Current Psychiatry Reports

, Volume 6, Issue 5, pp 332–338

Recent advances in the pharmacotherapy of alcoholism

  • Hugh Myrick
  • Raymond Anton
Article

Abstract

Alcoholism is a devastating illness that leads to great societal losses. Despite significant health consequences, there are few medically based treatments for alcoholism. During the past decade, a better understanding of the neuroscientific underpinnings of addiction has led to the use of novel pharmacotherapeutic treatments for alcoholism. In particular, there have been new developments in the understanding of the involvement of the dopamine, opiate, serotonin, gammaaminobutyric acid, and glutamate neurotransmitter systems in the pathophysiology of alcohol withdrawal, alcohol dependence, and in subtypes of individuals with alcoholism. In this article, new developments in the pharmacotherapy of alcohol dependence will be reviewed. In particular, the use of anticonvulsants in alcohol withdrawal and protracted abstinence syndromes will be discussed. Data on naltrexone, acamprosate, and topiramate will be highlighted. In addition, data concerning the use of serotonin reuptake inhibitors in subtypes of alcoholism and the use of combination pharmacotherapy will be reviewed.

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References and Recommended Reading

  1. 1.
    Reiger DA, Farmer ME, Rae DS, et al.: Comorbidity of mental disorders with alcohol and other drug abuse. JAMA 1990, 264:2511–2518.CrossRefGoogle Scholar
  2. 2.
    .Smothers BA, Yahr HT, Ruhl CE: Detection of alcohol use disorders in general hospital admissions in the United States. Arch Intern Med 2004, 164:749–756. This recent study suggests that the detection, inpatient intervention, and referral of individuals with alcohol use disorders are low. Recommendations are made to increase professional evaluation and treatment of patients.PubMedCrossRefGoogle Scholar
  3. 3.
    Ewing JA: Detecting alcoholism: The CAGE questionnaire. JAMA 1984, 252:1905–1907.PubMedCrossRefGoogle Scholar
  4. 4.
    Saunders JB, Aasland OG, Babor TF, et al.: Development of the Alcohol Use Disorders Screening Test (AUDIT). WHO collaborative project on early detection of persons with harmful alcohol consumption. Addiction 1993, 88:791–804.PubMedCrossRefGoogle Scholar
  5. 5.
    Mihas AA, Tavassoli M: Laboratory markers of ethanol intake and abuse: a critical appraisal. Am J Med Sci 1992, 303:415–428.PubMedCrossRefGoogle Scholar
  6. 6.
    Anton RF, Stout RL, Roberts JS, et al.: The effects of drinking intensity and frequency on serum carbohydrate-deficient transferrin and gamma-glutamyltransferase levels in outpatient alcoholics. Alcohol Clin Exp Res 1998, 22:1456–1462.PubMedCrossRefGoogle Scholar
  7. 7.
    Litten RZ, Allen JP, Fertig JB: Gamma-glutamyltransferase and carbohydrate deficient transferrin: Alternative measures of excessive alcohol consumption. Alcohol Clin Exp Res 1995, 19:1541–1546.PubMedCrossRefGoogle Scholar
  8. 8.
    Anton RF: Carbohydrate-deficient transferrin for detection and monitoring of sustained heavy drinking. What have we learned? Where do we go from here? Alcohol 2001, 25:185–188. This article is a thorough review of the use of CDT in detecting and monitoring heavy drinking. Issues such as comparing the sensitivity and specificity of CDT with GGT, gender issues in using CDT, and the use of CDT as a monitoring tool are addressed.PubMedCrossRefGoogle Scholar
  9. 9.
    Allen JP, Sillamaukee P, Anton R: Contribution of carbohydratedeficient transferrin to gamma-glutamyltranspeptidase in evaluating progress of patients in treatment of alcoholism. Alcohol Clin Exp Res 1999, 23:115–120.PubMedGoogle Scholar
  10. 10.
    Institute of Medicine: Prevention and Treatment of Alcohol Problems. Washington, DC: National Academy Press; 1990, 268–269.Google Scholar
  11. 11.
    Mayo-Smith MF: Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. JAMA 1997, 278:144–151.PubMedCrossRefGoogle Scholar
  12. 12.
    Saitz R, Mayo-Smith MF, Roberts MS, et al.: Individualized treatment for alcohol withdrawal: A randomized doubleblind controlled trial. JAMA 1994, 272:519–523.PubMedCrossRefGoogle Scholar
  13. 13.
    Malcolm R, Myrick H, Brady KT: Update on anticonvulsants for the treatment of alcohol withdrawal. Am J Addictions 2001, 10(suppl):16–23.Google Scholar
  14. 14.
    Brown ME, Anton RF, Malcolm R, et al.: Alcohol detoxification and withdrawal seizures: clinical support for a kindling hypothesis. Biol Psychiatry 1988, 23:507–514.PubMedCrossRefGoogle Scholar
  15. 15.
    Moak DH, Anton RF: Alcohol-related seizures and the kindling effect of repeated detoxifications: the influence of cocaine. Alcohol Alcohol 1996, 31:135–143.PubMedGoogle Scholar
  16. 16.
    Becker HC: Alcohol withdrawal: Neuroadaption and sensitization. CNS Spectrums 1999, 4:38–65.Google Scholar
  17. 17.
    Bastie Y: Suppression by depakene of epileptic crises caused by withdrawal in alcoholic detoxification. Ann Med Psychol (Paris) 1970, 128:200–204.Google Scholar
  18. 18.
    Bonfiglio C, Falli S, Pacini A: The use of sodium dipropylacetate to prevent and treat alcoholic delerium tremens. Minerva Med 1977, 63:4233–4255.Google Scholar
  19. 19.
    Lambie DG, Johnson RH, Vijayasenan ME, et al.: Sodium valproate in the treatment of the alcohol withdrawal syndrome. Aust N Z J Psychiatry 1980, 14:213–215.PubMedGoogle Scholar
  20. 20.
    Myrick H, Brady KT, Malcolm R: Divalproex in the treatment of alcohol withdrawal. Am J Drug Alcohol Abuse 2000, 26:155–160.PubMedCrossRefGoogle Scholar
  21. 21.
    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.PubMedCrossRefGoogle Scholar
  22. 22.
    Hillbom ME, Hjelm-Jager M: Should alcohol withdrawal seizures be treated with anti-epileptic drugs? Acta Neurol Scand 1984, 69:39–42.PubMedGoogle Scholar
  23. 23.
    Reoux JP, Saxon AJ, Malte CA, et al.: Divalproex sodium in alcohol withdrawal: a randomized double-blind placebo-controlled clinical trial. Alcohol Clin Exp Res 2001, 25:1324–1329.PubMedCrossRefGoogle Scholar
  24. 24.
    Bjorkqvist SE, Isohanni M, Makela R, et al.: Ambulant treatment of alcohol withdrawal symptoms with carbamazepine: a formal multicentre double-blind comparison with placebo. Acta Psychiatr Scand 1976, 53:333–342.PubMedGoogle Scholar
  25. 25.
    Sonck T, Malinen L, Hanne J: Carbamazepine in the treatment of acute withdrawal syndrome in alcoholics: methodological aspects. In Rationality of Drug Development. Excerpta Medica International Congress Series No. 383. Edited by Lucchelli PE, Bergamini N, Bachini V. Amsterdam: Excerpta Medica; 1976:251.Google Scholar
  26. 26.
    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.PubMedGoogle Scholar
  27. 27.
    Stuppaeck CH, Pycha R, Miller C, et al.: Carbamazepine versus oxazepam in the treatment of alcohol withdrawal: a double blind study. Alcohol Alcohol 1991, 27:153–158.Google Scholar
  28. 28.
    Malcolm R, Myrick H, Roberts J, et al.: The differential effects of medication on psychiatric and psychosocial outcomes in outpatient alcohol detoxification. Am J Addictions 2002, 11:141–150.CrossRefGoogle Scholar
  29. 29.
    Watson WP, Robinson E, Little HJ: The novel anticonvulsant, gabapentin, protects against both convulsant and anxiogenic aspects of the ethanol withdrawal syndrome. Neuropharmacology 1997, 36:1369–1375.PubMedCrossRefGoogle Scholar
  30. 30.
    Bailey CP, Molleman A, Little HJ: Comparison of the effects of drugs on hyperexcitability induced in hippocampal slices by withdrawal from chronic ethanol consumption. Br J Pharmacol 1998, 123:215–222.PubMedCrossRefGoogle Scholar
  31. 31.
    Myrick H, Malcolm R, Brady KT: Gabapentin treatment of alcohol withdrawal. Am J Psychiatry 1998, 155:1632.PubMedGoogle Scholar
  32. 32.
    Bonnet U, Banger M, Leweke FM, et al.: Treatment of alcohol withdrawal syndrome with gabapentin. Pharmacopsychiatry 1999, 32:107–109.PubMedGoogle Scholar
  33. 33.
    Fuller RK, Branchey L, Brightwell DR, et al.: Disulfiram treatment of alcoholism: a Veterans Administration cooperative study. JAMA 1986, 256:1449–1455.PubMedCrossRefGoogle Scholar
  34. 34.
    Chick J, Gough K, Falkowski W, et al.: Disulfiram treatment of alcoholism. Br J Psychiatry 1992, 161:84–89.PubMedGoogle Scholar
  35. 35.
    Anton RF, Swift RM: Current pharmacotherapies of alcoholism: a U.S. Perspective. Am J Addict, 2003 12(Suppl1):S53–68. This article is a comprehensive review of the pharmacotherapies used in the treatment of alcoholism. Particular emphasis is placed on naltrexone, acamprosate, and serotonergic agents.PubMedGoogle Scholar
  36. 36.
    Kranzler HR, Van Kirk J: Efficacy of naltrexone and acamprosate for alcoholism treatment: a meta-analysis. Alcohol Clin Exp Res 2001, 25:1335–1341.PubMedCrossRefGoogle Scholar
  37. 37.
    Streeton C, Whelan G: Naltrexone, a relapse prevention maintenance treatment of alcohol dependence: a meta-analysis of randomized controlled trials. Alcohol Alcohol 2001, 36:544–552.PubMedGoogle Scholar
  38. 38.
    Balldin J, Berglund M, Borg S, et al.: A 6-month controlled naltrexone study: combined effect with cognitive behavioral therapy in outpatient treatment of alcohol dependence. Alcohol Clin Exp Res 2003, 27:1142–1149.PubMedCrossRefGoogle Scholar
  39. 39.
    Kranzler HR, Modesto-Lowe V, Nuwayser ES: Sustained-release naltrexone for alcoholism treatment: a preliminary study. Alcohol Clin Exp Res 1998, 22:1074–1079.PubMedGoogle Scholar
  40. 40.
    Chick J, Anton R, Checinski K, Croop R, et al.: A multicentre, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse. Alcohol Alcohol 2000, 35:587–593.PubMedGoogle Scholar
  41. 41.
    Kranzler HR, Modesto-Lowe V, Van Kirk J: Naltrexone vs. nefazodone for treatment of alcohol dependence. A placebo-controlled trial. Neuropsychopharmacology 2000, 22:493–503.PubMedCrossRefGoogle Scholar
  42. 42.
    Krystal JH, Cramer JA, Krol WF, et al.: Naltrexone in the treatment of alcohol dependence. N Engl J Med 2001, 345:1734–1739.PubMedCrossRefGoogle Scholar
  43. 43.
    Oslin DW, Berrettini W, Kranzler HR, et al.: A functional polymorphism of the mu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients. Neuropsychopharmacology 2003, 28:1546–1552. This study evaluated the association between two specific polymorphisms of the gene encoding the mu opioid receptor and treatment outcomes in alcoholics treated with naltrexone or placebo. Lower relapse rates were found in individuals with one or two copies of the ASP40 allele who were treated with naltrexone suggesting that genes encoding the opioid receptor might predict treatment response.PubMedCrossRefGoogle Scholar
  44. 44.
    Littleton J: Acamprosate in alcohol dependence: How does it work? Addiction 1995, 90:1179–1188.PubMedCrossRefGoogle Scholar
  45. 45.
    Chick J, Lehert P, Landron F: Does acamprosate improve reduction of drinking as well as aiding abstinence? J Psychopharmacol 2003, 17:397–402.PubMedCrossRefGoogle Scholar
  46. 46.
    Mason B, Ownby R: Acamprosate for the treatment of alcohol dependence: A review of double-blind, placebo-controlled trials. CNS Spectrum 2000, 5:58–69.Google Scholar
  47. 47.
    Naranjo CA, Sellers EM, Sullivan JT, et al.: The serotonin uptake inhibitor citalopram attenuates ethanol intake. Clin Pharmacol Ther 1987, 41:266–274.PubMedCrossRefGoogle Scholar
  48. 48.
    Janiri L, Gobbi G, Mannelli P, et al.: Effects of fluoxetine and antidepressant doses on sort-term outcome of detoxified alcoholics. Int Clin Psychopharmacol 1996, 11:109–117.PubMedCrossRefGoogle Scholar
  49. 49.
    Angelone SM, Bellini L, Di Bella D, et al.: Effects of fluvoxamine and citalopram in maintaining abstinence in a sample of Italian detoxified alcoholics. Alcohol Alcohol 1998, 33:151–156.PubMedGoogle Scholar
  50. 50.
    Kranzler HR, Burleson JA, Korner P, et al.: Placebo-controlled trial of fluoxetine as an adjunct to relapse prevention in alcoholics. Am J Psychiatry 1995, 152:391–397.PubMedGoogle Scholar
  51. 51.
    Kabel D, Petty F: A double-blind study of fluoxetine in severe alcohol dependence: adjunctive therapy during and after inpatient treatment. Alcohol Clin Exp Res 1996, 20:780–784.PubMedCrossRefGoogle Scholar
  52. 52.
    Babor TF, Hofmann M, DelBoca FK, et al.: Types of alcoholics, I. Evidence for an empirically derived typology based on indicators of vulnerability and severity. Arch Gen Psychiatry 1992, 49:599–608.PubMedGoogle Scholar
  53. 53.
    Cloninger CR, Bohman M, Sigvardsson S: Inheritance of alcohol abuse. Cross-fostering analysis of adopted men. Arch Gen Psychiatry 1981, 38:861–868.PubMedGoogle Scholar
  54. 54.
    Tiihonen J, Ryynanen OP, Kauhanen J, et al.: Citalopram in the treatment of alcoholism: a double-blind placebo-controlled study. Pharmacopsychiatry 1996, 29:27–29.PubMedGoogle Scholar
  55. 55.
    Kranzler HR, Burleson JA, Brown J, et al.: Fluoxetine treatment seems to reduce the beneficial effects of cognitive-behavioral therapy in type B alcoholics. Alcohol Clin Exp Res 1996, 20:1534–1541.PubMedCrossRefGoogle Scholar
  56. 56.
    Pettinati HM, Volpicelli JR, Kranzler HR, et al.: Sertraline treatment for alcohol dependence: Interactive effects of medication and alcoholic subtype. Alcohol Clin Exp Res 2000, 24:1041–1049.PubMedCrossRefGoogle Scholar
  57. 57.
    Sellers EM, Toneatto T, Romach MK, et al.: Clinical efficacy of the 5-HT3 antagonist ondansetron in alcohol abuse and dependence. Alcohol Clin Exp Res 1994, 18:879–885.PubMedCrossRefGoogle Scholar
  58. 58.
    Mueller TI, Stout RL, Rudden S, et al.: A double-blind, placebocontrolled pilot study of carbamazepine for the treatment of alcohol dependence. Alcohol Clin Exp Res 1997, 21:86–92.PubMedGoogle Scholar
  59. 59.
    Brady KT, Myrick H, Henderson S, et al.: The use of divalproex in alcohol relapse prevention: a pilot study. Drug Alcohol Depend 2002, 67:323–330.PubMedCrossRefGoogle Scholar
  60. 60.
    Longo LP, Campbell T, Hubatch S: Divalproex sodium (Depakote) for alcohol withdrawal and relapse prevention. J Addict Dis 2002, 21:55–64.PubMedCrossRefGoogle Scholar
  61. 61.
    Johnson BA, Ait-Daoud N, Bowden CL, et al.: Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Lancet 2003, 361:1677–1685. This study is a randomized, placebo-controlled trial of the anticonvulsant topiramate in the treatment of alcoholism. Results indicate that patients treated with topiramate had multiple treatmentrelated improvements than compared with patients treated with placebo.PubMedCrossRefGoogle Scholar
  62. 62.
    Kiefer F, Jahn H, Tarnaske T, et al.: Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study. Arch Gen Psychiatry 2003, 60:92–99.PubMedCrossRefGoogle Scholar
  63. 63.
    Ait-Daoud N, Johnson BA, Prihoda TJ, et al.: Combining ondansetron and naltrexone reduces craving among biologically predisposed alcoholics: preliminary clinical evidence. Psychopharmacology (Berl) 2001, 154:23–27.CrossRefGoogle Scholar

Copyright information

© Current Science Inc 2004

Authors and Affiliations

  • Hugh Myrick
    • 1
  • Raymond Anton
  1. 1.Medical University of South Carolina Department of Psychiatry and Behavioral SciencesAlcohol Research CenterCharlestonUSA

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