What is the first line treatment for opioid use disorder?

First-Line Treatment for Opioid Use Disorder

Medication-assisted treatment with either buprenorphine or methadone, combined with behavioral therapies, is the first-line treatment for opioid use disorder, with methadone remaining the gold standard of care for adults and buprenorphine approved for patients 16 years and older. 1, 2

Medication Options

Buprenorphine (Preferred for Most Settings)

• Buprenorphine is a partial opioid agonist that can be prescribed in office-based settings by physicians who complete training and obtain a waiver, making it more accessible than methadone 1
• FDA-approved for patients 16 years and older, with extensive evidence demonstrating effectiveness in reducing opioid use and retaining patients in treatment 1, 3
• Available as sublingual/buccal formulations (typically 8-24 mg daily) or long-acting injectable formulations (Sublocade: 300 mg monthly for first two doses, then 100 mg monthly maintenance) 4, 3
• The partial agonist properties provide a ceiling effect on respiratory depression, making it safer than full agonists with lower overdose risk 3

Methadone (Gold Standard)

• Methadone is a full opioid agonist with the strongest evidence for effectiveness in treating opioid use disorder, doubling rates of opioid abstinence compared to placebo 2, 5
• Must be dispensed through federally certified Opioid Treatment Programs (OTPs), limiting accessibility but ensuring supervised administration 6, 5
• Federal regulations prohibit most methadone programs from admitting patients younger than 18 years 1
• Longer duration of treatment allows restoration of social connections and is associated with better outcomes 5

Naltrexone (Alternative for Specific Populations)

• Naltrexone is an opioid antagonist that may be considered for highly motivated patients who cannot or do not wish to take continuous opioid agonist therapy 1, 7
• Available as oral formulation (50 mg daily) or extended-release injection (Vivitrol: 380 mg monthly) 7, 8
• Critical requirement: patients must be completely opioid-free for 7-10 days before initiation to avoid precipitating severe withdrawal 8, 7
• Has limited potential for misuse or diversion compared to agonist therapies, making it suitable for patients in unstable housing or with co-occurring alcohol use disorder 1, 7
• Evidence for efficacy is weaker than agonist therapies, with poor adherence rates for oral formulation 2, 9

Essential Treatment Components

Behavioral Therapy Integration

• All medication-assisted treatment must be combined with behavioral therapies and substance use disorder counseling 1, 4, 10
• Psychosocial interventions reduce opioid misuse, increase treatment retention, and improve compliance 1, 11

Treatment Selection Algorithm

1. Assess severity using DSM-5 criteria for opioid use disorder (at least 2 criteria within 12 months) 1
2. For most patients: offer buprenorphine due to office-based accessibility and favorable safety profile 1, 9
3. For patients requiring highest level of structure or with severe addiction: refer for methadone at certified OTP 2, 5
4. For highly motivated patients preferring opioid-free treatment or with co-occurring alcohol use disorder: consider naltrexone after ensuring adequate opioid-free period 1, 7
5. For pregnant women: offer buprenorphine (without naloxone) or methadone, which improve maternal outcomes 1, 4
6. For adolescents 16+ years: offer buprenorphine as methadone programs typically cannot admit patients under 18 1

Critical Implementation Points

Pre-Treatment Requirements

• Verify opioid-free status before naltrexone initiation using naloxone challenge test if needed 8
• For buprenorphine: ensure patient is in mild-moderate withdrawal before first dose to prevent precipitated withdrawal 4
• Screen for depression, anxiety, and insomnia before initiating any medication-assisted treatment 7

Monitoring and Safety

• Provide naloxone for overdose prevention to all patients with opioid use disorder 1
• Monitor liver function tests at baseline and every 3-6 months for naltrexone due to hepatotoxicity risk 7
• Warn patients that discontinuing medication-assisted treatment increases risk of fatal overdose due to decreased opioid tolerance 7

Common Pitfalls to Avoid

• Never initiate naltrexone without ensuring adequate opioid-free period (minimum 7-10 days for short-acting opioids, up to 2 weeks for buprenorphine/methadone) as this precipitates severe withdrawal 8, 7
• Do not withhold medication-assisted treatment due to stigma or misconceptions—these medications are evidence-based treatments for a life-threatening chronic disease 1
• Avoid abrupt discontinuation of any medication-assisted treatment without tapering plan and close monitoring 7
• Do not prescribe naltrexone to patients requiring opioids for pain control as it blocks analgesic effects 7
• Recognize that only 34% of opioid-dependent patients in treatment programs receive medication despite 70% of mental health patients receiving medication—actively work to close this treatment gap 1