030?tool=bestpractice.com
[137]Schwenker R, Dietrich CE, Hirpa S, et al. Motivational interviewing for substance use reduction. Cochrane Database Syst Rev. 2023 Dec 12;12(12):CD008063.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD008063.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/38084817?tool=bestpractice.com
Enhanced care is offered if there is a poor response to standard care, or for patients with more complex needs.[67]Mitchell C, Dolan N, Dürsteler KM. Management of dependent use of illicit opioids. BMJ. 2020 Mar 9;368:m710.
http://www.ncbi.nlm.nih.gov/pubmed/32152035?tool=bestpractice.com
This may include a residential rehabilitation programme with high-intensity cognitive behavioural therapy.[67]Mitchell C, Dolan N, Dürsteler KM. Management of dependent use of illicit opioids. BMJ. 2020 Mar 9;368:m710.
http://www.ncbi.nlm.nih.gov/pubmed/32152035?tool=bestpractice.com
12-step-oriented groups such as Narcotics Anonymous may also be beneficial, preferably within a group supportive of pharmacotherapy.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
[138]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.
http://www.ncbi.nlm.nih.gov/pubmed/30387858?tool=bestpractice.com
UK Narcotics Anonymous
Opens in new window
Pain self-management programmes based on the principles of mindfulness and cognitive behavioural therapy may support moderate reductions in opioid use.[139]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.
https://www.bmj.com/content/377/bmj-2021-066375.long
http://www.ncbi.nlm.nih.gov/pubmed/35379650?tool=bestpractice.com
[140]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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8886485
http://www.ncbi.nlm.nih.gov/pubmed/35226053?tool=bestpractice.com
For drug use among parents, a Cochrane review found that psychosocial interventions addressing both parenting skills and substance misuse may have the greatest impact on abstinence (low-quality evidence).[141]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.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012823.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/33723860?tool=bestpractice.com
Monitoring of physical health problems (e.g., cardiovascular, respiratory, gastrointestinal), and HIV testing and counselling, as well as viral hepatitis screening and referral for treatment, should be integrated into a maintenance programme.
Adolescents
In general, young people need closer monitoring and regular supervision by adults. Adolescents with opioid use disorder often benefit from services designed specifically for them.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
There are also issues of consent and confidentiality with teenagers that differ from adults. Family and/or parental involvement is crucial for the evaluation and treatment of adolescents. Prior to commencing pharmacological treatment, it is important to establish a safe environment for adolescents to rehabilitate. Experienced specialists should be the primary providers initiating treatments and supervising non-specialists in the continuation of treatment.
The combination of buprenorphine with behavioural interventions is more efficacious in the treatment of opioid-dependent adolescents than the combination of clonidine and behavioural interventions.[142]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.
http://archpsyc.ama-assn.org/cgi/content/full/62/10/1157
http://www.ncbi.nlm.nih.gov/pubmed/16203961?tool=bestpractice.com
However, further research is needed to evaluate the efficacy and safety of longer-term treatment with buprenorphine for young people with opioid use disorder.[143]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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2610690
http://www.ncbi.nlm.nih.gov/pubmed/18984887?tool=bestpractice.com
[144]Feillin DA. Treatment of adolescent opioid dependence: no quick fix. JAMA. 2008 Nov 5;300(17):2057-9.
http://www.ncbi.nlm.nih.gov/pubmed/18984896?tool=bestpractice.com
Buprenorphine is generally preferred over methadone for induction and maintenance in adolescents because of its safety profile, except in instances of prior inadequate response to buprenorphine. It appears that adolescents with established opioid use disorder should be treated similarly to adults with respect to induction and longer-term stabilisation and maintenance with buprenorphine.
Methadone treatment is not usually given as a first-line treatment option in those under 18 years of age. When prescribing drugs for opioid use disorder in adolescents, clinicians should be aware that age restrictions, consent requirements, and prescribing criteria vary not only by country and jurisdiction, but also according to the specific drug being used. For example in the US, methadone treatment in patients <18 years is allowed only if they have relapsed to opioid use after two documented attempts at medically supervised withdrawal or short-term rehabilitation.[145]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.
http://www.ncbi.nlm.nih.gov/pubmed/12392810?tool=bestpractice.com
[146]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.
While buprenorphine and methadone are the most commonly used drugs for opioid use disorder in adolescents, other treatments, including those used in adults, may sometimes be used in practice depending on local availability and clinical context, under expert guidance.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
The usual supportive treatments should also be considered.
Pregnancy: antenatal management
Pregnant women with opioid use disorder experience increased obstetric and neonatal complications.[147]Dattel BJ. Substance abuse in pregnancy. Semin Perinatol. 1990 Apr;14(2):179-87.
http://www.ncbi.nlm.nih.gov/pubmed/2187251?tool=bestpractice.com
Medically supervised withdrawal is generally not recommended during pregnancy due to the risk of fetal distress and premature birth.[81]American College of Obstetricians and Gynecologists. Opioid use and opioid use disorder in pregnancy. Committee Opinion No 711. Aug 2017 (reaffirmed 2021) [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/08/opioid-use-and-opioid-use-disorder-in-pregnancy
[148]World Health Organization. Guidelines for identification and management of substance use and substance use disorders in pregnancy. 2014 [internet publication].
http://apps.who.int/iris/bitstream/10665/107130/1/9789241548731_eng.pdf?ua=1
[149]Terplan M, Laird HJ, Hand DJ, et al. Opioid detoxification during pregnancy: a systematic review. Obstet Gynecol. 2018 May;131(5):803-14.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034119
http://www.ncbi.nlm.nih.gov/pubmed/29630016?tool=bestpractice.com
[150]Substance Abuse and Mental Health Services Administration. Evidence-based, whole-person care for pregnant people who have opioid use disorder. Mar 2024 [internet publication].
https://www.samhsa.gov
However, if absolutely necessary, medically supervised withdrawal should be carried out in an inpatient setting.
Methadone and buprenorphine (with or without naloxone) are the drugs of choice for withdrawal or maintenance therapy.[81]American College of Obstetricians and Gynecologists. Opioid use and opioid use disorder in pregnancy. Committee Opinion No 711. Aug 2017 (reaffirmed 2021) [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/08/opioid-use-and-opioid-use-disorder-in-pregnancy
[150]Substance Abuse and Mental Health Services Administration. Evidence-based, whole-person care for pregnant people who have opioid use disorder. Mar 2024 [internet publication].
https://www.samhsa.gov
[151]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.
http://www.ncbi.nlm.nih.gov/pubmed/36449419?tool=bestpractice.com
There is limited evidence to suggest that methadone may be associated with a higher rate of birth defects compared to buprenorphine.[152]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.
http://www.ncbi.nlm.nih.gov/pubmed/38227945?tool=bestpractice.com
[153]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.
https://journals.sagepub.com/doi/10.4137/SART.S38887
http://www.ncbi.nlm.nih.gov/pubmed/27679504?tool=bestpractice.com
However, its use may be considered during pregnancy.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Methadone can lead to neonatal abstinence syndrome (NAS). Women treated with a stable methadone dose before pregnancy may require dose adjustments, especially in the third trimester, although this is not required in all women and should be determined on an individual clinical basis. Rapid metabolism may develop in pregnancy, particularly in the third trimester, and in this scenario split (rather than daily) dosage may be best at controlling withdrawal symptoms (and may be associated with a reduced risk of NAS).[81]American College of Obstetricians and Gynecologists. Opioid use and opioid use disorder in pregnancy. Committee Opinion No 711. Aug 2017 (reaffirmed 2021) [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/08/opioid-use-and-opioid-use-disorder-in-pregnancy
Buprenorphine with or without naloxone is a first-line alternative to methadone.[81]American College of Obstetricians and Gynecologists. Opioid use and opioid use disorder in pregnancy. Committee Opinion No 711. Aug 2017 (reaffirmed 2021) [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/08/opioid-use-and-opioid-use-disorder-in-pregnancy
[151]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.
http://www.ncbi.nlm.nih.gov/pubmed/36449419?tool=bestpractice.com
Buprenorphine monotherapy was previously recommended for pregnant women to avoid any potential antenatal exposure to naloxone.[81]American College of Obstetricians and Gynecologists. Opioid use and opioid use disorder in pregnancy. Committee Opinion No 711. Aug 2017 (reaffirmed 2021) [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/08/opioid-use-and-opioid-use-disorder-in-pregnancy
However, studies evaluating buprenorphine in combination with naloxone have since found no adverse effects in pregnant women.[81]American College of Obstetricians and Gynecologists. Opioid use and opioid use disorder in pregnancy. Committee Opinion No 711. Aug 2017 (reaffirmed 2021) [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/08/opioid-use-and-opioid-use-disorder-in-pregnancy
Buprenorphine appears to have a lower, but still significant, risk of NAS compared with methadone.[154]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.
http://www.ncbi.nlm.nih.gov/pubmed/16257138?tool=bestpractice.com
[155]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.
http://www.ncbi.nlm.nih.gov/pubmed/12492761?tool=bestpractice.com
[156]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.
http://www.ncbi.nlm.nih.gov/pubmed/18474065?tool=bestpractice.com
It also appears to result in improved birth weight due to longer gestation when compared with methadone treatment.[157]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.
http://www.ncbi.nlm.nih.gov/pubmed/18355989?tool=bestpractice.com
However, it should be noted that participants treated with buprenorphine in the study were required to present for daily dosing and received more intense psychosocial interventions than are typically offered in standard community care.[157]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.
http://www.ncbi.nlm.nih.gov/pubmed/18355989?tool=bestpractice.com
Multiple small case series have examined maternal buprenorphine concentrations in human milk. All concur that the amounts of buprenorphine in human milk are small and are unlikely to have short-term negative effects on the developing infant.[158]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.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10775244
http://www.ncbi.nlm.nih.gov/pubmed/37856658?tool=bestpractice.com
A 2020 systematic review and meta-analysis found no significant differences in pregnancy outcomes between women receiving buprenorphine/naloxone compared with methadone or buprenorphine monotherapy.[159]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.
http://www.ncbi.nlm.nih.gov/pubmed/33345863?tool=bestpractice.com
Similarly, a Cochrane review published in the same year found methadone and buprenorphine to be comparable in efficacy and safety in pregnancy.[160]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.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006318.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/33165953?tool=bestpractice.com
Pregnant women receiving treatment with methadone should not transition to buprenorphine because of a significant risk of precipitating withdrawal.[81]American College of Obstetricians and Gynecologists. Opioid use and opioid use disorder in pregnancy. Committee Opinion No 711. Aug 2017 (reaffirmed 2021) [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/08/opioid-use-and-opioid-use-disorder-in-pregnancy
Data are insufficient to recommend initiation of naltrexone in pregnancy.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
[82]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.
https://www.ajog.org/article/S0002-9378(19)30500-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/30928567?tool=bestpractice.com
[152]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.
http://www.ncbi.nlm.nih.gov/pubmed/38227945?tool=bestpractice.com
However, naltrexone may be continued in patients who are already on therapy and become pregnant after a careful assessment and risks/benefits discussion.[82]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.
https://www.ajog.org/article/S0002-9378(19)30500-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/30928567?tool=bestpractice.com
Ancillary pharmacotherapy in therapeutic doses may be required for symptomatic relief. Treatments are generally the same as for non-pregnant women; however, certain drugs should be avoided or only used when the benefits outweigh the risks. For example, ondansetron should not be used as a first-line agent for treating vomiting in pregnant women owing to a possible increased risk of cleft palate with its use during the first trimester of pregnancy.[161]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.
https://jamanetwork.com/journals/jama/fullarticle/2718793
http://www.ncbi.nlm.nih.gov/pubmed/30561479?tool=bestpractice.com
[162]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].
https://www.rcog.org.uk/media/y3fen1x1/gtg69-hyperemesis.pdf
[163]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].
https://www.gov.uk/drug-safety-update/ondansetron-small-increased-risk-of-oral-clefts-following-use-in-the-first-12-weeks-of-pregnancy
Consult a specialist for further guidance on the selection of suitable supportive therapies in pregnant women.
Pregnancy: delivery and postnatal management
Acute pain management is challenging in this population due to fear among providers and patients of triggering a relapse, and the fact that patients often have a high tolerance to opioid analgesics.[82]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.
https://www.ajog.org/article/S0002-9378(19)30500-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/30928567?tool=bestpractice.com
Women should be encouraged to have an epidural or combined spinal-epidural in early labour or as soon as contractions become uncomfortable.[82]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.
https://www.ajog.org/article/S0002-9378(19)30500-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/30928567?tool=bestpractice.com
Inhaled nitrous oxide should be avoided during delivery as it may be less effective in opioid-dependent women and is associated with increased sedation risk when taken concurrently with opioids.[82]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.
https://www.ajog.org/article/S0002-9378(19)30500-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/30928567?tool=bestpractice.com
First-line treatment for postnatal pain is oral or intravenous paracetamol.[82]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.
https://www.ajog.org/article/S0002-9378(19)30500-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/30928567?tool=bestpractice.com
If pain persists for more than 24 hours, a full opioid agonist such as fentanyl or hydromorphone may be considered.[82]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.
https://www.ajog.org/article/S0002-9378(19)30500-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/30928567?tool=bestpractice.com
In general, breastfeeding should be encouraged in women who are stable on opioid agonist treatment, who are not using illicit drugs, and who have no other contraindications (e.g., HIV).[81]American College of Obstetricians and Gynecologists. Opioid use and opioid use disorder in pregnancy. Committee Opinion No 711. Aug 2017 (reaffirmed 2021) [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/08/opioid-use-and-opioid-use-disorder-in-pregnancy
[150]Substance Abuse and Mental Health Services Administration. Evidence-based, whole-person care for pregnant people who have opioid use disorder. Mar 2024 [internet publication].
https://www.samhsa.gov
Women with opioid use disorder may require additional antenatal care; for example, expanded STI testing and additional ultrasounds to assess fetal weight.[81]American College of Obstetricians and Gynecologists. Opioid use and opioid use disorder in pregnancy. Committee Opinion No 711. Aug 2017 (reaffirmed 2021) [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/08/opioid-use-and-opioid-use-disorder-in-pregnancy
Babies born to mothers who used opioids during pregnancy (including methadone and buprenorphine) should be monitored after birth by a paediatrician for NAS, which neonates may develop shortly after birth.[81]American College of Obstetricians and Gynecologists. Opioid use and opioid use disorder in pregnancy. Committee Opinion No 711. Aug 2017 (reaffirmed 2021) [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/08/opioid-use-and-opioid-use-disorder-in-pregnancy
Duration of pharmacological treatment and treatment discontinuation
There is no recommended time limit for pharmacological treatment for opioid use disorder. Continued treatment with buprenorphine or methadone is associated with better outcomes than medically supervised withdrawal.[164]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.
https://jamanetwork.com/journals/jama/fullarticle/192476
http://www.ncbi.nlm.nih.gov/pubmed/10714729?tool=bestpractice.com
However, some patients may choose to stop opioid agonist therapy through gradually tapering the dose. Ensure that patients who discontinue pharmacological treatment are made aware of the risks associated with opioid overdose, particularly if they return to illicit opioid use.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
Discuss treatment alternatives (e.g., with another opioid agonist or an opioid antagonist) with all patients wishing to discontinue their maintenance treatment. For patients who wish to discontinue opioids but who are motivated to continue pharmacotherapy, maintenance treatment with naltrexone is a valuable option.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Methadone produces strong physical dependence. Discontinuation of methadone maintenance can lead to a protracted withdrawal syndrome that can last over 4 weeks. For withdrawal from methadone maintenance, the tapering schedule depends on the reasons for withdrawal. Guidelines on tapering vary by country and by clinical setting. For stable patients, some evidence suggests that a slow taper (<5%/ week) improves outcomes and increases the possibility of abstinence.[165]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.
https://pmc.ncbi.nlm.nih.gov/articles/PMC3376663
http://www.ncbi.nlm.nih.gov/pubmed/22385013?tool=bestpractice.com
[166]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.
http://www.ncbi.nlm.nih.gov/pubmed/7591348?tool=bestpractice.com
[167]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.
https://www.mdpi.com/1660-4601/16/15/2800
http://www.ncbi.nlm.nih.gov/pubmed/31390750?tool=bestpractice.com
Some studies suggest that only a minority of patients who discontinue methadone remain abstinent long term, particularly without ongoing psychosocial support.[97]Galanter M, Kleber HD, eds. The American Psychiatric Publishing textbook of substance abuse treatment. Washington, DC: American Psychiatric Publishing; 2008. Buprenorphine taper and discontinuation is also typically a slow process, generally accomplished over several months to years; close monitoring is recommended and patients should be encouraged to remain in treatment for ongoing monitoring past the point of discontinuation.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
Patients wishing to taper their opioid agonist should be offered psychosocial and recovery support.[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
Offer advice on overdose prevention with naloxone, and encourage patients to resume treatment with drug treatment quickly if they return to opioid use.[66]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.
https://sitefinitystorage.blob.core.windows.net/sitefinity-production-blobs/docs/default-source/guidelines/npg-jam-supplement.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32511106?tool=bestpractice.com
[69]Substance Abuse and Mental Health Services Administration. TIP 63: medications for opioid use disorder. Jul 2021 [internet publication].
https://library.samhsa.gov
The first 4 weeks after cessation of maintenance treatment is associated with a higher risk of death than in the remainder of time out of treatment, indicating a need during this time to focus clinical strategies in order to mitigate this risk.[116]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.
http://www.bmj.com/content/357/bmj.j1550.long
http://www.ncbi.nlm.nih.gov/pubmed/28446428?tool=bestpractice.com