What is the recommended approach for the acute management of opioid withdrawal?

Acute Management of Opioid Withdrawal

For acute opioid withdrawal, initiate buprenorphine in patients with confirmed active withdrawal symptoms (Clinical Opiate Withdrawal Scale score ≥8-12), starting with 2-4 mg sublingual and titrating every 2 hours until symptoms resolve, typically requiring 8-16 mg on day one. 1

Initial Assessment and Confirmation of Withdrawal

Use a validated withdrawal assessment tool to confirm active withdrawal before any intervention. 1

• The Clinical Opiate Withdrawal Scale (COWS) is the recommended standardized tool to assess withdrawal severity 1
• Look for objective signs: tachypnea, rising respiratory rate, accessory muscle use, grimacing, dilated pupils, excessive perspiration, and goose-flesh 1
• Document specific symptoms: lacrimation, rhinorrhea, abdominal cramps, body aches, tremors, tachycardia, nausea, vomiting, and diarrhea 2
• Family members should participate in assessments when available 1

First-Line Treatment: Buprenorphine

Buprenorphine is superior to other modalities for opioid withdrawal treatment and should be the primary agent. 1

Critical Timing Requirement

Only administer buprenorphine when the patient is in active withdrawal—never while opioids are still on board. 1

• Buprenorphine's high binding affinity and partial agonist properties will displace full agonists and precipitate severe withdrawal if given too early 1
• Patients must discontinue all opioids the night before initiation, with timing dependent on the half-life of their last opioid 1
• Transitioning from methadone to buprenorphine carries particularly high risk of severe and prolonged precipitated withdrawal 1

Dosing Protocol

Start with 2-4 mg sublingual buprenorphine, repeat at 2-hour intervals if well-tolerated until withdrawal symptoms resolve. 1

• Most patients require 4-8 mg total on the first day 1
• Reassess on day 2 and increase dose if needed 1
• The total dose given on day 2 becomes the daily maintenance dose 1
• Unlike treatment for opioid use disorder, buprenorphine for withdrawal should be divided into 3-4 daily doses 1

Special Case: Naloxone-Precipitated Withdrawal

For naloxone-precipitated withdrawal, buprenorphine can be administered immediately since withdrawal is already present. 3

• A case report demonstrated rapid symptom improvement with 4 mg/1 mg sublingual buprenorphine/naloxone, reducing COWS from 10 to 4 within 30 minutes 3
• This represents an exception to the usual timing rules since naloxone has already displaced opioids from receptors 3

Alternative and Adjunctive Medications

Alpha-2 Agonists

Use clonidine or lofexidine for autonomic symptoms when buprenorphine is contraindicated or as adjunctive therapy. 1, 4

• Clonidine addresses tachycardia, hypertension, sweating, and anxiety 1
• Average requirement is 1.6 tablets per patient 5
• Tizanidine is a newer alpha-2 agonist alternative 4

Symptom-Specific Agents

Treat specific withdrawal symptoms with targeted medications rather than increasing opioid doses. 5

• Antiemetics (promethazine or ondansetron) for nausea and vomiting 5
• Loperamide for diarrhea 5
• Benzodiazepines (2 mg IV midazolam for opioid-naive patients) for anxiety, muscle cramps, and agitation 1, 5
• Gabapentin as adjunctive therapy to reduce withdrawal symptoms 1

Methadone as Alternative

Methadone can be used when buprenorphine is unavailable or contraindicated, starting at 30-40 mg daily. 1

• This dose prevents acute withdrawal in most patients 1
• Increase by 5-10 mg increments if withdrawal persists 1
• Methadone binds less tightly to mu receptors than buprenorphine, allowing better response to additional analgesics 1
• Critical caveat: Do not convert outpatients to methadone for weaning due to complex pharmacokinetics, nonlinear morphine equivalency, and high lethality risk 1

Management of Protracted Withdrawal

Anticipate and treat protracted withdrawal symptoms that may persist for months after acute withdrawal resolves. 1

• Symptoms include dysphoria, irritability, insomnia, anhedonia, and vague sense of being unwell 1
• These symptoms cannot be easily differentiated from underlying chronic pain conditions 1
• Continue adjunctive medications (clonidine, gabapentin) as needed 1
• Consider cannabidiol (CBD) as adjunctive therapy for anxiety, pain, insomnia, and cue-induced craving, though evidence is preliminary 6

Critical Pitfalls to Avoid

Never administer buprenorphine to patients currently on opioids or not yet in withdrawal—this will precipitate severe withdrawal. 1

Do not combine buprenorphine with opioid antagonists (naloxone or naltrexone) as this precipitates withdrawal. 5

Avoid abrupt opioid discontinuation in patients on chronic therapy—this causes severe withdrawal requiring hospitalization. 7

Do not use opioid detoxification as primary treatment—it is associated with relapse and poor outcomes compared to medication-assisted treatment. 8

Recognize that fentanyl users experience more frequent, painful, and faster onset withdrawal compared to heroin users. 9

Transition to Maintenance Treatment

The acute management phase should transition directly to maintenance medication for opioid use disorder (MOUD) rather than detoxification alone. 8

• Treatment with methadone or buprenorphine is associated with superior outcomes and reduced relapse compared to detoxification 8
• Ensure adequate and timely follow-up arrangements before discharge 8
• Fear of precipitated withdrawal is a major barrier to treatment initiation and continuation—address this explicitly with patients 9

Documentation Requirements

Document the rationale for every dose of medication administered during withdrawal management. 1