Opioid withdrawal


  • Natural derivatives (Opiates): Heroin, Morphine, Codeine, Hydrocodone, Oxycodone (+ UDS)
  • Synthetic: Fentanyl, Hydromorphone, Buprenorphine, Methadone, Meperidine, Dextromethorphan (- UDS)
  • Opioid withdrawal can be precipitated with administration of antagonist (e.g. naloxone) or partial agonist (e.g. buprenorphine) [1] or as a result of cessation of use
  • Symptoms are usually uncomfortable but not life-threatening and manifest with agitation and restlessness but does not cause altered mental status
  • Symptoms may resemble those of Influenza [2]
    • Catecholamine surge during withdrawal may cause a level of hemodynamic instability that may not be tolerated by patients with co-morbid conditions
    • Withdrawal can be life-threatening in neonates

Adult Opioid Withdrawal

  • Heroin: onset 6-12 hours, peak 24-72 hours, duration 7-10 days[3]
  • Methadone: onset 24-72 hours, peak 4-6 days, duration 14 days or more
  • Fentanyl: onset 2-5 hours, peak 8-12 hours, duration 4-5 days
  • Buprenorphine: 4-48 hours, peak 96 hours, duration 14-21 days

Precipitated Withdrawal

  • Naloxone: onset 1-3 min, duration: 30-60min
  • Butorphanol or nalbuphine: 15 min, duration: 90 min
  • Naltrexone: 15-30min, duration 12-24hours
  • Buprenorphine: 10-15min, duration 12-24 hours

Neonatal Opioid Withdrawal

Clinical Features

Time to peak and duration of symptoms depends on the half-life of the drug involved

Early symptoms

  • Agitation/restlessness
  • Anxiety
  • Muscle aches
  • Increased tearing
  • Insomnia
  • Runny nose
  • Sweating
  • Yawning
  • Skin-Crawling
  • May be tachycardic and/or tachypneic but not necessarily

Late symptoms

  • Unlike alcohol or benzodiazepine withdrawal, patients rarely have seizures
  • Altered mental status is also not part of opiod withdrawal signs

Differential Diagnosis

Differential is largely based on clinical symptoms and history

Sedative/hypnotic withdrawal


  • Clinical diagnosis
    • Consider urine toxicology screen and BMP if signs of dehydration
    • Clinical Opiate Withdrawal Score (COWS) can be used to determine severity


Treatment is largely supportive without the need for any pharmacologic intervention in the ED unless there is serious hemodynamic abnormalities

Supportive Care

  • PO/IV hydration
  • Electrolyte repletion

Opioid replacement

  • Opioid administration such as morphine can be given as needed for symptom control


  • A central α2 agonist that does suppress the sympathetic hyperactivity that results during acute withdrawal
  • Dosing: 0.1mg PO (or 5mcg/kg PO if SBP >90 mmHg) every 60 minutes as needed for sympathetic symptoms
    • Major adverse effect is hypotension
  • Clonidine patches are not useful for acute withdrawal due to the 24hr delayed release[citation needed]


  • A newer central alpha2 agonist


  • Generally reserved for outpatient therapy
  • Decreases serotonergic activity[5]


  • Can be added along with with clonidine for adequate sedation



  • Consider if withdrawal was precipitated by interruption in opioid use, NOT if antagonist (e.g. narcan) was given
  • Dose: 10mg IM or 20mg PO


  • Patients who need long term detoxification can be admitted or transferred to detox facilities
  • If patients are going to continue to use opioids then those who are stable can be discharged
  • Patients with severe withdrawal requiring sedation and continued monitoring should be admitted

External Links

See Also


  1. Olmedo R, Hoffman RS. Withdrawal syndromes. Emerg Med Clin North Am. 2000;18(2):273–88.
  2. Kosten TR, O’Connor PG. Management of drug and alcohol withdrawal. N Engl J Med 2003;348:1786-95
  3. Herring, A et al. Managing opiod withdrawal in the emergency department with buprenorphine. Annals of Emergency Medicine. 2019.73(5) 481-487
  4. Doberczak TM et al. Relationship between maternal methadone dosage, maternal-neonatal methadone levels, and neonatal withdrawal. Obstet Gynecol. 1993. 81:936–940.
  5. Van den Brink W et al. Evidence-based treatment of opioid-dependent patients. Can J Psychiatry 2006; 51:635.