What medications are used to treat heroin withdrawal?

Medications for Heroin Withdrawal

Buprenorphine is the first-line medication for managing heroin withdrawal, demonstrating superior efficacy to all alternatives in reducing withdrawal severity and increasing treatment completion rates. 1, 2

First-Line Treatment: Buprenorphine

Buprenorphine should be initiated based on objective withdrawal severity using the Clinical Opioid Withdrawal Scale (COWS), with treatment starting only when patients demonstrate moderate to severe withdrawal (COWS >8). 1, 2

Critical Timing Requirements

• Wait >12 hours since last heroin use before administering buprenorphine to avoid precipitating a more severe withdrawal syndrome 3, 1
• For extended-release opioid formulations: wait >24 hours 1
• For patients on methadone maintenance: wait >72 hours 1

Dosing Protocol

For moderate to severe withdrawal (COWS >8):

• Administer 4-8 mg sublingual buprenorphine initially based on withdrawal severity 3, 1
• Reassess after 30-60 minutes and redose as needed 1, 2
• Target total first-day dose of 8-16 mg 1, 2
• Most patients require a maintenance dose of 16 mg daily 1, 2

For mild withdrawal (COWS <8):

• No buprenorphine indicated initially 3
• Reassess patient and COWS in 1-2 hours 3

Evidence Supporting Buprenorphine Superiority

Buprenorphine demonstrates an 85% probability of being the most effective treatment for opioid withdrawal, compared to 12.1% for methadone, 2.6% for lofexidine, and 0.01% for clonidine 4. Patients receiving buprenorphine experience less severe withdrawal symptoms (small to moderate effect size), stay in treatment longer (large effect size), and are more likely to complete withdrawal treatment compared to alpha-2 agonists 5. For every 4 patients treated with buprenorphine versus clonidine/lofexidine, 1 additional patient will complete treatment. 5

Second-Line Treatment: Alpha-2 Adrenergic Agonists

When buprenorphine is contraindicated or unavailable, use lofexidine (FDA-approved) or clonidine (off-label) as second-line agents, recognizing they are significantly less effective than buprenorphine. 1, 4, 2

Clinical Application

• Lofexidine is preferred in outpatient settings as it causes less hypotension than clonidine while maintaining similar efficacy 4
• Clonidine is used off-label for opioid withdrawal and lacks FDA approval for this indication 4
• Start at low doses and titrate based on withdrawal symptoms and blood pressure monitoring 4
• These agents reduce autonomic symptoms (sweating, tachycardia, hypertension, anxiety) by binding alpha-2 receptors 4

Methadone as Alternative

Methadone has similar efficacy to buprenorphine but is less commonly used in acute settings due to its long duration of action, potential to interfere with ongoing treatment programs, and regulatory restrictions 3, 1, 2. Buprenorphine and methadone appear equally effective in terms of treatment duration and completion rates, though withdrawal symptoms may resolve more quickly with buprenorphine 5.

Adjunctive Symptom-Directed Medications

Regardless of primary agent used, add symptom-specific medications to improve comfort and treatment retention: 3, 1, 2

• Antiemetics (promethazine) for nausea and vomiting 3, 1
• Loperamide for diarrhea 3, 1
• Benzodiazepines (lorazepam) for anxiety and muscle cramps 3, 1
  • Monitor closely for respiratory depression, especially when combined with opioids 2

Critical Pitfalls to Avoid

Precipitated withdrawal: Buprenorphine can precipitate severe withdrawal if administered before the patient is in active withdrawal due to its high binding affinity and partial agonist properties 1, 6. This risk is particularly elevated when transitioning from methadone or fentanyl 1.

Inadequate dosing: Underdosing buprenorphine leads to persistent withdrawal symptoms and treatment dropout. Target the full 16 mg daily dose for most patients 1, 2.

Abrupt discontinuation: Buprenorphine should not be abruptly discontinued in physically-dependent patients, as this can precipitate a withdrawal syndrome characterized by restlessness, lacrimation, rhinorrhea, perspiration, chills, myalgia, and mydriasis 6.

Post-Withdrawal Considerations

Provide overdose prevention education and naloxone kits at discharge, as patients become more sensitive to opioid effects after withdrawal symptom resolution, increasing overdose risk if they resume opioid use 1, 2. Consider hepatitis C and HIV screening, and reproductive health counseling 3.