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Opioid withdrawal syndrome
Other Resources UpToDate PubMed

Opioid withdrawal syndrome

Contributors: Shanna Yang, Benjamin L. Mazer MD, MBA, Michael W. Winter MD
Other Resources UpToDate PubMed


Opioid withdrawal syndrome is a set of characteristic physiologic responses to abstinence from opioid drugs after prolonged use. Characteristic symptoms include rhinorrhea, lacrimation, yawning, diaphoresis, and mydriasis. Neuropsychiatric disturbances like anxiety, restlessness, and insomnia are also common. Gastrointestinal symptoms are prominent later in the withdrawal, typically presenting within a few days of cessation from drug use.

Symptoms appear gradually during the first hours of withdrawal and remain for several days. Most symptoms resolve within 10 days. Use of narcotic antagonists (naloxone) can quickly induce symptoms of opioid withdrawal. Onset of symptoms and their severity depend in part on the properties of the particular opioid drug being used, such as its half-life. Two to three times the half-life of the withdrawn opioid is often used as a rough estimate of time to symptom onset.

Opiates can be derived naturally from poppy plants or produced via semi-synthetic or synthetic methods. Examples include morphine and codeine (natural opiates); heroin, oxycodone, oxymorphone, hydrocodone, hydromorphone, and buprenorphine (semi-synthetic opioids); and meperidine (Demerol), fentanyl, and methadone (synthetic opioids). Short-acting opioids include heroin and morphine, while methadone is a long-acting opioid.

Opioid withdrawal syndrome is rarely life threatening or likely to cause significant alterations in mental status. However, physical discomfort coupled with intense craving make it difficult for many patients to complete withdrawal treatment, which is often the required first step of long-term treatment such as residential rehabilitation. Due to the risk of inducing a precipitous withdrawal, some treatment options, such as opioid receptor antagonists, are prescribed only after patients have successfully completed medically supervised withdrawal. Devices with cranial nerve stimulation may also help reduce symptoms of acute opioid withdrawal.

Research is ongoing to continue developing effective temporizing measures as a bridge to the initiation of definitive medication-assisted therapy. As with any addictive disease, risk of relapse is overall high, particularly when strong support networks and abstinence efforts are not pursued.

Resources for opioid prescribing guidelines, as well as nonopioid alternatives, can be found here.

Related topics: neonatal abstinence syndrome, opioid use disorder, opioid overdose


F11.93 – Opioid use, unspecified with withdrawal

87132004 – Opioid withdrawal

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

  • Alcohol withdrawal syndrome
  • Cholinergic syndrome
  • Anticholinergic syndrome
  • Sympathomimetic toxicity
  • Drug side effects (eg, Cocaine intoxication and use disorder, Methamphetamine use disorder, MDMA, Acute salicylate poisoning)
  • Psychiatric disorder
  • Common cold
  • Influenza
  • Gastroenteritis
  • Inflammatory bowel disease (eg, Crohn disease, Ulcerative colitis)
  • Irritable bowel syndrome
  • Allergic rhinitis
  • Vasomotor rhinitis
  • HypoglycemiaHypoglycemia
  • Diabetic ketoacidosis
  • Adrenal crisis
  • Hyperthyroidism
  • Electrolyte disturbance (eg, hypomagnesemia, hypophosphatemia)

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Management Pearls

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Drug Reaction Data

Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.

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Last Reviewed:01/21/2019
Last Updated:11/08/2022
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Opioid withdrawal syndrome
A medical illustration showing key findings of Opioid withdrawal syndrome (Stage I) : Agitation, Anxiety, Irritability
Copyright © 2024 VisualDx®. All rights reserved.