Opioid withdrawal

Last updated: August 29, 2022

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Opioid withdrawal syndrome (OWS) refers to the constellation of symptoms that can develop after a sudden cessation or reduction of opioid use following a period of prolonged chronic use. This condition is characterized by sympathetic hyperactivity, flu-like symptoms, and gastrointestinal symptoms. OWS is a clinical diagnosis that can be supported using the DSM-V criteria; the severity of the condition can be scored using validated tools such as the Clinical Opioid Withdrawal Scale (COWS). Opioid replacement therapy with a long-acting opioid agonist (methadone or buprenorphine) and psychosocial support are the cornerstones of treatment. Management of withdrawal symptoms may help to bridge patients to outpatient medication-assisted treatment programs and provide an opportunity to reinforce harm reduction strategies for overdose and relapse prevention.

Epidemiological data refers to the US, unless otherwise specified.

Mechanism of physiologic dependence [2][3]

Symptoms are caused by sudden cessation or reduction of opioid intake after prolonged chronic use. The onset, peak, and duration of OWS varies primarily based on the half-life of the opioids used (e.g., heroin , methadone ). [2][4]

Use of short-acting opioids is associated with a higher risk of severe OWS compared to use of long-acting opioids. [5]

OWS can be severely uncomfortable, but it is generally not fatal unless the affected individual experiences severe dehydration and electrolyte disturbances that are left untreated. [3]

Approach [7]

A comprehensive clinical history is important, but completion of assessments should not delay or preclude initiating pharmacological treatment for opioid withdrawal. [7]

Diagnostic studies [7]

Opioid use and withdrawal are not usually associated with abnormal laboratory studies.

In many US states, individuals can be penalized for obtaining addiction treatment during pregnancy because substance use during pregnancy is classified as child abuse. Pregnant patients should give informed consent regarding potential legal consequences before receiving drug testing. [7][8]

Diagnostic criteria

DSM-5 diagnostic criteria for opioid withdrawal [9]
A) Fundamental criteria
  • Abrupt cessation or reduction in prolonged and heavy opioid use (weeks or more)
  • OR status post administration of an opioid antagonist (e.g., naloxone) after a period of opioid use
B) Presence of ≥ 3 symptoms/signs
C) Symptom characteristics
  • Features in criterion B cause significant distress or impairment (e.g., social, occupational).
D) Alternative diagnoses
  • Not attributable to or better explained by another medical, mental, or substance-related disorder
All criteria must be fulfilled to confirm the diagnosis.

Withdrawal severity assessment [10]

The Clinical Opioid Withdrawal Scale (COWS) is a validated tool that can be used to assess and classify the severity of opioid withdrawal. [11]

Clinical Opioid Withdrawal Scale

Symptoms Description
Minimum possible score (no symptoms) Maximum possible score (severe symptoms)
Pulse

≤ 80 BPM (0)

> 120 (4)
Sweating No chills, flushing, or sweating (0) Sweat streaming off the face (4)
Restlessness Able to sit still (0) Unable to sit still for more than a few seconds (5)
Pupil size Pinned or normal for room light (0) Only the rim of the iris is visible (5)
Bone, joint, or muscle aches None (0) Rubbing joints or muscles and unable to sit still due to discomfort (4)
Rhinorrhea or lacrimation Constantly running nose or streaming tears (4)
GI symptoms Multiple episodes of diarrhea or vomiting (5)
Tremor Gross tremor or muscle twitching (4)
Yawning Several times per minute (4)
Anxiety or irritability Irritability or anxiousness that makes participation in the assessment difficult (4)
Piloerection Prominent (5)

Interpretation (total combined score)

  • Score 0–4: absent
  • Score 5–12: mild withdrawal
  • Score 13–24: moderate withdrawal
  • Score 25–36: moderately severe withdrawal
  • Score > 36: severe withdrawal

The COWS is not designed to diagnose opioid withdrawal as most of the signs and symptoms are nonspecific. [7]

Approach [6][7]

Hospital admission is indicated for patients with severe opioid withdrawal who are unstable or have significant comorbidities (e.g., sepsis, polysubstance intoxication).

Psychosocial support [7][12]

The experience of withdrawal is strongly influenced by psychological distress, e.g., anxiety and concerns about withdrawal symptoms being unaddressed. [13]

A patient who declines to engage in shared decision making should not be excluded from prompt initiation of appropriate medication management. [7]

Approach [7]

Medication-assisted therapy (e.g., with methadone or buprenorphine) is the cornerstone of treatment for OUD.

During an episode of OWS, it is generally safe to resume outpatient methadone or buprenorphine dosing as long as active enrollment and accurate current outpatient dosing have been confirmed. [11]

Overview of long-acting medications for opioid use disorder [7]
Opioid agonists

Opioid antagonist

Methadone Buprenorphine Naltrexone
Indications
Risk of precipitating withdrawal
  • No
  • Yes
  • Yes
Important considerations
  • May cause QTc prolongation: obtain ECG prior to initiating therapy
  • Patients do not need to have objective signs of OWS to start therapy.
  • Prior to starting therapy, patients must have objective signs of OWS to avoid precipitated withdrawal.
  • Typically used in combination with naloxone (buprenorphine/naloxone)
  • May also be used as monotherapy in certain settings
  • May only be used in outpatient WM when prescribed by a practitioner with a buprenorphine waiver.
  • Prior to initiating therapy, patients must be opioid-free for 7–14 days to avoid precipitated withdrawal.
  • Inform patients that there is an increased risk of overdose when opioid use is resumed after discontinuation of naltrexone.
  • Treatment should be discontinued 30 days before a planned surgical procedure.
Withdrawal treatment setting
  • Outpatient WM (i.e., office-based treatment program)
  • Supervised settings

Methadone [7]

  • Indication: subjective features of OWS
  • Contraindications: QTc ≥ 500 ms; sedation (e.g., due to substance use, prescribed medications, severe illness) [14]
  • First-day dosages
    • Start an initial methadone dose under medical supervision. [14]
    • Use lower initial methadone dosages for patients in whom low tolerance is expected. [7]
    • If cravings and symptoms persist: Give additional lower dosages after 2–4 hours as needed.
  • Subsequent dosages
    • On day 2: Use the total dose given on day 1 as a single morning dose.
    • For patients withdrawing from short-acting opioids: Continue a stabilizing dose for 2–3 days , then consider a taper in 6 to 10 days. [7]
    • For all other patients: Titrate dose by no more than 10 mg every ∼5 days until a regular maintenance dose is reached. [7]

Methadone can only be prescribed in supervised settings. Unsupervised use of methadone may lead to diversion and is associated with an increased risk of overdose.

Buprenorphine [2][7]

  • Indication: objective features of OWS
  • First-day dosages
    • Start an initial dosage under medical supervision.
    • If cravings and symptoms persist: Give additional dosages every 1–2 hours as needed. [15]
  • Subsequent dosages [2]
    • On day 2: Use the total dose given on day 1, administered in 2–3 divided doses (max. dose: 16 mg/24 hours).
    • Titrate dose by 2–4 mg every day until a regular maintenance dose is reached. [2][7]

To avoid precipitated withdrawal symptoms, buprenorphine should not be initiated until mild or moderate objective signs of withdrawal are observed. [2]

  • Indications
    • Symptomatic therapy for patients who decline MOUDs
    • Adjunctive therapy to MOUDs (to reduce residual OWS)
  • Monitoring [7]
    • Observe for respiratory depression and sedation.
    • Consider drug interactions with MOUDs.
Medications for symptom-based treatment of opioid withdrawal [1][3][16][17]
Symptom type Treatment regimens
Sympathetic hyperactivity Autonomic symptoms
Anxiety
Insomnia
Musculoskeletal Myalgias/arthralgias [18]
Muscle spasms
Gastrointestinal Nausea and vomiting
Diarrhea
Abdominal cramps
  • Hyoscyamine sulfate (off label) [16]

Coadministration of opioids with benzodiazepines (or other sedative hypnotics) increases the risk of respiratory depression. However, the harm caused by untreated opioid withdrawal can outweigh this risk and warrants case-by-case risk-benefit analysis. [7]

Prescribe naloxone to all patients with OUD at discharge (or outpatient followup) and train patients and family members in the use of naloxone for treating opioid overdose. [7]

Neonatal abstinence syndrome [20][21][22]

Neonatal abstinence syndrome is caused by maternal drug use during pregnancy (typically opioids) that subsequently leads to a withdrawal reaction in the infant.

Clinical features

Treatment [22][23]

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  2. Theisen-Toupal J, Ronan MV, Moore A, Rosenthal ES. Inpatient Management of Opioid Use Disorder: A Review for Hospitalists. Journal of Hospital Medicine. 2017; 12 (5): p.369-374. doi: 10.12788/jhm.2731 . | Open in Read by QxMD
  3. Donroe JH, Holt SR, Tetrault JM. Caring for patients with opioid use disorder in the hospital.. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2016; 188 (17-18): p.1232-1239. doi: 10.1503/cmaj.160290 . | Open in Read by QxMD
  4. Crotty K, Freedman KI, Kampman KM. Executive Summary of the Focused Update of the ASAM National Practice Guideline for the Treatment of Opioid Use Disorder. J Addict Med. 2020; 14 (2): p.99-112. doi: 10.1097/adm.0000000000000635 . | Open in Read by QxMD
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  7. Kosten TR, Baxter LE. Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. The American Journal on Addictions. 2019; 28 (2): p.55-62. doi: 10.1111/ajad.12862 . | Open in Read by QxMD
  8. Kosten TR, O’Connor PG. Management of Drug and Alcohol Withdrawal. N Engl J Med. 2003; 348 (18): p.1786-1795. doi: 10.1056/nejmra020617 . | Open in Read by QxMD
  9. Kleber HD. Pharmacologic treatments for opioid dependence: detoxification and maintenance options.. Dialogues Clin Neurosci. 2007; 9 (4): p.455-70.
  10. Miller SC, Fiellin DA, Rosenthal RN, Saitz R. The ASAM Principles of Addiction Medicine. LWW ; 2018
  11. Faherty LJ, Kranz AM, Russell-Fritch J, Patrick SW, Cantor J, Stein BD. Association of Punitive and Reporting State Policies Related to Substance Use in Pregnancy With Rates of Neonatal Abstinence Syndrome. JAMA Netw Open. 2019; 2 (11): p.e1914078. doi: 10.1001/jamanetworkopen.2019.14078 . | Open in Read by QxMD
  12. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM–5). undefined. 2013 . doi: 10.1176/appi.books.9780890425596 . | Open in Read by QxMD
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  14. Broome L, So T-Y. Neonatal abstinence syndrome: the use of clonidine as a treatment option. NeoReviews. 2011; 12 (10): p.e575-e584. doi: 10.1542/neo.12-10-e575 . | Open in Read by QxMD
  15. Bada HS, Sithisarn T, Gibson J, et al. Morphine versus clonidine for neonatal abstinence syndrome. Pediatrics. 2015; 135 (2): p.e383-e391. doi: 10.1542/peds.2014-2377 . | Open in Read by QxMD
  16. Hudak ML, Tan RC. Neonatal Drug Withdrawal. Pediatrics. 2012; 129 (2): p.e540-e560. doi: 10.1542/peds.2011-3212 . | Open in Read by QxMD
  17. Butcher C, Prunty L, Attarabeen O, Babcock CCK, Patel I. Pharmacological Interventions for Neonatal Abstinence Syndrome. Journal of Addictions Nursing. 2018; 29 (4): p.231-232. doi: 10.1097/jan.0000000000000256 . | Open in Read by QxMD
  18. Rodríguez-Espinosa S, Coloma-Carmona A, Pérez-Carbonell A, Román-Quiles JF, Carballo JL. Clinical and psychological factors associated with interdose opioid withdrawal in chronic pain population.. J Subst Abuse Treat. 2021; 129 : p.108386. doi: 10.1016/j.jsat.2021.108386 . | Open in Read by QxMD
  19. WHO task force. Clinical Guidelines for Withdrawal Management and Treatment of Drug Dependence in Closed Settings. World Health Organization ; 2009
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  23. Herring AA, Vosooghi AA, Luftig J, et al. High-Dose Buprenorphine Induction in the Emergency Department for Treatment of Opioid Use Disorder. JAMA Netw Open. 2021; 4 (7): p.e2117128. doi: 10.1001/jamanetworkopen.2021.17128 . | Open in Read by QxMD

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