How should withdrawal symptoms be managed when discontinuing opioids in opioid-dependent patients?


Opioid withdrawal syndrome encompasses the signs and symptoms that occur as a result of a rapid decrease or cessation of opioids after prolonged use.1 For short-acting opioids, opioid withdrawal symptoms present within approximately 12 hours of last dose and continue for about 3-5 days. For long-acting opioids, withdrawal symptoms occur within approximately 30 hours of last dose and continue for up to 10 days. While opioid withdrawal syndrome is rarely life threatening, it may lead to relapse if not managed properly.


According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), opioid withdrawal syndrome must be precipitated by a rapid decrease or sudden cessation of opioid use.2 It may also be triggered by the administration of an opioid antagonist. Patients must demonstrate 3 or more of the following signs and symptoms to be diagnosed with opioid withdrawal: dysphoric mood, nausea or vomiting, muscle aches, lacrimation, rhinorrhea, pupillary dilation, piloerection, sweating, diarrhea, yawning, fever, or insomnia. These signs and symptoms must cause clinically significant distress or impairment, and they must not be attributable to another medical condition or substance use.


There are various scales for the assessment of opioid withdrawal syndrome including the Objective Opioid Withdrawal Scale (OOWS), the Clinical Opioid Withdrawal Scale (COWS), and the Subjective Opioid Withdrawal Scale (SOWS).3 These scales help to measure the effectiveness of withdrawal management as they are repeated regularly throughout treatment.


One method of managing opioid withdrawal syndrome is using gradual, tapered doses of opioid agonists such as methadone or buprenorphine.1 Methadone may only be administered in an inpatient setting or in an approved opioid treatment program. Buprenorphine may be prescribed in either inpatient or outpatient settings. Prescribers certified through the Drug Addiction Treatment Act of 2000 may prescribe buprenorphine from their office settings.

Alpha-2 adrenergic agonists, such as clonidine, can also be used to manage withdrawal symptoms.1 Many signs and symptoms of opioid withdrawal are due to the overstimulation of the noradrenergic system, and alpha-2 adrenergic agonists help to mitigate this activity. Clonidine may potentially be combined with other non-opioid medications (as seen in the table below) to manage specific symptoms of withdrawal.4,5

Table. Pharmacologic options for opioid withdrawal symptoms.
Symptoms Medications
Autonomic symptoms First Line: clonidine 0.1-0.2 mg every 6-8 hours
Baclofen 5 mg 3 times daily
Gabapentin 100-300 mg 2 to 3 times daily, up to 2100 mg in 2-3 daily doses
Tizanidine 4 mg 3 times daily
Anxiety, dysphoria, lacrimation, rhinorrhea Hydroxyzine 25-50 mg 3 times a day as needed
Diphenhydramine 25 mg every 6 hours as needed
Myalgia Naproxen 375-500 mg twice daily
Ibuprofen 400-600 mg 4 times a day as needed
Acetaminophen 650 mg oral every 6 hours as needed
Topical (menthol/methyl salicylate cream, lidocaine cream or ointment)
Insomnia Trazodone 25-300 mg at bedtime
Nausea Prochlorperazine 5-10 mg every 4 hours as needed
Promethazine 25 mg every 6 hours as needed
Ondansetron 4 mg every 6 hours as needed
Abdominal cramping Dicyclomine 20 mg every 6-8 hours as needed
Diarrhea Loperamide 4 mg first dose, then 2 mg with each loose stool (max daily dose of 16 mg)
Bismuth subsalicylate 524 mg every 0.5-1 hour (max daily dose of 4192 mg)
Adapted from VA/DoD Clinical Practice Guidelines: Tapering and Discontinuing Opioids – Updated June 20174


  1. Kampman K, Jarvis M. American Society of Addiction Medicine (ASAM) national practice guideline for the use of medications in the treatment of addiction involving opioid use. J Addict Med. 2015;9(5):358-367.
  2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.
  3. Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence. Geneva: World Health Organization; 2009. Accessed November 27, 2019.
  4. Tapering and discontinuing opioids. Accessed November 27, 2019.
  5. U.S. Department of Veterans Affairs, VA Academic Detailing Services. Opioid taper decision tool. (2017). Retrieved from Accessed November 27, 2019.
Prepared by:
Zhen Ou, PharmD
Clinical Instructor
University of Illinois at Chicago
College of Pharmacy

The information presented is current as of November 2019. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.