Medications for Opioid Use Disorder

Buprenorphine or Buprenorphine/Naloxone 

Buprenorphine is a schedule III-controlled medication and is approved by the U.S. Food and Drug Administration (FDA) is primarily used to treat opioid use disorder (OUD) and pain. It is the first medication to treat opioid use disorder (OUD) that can reduce overdose mortality AND be prescribed or dispensed in physician offices, significantly increasing access to life-saving treatment. 

Buprenorphine is a partial opioid agonist that binds to the mu-opioid receptors in the brain but activates the receptors to a lesser extent than full opioid agonists such as heroin or methadone. This partial activation provides analgesia and relief from withdrawal symptoms and cravings without the full respiratory depressive effects seen with full agonists. This helps protect against overdose.  Buprenorphine binds very tightly to opioid receptors, which makes it effective in blocking other opioids. Buprenorphine stabilizes the receptors in the brain and decreases disruption of the pleasure reward pathways. Buprenorphine is available in various forms including long acting injectables and is often combined with naloxone to further deter misuse and diversion. 

Buprenorphine Formulations³

Approved for OUD:

• Buprenorphine extended‐release (Brixadi®) injection for subcutaneous use
• Buprenorphine extended‐release (Sublocade®) injection for subcutaneous use
• Buprenorphine/naloxone film (Suboxone®) for sublingual or buccal use
• Buprenorphine/naloxone (Zubsolv®) tablets for sublingual use
• Buprenorphine (Subutex®) tablets for sublingual use

Other formulations approved for pain:

• Buprenorphine (Buprenex®) for IV/IM Injectable
• Buprenorphine (Butrans®) Transdermal Patch
• Buprenorphine (Belbuca®) for buccal use

Naltrexone

Extended-release, injectable naltrexone (Vivitrol) is an (FDA) approved opioid antagonist used to treat OUD. It is also available in pill form but that is not approved for OUD. It is not a controlled substance. Naltrexone blocks the effects of opioids, preventing intoxication and physical dependence. This reduces the rewarding aspects of opioid use that create cravings for more. Naltrexone can be prescribed and administered by any clinician with a license to prescribe medications and is administered monthly by a clinician. Naltrexone does not help acute opioid detoxification and withdrawal symptoms. An individual must complete detoxification and withdrawal from opioids before starting Naltrexone to avoid precipitated withdrawal. 

• Naltrexone is best for patients who:
  • Do not want to take opioids or daily medication 
  • Have minimal withdrawal symptoms or opioid cravings 
  • AST/ALT <3-5x upper limit of normal 
  • Ability to make it to clinic to receive medication monthly 
  • Have co-occurring alcohol use disorder
• Naltrexone is not recommended for patients who are:
  • Pregnant or breastfeeding
  • On opioid agonist therapy
  • In acute hepatitis or liver failure 

Naltrexone Formulations³

• Vivitrol® (naltrexone for extended-release injectable suspension) intramuscular
• Of note, other formulations of naltrexone are available but are not approved by the FDA to treat OUD.

Methadone 

Methadone is a schedule II-controlled medication and is a long-acting full opioid agonist. It reduces cravings and withdrawal symptoms by acting on opioid receptors in the brain. Methadone can only be dispensed through a SAMHSA certified Opioid Treatment Program (OTP). Methadone is the most studied pharmacotherapy for OUD and has by far the longest track record (nearly 50 years).

Methadone Formulations³

• Methadone hydrochloride tablets for oral suspension
• Methadose® (methadone hydrochloride) oral concentrate and tablets for oral suspension
• Methadone hydrochloride oral concentrate

Intake and Assessment Considerations⁴

The information below is meant to be used as a general guide when completing an assessment for substance use. For tools, algorithms, and documentation tips, visit: OBAT Clinical Tools and Forms | Resources | Grayken Center for Addiction TTA | Boston Medical Center.

Before Starting Buprenorphine

Once the provider and patient decide together to move forward with starting buprenorphine consider the following steps. 

1. Obtain Informed Consent
   • Consider the following in discussion: 
     • Potential for relapse and overdose if buprenorphine is discontinued.
     • Education about the effects of using opioids and other drugs while taking the prescribed medication, with particular focus on the risk of combining buprenorphine with sedatives.
     • Potential for overdose if opioid use is resumed after tolerance is lost.
     • Discussion about birth control if pregnancy is not desired.
   • Sample Consent Form:  Treatment Consent Forms: Transmucosal Buprenorphine Consent Form
2. Review Treatment Agreement and Start Talking Form
   • Utilizing a treatment agreement is at the discretion of the prescribing clinician and/or practice. Here is a draft agreement you can tailor to your needs: 
     • Sample Buprenorphine Treatment Agreement
   • The State of Michigan Start Talking form is required any time an opioid is prescribed
     • Forms and Resources
3. Consider Lab Work
   • Lab work is not required prior to initiation but recommended at time of initiation. 
   • While there is no gold standard for types of labs, consider the following based on each patient: 
     • CMP 
     • Hepatitis B surface antigen and antibody
     • Hepatitis C antibody
     • HIV 
     • Liver enzymes
     • Pregnancy test
     • Urine drug screen
4.  Administer the Clinical Opiate Withdrawal Scale (COWS).
   • The COWS is an 11-item scale designed to be administered by a clinician. This tool can be used in both inpatient and outpatient settings to reproducibly rate common signs and symptoms of opiate withdrawal and monitor these symptoms over time.

Questions about initiation? Utilize OPEN’s expert consultation service!

In general, there are three methods for initiating buprenorphine, but strategies for initiation in practice can vary greatly based on clinician and patient. Standard and low dose initiation are safe and effective as home-based initiation. A third strategy, high dose initiation, is being explored but currently not used widely in the outpatient setting. All strategies are most effective with check-ins from a clinical staff member during the initiation process. Evidence shows that a higher initiation dose of buprenorphine (at least 16 mg) is associated with decreased return to opioid use and better retention in treatment, particularly for patients using fentanyl (thus with high tolerance).

General Considerations:

• For patients using illicit opioids, symptom burden guides timing of buprenorphine initiation, not time of abstaining from use. 
  • For patients using illicit fentanyl, anticipate a waiting period of approximately 24-72+ hours when initiating buprenorphine
    • Target is a COWs ≥ 12, SOWS ≥ 17
•  For patients using prescribed short-acting opioids, anticipate a waiting period of approximately 12-16 hours prior to buprenorphine initiation
  • Many patients will have no or minimal opioid withdrawal symptoms, so do not use a symptom triggered protocol with COWs 
•  ASAM 2020 Opioid Use Disorder National practice guidelines state both office-based and home-based observation is considered safe and effective.¹ Unsupervised initiation is standard practice with rare exceptions. There are many benefits to unsupervised initiation such as:
  • A patient’s in their own space
  • Do not need driver
  • No need to delay initiation due to scheduling
  • Lesser burden on clinical time/resources
  • Anonymity compromised if in withdrawal in waiting room

Standard Dose Initiation

This strategy requires the patient to be in opioid withdrawal. The patient stops their full opioid for approximately 12-72 hours (depending on type of opioid used), experiences withdrawal symptoms, and then begins buprenorphine. Withdrawal support medications can aid in this process.

• Does not have the ability to access fuller opioid agonist
• Is in an outpatient setting
• Is already in withdrawal or desires to stop use of their full opioid agonist immediately
• Example protocol: Buprenorphine Standard Initiation

Low Dose Initiation

This strategy requires that the patient continues their full agonist while increasing buprenorphine. The patient initiates a very low dose of buprenorphine (typically starting at 0.5mg), slowly increasing the dose daily over a period of time while continuing to use their full opioid agonist at their usual dose. Continuation of the full opioid agonist is vital to success with this strategy. Only after the period of initiation is over (typically 7 days, though 3 day protocols are also used at times) does the patient stop their full opioid agonist. When carried out correctly, the patient should never experience any withdrawal symptoms.

• Is primarily using fentanyl
• Did not tolerate traditional induction in the past
• Has safe full-agonist supply for one week
• Has comorbid chronic pain
• Can understand and follow detailed instruction
• Example protocol: Buprenorphine Low Dose Initiation

Always offer opioid withdrawal support medications, for any type of initiation. If pursuing traditional or high dose initiation, encourage patients to start withdrawal support medications prior to their most significant withdrawal symptoms. Discuss with patients which medications are helpful for which symptom. These medications can be helpful to start a few hours after last use and prior to onset of withdrawal symptoms:

• Clonidine*, tizanidine*, lofexidine (hyperadrenergic state)
• NSAIDS (muscle cramps and pain)
• Benzodiazepines (insomnia)
• Dicyclomine (abdominal cramps)
• Bismuth Subsalicylate or loperamide (diarrhea)

*Off-label use.

Stabilizing a patient on buprenorphine involves transitioning the patient from a state of opioid dependence or addiction to a stable state where cravings and withdrawal symptoms are effectively managed. Once stabilized on OUD medication, many patients stop using illicit opioids completely. Others continue to use for some time, but less frequently and in smaller amounts, which reduces their risk of morbidity and overdose death. 

Schedule regular appointments to monitor the patient’s progress, adherence, and any side effects. Determining the patient’s follow up schedule should be done through good clinical judgment and shared decision making with the patient. According to the Boston Medical Center Office Based Addiction Treatment manual, “Once stable, clinic visits can be every 2 to 4 weeks with refills that coincide with visits.” Initially, visits may be weekly for the first month and then gradually increase the time in between as the patient makes progress. During these visits, talk to the patient about how they are doing and make adjustments to ensure the dose of medication is effective and tailored based on withdrawal symptoms, cravings, side effects, current substance use, social supports, etc.⁵ 

Although research on the optimal duration of addiction treatment is limited, existing studies generally indicate that longer treatment periods lead to better outcomes according to the American Society of Addiction Medicine’s 2020 Clinical Guidelines.² Similarly, SAMHSA’s TIP 63 Medications for Opioid Use Disorders (2021) states that the most favorable results are achieved when patients continue to receive medication for as long as it remains beneficial, a strategy often referred to as “maintenance treatment.”⁵  Studies suggest rates of 50-90% of patients return to opioid use at least one month after buprenorphine taper/discontinuation. Evidence supports better outcomes with longer retention in treatment. 

If a patient expresses a desire to discontinue treatment, talk to them about things such as:

• Why do they want to taper? Why now? 
• What is different than before? 
• What is their safety plan? 
• Educate patient on loss of tolerance and increased risk of overdose 
• Continue to follow-up with patient after taper completion

People with substance use disorder experience incidents of relapse just like others do with chronic diseases like diabetes, hypertension, and asthma.⁶

Using medication to treat opioid use disorder, combined with supportive counseling and therapy that addresses both the physical and psychological aspects of addiction, produces the best remission outcomes. Precipitants to return to use often include negative affect, response to stressors and stimuli, or family/relational conflict. Cravings/cues like people, places, things, social pressures, and stress can precipitate a return to use. 

If a patient has returned to use, do NOT discharge them from your care but rather attempt to re-engage with the patient. Use this as an opportunity to re-evaluate a patient’s care plan, explore other opportunities, and determine if a higher level of care may be appropriate just as we do for other chronic diseases.

General Goal

“Providers should order the right test, for the right patient, at the right time, with the goal of conducting toxicology screening only as often as needed to create an appropriate treatment plan that supports patient safety and recovery goals.”⁵ Urine drug screening (UDS) practices should focus on supporting patient wellness and recovery, not surveillance or punishment, and drug screening results should never be the sole basis for a treatment decision. It is important to recognize that because UDS is used in many different settings including legal and carceral settings, patients may be apprehensive about UDS due to the historical punitive nature of these contexts. Patients should always be informed that a UDS is ordered and never done blindly without a patient’s knowledge.

Below is a list of frequently asked questions from our Medication for Opioid Use Disorder Trainings. Interested in attending a training? Check out our events page!

TIP 63: Medications for Opioid Use Disorder

OBAT Clinical Guidelines

Practical Tools for Prescribing and Promoting Buprenorphine in Primary Care Settings

Reimbursement for Medications for Addiction Treatment Toolkit

OBAT Clinical Tools and Forms

Guidelines for the Treatment of Opioid Use Disorder in Pregnant and Parenting Patients

The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder

Telehealth for Opioid Use Disorder Toolkit: Guidance to Support High-Quality Care

Substance Use Confidentiality Regulations

Disclosure of Substance Use Disorder Patient Records: Does Part 2 Apply to Me?

Fact Sheet 42 CFR Part 2 Final Rule

Frequently Asked Questions: Applying the Substance Abuse Confidentiality Regulations to Health Information Exchange (HIE)

1. Wakeman SE, Larochelle MR, Ameli O, et al. Comparative Effectiveness of Different Treatment Pathways for Opioid Use Disorder. JAMA Netw Open. 2020;3(2):e1920622. doi:10.1001/jamanetworkopen.2019.20622
2. The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder. (2020). ASAM, 1-95. Retrieved from: https://www.asam.org/docs/default-source/quality-science/npg-jam-supplement.pdf?sfvrsn=a00a52c2_2
3. https://www.fda.gov/drugs/information-drug-class/information-about-medications-opioid-use-disorder-moud#:~:text=There%20are%20three%20medications%20approved,to%20be%20safe%20and%20effective.
4. Wason, K.F.; Potter, A.L.; Alves, J.D.; Loukas, V.L.; Lastimoso, C.S.; Sodder, S.B.; Caputo, A.M.; and LaBelle, C.T. Massachusetts Nurse Care Manager Model of Office Based Addiction Treatment: Clinical Guidelines. Unpublished treatment manual, Boston Medical Center, May 2021.
5. Substance Abuse and Mental Health Services Administration. Medications for Opioid Use Disorder. Treatment Improvement Protocol (TIP) Series 63 Publication No. PEP21-02-01-002. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2021.
6. McLellan AT, Lewis DC, O’Brien CP, Kleber HD. Drug Dependence, a Chronic Medical Illness: Implications for Treatment, Insurance, and Outcomes Evaluation. JAMA. 2000;284(13):1689–1695. doi:10.1001/jama.284.13.1689

The content on this page presented by the Overdose Prevention Engagement Network (OPEN) is intended solely to inform and educate healthcare professionals, and shall not be used for medical advice and is not a substitute for the advice or treatment of a qualified medical professional. For specific patient questions, submit a consultation request to OPEN.