What are the pharmacologic treatment options for severe opioid use disorder?

Pharmacologic Treatment Options for Severe Opioid Use Disorder

Medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies is the most effective pharmacologic treatment for severe opioid use disorder. 1

First-Line Medication Options

Methadone

• Full opioid agonist with long half-life
• Most established treatment with strongest evidence for effectiveness
• Ameliorates the cycle of euphoria and withdrawal associated with opioid use
• Higher treatment retention rates than other options
• Requires administration through federally certified Opioid Treatment Programs (OTPs)
• Federal regulations restrict most methadone programs from admitting patients younger than 18 years 2
• Indicated specifically for detoxification and maintenance treatment of opioid addiction 3

Buprenorphine

• Partial opioid agonist with high receptor affinity
• FDA-approved for patients 16 years and older since 2002 2
• Can be prescribed in office-based settings by physicians with appropriate DEA waiver
• Provides gentle stimulation of the opioid system, reducing highs and lows
• Available in various formulations:
  • Sublingual tablets
  • Buprenorphine/naloxone combination (preferred for most patients due to abuse-deterrent properties) 1
  • Long-acting injectable formulations (may improve adherence and reduce diversion risk) 4
• Starting dose typically 4-8 mg sublingually, targeting total first-day dose of 16 mg 1

Naltrexone

• Opioid antagonist with high receptor affinity
• Blocks effects of opioids, preventing euphoria
• Very limited potential for misuse or diversion
• Available as oral tablets or extended-release injectable formulation
• Requires 7-10 day opioid-free period before initiation 5
• May be particularly suitable for:
  • Highly motivated patients
  • Patients with co-occurring alcohol use disorder
  • Those living in unstable or unsupervised housing 2
• Initial dose of 25 mg, increasing to 50 mg daily if no withdrawal signs occur 5

Treatment Selection Algorithm

1. Assess severity and patient factors:

   • Severity of opioid use disorder
   • Patient preference and motivation
   • Access to treatment facilities
   • Co-occurring conditions (especially alcohol use disorder)
   • Housing stability
   • Pregnancy status (buprenorphine without naloxone preferred) 1

2. For most patients with severe OUD:

   • Methadone or buprenorphine are first-line options 2, 1
   • Methadone if higher treatment retention is priority and patient can attend daily clinic visits
   • Buprenorphine if office-based treatment is preferred or methadone access is limited

3. Consider naltrexone when:

   • Patient is highly motivated and can complete 7-10 day opioid-free period
   • Risk of diversion is high
   • Co-occurring alcohol use disorder is present
   • Patient prefers non-opioid treatment option

Implementation Considerations

For Buprenorphine:

• Verify patient is in moderate withdrawal before first dose to avoid precipitated withdrawal
• Patients transitioning from methadone may be vulnerable to withdrawal for up to 2 weeks 1
• Monitor for side effects, especially when combined with other CNS depressants
• Dose adjustments needed for patients with severe hepatic impairment 1

For Methadone:

• Must be administered through certified OTPs
• Requires more intensive monitoring due to risk of QT prolongation and respiratory depression
• Significant drug interactions require careful medication review

For Naltrexone:

• Confirm opioid-free status with naloxone challenge test if uncertain 5
• Monitor for signs of withdrawal during initiation
• Consider alternative dosing schedules (e.g., 100 mg every other day or 150 mg every third day) for supervised administration 5

Treatment Duration and Monitoring

• Indefinite treatment is recommended to reduce relapse risk 1
• Discontinuation significantly increases risk of relapse and mortality
• Regular monitoring schedule:
  • Weekly visits initially
  • Monthly visits once stable
  • Urine drug testing to verify adherence 1
• Enhanced monitoring for patients at high risk of respiratory depression (e.g., those taking benzodiazepines) 1

Common Pitfalls and Caveats

1. Undertreatment: Less than 50% of addiction treatment programs offer medication for opioid use disorders, and even among those that do, medication is significantly underutilized 2

2. Premature discontinuation: Discontinuing pharmacotherapy increases relapse risk; patients should be encouraged to continue treatment indefinitely 6

3. Precipitated withdrawal: Can occur if buprenorphine is initiated before patient is in moderate withdrawal 1

4. Concurrent benzodiazepine use: Increases risk of respiratory depression and should be avoided 2, 1

5. Inadequate behavioral support: Medication should be combined with behavioral therapies for optimal outcomes 2, 1

6. Stigma and access barriers: Despite effectiveness, stigma and limited resources restrict access to medication-assisted treatment 2, 7

By implementing evidence-based medication-assisted treatment with appropriate behavioral support, providers can significantly reduce mortality, decrease illicit opioid use, and improve quality of life for patients with severe opioid use disorder.