Alcohol Withdrawal: Treatment and Application

Chapter

Abstract

Severe alcohol withdrawal has a significant morbidity and mortality rate, especially with a pre-existing co-morbid state. Repeated alcohol withdrawal episodes may sensitize the patient, making future episodes more severe and harder to treat. Benzodiazepines have been found to be safe and effective in the treatment of alcohol withdrawal. However, their abuse liability, their cross-tolerance with alcohol, and the increased risk of relapse to other drugs of abuse limit their use in outpatient settings. The authors discuss some of the neuropharmacological aspects of alcohol withdrawal and drug treatment options with a focus on anticonvulsant drugs. Medications such as sodium valproate, carbamazepine, gabapentin, and topiramate are discussed and their role in the clinical setting addressed. Finally, the authors discuss the potential utility of newer approaches in managing anxiety associated with alcohol withdrawal, such as the use of neurosteroids.

Keywords

Alcohol withdrawal Anticonvulsants Sodium valproate Carbamazepine Gabapentin Topiramate Neurosteroids 

References

  1. 1.
    American Psychiatric Association (2000) Substance-related disorders. In: Diagnostic and statistical manual of mental disorders, 4th edn, text revision. American Psychiatric Association, Washington, DCGoogle Scholar
  2. 2.
    Bailey CP, Molleman A, Little HJ (1998) Comparison of the effects of drugs on hyperexcitability induced in hippocampal slices by withdrawal from chronic ethanol consumption. Br J Pharmacol 123:215–222PubMedCrossRefGoogle Scholar
  3. 3.
    Becker HC (2000) Alcohol withdrawal: neuroadaptation and sensitization. CNS Spectrums 4:38–65Google Scholar
  4. 4.
    Bonnet U, Banger M, Leweke FM et al (1999) Treatment of alcohol withdrawal syndrome with gabapentin. Pharmacopsychiatry 32:107–109PubMedCrossRefGoogle Scholar
  5. 5.
    Bonnet U, Banger M, Leweke FM et al (2003) Treatment of acute alcohol withdrawal with gabapentin: results from a controlled two-center trial. J Clin Psychopharmacol 23:514–519PubMedCrossRefGoogle Scholar
  6. 6.
    Bozikas V, Petrikis P, Gamvrula K et al (2002) Treatment of alcohol withdrawal with gabapentin. Prog Neuropsychopharmacol Biol Psychiatry 26:197–199PubMedCrossRefGoogle Scholar
  7. 7.
    Brady KT, Myrick H, Henderson S et al (2002) The use of divalproex in alcohol relapse prevention: a pilot study. Drug Alcohol Depend 67:323–330PubMedCrossRefGoogle Scholar
  8. 8.
    Burns M, Price J, Lekawa ME (2008) Delirium tremens: eMedicine critical care. emedicine.medscape.com. http://emedicine.medscape.com/article/166032-overview. Retrieved on June 23, 2009
  9. 9.
    Chatterjee CR, Ringold AL (1999) A case report of reduction in alcohol craving and protection against alcohol withdrawal by gabapentin. J Clin Psychiatry 60:617PubMedCrossRefGoogle Scholar
  10. 10.
    Choi EA, Ki SW, Kim SE et al (2005) The efficacy and safety of topiramate in the treatment of alcohol withdrawal. J Korean Neuropsychiatr Assoc 44:328–333Google Scholar
  11. 11.
    el-Guebaly N, el-Guebaly A (1981) Alcohol abuse in ancient Egypt: the recorded evidence. Int J Addict 16:1207–1221PubMedGoogle Scholar
  12. 12.
    Garnett WR (2000) Clinical pharmacology of topiramate: a review. Epilepsia 41(Suppl 1):S61–S65PubMedCrossRefGoogle Scholar
  13. 13.
    Hauser WA (1990) Epidemiology of alcohol use and of epilepsy: the magnitude of the problem. In: Porter RJ, Mattson RH, Cramer JA, Diamond I (eds) Alcohol and seizures: basic mechanisms and clinical concepts. F.A. Davis Company, PhiladelphiaGoogle Scholar
  14. 14.
    Herrero AI, Del Olmo N, Gonzalez-Escalada JR et al (2002) Two new actions of topiramate: inhibition of depolarizing GABA(A)-mediated responses and activation of a potassium conductance. Neuropharmacology 42:210–220PubMedCrossRefGoogle Scholar
  15. 15.
    Isbell H, Fraser HF, Wikler A, Belleville RE, Eisenman AJ (1955) An experimental study of the etiology of ‘rum fits’ and delirium tremens. Q J Stud Alcohol 16:1–33PubMedGoogle Scholar
  16. 16.
    Johnson BA, Ait-Daoud N, Bowden CL et al (2003) Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Lancet 361:1677–1685PubMedCrossRefGoogle Scholar
  17. 17.
    Johnson BA, Rosenthal N, Capece JA et al (2007) Topiramate for treating alcohol dependence: a randomized controlled trial. JAMA 298:1641–1651PubMedCrossRefGoogle Scholar
  18. 18.
    Karam-Hage M, Brower KJ (2000) Gabapentin treatment for insomnia associated with alcohol dependence. Am J Psychiatry 157:151PubMedGoogle Scholar
  19. 19.
    Knapp DJ, Overstreet DH, Breese GR (2005) Modulation of ethanol withdrawal-induced anxiety-like behavior during later withdrawals by treatment of early withdrawals with benzodiazepine/gamma-aminobutyric acid ligands. Alcohol Clin Exp Res 29:553–563PubMedCrossRefGoogle Scholar
  20. 20.
    Krupitsky EM, Rudenko AA, Burakov AM, Slavina TY, Grinenko AA, Pittman B et al (2007) Antiglutamatergic strategies for ethanol detoxification: comparison with placebo and diazepam. Alcohol Clin Exp Res 31:604–611PubMedGoogle Scholar
  21. 21.
    Leibowitz JO (1957) Acute alcoholism in Greek and Roman medicine. Br J Addict 62:83–86CrossRefGoogle Scholar
  22. 22.
    Longo LP, Campbell T, Hubatch S (2002) Divalproex sodium (Depakote) for alcohol withdrawal and relapse prevention. J Addict Dis 21:55–64PubMedCrossRefGoogle Scholar
  23. 23.
    Malcolm RJ (2003) GABA systems, benzodiazepines, and substance dependence. J Clin Psychiatry 64(Suppl 3):36–40PubMedGoogle Scholar
  24. 24.
    Malcolm R, Myrick H, Brady KT et al (2001) Update on anticonvulsants for the treatment of alcohol withdrawal. Am J Addict 10(Suppl):16–23PubMedGoogle Scholar
  25. 25.
    Malcolm R, Myrick H, Roberts J et al (2002) The differential effects of medication on mood, sleep disturbance, and work ability in outpatient alcohol detoxification. Am J Addict 11:141–150PubMedCrossRefGoogle Scholar
  26. 26.
    Malcolm R, Myrick H, Roberts J et al (2002) The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial. J Gen Intern Med 17:349–355PubMedGoogle Scholar
  27. 27.
    Malcolm R, Myrick LH, Veatch LM et al (2007) Self-reported sleep, sleepiness, and repeated alcohol withdrawals: a randomized, double blind, controlled comparison of lorazepam vs gabapentin. J Clin Sleep Med 3:24–32PubMedGoogle Scholar
  28. 28.
    McLean MJ (1999) Gabapentin in the management of convulsive disorders. Epilepsia 40(Suppl 6):S39–S50PubMedCrossRefGoogle Scholar
  29. 29.
    Miller MS, Kipnis SS (2006) Detoxification and substance abuse treatment. U.S. Department of Health and Human Services publication number 06-4131Google Scholar
  30. 30.
    Mueller TI, Stout RL, Rudden S et al (1997) A double-blind, placebo-controlled pilot study of carbamazepine for the treatment of alcohol dependence. Alcohol Clin Exp Res 21:86–92PubMedCrossRefGoogle Scholar
  31. 31.
    Myrick H, Malcolm R, Brady KT (1998) Gabapentin treatment of alcohol withdrawal. Am J Psychiatry 155:1632PubMedGoogle Scholar
  32. 32.
    Ortho-McNeil Pharmaceutical, Inc. (2003) Topamax® [package insert]. Ortho-McNeil Pharmaceutical, Inc., Raritan, NJGoogle Scholar
  33. 33.
    Petroff OA, Hyder F, Rothman DL et al (2000) Effects of gabapentin on brain GABA, homocarnosine, and pyrrolidinone in epilepsy patients. Epilepsia 41:675–680PubMedCrossRefGoogle Scholar
  34. 34.
    Polycarpou A, Papanikolaou P, Ioannidis J et al (2005) Anticonvulsants for alcohol withdrawal. Cochrane Database Syst Rev (3):CD005064Google Scholar
  35. 35.
    Reoux JP, Saxon AJ, Malte CA et al (2001) Divalproex sodium in alcohol withdrawal: a randomized double-blind placebo-controlled clinical trial. Alcohol Clin Exp Res 25:1324–1329PubMedCrossRefGoogle Scholar
  36. 36.
    Rolleston JD (1927) Alcoholism in classical antiquity. Br J Inebriation 24:101–120Google Scholar
  37. 37.
    Romano J (1941) Early contributions to the study of delirium tremens. Med Hist 3:128–139Google Scholar
  38. 38.
    Rustembegovic A, Sofic E, Kroyer G (2002) A pilot study of topiramate (Topamax) in the treatment of tonic-clonic seizures of alcohol withdrawal syndromes. Med Arh 56:211–212PubMedGoogle Scholar
  39. 39.
    Rustembegovic A, Sofic E, Tahirovic I et al (2004) A study of gabapentin in the treatment of tonic-clonic seizures of alcohol withdrawal syndrome. Med Arh 58:5–6PubMedGoogle Scholar
  40. 40.
    Salloum IM, Cornelius JR, Daley DC et al (2005) Efficacy of valproate maintenance in patients with bipolar disorder and alcoholism: a double-blind placebo-controlled study. Arch Gen Psychiatry 62:37–45PubMedCrossRefGoogle Scholar
  41. 41.
    Sarup A, Larsson OM, Schousboe A (2003) GABA transporters and GABA-transaminase as drug targets. Curr Drug Targets CNS Neurol Disord 2:269–277PubMedCrossRefGoogle Scholar
  42. 42.
    Shank RP, Gardocki JF, Streeter AJ et al (2000) An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia 41(Suppl 1):S3–S9PubMedCrossRefGoogle Scholar
  43. 43.
    Sullivan JT, Sykora K, Schneiderman J et al (1989) Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict 84:1353–1357PubMedCrossRefGoogle Scholar
  44. 44.
    Victor M, Adams RD (1953) The effect of alcohol on the nervous system. In: Association for Research in Nervous and Mental Disease (ed) Metabolic and toxic diseases of the nervous system; proceedings of the association, December 12 and 13, 1952. Williams & Wilkins, BaltimoreGoogle Scholar
  45. 45.
    Voris J, Smith NL, Rao SM et al (2003) Gabapentin for the treatment of ethanol withdrawal. Subst Abuse 24:129–132Google Scholar
  46. 46.
    Watson WP, Robinson E, Little HJ (1997) The novel anticonvulsant, gabapentin, protects against both convulsant and anxiogenic aspects of the ethanol withdrawal syndrome. Neuropharmacology 36:1369–1375PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Psychiatry and Neurobehavioral SciencesUniversity of VirginiaCharlottesvilleUSA
  2. 2.Department of Psychiatry and Behavioral SciencesMedical University of South CarolinaCharlestonUSA

Personalised recommendations