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Withdrawal Syndromes Medication

  • Author: Nathanael J McKeown, DO; Chief Editor: Asim Tarabar, MD  more...
Updated: Aug 12, 2016

Medication Summary

Treatment involves administering a substitute medication that has cross-tolerance with the chronically ingested substance. These medications either interact at specific receptors (eg, methadone in opiate withdrawal) or have generalized effects that reduce withdrawal symptoms (eg, barbiturates in alcohol withdrawal). Probably the most common treatment of withdrawal symptoms from alcohol or illicit drugs is the self-administration of more alcohol or drugs.

Many regimens for treating withdrawal involve cross-tolerant medications titrated to the severity of the withdrawal by gradually decreasing the dose and by increasing the dosing interval to wean the patient from the original substance. For alcohol withdrawal syndrome, these regimens include benzodiazepines, barbiturates,[18] propofol, and ethanol,[35, 17] and clomethiazole (in Europe). Carbamazepine, valproic acid, gabapentin, gamma-hydroxybutyrate, propranolol, and clonidine all have been used as an adjunctive therapy and are effective, but should not be used as monotherapy.



Class Summary

These drugs produce sedative effects by enhancing GABA neurotransmission from binding to GABAA receptors. All benzodiazepines appear similarly effective in the treatment of alcohol withdrawal syndrome. In moderate-to-severe withdrawal, long-acting agents are preferred over short-acting drugs. Symptom-triggered therapy is preferred over fixed-schedule therapy because it decreases the duration and total dose of treatment to resolve symptoms. Fixed-dose therapy is appropriate in mild-to-moderate withdrawal.

Lorazepam (Ativan)


Has advantages of non–liver-dependent metabolism, intermediate half-life, and ease of administration (PO/IV/IM), making it ideal medication for alcohol withdrawal; may be drug of choice. After some sedation achieved, can start 2 mg IV q8h on day 1. Can decrease to 1 mg tid on day 2 and gradually eliminate over next 2 d if patient responding well.

Diazepam (Valium)


Depresses all levels of CNS (eg, limbic, reticular formation), possibly by increasing GABA activity. Individualize dosage and increase cautiously to avoid adverse effects. Idiosyncratic apnea can occur in addition to progressive depression of respiratory drive and hypotension with accumulating doses. After stabilization, oral diazepam can be started at 10 mg tid/qid.

Oxazepam (Serax)


Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. Half-life is relatively brief compared with that of diazepam. Titrated to treat mild alcohol withdrawal in outpatients and in those who can tolerate PO medications.

Chlordiazepoxide (Librium)


Depresses all levels of CNS, including limbic and reticular formation, possibly by increasing GABA activity, major inhibitory neurotransmitter. Long considered standard therapy for alcohol withdrawal; has relatively long half-life and inexpensive and effective. Parenteral chlordiazepoxide is currently not available commercially in the United States.

Midazolam (Versed)


As with other benzodiazepines, can sedate patients in alcohol withdrawal. However, brief half-life requires constant infusion to maintain sedation. More expensive than many alternatives, requires more nursing attention for constant infusion than other drugs, and no more effective than other benzodiazepines. Not recommended for routine use in DT. Because of its relatively rapid effects and clinically significant bioavailability when given IM, may be of special use when IV access unavailable.


Cardiovascular agents

Class Summary

Clonidine has been used in alcohol withdrawal because its central alpha 2 -agonist activity reduces central output of adrenergic neurotransmitters. Because excessive adrenergic neurotransmission may be the basis for withdrawal symptoms, clonidine is a logical choice and has been effective. It is most commonly used in opioid withdrawal.Many of the aberrant vital signs associated with alcohol withdrawal improve with beta-adrenergic blockade. Blockade can mask the development of adrenergic symptoms and blunts warning signs of DT. It does not prevent delirium, seizures, or hallucinations.

Clonidine (Catapres)


Not to be used as monotherapy. Reduces central adrenergic discharge and decreases blood pressure and pulse, though effect on pulse less predictable than other effect. Also useful in opiate withdrawal; decreases some symptoms (eg, lacrimation, diarrhea, tachycardia). Transdermal patches deliver 0.1, 0.2, or 0.3 mg/d for 7 d.

Propranolol (Inderal)


Decreases blood pressure, pulse rate, and tremor. Does not decrease incidence or severity of seizures or delirium; does not affect craving for alcohol.



Class Summary

Thiamine (vitamin B-1), folic acid (folate), cyanocobalamin (vitamin B-12), and other water-soluble vitamins are often depleted in persons with chronic alcoholism, who are also frequently malnourished. Replenishing these vitamins can prevent or treat Wernicke-Korsakoff syndrome (with thiamine), correct megaloblastic anemia (with folic acid and cyanocobalamin), correct high-output CHF (with thiamine), and halt peripheral neuropathy (with cyanocobalamin). Although the effects of these treatments are typically not apparent in the ED, vitamins are commonly administered in the ED because deficiencies are common in this population and because the manifestations are often subtle.

Thiamine (Vitamin B-1; Thiamilate)


Essential cofactor in multiple metabolic processes. Deficiency can occur relatively quickly in starvation states, as body stores are limited. Manifestations of deficiency include wet beriberi and Wernicke-Korsakoff syndrome, which glucose administration in chronic thiamine deficiency can precipitate.

Phytonadione (Vitamin K-1, AquaMEPHYTON)


Correction of vitamin K deficiency may increase synthesis of liver-dependent clotting factors and correct prolonged PT common in chronic alcoholism and cirrhosis. Use only in patients with hypoprothrombinemia.



Class Summary

These drugs are acceptable alternative to benzodiazepines. GABA agonists are similar to benzodiazepines but directly open chloride channels in large doses. In contrast to benzodiazepines, barbiturates prolong GABA response by delaying closure of the GABA channels. Benzodiazepines increase the frequency of opening events in GABA chloride channels, whereas barbiturates maintain the channel open longer. Use barbiturates as the second-line drug in patients not responding to an adequate trial of benzodiazepines.

Phenobarbital (Barbita, Luminal)


Effectively reduces signs and symptoms of alcohol withdrawal by producing a generalized decrease in neurotransmission. Can produce sedation in almost all patients in alcohol withdrawal, but the hypotension and respiratory depression it produces limit its use.


Pharmacologic antidotes

Class Summary

As with other withdrawal syndromes, replacement of the chronically ingested substance is an effective means of terminating the withdrawal. In rare cases that do not respond to cross-tolerant sedatives, an infusion of ethanol may be used as a last resort in achieving sedation.



IV administration may cause thrombophlebitis; PO administration may cause severe gastritis. Low doses may effectively prevent alcohol withdrawal syndrome in surgical patients. Use in established alcohol withdrawal syndrome not studied.


Electrolyte Replacement

Class Summary

At pharmacologic doses, magnesium sulfate has many effects, including anticonvulsant action, decreased nerve-conduction velocity, relaxation of smooth muscle, and antidysrhythmic actions. In addition, it appears to act as a sedating agent. Patients with chronic alcoholism have a total body deficit of magnesium that may exacerbate symptoms of alcohol withdrawal. Replacement of magnesium appears to decrease the total dose of benzodiazepines required to achieve sedation.

Magnesium sulfate


Many patients with chronic alcoholism have clinically significant magnesium deficiency due to malnutrition and chronic diuresis from alcohol ingestion. Symptoms are similar to those of alcohol withdrawal and include tachycardia, seizures, tremor, and hyperreflexia. Magnesium replacement decreases total sedation required and decreases incidence of seizures, but a recent study shows that deficiencies are self-limited and treatment might not be required.



Class Summary

Consider propofol as a last-resort drug in refractory DT and status epilepticus that does not respond to adequate trial of benzodiazepines and barbiturates. It not only directly activates GABAA receptors but also inhibits NMDA receptors. It causes rapid recovery from sedation after it is discontinued, as it is highly lipophilic. The emulsion containing propofol causes a high lipid load and may result in hyperlipidemia if its use is prolonged. Propofol-induced hypertriglyceridemia has been causally associated with pancreatitis. Propofol infusions have been titrated up to 90 mcg/kg/min in case series describing the treatment of alcohol withdrawal syndrome refractory to other medications.



Phenolic compound unrelated to other types of anticonvulsants. General anesthetic properties when administered IV.

Contributor Information and Disclosures

Nathanael J McKeown, DO Assistant Professor, Department of Emergency Medicine, Oregon Health and Science University School of Medicine; Medical Toxicologist, Oregon Poison Center; Attending Physician, Emergency Medicine, Portland Veteran Affairs Medical Center

Nathanael J McKeown, DO is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.


Patrick L West, MD Clinical Instructor, Medical Toxicology Fellow, Department of Emergency Medicine, Oregon Health and Sciences University; Staff Physician, Department of Emergency Medicine, Portland Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Specialty Editor Board

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Michael J Burns, MD Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center

Michael J Burns, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Additional Contributors

Theodore J Gaeta, DO, MPH, FACEP Clinical Associate Professor, Department of Emergency Medicine, Weill Cornell Medical College; Vice Chairman and Program Director of Emergency Medicine Residency Program, Department of Emergency Medicine, New York Methodist Hospital; Academic Chair, Adjunct Professor, Department of Emergency Medicine, St George's University School of Medicine

Theodore J Gaeta, DO, MPH, FACEP is a member of the following medical societies: American College of Emergency Physicians, New York Academy of Medicine, Society for Academic Emergency Medicine, Council of Emergency Medicine Residency Directors, Clerkship Directors in Emergency Medicine, Alliance for Clinical Education

Disclosure: Nothing to disclose.

  1. Nagy J. Alcohol Related Changes in Regulation of NMDA Receptor Functions. Curr Neuropharmacol. 2008 Mar. 6(1):39-54. [Medline]. [Full Text].

  2. Center for Behavioral Health Statistics and Quality. Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health. NSDUH Series H-50; 2015. HHS Publication No. SMA 15-4927: [Full Text].

  3. Monte R, Rabunal R, Casariego E, Lopez-Agreda H, Mateos A, Pertega S. Analysis of the factors determining survival of alcoholic withdrawal syndrome patients in a general hospital. Alcohol Alcohol. 2010 Mar-Apr. 45(2):151-8. [Medline].

  4. Goodson CM, Clark BJ, Douglas IS. Predictors of severe alcohol withdrawal syndrome: a systematic review and meta-analysis. Alcohol Clin Exp Res. 2014 Oct. 38 (10):2664-77. [Medline].

  5. Tarabar AF, Nelson LS. The gamma-hydroxybutyrate withdrawal syndrome. Toxicol Rev. 2004. 23(1):45-9. [Medline].

  6. Wojtowicz JM, Yarema MC, Wax PM. Withdrawal from gamma-hydroxybutyrate, 1,4-butanediol and gamma-butyrolactone: a case report and systematic review. CJEM. 2008 Jan. 10(1):69-74. [Medline].

  7. Mancino MJ, Gentry BW, Feldman Z, Mendelson J, Oliveto A. Characterizing methamphetamine withdrawal in recently abstinent methamphetamine users: a pilot field study. Am J Drug Alcohol Abuse. 2011 Mar. 37(2):131-6. [Medline]. [Full Text].

  8. Findley JK, Park LT, Siefert CJ, Chiou GJ, Lancaster RT, Demoya M, et al. Two Routine Blood Tests-Mean Corpuscular Volume and Aspartate Aminotransferase-as Predictors of Delirium Tremens in Trauma Patients. J Trauma. 2010 Jan 20. [Medline].

  9. Chenet L, McKee M, Leon D, Shkolnikov V, Vassin S. Alcohol and cardiovascular mortality in Moscow; new evidence of a causal association. J Epidemiol Community Health. 1998 Dec. 52(12):772-4. [Medline].

  10. Alexandre J, Benouda L, Champ-Rigot L, Labombarda F. Takotsubo cardiomyopathy triggered by alcohol withdrawal. Drug Alcohol Rev. 2011 Jul. 30(4):434-7. [Medline].

  11. Otero-Anton E, Gonzalez-Quintela A, Saborido J, Torre JA, Virgos A, Barrio E. Prolongation of the QTc interval during alcohol withdrawal syndrome. Acta Cardiol. 1997. 52(3):285-94. [Medline].

  12. LeTourneau JL, Hagg DS, Smith SM. Baclofen and gamma-hydroxybutyrate withdrawal. Neurocrit Care. 2008. 8(3):430-3. [Medline]. [Full Text].

  13. Anderson P. New Guideline on Opioid Withdrawal in Children. Available at Accessed: September 20, 2015.

  14. Galinkin J, Koh JL. Recognition and management of iatrogenically induced opioid dependence and withdrawal in children. Pediatrics. 2014 Jan. 133(1):152-5. [Medline].

  15. Ista E, van Dijk M, de Hoog M, Tibboel D, Duivenvoorden HJ. Construction of the Sophia Observation withdrawal Symptoms-scale (SOS) for critically ill children. Intensive Care Med. 2009 Jun. 35 (6):1075-81. [Medline]. [Full Text].

  16. Dixit D, Endicott J, Burry L, Ramos L, Yeung SY, Devabhakthuni S, et al. Management of Acute Alcohol Withdrawal Syndrome in Critically Ill Patients. Pharmacotherapy. 2016 Jul. 36 (7):797-822. [Medline].

  17. Fisher CM. Prompt responses to the administration of ethanol in the treatment of the alcohol withdrawal syndrome (AWS). Neurologist. 2009 Sep. 15(5):242-4. [Medline].

  18. Mo Y, Thomas MC, Karras GE Jr. Barbiturates for the treatment of alcohol withdrawal syndrome: A systematic review of clinical trials. J Crit Care. 2016 Apr. 32:101-7. [Medline].

  19. Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict. 1989 Nov. 84 (11):1353-7. [Medline].

  20. Cassidy EM, O'Sullivan I, Bradshaw P, Islam T, Onovo C. Symptom-triggered benzodiazepine therapy for alcohol withdrawal syndrome in the emergency department: a comparison with the standard fixed dose benzodiazepine regimen. Emerg Med J. 2011 Oct 19. [Medline].

  21. Hack JB, Hoffmann RS, Nelson LS. Resistant alcohol withdrawal: does an unexpectedly large sedative requirement identify these patients early?. J Med Toxicol. 2006 Jun. 2(2):55-60. [Medline].

  22. Subramaniam K, Gowda RM, Jani K, et al. Propofol combined with lorazepam for severe poly substance misuse and withdrawal states in intensive care unit: a case series and review. Emerg Med J. 2004 Sep. 21(5):632-4. [Medline]. [Full Text].

  23. Lyon JE, Khan RA, Gessert CE, Larson PM, Renier CM. Treating alcohol withdrawal with oral baclofen: a randomized, double-blind, placebo-controlled trial. J Hosp Med. 2011 Oct. 6(8):469-74. [Medline].

  24. Eyer F, Schreckenberg M, Hecht D, Adorjan K, Schuster T, Felgenhauer N, et al. Carbamazepine and valproate as adjuncts in the treatment of alcohol withdrawal syndrome: a retrospective cohort study. Alcohol Alcohol. 2011 Mar-Apr. 46(2):177-84. [Medline].

  25. Muzyk AJ, Fowler JA, Norwood DK, Chilipko A. Role of a2-agonists in the treatment of acute alcohol withdrawal. Ann Pharmacother. 2011 May. 45(5):649-57. [Medline].

  26. Kahkonen S, Bondarenko B, Lipsanen J, et al. Cardiovascular effects of propranolol in patients with alcohol dependence during withdrawal. Int J Psychophysiol. 2007 Dec. 66(3):225-30. [Medline].

  27. Rayner SG, Weinert CR, Peng H, Jepsen S, Broccard AF,. Dexmedetomidine as adjunct treatment for severe alcohol withdrawal in the ICU. Ann Intensive Care. 2012. 2(1):12. [Medline].

  28. Tolonen J, Rossinen J, Alho H, Harjola VP. Dexmedetomidine in addition to benzodiazepine-based sedation in patients with alcohol withdrawal delirium. Eur J Emerg Med. 2013 Dec. 20(6):425-7. [Medline].

  29. Muzyk AJ, Revollo JY, Rivelli SK. The use of dexmedetomidine in alcohol withdrawal. J Neuropsychiatry Clin Neurosci. 2012 Summer. 24(3):E45-6. [Medline].

  30. Wong A, Benedict NJ, Armahizer MJ, Kane-Gill SL. Evaluation of adjunctive ketamine to benzodiazepines for management of alcohol withdrawal syndrome. Ann Pharmacother. 2015 Jan. 49 (1):14-9. [Medline].

  31. Bonnet U, Hamzavi-Abedi R, Specka M, Wiltfang J, Lieb B, Scherbaum N. An open trial of gabapentin in acute alcohol withdrawal using an oral loading protocol. Alcohol Alcohol. 2010 Mar-Apr. 45(2):143-5. [Medline].

  32. Oulis P, Konstantakopoulos G. Pregabalin in the treatment of alcohol and benzodiazepines dependence. CNS Neurosci Ther. 2010 Spring. 16(1):45-50. [Medline].

  33. 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. [Medline].

  34. Leung JG, Hall-Flavin D, Nelson S, Schmidt KA, Schak KM. The role of gabapentin in the management of alcohol withdrawal and dependence. Ann Pharmacother. 2015 Aug. 49 (8):897-906. [Medline].

  35. Weinberg JA, Magnotti LJ, Fischer PE, et al. Comparison of intravenous ethanol versus diazepam for alcohol withdrawal prophylaxis in the trauma ICU: results of a randomized trial. J Trauma. 2008 Jan. 64(1):99-104. [Medline].

  36. Hayner CE, Wuestefeld NL, Bolton PJ. Phenobarbital treatment in a patient with resistant alcohol withdrawal syndrome. Pharmacotherapy. 2009 Jul. 29(7):875-8. [Medline].

  37. Bamgbade OA. Dexmedetomidine for peri-operative sedation and analgesia in alcohol addiction. Anaesthesia. 2006 Mar. 61(3):299-300. [Medline].

  38. Bayard M, McIntyre J, Hill KR, et al. Alcohol withdrawal syndrome. Am Fam Physician. 2004 Mar 15. 69(6):1443-50. [Medline]. [Full Text].

  39. Darrouj J, Puri N, Prince E, Lomonaco A, Spevetz A, Gerber DR. Dexmedetomidine infusion as adjunctive therapy to benzodiazepines for acute alcohol withdrawal. Ann Pharmacother. 2008 Nov. 42(11):1703-5. [Medline].

  40. DeBellis R, Smith BS, Choi S, et al. Management of delirium tremens. J Intensive Care Med. 2005 May-Jun. 20(3):164-73. [Medline].

  41. Kosten TR, O'Connor PG. Management of drug and alcohol withdrawal. N Engl J Med. 2003 May 1. 348(18):1786-95. [Medline].

  42. 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. [Medline].

  43. McCowan C, Marik P. Refractory delirium tremens treated with propofol: a case series. Crit Care Med. 2000 Jun. 28(6):1781-4. [Medline].

  44. Nimmerrichter AA, Walter H, Gutierrez-Lobos KE, Lesch OM. Double-blind controlled trial of gamma-hydroxybutyrate and clomethiazole in the treatment of alcohol withdrawal. Alcohol Alcohol. 2002 Jan-Feb. 37(1):67-73. [Medline]. [Full Text].

  45. Olmedo R, Hoffman RS. Withdrawal syndromes. Emerg Med Clin North Am. 2000 May. 18(2):273-88. [Medline].

  46. Reoux JP, Miller K. Routine hospital alcohol detoxification practice compared to symptom triggered management with an Objective Withdrawal Scale (CIWA-Ar). Am J Addict. 2000 Spring. 9(2):135-44. [Medline].

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