Outpatient Alcohol Withdrawal Treatment and Management of Alcohol Use Disorder

Full update January 2024

Binge drinking (≥5 drinks [males] or ≥4 drinks [females] on one occasion) and heavy alcohol use (binge drinking on ≥5 days in the last month) increase the risk of alcohol use disorder.1,2 Ask patients how many times in the last year they’ve had (4 for females, 5 for males) or more drinks in a day (Single Alcohol Screening Question [SASQ]) or use a quick screening test (Alcohol Use Disorder Identification Test [AUDIT-C] https://www.hepatitis.va.gov/alcohol/treatment/audit-c.asp#S1X).3 Patients with heavy alcohol use should be further screened for Alcohol Use Disorder (AUD).Patients with AUD should get thiamine 100 mg once daily for three to five days for prevention of Wernicke-Korsakoff syndrome.Also supplement with folic acid and a multivitamin.6,7 Alcohol withdrawal symptoms usually begin six to 24 hours after the last drink and last about two days (unless withdrawal has progressed to more serious symptoms).5,8 The CIWA-AR can be used to monitor patients (https://umem.org/files/uploads/1104212257_CIWA-Ar.pdf).8

  • Inpatient alcohol detox is safer for higher-risk patients (severe symptoms [e.g., CIWA-AR score >15], serious/unstable psychiatric or medical comorbidities, pregnancy, a history of delirium or seizures, withdrawal symptoms despite a blood alcohol level >1 g/dL, HR >120 beats per minute, infection).7,8
  • Generally reserve outpatient alcohol detox for patients at low risk of severe withdrawal.8
    • Requires follow-up and a responsible person to monitor the patient.8
    • Patients should seek immediate medical care for more serious symptoms (e.g., fever, seizures, hallucinations, or disorientation).7

Psychosocial interventions (e.g., cognitive behavioral therapy, family therapy, 12-step approaches) are the cornerstone of AUD treatment. Adding medications may provide benefit in reducing alcohol consumption and/or maintaining abstinence (especially in patients with severe AUD), if there is an immediate need to stop drinking, or after multiple attempts to stop.9 The charts below provide examples of outpatient alcohol detox regimens and relapse prevention meds. In addition, examples of support groups (both spiritual and secular) are provided at the end of the document.

Outpatient Alcohol Detox Regimens

Drug

Dose

Comments

Benzodiazepines are the drugs of choice for management of acute alcohol withdrawal.6,7,10 Longer acting agents usually preferred due to a more steady level of symptom control (i.e., “self-tapering”).Hold doses for oversedation or marked ataxia.

Chlordiazepoxide

  • 50 to 100 mg, repeated as needed up to a total daily dose of 300 mg, then reduced as tolerated (FDA-approved regimen).11

OR

  • Day 1: 50 mg every 6 hours, Day 2: 50 mg every 8 hours, Day 3: 50 mg every
    12 hours, Day 4: 50 mg at night. Can also give 50 mg as needed.7

OR

  • 100 mg on days 1 to 3, 75 mg on day 4, 50 mg on day 5, and 25 mg on day 6.6

Long-acting.7

May have lower abuse potential than diazepam.12

Diazepam

  • 10 mg TID or QID for 24 hours, then 5 mg TID or QID as needed (FDA/Health Canada-approved regimen).13,14

OR

  • Day 1: 10 mg every six hours, Day 2: 10 mg every 8 hours, Day 3: 10 mg every 12 hours, Day 4: 10 mg at night. Can also give 10 mg as needed.7

Relatively fast onset of action.10

Long-acting.7

May have higher abuse potential than oxazepam.12

Lorazepam

(off-label)

  • Days 1 and 2: 2 mg every 8 hours, Day 3: 1 mg every 8 hours, Day 4: 1 mg every 12 hours, Day 5: 1 mg at bedtime.8

Consider over diazepam or chlordiazepoxide when prolonged sedation is a concern (e.g., liver impairment, older age).10

Shorter-acting; may be associated with more breakthrough or rebound symptoms compared to longer-acting benzodiazepines.7

Oxazepam

  • 15 mg to 30 mg TID or QID (FDA-approved regimen).15

OR

  • 30 mg to 120 mg daily, in divided doses (Health Canada-approved regimen).16

Consider over diazepam or chlordiazepoxide when prolonged sedation is a concern (e.g., liver impairment, older age).10

Shorter-acting; may be associated with more breakthrough or rebound symptoms compared to longer-acting benzodiazepines.7

Anticonvulsants: Considered an (off-label) alternative to benzodiazepines.7 Pregabalin, topiramate, and levetiracetam are not recommended due to lack of good data.17-19 Valproic acid (combined with a benzodiazepine) use is limited by adverse effects and precautions (e.g., liver disease).7

Carbamazepine

  • 200 mg every 8 hours OR 400 mg every 12 hours. Taper dose to a daily dose of 200 mg to 400 mg over four to nine days.8

Consider when a benzodiazepine is not desirable (e.g., when abuse potential or sedation is a concern).7

Use limited by drug interactions.

Gabapentin

Loading dose:8

  • 1,200 mg loading dose, then 600 mg every six hours on day one

OR

  • 400 mg TID for one to three days

Then, taper to a daily dose of 300 mg to 600 mg for up to four to seven days, with additional doses as needed.8

Consider when a benzodiazepine is not desirable (e.g., when abuse potential or sedation is a concern), or plan to continue gabapentin for treatment of AUD.7

Has potential for misuse.9

 

Pharmacotherapy for Alcohol Use Disorder

Alcohol use disorder is a chronic condition often associated with relapse. Optimal duration of use of relapse prevention agents is unknown. Experts recommend at least six months of treatment. If necessary, medications can be continued indefinitely.9

FDA/Health Canada-Approved Alcohol Use Disorder Medications

Drug/Costa

Comments

Naltrexone

(oral: ReVia [Canada], generics.

injection: Vivitrol* [US only]; Canada: only available via Special Access Program.20)

(50 mg orally once daily):

US: ~$50

Canada: ~$90

(380 mg IM every four weeks):

US: $1,600

*Vivitrol has a REMS (US)

50 mg orally once daily for about three months prevents relapse to heavy drinking (NNT = 11) and relapse to any drinking (NNT = 18), compared to placebo [Evidence Level A-2].37

May be more effective with longer periods of abstinence prior to starting therapy.22

May be more effective than acamprosate at reducing cravings and risk of heavy drinking.21,22

Combining with acamprosate is unlikely to provide additional benefit.23

Avoid in patients on opioids (i.e., opioids in the past seven to 14 days, depending on the half-life of the opioid), due to opioid withdrawal symptoms.24-26,36

  • Work with pain service if opioids are needed (e.g., post-operative pain control).
    • Ideally, stop oral naltrexone at least 72 hours prior, to avoid blocking the opioid’s effects.27
    • Depot naltrexone injection blocks effects of opioids for approximately 28 days.24

Contraindicated in patients with acute hepatitis or liver failure, and use in patients with any liver disease should be considered carefully.26

Oral dose is usually 50 mg once daily, but doses of 100 mg once daily have been used.9

Depot naltrexone dose is 380 mg given intramuscularly every four weeks.24

Patients should carry identification to alert emergency personnel that they are on naltrexone.24,25

Common side effects include abdominal pain, reduced appetite, dizziness, somnolence, nausea, and vomiting.9

Injections are given by a healthcare professional; can be associated with very severe injection-site reactions.24

If a dose is missed, take as soon as able or at the time of the next scheduled dose. Titration is not needed.9

Acamprosate

(Campral [Canada]; generics [US])

(666 mg orally TID):

US: ~$230

­­Canada: ~$160

666 mg orally three times daily for about three to six months prevents relapse to any drinking (NNT = 11), compared to placebo [Evidence Level A-2].37

  • May be more effective than naltrexone for maintaining abstinence.21,22

Combining with naltrexone is unlikely to provide additional benefit.23

Preferred over naltrexone for patients with liver disease or taking an opioid.9,28

Dose is 666 mg TID.2­­­9,30

  • Avoid in patients with severe kidney impairment (e.g., CrCl ≤30 mL/min).28-30
  • Reduce dose to 333 mg TID in patients with moderate kidney impairment (e.g., CrCl 30 to 50 mL/min).28-30
  • Should be swallowed whole; do not split, chew, or crush.29,30

Most common side effect is diarrhea (up to ~25% of patients).9

If a dose is missed, feel comfortable resuming patient’s usual dose as soon as able or at discharge.30

Disulfiram (US)*

(generics)

*In Canada only available as a compounded product.35

(250 mg once daily):

US: ~$75

Limited evidence to support efficacy in preventing relapse.31

  • Response to therapy seems to improve with supervised adherence (e.g., friend or family member).9

Does not reduce cravings.32

Patient must be motivated and adherent.32

  • Patients must be abstinent (at least 12 hours since last drink) before starting disulfiram in order to reduce the likelihood of a disulfiram-alcohol reaction (e.g., flushing, headache, sweating, syncope, vomiting).33
  • Advise patients to avoid alcohol from all sources (e.g., extracts, liquid medications [e.g., some cough syrups, dronabinol oral solution, sertraline oral solution], mouthwash).34

Initial dose is 500 mg once daily for one to two weeks, then 250 mg (range 125 to 500 mg) once daily.33

Most common side effect is sedation or drowsiness (can be moderate to severe in about 8% of patients).9

  • Take at bedtime or reduce the dose if sedation is problematic.33

Off-Label Use (Alcohol Use Disorder)

Topiramate

Can consider third-line after naltrexone and acamprosate.36 May reduce binge drinking and improve abstinence [Evidence Level B-2].9

Use may be limited by adverse effects (e.g., anorexia, mental clouding, paresthesias, taste disturbance).37

Initial dose is 25 mg at bedtime, increased if needed to a max of 300 mg, divided twice daily.8,9

Gabapentin

Can consider third-line after naltrexone and acamprosate.36 May reduce heavy drinking days and increase abstinence [Evidence Level B-1].31

Some conflicting efficacy data.9

Day 1: 300 mg at bedtime, Day 2: 300 mg BID, Day 3: 300 mg TID, then titrate up over four to seven days to target dose. Dose range is typically 600 mg to 1,800 mg/day in three divided doses.9

Baclofen

Insufficient evidence to recommend.5

For patients who are already abstinent.32

Might improve duration of abstinence, especially in patients with higher daily alcohol use.9

Prazosin

Very limited data suggest it might reduce heavy drinking and number of drinks per week.38

  • Does not appear to reduce cravings or number of drinking days per week.38

Varenicline (Chantix [US], generics)

Limited data suggest it may reduce alcohol cravings and consumption in patients who also smoke.39,40

Can be considered for patients trying to quit smoking who are also heavy drinkers.39

Abbreviations: AUD = alcohol use disorder; BID = twice daily; CrCl = creatinine clearance; DSM-5 = Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; HR = heart rate; NNT = number need to treat; QID = four times daily; TID = three times daily.

  1. Pricing based on wholesale acquisition cost (WAC) for a one-month supply at the dose indicated, for the generic when available. US medication pricing by Elsevier, accessed December 2023.

Examples of support group options to assist with alcohol use disorder treatment and relapse prevention:

  • Alcoholics Anonymous (www.aa.org)
    • Uses a spiritually-based 12-step program to assist with abstinence.
  • Celebrate Recovery (www.celebraterecovery.com)
    • Uses a spiritually-based 12-step program to assist with abstinence.
  • LifeRing Secular Recovery (www.lifering.org)
    • Offers secular peer support to assist with abstinence.
  • Moderation Management (www.moderation.org)
    • Offers support to reduce harm associated with alcohol use encouraging moderation or abstinence.
  • Secular Organization for Sobriety (www.sossobriety.org)
    • Offers secular peer support to assist with abstinence.
  • Self-Management and Recovery Training (SMART) Recovery (www.addictioncenter.com/treatment/smart-recovery/)
    • Offers secular peer support to assist with abstinence.

Levels of Evidence

In accordance with our goal of providing Evidence-Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish.

Level

Definition

Study Quality

A

Good-quality patient-oriented evidence.*

  1. High-quality randomized controlled trial (RCT)
  2. Systematic review (SR)/Meta-analysis of RCTs with consistent findings
  3. All-or-none study

B

Inconsistent or limited-quality patient-oriented evidence.*

  1. Lower-quality RCT
  2. SR/Meta-analysis with low-quality clinical trials or of studies with inconsistent findings
  3. Cohort study
  4. Case control study

C

Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening.

*Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life).

[Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69:548-56. https://www.aafp.org/pubs/afp/issues/2004/0201/p548.html.]

References

  1. National Institute on Alcohol Abuse and Alcoholism. Alcohol’s effects on health: drinking levels defined. Updated 2023. https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking. (Accessed December 11, 2023).
  2. Paradis C, Butt P, Shield K, et al. Canada's Guidance on Alcohol and Health: Final Report Ottawa, ON: Canadian Centre on Substance Use and Addiction; January 2023. https://www.ccsa.ca/sites/default/files/2023-01/CCSA_Canadas_Guidance_on_Alcohol_and_Health_Final_Report_en.pdf. (Accessed December 11, 2023).
  3. National Institute on Alcohol Abuse and Alcoholism. Screen and assess: use quick, effective methods. September 22, 2023. https://www.niaaa.nih.gov/health-professionals-communities/core-resource-on-alcohol/screen-and-assess-use-quick-effective-methods#pub-toc2. (Accessed December 11, 2023).
  4. NIH. National Institute on Alcohol Abuse and Alcoholism. Alcohol use disorder: a comparison between DSM-IV and DSM-5. Updated April 2021. https://pubs.niaaa.nih.gov/publications/dsmfactsheet/dsmfact.htm. (Accessed December 7, 2023).
  5. The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management. J Addict Med. 2020 May/Jun;14(3S Suppl 1):1-72. Erratum in: J Addict Med. 2020 Sep/Oct;14(5):e280.
  6. Stock CJ, Carpenter L, Ying J, Greene T. Gabapentin versus chlordiazepoxide for outpatient alcohol detoxification treatment. Ann Pharmacother. 2013 Jul-Aug;47(7-8):961-9.
  7. Holt SR, Tetrault JM. Alcohol withdrawal: ambulatory management. (Last updated October 6, 2022). In UpToDate, Post TW (ed), UpToDate, Waltham, MA 02013.
  8. Clinical Pharmacology powered by ClinicalKey. Tampa (FL): Elsevier. 2023. http://www.clinicalkey.com. (Accessed December 9, 2023)
  9. Kranzler HR, Soyka M. Diagnosis and Pharmacotherapy of Alcohol Use Disorder: A Review. JAMA. 2018 Aug 28;320(8):815-824.
  10. Mayo-Smith MF, Beecher LH, Fischer TL, et al. Management of alcohol withdrawal delirium. An evidence-based practice guideline. Arch Intern Med. 2004 Jul 12;164(13):1405-12. Erratum in: Arch Intern Med. 2004 Oct 11;164(18):2068. Dosage error in article text.
  11. Product information for chlordiazepoxide. Teva Pharmaceuticals USA. North Wales, PA 19454. December 2022.
  12. Manasco A, Chang S, Larriviere J, et al. Alcohol withdrawal. South Med J. 2012 Nov;105(11):607-12.
  13. Product information for Valium. Roche Laboratories. Little Falls, NJ 07424. February 2021.
  14. Product monograph for Valium. Searchlight Pharma. Montreal, QC. H0H - H9X. May 2023.
  15. Product information for oxazepam. Teva Pharmaceuticals. Parsippany, NJ 07054. August 2023.
  16. Product monograph for Riva-Oxazepam. Laboratoire Riva. Blainville, QC J7C 3V4.December 2022.
  17. Le Strat Y. Levetiracetam in the treatment of alcohol dependence: toward the end of the story? Alcohol Clin Exp Res. 2012 Aug;36(8):1309-10.
  18. Likhitsathian S, Uttawichai K, Booncharoen H, et al. Topiramate treatment for alcoholic outpatients recently receiving residential treatment programs: a 12-week, randomized, placebo-controlled trial. Drug Alcohol Depend. 2013 Dec 1;133(2):440-6.
  19. Guglielmo R, Martinotti G, Clerici M, Janiri L. Pregabalin for alcohol dependence: a critical review of the literature. Adv Ther. 2012 Nov;29(11):947-57.
  20. Families for Addiction Recovery. Medications. https://www.farcanada.org/treatment/medications/. (Accessed December 9, 2023).
  21. Rösner S, Leucht S, Lehert P, Soyka M. Acamprosate supports abstinence, naltrexone prevents excessive drinking: evidence from a meta-analysis with unreported outcomes. J Psychopharmacol. 2008 Jan;22(1):11-23.
  22. Maisel NC, Blodgett JC, Wilbourne PL, et al.Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful? Addiction. 2013 Feb;108(2):275-93.
  23. Canadian Agency for Drugs and Technologies in Health. Naltrexone in combination with acamprosate for the treatment of alcohol dependence: a review of the clinical and cost-effectiveness. October 8, 2009. https://www.cadth.ca/sites/default/files/pdf/L0123_Naltrexone_and_Acamprosate_final.pdf. (Accessed December 8, 2023).
  24. Product information for Vivitrol. Alkermes. Waltham, MA 02451. September 2022.
  25. Product information for naltrexone tablets. Chartwell Rx. Congers, NY 10920. December 2021.
  26. Product monograph for ReVia. Teva Canada. Toronto, ON M1B 2K9. July 2020.
  27. Agency for Healthcare Research and Quality. Chou R. A painful medication reconciliation mishap. January 2018. https://psnet.ahrq.gov/webmm/case/431/A-Painful-Medication-Reconciliation-Mishap. (Accessed December 8, 2023).
  28. US Department of Veterans Affairs. VA/DoD clinical practice guideline for the management of substance use disorders. 2015. https://www.healthquality.va.gov/guidelines/MH/sud/VADoDSUDCPGRevised22216.pdf. (Accessed December 8, 2023).
  29. Product information for acamprosate. Mylan Pharmaceuticals. Morgantown, WV 26505. November 2022.
  30. Product monograph for Campral. Mylan Pharmaceuticals. Etobicoke, ON M8Z 2S6. September 2011.
  31. Anton RF, Latham P, Voronin K, et al.Efficacy of Gabapentin for the Treatment of Alcohol Use Disorder in Patients With Alcohol Withdrawal Symptoms: A Randomized Clinical Trial. JAMA Intern Med. 2020 May 1;180(5):728-736.
  32. Johnson BA. Medication treatment of different types of alcoholism. Am J Psychiatry. 2010 Jun;167(6):630-9.
  33. Product information for disulfiram. Alvogen. Morristown, NJ 07960. January 2020.
  34. Mayo Clinic. Drugs and supplements. Disulfiram oral route: precautions. Updated December 1, 2023. https://www.mayoclinic.org/drugs-supplements/disulfiram-oral-route/precautions/drg-20063488. (Accessed December 9, 2023).
  35. Spithoff S, Turner S, Gomes T, et al. First-line medications for alcohol use disorders among public drug plan beneficiaries in Ontario. Can Fam Physician. 2017 May;63(5):e277-e283.
  36. Reus VI, Fochtmann LJ, Bukstein O, et al.The American Psychiatric Association Practice Guideline for the Pharmacological Treatment of Patients With Alcohol Use Disorder. Focus (Am Psychiatr Publ). 2019 Apr;17(2):158-162.
  37. McPheeters M, O'Connor EA, Riley S, et al. Pharmacotherapy for Alcohol Use Disorder: A Systematic Review and Meta-Analysis. JAMA. 2023 Nov 7;330(17):1653-1665.
  38. Simpson TL, Saxon AJ, Stappenbeck C, et al.Double-Blind Randomized Clinical Trial of Prazosin for Alcohol Use Disorder. Am J Psychiatry. 2018 Dec 1;175(12):1216-1224.
  39. Fucito LM, Toll BA, Wu R, et al. A preliminary investigation of varenicline for heavy drinking smokers. Psychopharmacology (Berl). 2011 Jun;215(4):655-63.
  40. Litten RZ, Ryan ML, Fertig JB, et al.A double-blind, placebo-controlled trial assessing the efficacy of varenicline tartrate for alcohol dependence. J Addict Med. 2013 Jul-Aug;7(4):277-86.

Cite this document as follows: Clinical Resource, Outpatient Alcohol Withdrawal Treatment and Management of Alcohol Use Disorder. Pharmacist’s Letter/Pharmacy Technician’s Letter/Prescriber Insights. January 2024. [400108]

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