• Matthew E. Sloan
  • Robert B. Werner
  • Stephanie Yarnell-MacGrory
  • Ismene PetrakisEmail author


Alcohol consumption remains a leading cause of death and disability, with recent evidence suggesting that the prevalence of alcohol use and abuse is rising. This chapter reviews the diagnosis and treatment of alcohol intoxication, withdrawal, and alcohol use disorder. Alcohol primarily exerts its intoxicating effects by acting at GABAergic and glutamatergic synapses, whereas withdrawal symptoms are thought to be caused by altered activity at these synapses due to sudden reductions in alcohol consumption Clinical management of both intoxication and withdrawal depends on drinking history, recent consumption, and presenting symptoms. In heavy drinkers, alcohol use disorder can be diagnosed when an individual meets two of eleven diagnostic criteria that include signs of physiologic dependence (tolerance and withdrawal), loss of control over drinking, and continued consumption despite harm. This condition can be treated with psychotherapy, pharmacotherapy, or a combination of both modalities. Abstinence can then be monitored using a range of direct and indirect laboratory tests.


Alcohol use disorder Alcoholism Alcoholic Intoxication Substance Withdrawal Syndrome Alcohol Dehydrogenase Acamprosate Naltrexone Disulfiram 


  1. 1.
    Stanaway JD, Afshin A, Gakidou E, Lim SS, Abate D, Abate KH, et al. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet (London, England). 2018;392(10159):1923–94.CrossRefGoogle Scholar
  2. 2.
    Xu J, Murphy S, Kochanek K, Bastian B, Arias E. Deaths: final data for 2016. National vital statistics reports: from the Centers for Disease Control and Prevention, National Center for Health Statistics. National Vital Statistics System. 2018;67(5):1.Google Scholar
  3. 3.
    QuickStats: age-adjusted death rates∗ attributable to alcohol-induced causes,(dagger) by race/ethnicity – United States, 1999–2015. MMWR Morb Mortal Wkly Rep. 2017;66(18):491.Google Scholar
  4. 4.
    Grant BF, Goldstein RB, Saha TD, Chou SP, Jung J, Zhang H, et al. Epidemiology of DSM-5 alcohol use disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions III. JAMA Psychiat. 2015;72(8):757–66.CrossRefGoogle Scholar
  5. 5.
    Grant BF, Chou SP, Saha TD, Pickering RP, Kerridge BT, Ruan WJ, et al. Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the United States, 2001-2002 to 2012-2013: results from the National Epidemiologic Survey on Alcohol and Related Conditions. JAMA Psychiat. 2017;74(9):911–23.CrossRefGoogle Scholar
  6. 6.
    Hasin DS, Stinson FS, Ogburn E, Grant BF. Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2007;64(7):830–42.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Tan CH, Denny CH, Cheal NE, Sniezek JE, Kanny D. Alcohol use and binge drinking among women of childbearing age – United States, 2011–2013. MMWR Morb Mortal Wkly Rep. 2015;64(37):1042–6.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Brady KT, Randall CL. Gender differences in substance use disorders. Psychiatr Clin North Am. 1999;22(2):241–52.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Kanny D, Naimi TS, Liu Y, Lu H, Brewer RD. Annual total binge drinks consumed by U.S. adults, 2015. Am J Prev Med. 2018;54(4):486–96.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Grant BF, Dawson DA. Age at onset of alcohol use and its association with DSM-IV alcohol abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey. J Subst Abus. 1997;9:103–10.CrossRefGoogle Scholar
  11. 11.
    Leggio L, Kenna GA, Fenton M, Bonenfant E, Swift RM. Typologies of alcohol dependence. From Jellinek to genetics and beyond. Neuropsychol Rev. 2009;19(1):115–29.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Fifth Edition. Arlington, VA, American Psychiatric Association, 2013.Google Scholar
  13. 13.
    Gowin JL, Sloan ME, Stangl BL, Vatsalya V, Ramchandani VA. Vulnerability for alcohol use disorder and rate of alcohol consumption. Am J Psychiatry. 2017;174(11):1094–101.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Verhulst B, Neale MC, Kendler KS. The heritability of alcohol use disorders: a meta-analysis of twin and adoption studies. Psychol Med. 2015;45(5):1061–72.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Edenberg HJ, McClintick JN. Alcohol dehydrogenases, aldehyde dehydrogenases, and alcohol use disorders: a critical review. Alcohol Clin Exp Res. 2018;42(12):2281–97.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Walters RK, Polimanti R, Johnson EC, McClintick JN, Adams MJ, Adkins AE, et al. Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders. Nat Neurosci. 2018;21(12):1656–69.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Li D, Zhao H, Gelernter J. Strong association of the alcohol dehydrogenase 1B gene (ADH1B) with alcohol dependence and alcohol-induced medical diseases. Biol Psychiatry. 2011;70(6):504–12.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Tawa EA, Hall SD, Lohoff FW. Overview of the genetics of alcohol use disorder. Alcohol Alcohol (Oxford, Oxfordshire). 2016;51(5):507–14.CrossRefGoogle Scholar
  19. 19.
    Brooks PJ, Enoch MA, Goldman D, Li TK, Yokoyama A. The alcohol flushing response: an unrecognized risk factor for esophageal cancer from alcohol consumption. PLoS Med. 2009;6(3):e50.PubMedCrossRefGoogle Scholar
  20. 20.
    Cederbaum AI. Alcohol metabolism. Clin Liver Dis. 2012;16(4):667–85.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    National Institute on Alcohol Abuse and Alcoholism. Alcohol alert: alcohol metabolism. No. 35, PH 371. Bethesda: The Institute; 1997.Google Scholar
  22. 22.
    Hernandez-Munoz R, Caballeria J, Baraona E, Uppal R, Greenstein R, Lieber CS. Human gastric alcohol dehydrogenase: its inhibition by H2-receptor antagonists, and its effect on the bioavailability of ethanol. Alcohol Clin Exp Res. 1990;14(6):946–50.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Kumar S, Porcu P, Werner DF, Matthews DB, Diaz-Granados JL, Helfand RS, et al. The role of GABA(A) receptors in the acute and chronic effects of ethanol: a decade of progress. Psychopharmacology. 2009;205(4):529–64.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Lovinger DM, White G, Weight FF. Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science. 1989;243(4899):1721–4.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Gass JT, Olive MF. Glutamatergic substrates of drug addiction and alcoholism. Biochem Pharmacol. 2008;75(1):218–65.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Vonghia L, Leggio L, Ferrulli A, Bertini M, Gasbarrini G, Addolorato G. Acute alcohol intoxication. Eur J Intern Med. 2008;19(8):561–7.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    National Institute on Alcohol Abuse and Alcoholism. Understanding the Dangers of Alcohol Overdose 2018. Available from:
  28. 28.
    Jung YC, Namkoong K. Alcohol: intoxication and poisoning – diagnosis and treatment. Handb Clin Neurol. 2014;125:115–21.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Marco CA, Kelen GD. Acute intoxication. Emerg Med Clin North Am. 1990;8(4):731–48.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Allison MG, McCurdy MT. Alcoholic metabolic emergencies. Emerg Med Clin North Am. 2014;32(2):293–301.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Center for Substance Abuse Treatment. Detoxification and Substance Abuse Treatment. Treatment Improvement Protocol (TIP) Series, No. 45. HHS publication no. (SMA) 15-4131. Rockville: Center for Substance Abuse Treatment; 2006.Google Scholar
  32. 32.
    Bayard M, McIntyre J, Hill KR, Woodside J Jr. Alcohol withdrawal syndrome. Am Fam Physician. 2004;69(6):1443–50.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Rathlev NK, Ulrich AS, Delanty N, D'Onofrio G. Alcohol-related seizures. J Emerg Med. 2006;31(2):157–63.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Tovar R. Diagnosis and treatment of alcohol withdrawal. JCOM. 2011;18(8):361–70.Google Scholar
  35. 35.
    Schuckit MA. Recognition and management of withdrawal delirium (delirium tremens). N Engl J Med. 2014;371(22):2109–13.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Mayo-Smith MF, Beecher LH, Fischer TL, Gorelick DA, Guillaume JL, Hill A, et al. Management of alcohol withdrawal delirium. An evidence-based practice guideline. Arch Intern Med. 2004;164(13):1405–12.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Helander A, Bottcher M, Fehr C, Dahmen N, Beck O. Detection times for urinary ethyl glucuronide and ethyl sulfate in heavy drinkers during alcohol detoxification. Alcohol Alcohol. 2009;44(1):55–61.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Jatlow PI, Agro A, Wu R, Nadim H, Toll BA, Ralevski E, et al. Ethyl glucuronide and ethyl sulfate assays in clinical trials, interpretation, and limitations: results of a dose ranging alcohol challenge study and 2 clinical trials. Alcohol Clin Exp Res. 2014;38(7):2056–65.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Wojcik MH, Hawthorne JS. Sensitivity of commercial ethyl glucuronide (ETG) testing in screening for alcohol abstinence. Alcohol Alcohol (Oxford, Oxfordshire). 2007;42(4):317–20.CrossRefGoogle Scholar
  40. 40.
    Hansson P, Caron M, Johnson G, Gustavsson L, Alling C. Blood phosphatidylethanol as a marker of alcohol abuse: levels in alcoholic males during withdrawal. Alcohol Clin Exp Res. 1997;21(1):108–10.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Allen JP, Sillanaukee P, Strid N, Litten RZ. In: Allen JP, Wilson VB, editors. Biomarkers of heavy drinking. Bethesda: U.S. Department of Health and Human Services; 2003. p. 37–53.Google Scholar
  42. 42.
    Babor TF, Higgins-Biddle JC, Saunders JB, Monteiro MG. The alcohol use disorders identification test. Guidelines for use in primary health care. Geneva: World Health Organization; 1992.Google Scholar
  43. 43.
    Mayfield D, McLeod G, Hall P. The CAGE questionnaire: validation of a new alcoholism screening instrument. Am J Psychiatry. 1974;131(10):1121–3.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Anton RF, O’Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006;295(17):2003–17.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Kranzler HR, Soyka M. Diagnosis and pharmacotherapy of alcohol use disorder: a review. JAMA. 2018;320(8):815–24.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Center for Substance Abuse Treatment. Incorporating alcohol pharmacotherapies into medical practice. Treatment Improvement Protocol (TIP) series 49. HHS publication no. (SMA) 09-4380. Substance Abuse and Mental Health Services Administration: Rockville; 2009.Google Scholar
  47. 47.
    Skinner MD, Lahmek P, Pham H, Aubin HJ. Disulfiram efficacy in the treatment of alcohol dependence: a meta-analysis. PLoS One. 2014;9(2):e87366.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Jonas DE, Amick HR, Feltner C, Bobashev G, Thomas K, Wines R, et al. Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis. JAMA. 2014;311(18):1889–900.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Kalk NJ, Lingford-Hughes AR. The clinical pharmacology of acamprosate. Br J Clin Pharmacol. 2014;77(2):315–23.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Kenna GA, Lomastro TL, Schiesl A, Leggio L, Swift RM. Review of topiramate: an antiepileptic for the treatment of alcohol dependence. Curr Drug Abuse Rev. 2009;2(2):135–42.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Mason BJ, Quello S, Shadan F. Gabapentin for the treatment of alcohol use disorder. Expert Opin Investig Drugs. 2018;27(1):113–24.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Anton RF, Myrick H, Wright TM, Latham PK, Baros AM, Waid LR, et al. Gabapentin combined with naltrexone for the treatment of alcohol dependence. Am J Psychiatry. 2011;168(7):709–17.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Falk DE, Ryan ML, Fertig JB, Devine EG, Cruz R, Brown ES, et al. Gabapentin Enacarbil extended-release for alcohol use disorder: a randomized, double-blind, placebo-controlled, multisite trial assessing efficacy and safety. Alcohol Clin Exp Res. 2019;43(1):158–69.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Evoy KE, Morrison MD, Saklad SR. Abuse and misuse of Pregabalin and gabapentin. Drugs. 2017;77(4):403–26.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    de Beaurepaire R, Sinclair JMA, Heydtmann M, Addolorato G, Aubin HJ, Beraha EM, et al. The use of baclofen as a treatment for alcohol use disorder: a clinical practice perspective. Front Psych. 2018;9:708.CrossRefGoogle Scholar
  56. 56.
    Agabio R, Sinclair JM, Addolorato G, Aubin HJ, Beraha EM, Caputo F, et al. Baclofen for the treatment of alcohol use disorder: the Cagliari statement. Lancet Psychiatry. 2018;5(12):957–60.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Matthew E. Sloan
    • 1
  • Robert B. Werner
    • 1
  • Stephanie Yarnell-MacGrory
    • 1
  • Ismene Petrakis
    • 1
    • 2
    Email author
  1. 1.Yale University School of Medicine, Department of PsychiatryNew HavenUSA
  2. 2.VA Connecticut Healthcare System #116-AWest HavenUSA

Personalised recommendations