What is the recommended treatment for opioid withdrawal?

Treatment of Opioid Withdrawal

Buprenorphine is the first-line treatment for moderate to severe opioid withdrawal (COWS >8), with an initial dose of 4-8 mg sublingual, targeting a total of 16 mg daily for most patients. 1

Assessment and Timing

Confirm withdrawal severity before initiating treatment:

• Use the Clinical Opiate Withdrawal Scale (COWS) to objectively assess withdrawal severity 1
• Mild withdrawal (COWS <8): No buprenorphine indicated; reassess in 1-2 hours 1
• Moderate to severe withdrawal (COWS >8): Administer buprenorphine 4-8 mg sublingual based on severity 1

Critical timing requirements to prevent precipitated withdrawal:

• Short-acting opioids (heroin, morphine IR): Wait >12 hours since last use 1
• Extended-release formulations (OxyContin): Wait >24 hours since last use 1
• Methadone maintenance: Wait >72 hours; consider continuing methadone instead 1
• Chronic fentanyl use increases risk of precipitated withdrawal; consider alternative dosing strategies 2

First-Line Treatment: Buprenorphine

Buprenorphine is superior to all other modalities for opioid withdrawal, with less severe withdrawal symptoms, fewer adverse effects, and better treatment retention compared to clonidine or lofexidine 1

Dosing protocol:

• Initial dose: 4-8 mg sublingual for moderate to severe withdrawal 1
• Reassess after 30-60 minutes 1
• Target total dose: 16 mg sublingual daily for most patients 1
• X-waivered providers: Prescribe buprenorphine/naloxone 16 mg daily for 3-7 days until follow-up 1
• Non-X-waivered providers: Can administer (but not prescribe) for up to 3 consecutive days in ED/hospital setting 1

Critical safety consideration: Only administer buprenorphine to patients in active withdrawal confirmed by history and physical examination, as its high binding affinity and partial agonist properties can precipitate severe withdrawal if given too early 1, 2

Second-Line Treatment: Methadone

Methadone is equally effective to buprenorphine for opioid withdrawal but has practical limitations in acute care settings 1

• Can be administered for up to 72 hours without opioid treatment program participation 1
• Long duration of action (hours to days) extends beyond ED visit 1
• May interfere with ongoing opioid treatment program adherence 1
• Should not be used for outpatient tapering due to complex pharmacokinetics, nonlinear morphine equivalency, and high lethality 1
• Preferred for patients already on methadone maintenance 1

Adjunctive Symptomatic Treatment

Alpha-2 adrenergic agonists directly attenuate opioid withdrawal:

• Clonidine: 0.1-0.2 mg orally every 4-6 hours, maximum 0.8 mg daily 3
• Withhold if systolic BP <90 mmHg or diastolic BP <60 mmHg 3
• Taper by reducing dose 0.1-0.2 mg every 1-2 days as symptoms improve 3
• Lofexidine: Similar efficacy with less hypotension 1, 3
• Tizanidine: Less effective but also less likely to cause hypotension 1, 3

Additional symptomatic medications:

• Antiemetics (promethazine) for nausea and vomiting 1
• Benzodiazepines to reduce catecholamine release, muscle cramps, and anxiety 1
• Loperamide for diarrhea (caution: can be abused and cause arrhythmias in high doses) 1
• Trazodone, tricyclic antidepressants, gabapentin, or mirtazapine for short-term management of anxiety, insomnia, and irritability 1

Hospital-Specific Considerations

Inpatient management allows for more aggressive treatment:

• Continue stable doses of opioids if patient already comfortable 1
• Can use short-acting full agonist opioids (SAFAO) in addition to methadone/buprenorphine for severe withdrawal 4
• Average 278 mg oral morphine equivalents daily of SAFAO during first week correlates with reduced withdrawal severity 4
• Methadone or buprenorphine can be legally initiated during hospitalization and transitioned to outpatient clinic after discharge 5, 6

Management of Precipitated Withdrawal

If buprenorphine precipitates withdrawal, treat with additional buprenorphine plus symptomatic management 2

• This strategy has pharmacological basis and proven effectiveness in case reports 2
• Additional symptom-based supportive care as outlined above 2
• Most cases have benign course but may significantly reduce future buprenorphine acceptance 2

Critical Pitfalls to Avoid

Do not:

• Administer buprenorphine before adequate withdrawal symptoms develop (COWS >8) 1, 2
• Transition from methadone to buprenorphine without extended waiting period (>72 hours) due to severe precipitated withdrawal risk 1, 2
• Use opioid detoxification alone without maintenance treatment—this is associated with relapse and poor outcomes 6
• Prescribe methadone for outpatient tapering without specialized experience 1
• Combine buprenorphine with benzodiazepines or other CNS depressants without careful monitoring for respiratory depression 7

Discharge Planning and Harm Reduction

Essential discharge components:

• Provide overdose prevention education and take-home naloxone kit 1
• Screen for hepatitis C and HIV 1
• Offer reproductive health counseling 1
• Ensure timely follow-up with addiction treatment services 1, 6
• Bridge to outpatient medication-assisted treatment (methadone clinic or buprenorphine prescriber) 1, 5, 6