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Topiramate in Alcohol Use Disorders: Review and Update

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Abstract

To date, a limited number of pharmacological agents exist to treat alcohol use disorders (AUDs), and there is growing interest in new therapeutic tools. In this framework, topiramate may represent a useful treatment option, although its use is not yet approved for AUDs. The main focus of this review is to discuss all the existing data supporting the use of topiramate in AUDs, with an emphasis on the most recent and relevant clinical implications. In addition, the profile of the alcoholic patient who may benefit more from the use of topiramate is outlined. In this regard, the authors conducted a PubMed search of clinical human studies published in English using the following key words: topiramate alcohol dependence, topiramate alcohol withdrawal and topiramate alcoholism. The evidence suggests that topiramate could be an effective treatment option for the management of AUDs, while there are limited results for its use to treat alcohol withdrawal syndrome. In particular, topiramate shows a greater beneficial effect in subjects with a typology of craving characterised by drinking obsessions and automaticity of drinking. Topiramate, within the dosage range of 75–300 mg/day, could be considered as a first-line treatment option for the management of AUDs. Its use appears to be safe and well-tolerated, especially in light of very recent findings.

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References

  1. Valenzuela CF. Alcohol and neurotransmitter interactions. Alcohol Health Res World. 1997;21(2):144–8.

    CAS  PubMed  Google Scholar 

  2. Mueller TI, Stout RL, Rudden S, Brown RA, Gordon A, Solomon DA, et al. A double-blind, placebo-controlled pilot study of carbamazepine for the treatment of alcohol dependence. Alcohol Clin Exp Res. 1997;21(1):86–92.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  4. Johnson BA, Ait-Daoud N, Bowden CL, DiClemente CC, Roache JD, Lawson K, et al. Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Lancet. 2003;361(9370):1677–85.

    Article  CAS  PubMed  Google Scholar 

  5. Martinotti G, Di Nicola M, Romanelli R, Andreoli S, Pozzi G, Moroni N, et al. High and low dosage oxcarbazepine versus naltrexone for the prevention of relapse in alcohol-dependent patients. Hum Psychopharmacol. 2007;22(3):149–56.

    Article  CAS  PubMed  Google Scholar 

  6. Furieri FA, Nakamura-Palacios EM. Gabapentin reduces alcohol consumption and craving: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2007;68(11):1691–700.

    Article  CAS  PubMed  Google Scholar 

  7. Guglielmo R, Martinotti G, Clerici M, Janiri L. Pregabalin for alcohol dependence: a critical review of the literature. Adv Ther. 2012;29(11):947–57.

    Article  CAS  PubMed  Google Scholar 

  8. Johnson BA, Ait-Daoud N. Topiramate in the new generation of drugs: efficacy in the treatment of alcoholic patients. Curr Pharm Des. 2010;16(19):2103–12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. 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.

    Article  CAS  PubMed  Google Scholar 

  10. Olmsted CL, Kockler DR. Topiramate for alcohol dependence. Ann Pharmacother. 2008;42(10):1475–80.

    Article  CAS  PubMed  Google Scholar 

  11. De Sousa A. The role of topiramate and other anticonvulsants in the treatment of alcohol dependence: a clinical review. CNS Neurol Disord Drug Targets. 2010;9(1):45–9.

    Article  PubMed  Google Scholar 

  12. Johnson BA. Uses of topiramate in the treatment of alcohol dependence. Expert Rev Neurother. 2004;4(5):751–8.

    Article  CAS  PubMed  Google Scholar 

  13. Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia. 2000;41(Suppl 1):S3–9.

    Article  CAS  PubMed  Google Scholar 

  14. Kawasaki H, Tancredi V, D’Arcangelo G, Avoli M. Multiple actions of the novel anticonvulsant drug topiramate in the rat subiculum in vitro. Brain Res. 1998;807(1–2):125–34.

    Article  CAS  PubMed  Google Scholar 

  15. White HS, Brown SD, Woodhead JH, Skeen GA, Wolf HH. Topiramate modulates GABA-evoked currents in murine cortical neurons by a nonbenzodiazepine mechanism. Epilepsia. 2000;41(Suppl 1):S17–20.

    Article  CAS  PubMed  Google Scholar 

  16. Angehagen M, Ronnback L, Hansson E, Ben-Menachem E. Topiramate reduces AMPA-induced Ca(2+) transients and inhibits GluR1 subunit phosphorylation in astrocytes from primary cultures. J Neurochem. 2005;94(4):1124–30.

    Article  PubMed  Google Scholar 

  17. Zhang X, Velumian AA, Jones OT, Carlen PL. Modulation of high-voltage-activated calcium channels in dentate granule cells by topiramate. Epilepsia. 2000;41(Suppl 1):S52–60.

    Article  CAS  PubMed  Google Scholar 

  18. Dodgson SJ, Shank RP, Maryanoff BE. Topiramate as an inhibitor of carbonic anhydrase isoenzymes. Epilepsia. 2000;41(Suppl 1):S35–9.

    Article  CAS  PubMed  Google Scholar 

  19. Herrero AI, Del Olmo N, Gonzalez-Escalada JR, Solis JM. Two new actions of topiramate: inhibition of depolarizing GABA(A)-mediated responses and activation of a potassium conductance. Neuropharmacology. 2002;42(2):210–20.

    Article  CAS  PubMed  Google Scholar 

  20. Wauquier A, Zhou S. Topiramate: a potent anticonvulsant in the amygdala-kindled rat. Epilepsy Res. 1996;24(2):73–7.

    Article  CAS  PubMed  Google Scholar 

  21. McElroy SL, Arnold LM, Shapira NA, Keck PE Jr, Rosenthal NR, Karim MR, et al. Topiramate in the treatment of binge eating disorder associated with obesity: a randomized, placebo-controlled trial. Am J Psychiatry. 2003;160(2):255–61.

    Article  PubMed  Google Scholar 

  22. Rho JM, Sankar R. The pharmacologic basis of antiepileptic drug action. Epilepsia. 1999;40(11):1471–83.

    Article  CAS  PubMed  Google Scholar 

  23. Schiffer WK, Gerasimov MR, Marsteller DA, Geiger J, Barnett C, Alexoff DL, et al. Topiramate selectively attenuates nicotine-induced increases in monoamine release. Synapse. 2001;42(3):196–8.

    Article  CAS  PubMed  Google Scholar 

  24. Garnett WR. Clinical pharmacology of topiramate: a review. Epilepsia. 2000;41(Suppl 1):S61–5.

    Article  CAS  PubMed  Google Scholar 

  25. Mula M. Anticonvulsants–antidepressants pharmacokinetic drug interactions: the role of the CYP450 system in psychopharmacology. Curr Drug Metab. 2008;9(8):730–7.

    Article  CAS  PubMed  Google Scholar 

  26. Johnson BA, Ait-Daoud N, Akhtar FZ, Ma JZ. Oral topiramate reduces the consequences of drinking and improves the quality of life of alcohol-dependent individuals: a randomized controlled trial. Arch Gen Psychiatry. 2004;61(9):905–12.

    Article  CAS  PubMed  Google Scholar 

  27. Ma JZ, Ait-Daoud N, Johnson BA. Topiramate reduces the harm of excessive drinking: implications for public health and primary care. Addiction. 2006;101(11):1561–8.

    Article  PubMed  Google Scholar 

  28. Johnson BA, Rosenthal N, Capece JA, Wiegand F, Mao L, Beyers K, et al. Topiramate for treating alcohol dependence: a randomized controlled trial. JAMA. 2007;298(14):1641–51.

    Article  CAS  PubMed  Google Scholar 

  29. Johnson BA, Rosenthal N, Capece JA, Wiegand F, Mao L, Beyers K, et al. Improvement of physical health and quality of life of alcohol-dependent individuals with topiramate treatment: US multisite randomized controlled trial. Arch Intern Med. 2008;168(11):1188–99.

    Article  CAS  PubMed  Google Scholar 

  30. Rubio G, Ponce G, Jimenez-Arriero MA, Palomo T, Manzanares J, Ferre F. Effects of topiramate in the treatment of alcohol dependence. Pharmacopsychiatry. 2004;37(1):37–40.

    Article  CAS  PubMed  Google Scholar 

  31. Rubio G, Martinez-Gras I, Manzanares J. Modulation of impulsivity by topiramate: implications for the treatment of alcohol dependence. J Clin Psychopharmacol. 2009;29(6):584–9.

    Article  CAS  PubMed  Google Scholar 

  32. Huguelet P, Morand-Collomb S. Effect of topiramate augmentation on two patients suffering from schizophrenia or bipolar disorder with comorbid alcohol abuse. Pharmacol Res. 2005;52(5):392–4.

    Article  CAS  PubMed  Google Scholar 

  33. Chiu YH, Lee TH, Shen WW. Use of low-dose topiramate in substance use disorder and bodyweight control. Psychiatry Clin Neurosci. 2007;61(6):630–3.

    Article  CAS  PubMed  Google Scholar 

  34. Fernandez Miranda JJ, Marina Gonzalez PA, Montes Perez M, Diaz Gonzalez T, Gutierrez Cienfuegos E, Antuna Diaz MJ, et al. Topiramate as add-on therapy in non-respondent alcohol dependant patients: a 12 month follow-up study. Actas Esp Psiquiatr. 2007;35(4):236–42.

    CAS  PubMed  Google Scholar 

  35. Likhitsathian S, Uttawichai K, Booncharoen H, Wittayanookulluk A, Angkurawaranon C, Srisurapanont M. Topiramate treatment for alcoholic outpatients recently receiving residential treatment programs: a 12-week, randomized, placebo-controlled trial. Drug Alcohol Depend. 2013;133(2):440–6.

    Article  CAS  PubMed  Google Scholar 

  36. Kampman KM, Pettinati HM, Lynch KG, Spratt K, Wierzbicki MR, O’Brien CP. A double-blind, placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence. Drug Alcohol Depend. 2013;133(1):94–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. De Sousa AA, De Sousa J, Kapoor H. An open randomized trial comparing disulfiram and topiramate in the treatment of alcohol dependence. J Subst Abuse Treat. 2008;34(4):460–3.

    Article  PubMed  Google Scholar 

  38. Florez G, Garcia-Portilla P, Alvarez S, Saiz PA, Nogueiras L, Bobes J. Using topiramate or naltrexone for the treatment of alcohol-dependent patients. Alcohol Clin Exp Res. 2008;32(7):1251–9.

    Article  CAS  PubMed  Google Scholar 

  39. Baltieri DA, Daro FR, Ribeiro PL, de Andrade AG. Comparing topiramate with naltrexone in the treatment of alcohol dependence. Addiction. 2008;103(12):2035–44.

    Article  PubMed  Google Scholar 

  40. Florez G, Saiz PA, Garcia-Portilla P, Alvarez S, Nogueiras L, Bobes J. Topiramate for the treatment of alcohol dependence: comparison with naltrexone. Eur Addict Res. 2011;17(1):29–36.

    Article  PubMed  Google Scholar 

  41. Arbaizar B, Diersen-Sotos T, Gomez-Acebo I, Llorca J. Topiramate in the treatment of alcohol dependence: a meta-analysis. Actas Esp Psiquiatr. 2010;38(1):8–12.

    CAS  PubMed  Google Scholar 

  42. Blodgett JC, Del Re AC, Maisel NC, Finney JW. A meta-analysis of topiramate’s effects for individuals with alcohol use disorders. Alcohol Clin Exp Res. 2014;38(6):1481–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Maisel NC, Blodgett JC, Wilbourne PL, Humphreys K, Finney JW. Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful? Addiction. 2013;108(2):275–93.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Paparrigopoulos T, Tzavellas E, Karaiskos D, Kourlaba G, Liappas I. Treatment of alcohol dependence with low-dose topiramate: an open-label controlled study. BMC Psychiatry. 2011;11:41.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Martinotti G, Di Nicola M, De Vita O, Hatzigiakoumis DS, Guglielmo R, Santucci B, et al. Low-dose topiramate in alcohol dependence: a single-blind, placebo-controlled study. J Clin Psychopharmacol. 2014;34(6):709–15.

    Article  CAS  PubMed  Google Scholar 

  46. Miranda R Jr, MacKillop J, Monti PM, Rohsenow DJ, Tidey J, Gwaltney C, et al. Effects of topiramate on urge to drink and the subjective effects of alcohol: a preliminary laboratory study. Alcohol Clin Exp Res. 2008;32(3):489–97.

    Article  CAS  PubMed  Google Scholar 

  47. Kranzler HR, Covault J, Feinn R, Armeli S, Tennen H, Arias AJ, et al. Topiramate treatment for heavy drinkers: moderation by a GRIK1 polymorphism. Am J Psychiatry. 2014;171(4):445–52.

    Article  PubMed Central  PubMed  Google Scholar 

  48. Ray LA, Miranda R Jr, MacKillop J, McGeary J, Tidey JW, Rohsenow DJ, et al. A preliminary pharmacogenetic investigation of adverse events from topiramate in heavy drinkers. Exp Clin Psychopharmacol. 2009;17(2):122–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Rustembegovic A, Sofic E, Kroyer G. A pilot study of Topiramate (Topamax) in the treatment of tonic–clonic seizures of alcohol withdrawal syndromes. Med Arh. 2002;56(4):211–2.

    PubMed  Google Scholar 

  50. Krupitsky EM, Rudenko AA, Burakov AM, Slavina TY, Grinenko AA, Pittman B, et al. Antiglutamatergic strategies for ethanol detoxification: comparison with placebo and diazepam. Alcohol Clin Exp Res. 2007;31(4):604–11.

    CAS  PubMed  Google Scholar 

  51. Littleton J. Neurochemical mechanisms underlying alcohol withdrawal. Alcohol Health Res World. 1998;22(1):13–24.

    CAS  PubMed  Google Scholar 

  52. Prado-Lima PA. Pharmacological treatment of impulsivity and aggressive behaviour [in Portuguese]. Rev Bras Psiquiatr. 2009;31(Suppl 2):S58–65.

    PubMed  Google Scholar 

  53. Leung KS, Cottler LB. Treatment of pathological gambling. Curr Opin Psychiatry. 2009;22(1):69–74.

    Article  PubMed  Google Scholar 

  54. McElroy SL, Guerdjikova AI, Martens B, Keck PE Jr, Pope HG, Hudson JI. Role of antiepileptic drugs in the management of eating disorders. CNS Drugs. 2009;23(2):139–56.

    Article  CAS  PubMed  Google Scholar 

  55. Berlin HA, Koran LM, Jenike MA, Shapira NA, Chaplin W, Pallanti S, et al. Double-blind, placebo-controlled trial of topiramate augmentation in treatment-resistant obsessive–compulsive disorder. J Clin Psychiatry. 2011;72(5):716–21.

    Article  CAS  PubMed  Google Scholar 

  56. Cloninger CR, Svrakic DM, Przybeck TR. A psychobiological model of temperament and character. Arch Gen Psychiatry. 1993;50(12):975–90.

    Article  CAS  PubMed  Google Scholar 

  57. Bandelow B, Zohar J, Hollander E, Kasper S, Moller HJ, Allgulander C, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive–compulsive and post-traumatic stress disorders—first revision. World J Biol Psychiatry. 2008;9(4):248–312.

    Article  PubMed  Google Scholar 

  58. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, DSM-IV. 4th ed. Washington, DC: American Psychiatric Association; 1994.

    Google Scholar 

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Acknowledgments

The authors thank Rita Santacroce for language revision.

Conflict of interest

Drs. R. G., G. M., M. Q., L. I., I. K., M. D. N. and L. J., report no proprietary or commercial interest in any product mentioned or concept discussed in this article. In addition, we state that no funding was used to assist with the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Geriatrics, Neuroscience and Orthopedics, Institute of Psychiatry, Catholic University Medical School of Rome, Rome, Italy

    Riccardo Guglielmo, Marianna Quatrale, Lucia Ioime, Irket Kadilli, Marco Di Nicola & Luigi Janiri

  2. Department of Neuroscience and Imaging, University “G. D’Annunzio”, Chieti, Italy

    Giovanni Martinotti

  3. Department of Human Science, Lumsa University of Rome, Rome, Italy

    Lucia Ioime

  4. Via Padre Pio, 16, 81042, Calvi Risorta, Italy

    Riccardo Guglielmo

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  1. Riccardo Guglielmo
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Correspondence to Riccardo Guglielmo.

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Guglielmo, R., Martinotti, G., Quatrale, M. et al. Topiramate in Alcohol Use Disorders: Review and Update. CNS Drugs 29, 383–395 (2015). https://doi.org/10.1007/s40263-015-0244-0

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