What are the recommended treatment options for opioid use disorder?

Treatment Options for Opioid Use Disorder

First-Line Medication-Assisted Treatment

For most patients with opioid use disorder, initiate treatment with buprenorphine or methadone combined with behavioral therapies, as these medications have the strongest evidence for reducing mortality and improving treatment retention. 1

Buprenorphine (Preferred First-Line for Most Settings)

• Buprenorphine is recommended as first-line treatment for patients 16 years and older due to its accessibility, favorable safety profile, and ability to be prescribed in office-based settings. 1
• Buprenorphine functions as a partial opioid agonist that suppresses withdrawal symptoms and attenuates the effects of other opioids while having a ceiling effect that reduces overdose risk. 2, 3
• Ensure patients are in mild-to-moderate withdrawal before administering the first dose to prevent precipitated withdrawal—this is a critical implementation point that cannot be overlooked. 1
• Standard dosing involves stabilization on 8-24 mg daily of sublingual/buccal buprenorphine, typically combined with naloxone to reduce diversion risk. 4, 5
• Long-acting injectable formulations (Sublocade) are available for patients stabilized on transmucosal buprenorphine, with initial 300 mg monthly doses followed by 100 mg monthly maintenance. 5

Methadone (Gold Standard with Access Limitations)

• Methadone maintenance therapy remains the gold standard of care for adults with opioid use disorder, with the strongest evidence for effectiveness and longest track record of reducing mortality. 1, 2, 6
• Methadone acts as a full opioid agonist that eliminates withdrawal symptoms and blocks euphoric effects of other opioids when dosed appropriately. 2
• Federal regulations severely limit methadone access by requiring administration only through certified Opioid Treatment Programs (OTPs), making it less accessible than buprenorphine despite superior efficacy data. 1, 7
• Longer duration of methadone treatment allows restoration of social connections and is associated with better long-term outcomes. 2

Naltrexone (Third-Line for Highly Motivated Patients)

• Naltrexone may be considered for highly motivated patients who cannot or do not wish to take continuous opioid agonist therapy, but it is not first-line due to adherence challenges. 1, 8
• Patients must be completely opioid-free for a minimum of 7-10 days before starting naltrexone to avoid precipitating severe withdrawal—this opioid-free requirement is a major barrier to treatment initiation. 9
• Patients transitioning from buprenorphine or methadone may be vulnerable to precipitated withdrawal for as long as 2 weeks. 9
• Extended-release injectable naltrexone (Vivitrol) 380 mg monthly improves adherence compared to daily oral formulations. 8
• Naltrexone cannot be used in patients requiring opioids for pain control as it blocks all opioid receptor activity, including analgesia. 8

Essential Treatment Components Beyond Medication

Behavioral Therapies (Non-Negotiable Adjunct)

• Combine all medication-assisted treatment with behavioral therapies and substance use disorder counseling—this combination reduces opioid misuse, increases treatment retention, and improves compliance. 4, 1
• Behavioral therapies are particularly important during maintenance therapy and after detoxification to address underlying psychological factors driving addiction. 4
• Integrated treatment approaches that address substance use disorders alongside other health issues show improved outcomes. 5

Overdose Prevention

• Provide naloxone for overdose prevention to all patients with opioid use disorder regardless of which medication-assisted treatment they receive. 1
• Patients who discontinue naltrexone treatment have markedly increased risk of opioid overdose and death due to decreased opioid tolerance. 8

Special Populations

Pregnant Women

• Offer buprenorphine (without naloxone) or methadone to pregnant women with opioid use disorder—medication-assisted therapy has been associated with improved maternal outcomes and should not be withheld. 4, 5
• Buprenorphine monotherapy (without naloxone) is preferred during pregnancy. 6

Adolescents

• Medication-assisted treatment, including all three FDA-approved options, should be considered for adolescents with opioid use disorder. 8
• Buprenorphine is recommended as first-line for patients 16 years and older. 1

Critical Implementation Algorithm

Step 1: Assess for Opioid Use Disorder

• Use DSM-5 criteria to diagnose opioid use disorder, or arrange for assessment by a substance use disorder specialist. 4

Step 2: Select Medication Based on Patient Factors

• Default to buprenorphine for most patients due to office-based accessibility and safety profile. 1
• Consider methadone if patient has failed buprenorphine, has severe opioid use disorder, or has access to an OTP. 1, 2
• Reserve naltrexone for highly motivated patients who refuse agonist therapy or have completed medically supervised withdrawal. 1, 8

Step 3: Verify Readiness for Medication Initiation

• For buprenorphine: Confirm patient is in mild-to-moderate withdrawal (COWS score 8-12) before first dose. 1
• For naltrexone: Verify minimum 7-10 day opioid-free period; consider naloxone challenge test if uncertain. 9
• For methadone: Can initiate without withdrawal symptoms present. 7

Step 4: Combine with Behavioral Support

• Arrange behavioral therapies, counseling, and psychosocial support concurrently with medication initiation. 4, 1

Step 5: Monitor and Adjust

• Monitor liver function tests at baseline and every 3-6 months for naltrexone due to hepatotoxicity risk. 1, 8
• Follow up frequently (at least monthly) during treatment. 8

Common Pitfalls to Avoid

• Never initiate buprenorphine in a patient who is not in withdrawal—this will precipitate severe withdrawal symptoms that can derail treatment engagement. 1, 5
• Never initiate naltrexone without ensuring adequate opioid-free period—precipitated withdrawal from naltrexone can be severe and prolonged. 1, 9
• Never withhold medication-assisted treatment due to stigma or misconceptions about "replacing one drug with another"—agonist therapy saves lives and has the strongest evidence base. 1
• Do not dismiss patients from your practice because of substance use disorder, as this represents patient abandonment and eliminates opportunity for life-saving intervention. 4
• Do not abruptly discontinue any medication-assisted treatment without a tapering plan and close monitoring. 1
• Do not perform naloxone challenge testing in patients showing clinical signs of withdrawal or with opioids detected in urine. 9

Provider Requirements and System Considerations

• Physicians can obtain SAMHSA waiver certification to prescribe buprenorphine in office-based settings—physicians in communities without sufficient OUD treatment capacity should strongly consider obtaining this waiver. 4, 5
• No waiver is required to prescribe naltrexone. 4
• Identify treatment resources for opioid use disorder in your community and work to ensure sufficient treatment capacity. 4, 5
• Arrange for coordination of care with substance use disorder specialists when needed, but do not make "cold referrals" to clinicians who have not agreed to accept the patient. 8