What medications are used to manage opiate withdrawal?

Medications for Managing Opioid Withdrawal

Buprenorphine is the most effective medication for managing opioid withdrawal symptoms, demonstrating superior outcomes compared to alpha-2 adrenergic agonists (clonidine and lofexidine) in terms of withdrawal symptom severity, treatment retention, and completion rates. 1, 2

First-Line Medications

Buprenorphine

• Partial opioid agonist that effectively reduces withdrawal symptoms with less severe side effects than other options 1
• Associated with higher treatment completion rates compared to alpha-2 adrenergic agonists (NNT = 4) 2
• Dosing should be based on withdrawal severity using Clinical Opiate Withdrawal Scale (COWS) 1:
  • For moderate to severe withdrawal (COWS > 8): 4-8 mg SL initially
  • Reassess after 30-60 minutes and titrate as needed
  • Target 16 mg SL total for most patients 1
• Must be administered only to patients in active withdrawal to avoid precipitating withdrawal 1
• Timing of administration depends on last opioid use 1:
  • Short-acting opioids (heroin, morphine IR): >12 hours
  • Extended-release formulations: >24 hours
  • Methadone maintenance: >72 hours

Methadone

• Synthetic long-acting opioid that can effectively manage withdrawal symptoms 1
• Similar effectiveness to buprenorphine for withdrawal management 2
• Less commonly used in emergency settings due to:
  • Long duration of action (hours to days)
  • Potential to interfere with ongoing opioid treatment programs 1
• Can be administered for up to 72 hours without participation in an opioid treatment program 1

Second-Line Medications

Alpha-2 Adrenergic Agonists

• Include clonidine and lofexidine 1
• Less effective than buprenorphine or methadone for managing withdrawal 2
• Lofexidine (FDA-approved in 2018) is indicated for management of opioid withdrawal symptoms 3
• Common side effects include hypotension, dizziness, and sedation 3
• Caution with lofexidine: risk of low blood pressure, slow heart rate, and fainting 3

Adjunctive Medications for Symptom Management

• Antiemetics (e.g., promethazine) for nausea and vomiting 1
• Benzodiazepines for anxiety, muscle cramps, and reducing catecholamine release 1
• Loperamide for diarrhea 1

Special Considerations

Risk of Precipitated Withdrawal

• Buprenorphine can precipitate withdrawal due to its high binding affinity and partial agonist properties 1
• Particularly problematic when transitioning from methadone or fentanyl 4
• If precipitated withdrawal occurs, paradoxically, high-dose buprenorphine (up to 20mg) may effectively reverse symptoms 5

Medication for Addiction Treatment (MAT)

• Buprenorphine is not just for withdrawal management but also for long-term treatment of opioid use disorder 1
• Providers with X-waivers can prescribe buprenorphine/naloxone for 3-7 days or until follow-up 1
• Non-waivered providers can administer (but not prescribe) buprenorphine for up to 72 hours while arranging referral 1

Monitoring and Follow-up

• Assess withdrawal severity using standardized tools like COWS 1
• Provide overdose prevention education and naloxone kits at discharge 1
• Consider hepatitis C and HIV screening 1

Comparative Effectiveness

• Buprenorphine and methadone are the most effective methods for opioid detoxification 1
• Buprenorphine is associated with:
  • Less severe withdrawal symptoms compared to clonidine/lofexidine 2
  • Longer treatment retention (SMD 0.92) 2
  • Higher completion rates (RR 1.59) 2
  • Fewer adverse effects 2

Potential Risks

• All opioid medications carry risk of abuse and dependence 6
• Concurrent use of buprenorphine with alcohol or CNS depressants increases risk of respiratory depression 6
• After a period of abstinence, patients may have increased sensitivity to opioids, raising overdose risk 3