Evidence-Based Reviews

Alcohol withdrawal: When to choose an adjunctive anticonvulsant

Current Psychiatry. 2010 April;9(4):27-39

References

1. Mayo-Smith MF, Cushman P, Hill AJ, et al. Pharmacological management of alcohol withdrawal. JAMA. 1997;278:144-151.

2. Myrick H, Brady KT, Malcom R. Divalproex in the treatment of alcohol withdrawal—statistical data included. Am J Drug Alcohol Abuse. 2000;26(1):155-160.

3. Johnson BA, Swift RM, Addolorato G, et al. Safety and efficacy of GABAergic medications for treating alcoholism. Alcohol Clin Exp Res. 2005;29(2):248-254.

4. Lum E, Gorman SK, Slavik RS. Valproic acid management of acute alcohol withdrawal. Ann Pharmacother. 2006;40(3):441-448.

5. Trevisan LA, Boutros N, Petrakis IL, et al. Complications of alcohol withdrawal: pathophysiological insights. Alcohol Health Res World. 1998;22(1):61-66.

6. Esel E. Neurobiology of alcohol withdrawal inhibitory and excitatory neurotransmitters. Turk Psikiyatri Derg. 2006;7(2):129-138.

7. Myrick H, Brady KT. The use of divalproex in the treatment of addictive disorders. Psychopharmacol Bull. 2003;37(suppl 2):89-97.

8. Brady KT, Myrick H, Henderson S, et al. The use of divalproex in alcohol relapse prevention: a pilot study. Drug Alcohol Depend. 2002;67(3):323-330.

9. Longo L, Campbell T, Hubatch S. Divalproex sodium (Depakote) for alcohol withdrawal and relapse prevention. J Addict Dis. 2002;21(2):55-64.

10. Sarid-Segal O, Piechniczek-Buczek J, Knapp C, et al. The effects of levetiracetam on alcohol consumption in alcohol-dependent subjects: an open label study. Am J Drug Alcohol Abuse. 2008;34(4):441-447.

11. American Psychiatric Association. Treatments of psychiatric disorders: a task force report of the American Psychiatric Association. Washington, DC: American Psychiatric Association Press; 1989:187.

12. Mason BJ, Light JM, Williams LD, et al. Proof-of-concept human laboratory study for protracted abstinence in alcohol dependence: effects of gabapentin. Addict Biol. 2009;14(1):73-83.

13. Physicians’ Desk Reference 2009. 63rd ed. Montvale, NJ: Physicians’ Desk Reference; 2008:423-431.

14. Malcolm R, Ballenger JC, Sturgis ET, et al. Double-blind controlled trial comparing carbamazepine to oxazepam treatment of alcohol withdrawal. Am J Psychiatry. 1989;146:617-621.

15. Myrick H, Anton R, Voronin K, et al. A double-blind evaluation of gabapentin on alcohol effects and drinking in a clinical laboratory paradigm. Alcohol Clin Exp Res. 2007;31(2):221-227.

16. Malcolm R, Myrick H, Brady KT, et al. Update on anticonvulsants for the treatment of alcohol withdrawal. Am J Addict. 2001;10(suppl):16-23.

17. Davis LL, Ryan W, Adinoff B, et al. Comprehensive review of the psychiatric uses of valproate. J Clin Psychopharm. 2000;20(1 suppl 1):1S-17S.

18. Rosenthal RN, Perkel C, Singh P, et al. A pilot open randomized trial of valproate and phenobarbital in the treatment of acute alcohol withdrawal. Am J Addict. 1998;7:189-197.

19. Book SW, Myrick H. Novel anticonvulsants in the treatment of alcoholism. Expert Opin Investig Drugs. 2005;14(4):371-376.

20. Krebs M, Leopold K, Richter C, et al. Levetiracetam for the treatment of alcohol withdrawal syndrome: an open-label pilot trial. J Clin Psychopharmacol. 2006;26(3):347-349.

21. LaRoche SM, Helmers SL. The new antiepileptic drugs: scientific review. JAMA. 2004;291:605-614.

22. Chabolla DR, Harnois DM, Meschia JF. Levetiracetam monotherapy for liver transplant patients with seizures. Transplant Proc. 2003;35:1480-1481.

23. Paul F, Meencke HJ. Levetiracetam in focal epilepsy and hepatic porphyria: a case report. Epilepsia. 2004;45:559-560.

24. Ntais C, Pakos E, Kyzas P, et al. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev. 2005;(3):CD005063.-

25. Physicians’ Desk Reference 2009. 63rd ed. Montvale, NJ: Physicians’ Desk Reference; 2008:3131-3143.

26. Saias T, Gallarda T. Paradoxical aggressive reactions to benzodiazepine use: a review. Encephale. 2008;34(4):330-336.

27. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation–Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002;166:1338-1344.

28. Bonnet U, Banger M, Leweke FM, et al. Treatment of acute alcohol withdrawal with gabapentin: results from a controlled two-center trial. J Clin Psychopharmacol. 2003;23(5):514-519.

29. Myrick H, Malcolm R, Brady KT. Gabapentin treatment of alcohol withdrawal. Am J Psychiatry. 1998;155:1626.-

30. Bonnet U, Banger M, Leweke FM, et al. Treatment of alcohol withdrawal syndrome with gabapentin. Pharmacopsychiatry. 1999;32:107-109.

31. Mariani JJ, Rosenthal RN, Tross S, et al. A randomized, open-label, controlled trial of gabapentin and phenobarbital in the treatment of alcohol withdrawal. Am J Addict. 2006;15(1):76-84.

32. Voris J, Smith NL, Rao SM, et al. Gabapentin for the treatment of ethanol withdrawal. Subst Abus. 2003;24(2):129-132.

33. Furieri FA, Nakamura-Palacios EM. Gabapentin reduces alcohol consumption and craving: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2007;68(11):1691-1700.

34. Bisaga A, Evans SM. The acute effects of gabapentin in combination with alcohol in heavy drinkers. Drug Alcohol Depend. 2006;83(1):25-32.

Mr. B requires a total of 2 mg of lorazepam throughout hospitalization. He finishes alcohol detoxification on day 4 and is discharged with a prescription for gabapentin, 1,200 mg tid. Two weeks later, when he is admitted to a 28-day inpatient alcohol rehabilitation unit, Mr. B has not relapsed.

More abstinent days

Clinical Point

By increasing the number of abstinent days, gabapentin may help patients maintain abstinence

Gabapentin is FDA-approved as adjunctive therapy for partial seizures. Off-label, it has been generally efficacious as an adjunct in alcohol detoxification.^29-32 We chose adjunctive anticonvulsant therapy for Mr. B because of his history of alcohol-induced seizures. We chose gabapentin instead of valproic acid because of Mr. B’s liver damage and gabapentin’s lack of hepatic metabolism.

Clinical Point

Gabapentin does not appear to interact clinically with alcohol

Gabapentin may reduce alcohol consumption and craving in alcohol-dependent patients. By increasing the number of abstinent days, gabapentin may help patients maintain abstinence.³³ Gabapentin does not appear to interact clinically with alcohol, causing neither sedation nor synergistic effects.³⁴ Its relative lack of abuse potential may be valuable in outpatient alcohol withdrawal treatment and in maintaining alcohol abstinence after detoxification.

Related resource

Asplund CA, Aaronson JW, Aaronson HE. 3 regimens for alcohol withdrawal and detoxification. J Fam Pract. 2004;53(7):545-554. www.jfponline.com/Pages.asp?AID=1730.

Drug brand names

Acamprosate • Campral
Alprazolam • Xanax
Carbamazepine • Carbatrol
Cimetidine • Tagamet
Clonazepam • Klonopin
Clonidine • Catapres
Diazepam • Valium
Disulfiram • Antabuse
Felbamate • Felbatol
Fluoxetine • Prozac
Gabapentin • Neurontin
Isoniazid • Nydrazid
Lamotrigine • Lamictal
Levetiracetam • Keppra
Lorazepam • Ativan
Naltrexone • ReVia, Vivitrol
Oxazepam • Serax
Phenobarbital • Luminal
Phenytoin • Dilantin
Propranolol • Inderal
Rifampin • Rifadin
Ritonavir • Norvir
Temazepam • Restoril
Triazolam • Halcion
Valproic acid • Depakote, Depakene

Disclosures

Dr. Spiegel is a speaker for Pfizer Inc. and GlaxoSmithKline.

Dr. Radac reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgment

The authors thank Rishi Laroia, MD, Robert Swanson, MD, and Adam W. Coe, MD for their contributions to this article.