Download PDF
Pharmacopsychiatry 2010; 43(7): 257-262
DOI: 10.1055/s-0030-1263168
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

Zonisamide versus Diazepam in the Treatment of Alcohol Withdrawal Syndrome

G. Rubio1 , F. López-Muñoz2 , G. Ponce1 , J. M. Pascual3 , I. Martínez-Gras1 , F. Ferre3 , M. Á. Jiménez-Arriero1 , C. Alamo2
  • 1Department of Psychiatry, “Doce de Octubre” University Hospital, Complutense University, Madrid, Spain
  • 2Pharmacology Department, Faculty of Medicine, University of Alcalá, Madrid, Spain
  • 3Department of Psychiatry, “Gregorio Marañón” University Hospital, Complutense University, Madrid, Spain
Further Information

Publication History

received 31.03.2010 revised 12.07.2010

accepted 23.07.2010

Publication Date:
06 October 2010 (online)

Also available at
    Permissions and Reprints

Abstract

Introduction: Anticonvulsant drugs have been used in the treatment of alcohol detoxification. The purpose of the present study was to evaluate the efficacy and safety of zonisamide in a sample of patients presenting alcohol withdrawal syndrome.

Method: In this 3-week, randomized, flexible-dose trial, 40 inpatients with alcohol dependence disorder received zonisamide or diazepam for detoxification. Zonisamide was started at a dose of 400–600 mg/day (week 1), tapering to a minimum dose of 100–300 mg/day (week 3). Diazepam was administered using a similar regimen (from 130–50 mg/day tapering to 5–15 mg/day). Subjects were treated initially (weeks 1 and 2) in an inpatient unit and for the final week in an outpatient facility. During the inpatient period, the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) was used to assess the efficacy of each substance. During the outpatient period the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, and a craving scale were used.

Results: All subjects completed the study. During the inpatient period both drugs reduced alcohol withdrawal symptoms, but the decrease was more marked in the zonisamide group. At the end of the study (week 3) participants treated with zonisamide showed lower CIWA-Ar scores than subjects receiving diazepam. Also, individuals in the zonisamide group had less craving for alcohol, less anxiety, and less daytime sedation compared with participants treated with diazepam.

Conclusion: Zonisamide can be a valuable alternative to benzodiazepines in the prevention of alcohol withdrawal syndrome.

References

  • 1 American Psychiatric Association .Diagnostic and Statistical Manual of Mental Disorders. 4th edn. Text Rev. Washington, DC: American Psychiatric Association; 2000
    Google Scholar
  • 2 Victor M. The effects of alcohol on the nervous system. In: Mendelson JH, Mello NK editors Medical diagnosis and treatment of alcoholism. New Cork: McGraw-Hill; 1992: 201-261
    Google Scholar
  • 3 Salloum IM, Cornelius JR, Daley DC. et al . The utility of diazepam loading in the treatment of alcohol withdrawal among psychiatric inpatients.  Psychopharmacol Bull. 1995;  31 305-310
    PubMedGoogle Scholar
  • 4 Williams D, McBride AJ. The drug treatment of alcohol withdrawal symptoms: a systematic review.  Alcohol Alcoholism. 1998;  33 103-115
    PubMedGoogle Scholar
  • 5 Myrick H, Malcolm R, Randall PK. et al . A double-blind trial of gabapentin versus lorazepam in the treatment of alcohol withdrawal.  Alcoholism Clin Exp Res. 2009;  33 1582-1588
    CrossrefPubMedGoogle Scholar
  • 6 O’Brien JE, Meyer RE, Thoms DC. Double-blind comparison of lorazepam and diazepam in the treatment of the acute alcohol abstinence syndrome.  Current Therapy Research. 1983;  34 825-829
    PubMedGoogle Scholar
  • 7 Miller WC, McCurdy L. A double-blind comparison of the efficacy and safety of lorazepam and diazepam in the treatment of acute alcohol withdrawal syndrome.  Clinical Therapy. 1984;  6 364-370
    PubMedGoogle Scholar
  • 8 Mayo-Smith MF, Bernard D. Late-onset seizures in alcohol withdrawal.  Alcohol Clin Exp Res. 1995;  19 656-659
    CrossrefPubMedGoogle Scholar
  • 9 Lucht M, Kuehn KU, Armbruster J. et al . Alcohol withdrawal treatment in intoxicated vs non-intoxicated patients: A controlled open-label study with tiapride/carbamazepine, clomethiazole and diazepam.  Alcohol Alcoholism. 2003;  38 168-175
    CrossrefPubMedGoogle Scholar
  • 10 Malcolm R, Myrick H, Brady KT. et al . Update on anticonvulsants for the treatment of alcohol withdrawal.  Am J Addict. 2001;  10 (Suppl. 1) 16-23
    PubMedGoogle Scholar
  • 11 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
    CrossrefPubMedGoogle Scholar
  • 12 Agricola R, Mazzarino M, Urani R. et al . Treatment of acute alcohol withdrawal syndrome with carbamazepine: a double-blind comparison with tiapride.  J Int Med Res. 1982;  10 160-165
    PubMedGoogle Scholar
  • 13 Stuppaeck CH, Pycha R, Miller C. et al . Carbamazepine versus oxazepam in the treatment of alcohol withdrawal: a double-blind study.  Alcohol Alcoholism. 1992;  27 153-158
    PubMedGoogle Scholar
  • 14 Malcolm R, Myrick H, Roberts J. et al . The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial.  J Gen Intern Med. 2002;  17 349-355
    CrossrefPubMedGoogle Scholar
  • 15 Seifert J, Peters E, Jahn K. et al . Treatment of alcohol withdrawal: chlormethiazole versus carbamazepine and the effect on memory performance a pilot study.  Addict Biol. 2004;  9 43-51
    CrossrefPubMedGoogle Scholar
  • 16 Myrick H, Brady KT, Malcolm R. Divalproex in the treatment of alcohol withdrawal.  Am J Drug Alcohol Abuse. 2000;  26 155-160
    CrossrefPubMedGoogle Scholar
  • 17 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
    CrossrefPubMedGoogle Scholar
  • 18 Bonnet U, Banger M, Leweke FM. et al . Treatment of acute alcohol withdrawal with gabapentin: results from a controlled 2-center trial.  J Clin Psychopharmacol. 2003;  23 514-519
    CrossrefPubMedGoogle Scholar
  • 19 Ponce G, Rodríguez-Jiménez R, Ortiz H. et al . Oxcarbazepina para la prevención de patología epiléptica en la desintoxicación alcohólica.  Rev Neurol. 2005;  40 577-580
    PubMedGoogle Scholar
  • 20 Koethe D, Juelicher A, Nolden BM. et al . Oxcarbazepine-efficacy and tolerability during treatment of alcohol withdrawal: a double-blind, randomized, placebo-controlled multicenter pilot study.  Alcohol Clin Exp Res. 2007;  31 1188-1194
    CrossrefPubMedGoogle Scholar
  • 21 Baulac M. Introduction to zonisamide.  Epilepsy Res. 2006;  68 (Suppl. 2) S3-S9
    CrossrefPubMedGoogle Scholar
  • 22 Frampton JE, Scott LJ. Zonisamide. A review of its use in the management of partial seizures in epilepsy.  CNS Drugs. 2005;  19 347-367
    CrossrefPubMedGoogle Scholar
  • 23 Kothare SV, Kaleyias J. Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety.  Expert Opin Drug Metab Toxicol. 2008;  4 493-506
    CrossrefPubMedGoogle Scholar
  • 24 McElroy SL, Guerdjikova AI, Martens B. et al . Role of antiepileptic drugs in the management of eating disorders.  CNS Drugs. 2009;  23 139-156
    CrossrefPubMedGoogle Scholar
  • 25 Sarid-Segal O, Knapp CM, Burch W. et al . The anticonvulsant zonisamide reduces ethanol self-administration by risky drinkers.  Am J Drug Alcohol Abuse. 2009;  35 316-319
    CrossrefPubMedGoogle Scholar
  • 26 Knapp CM, Sarid-Segal O, Richardson MA. et al . Open label trial of the tolerability and efficacy of Zonisamide in the treatment of alcohol dependence.  Am J Drug Alcohol Abuse. 2010;  36 102-105
    CrossrefPubMedGoogle Scholar
  • 27 Arias A, Reinn R, Oncken C. et al . Placebo-controlled trial of Zonisamide for the treatment of alcohol dependence.  J Clin Psychopharmacol. 2010;  30 318-322
    CrossrefPubMedGoogle Scholar
  • 28 First MB, Spitzer RL, Gibbon M. et al .Structures Clinical Interview for DSM-IV Axis I disorders (SCID-I) (clinical version). Washington, DC: American Psychiatric Publishing Inc.; 1997
    Google Scholar
  • 29 Sullivan JT, Sykora K, Schneiderman J. et al . Assessment of alcohol withdrawal: the revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-AR).  Br J Addict. 1989;  84 1353-1357
    CrossrefPubMedGoogle Scholar
  • 30 Rubio G, Urosa B, Santo-Domingo J. Validación de la escala de la intensidad de la dependencia alcohólica (EIDA).  Psiquiatr Biol. 1998;  10 (Suppl. 1) 44-47
    PubMedGoogle Scholar
  • 31 Sobell LC, Sobell MB, Leo GI. et al . Reliability of a timeline method: assessing normal drinkers’ reports of recent drinking and a comparative evaluation across several populations.  Br J Addict. 1998;  83 393-402
    CrossrefPubMedGoogle Scholar
  • 32 Hamilton M. The assessment of anxiety states by rating.  Br J Med Psychol. 1959;  32 50-55
    CrossrefPubMedGoogle Scholar
  • 33 Hamilton M. Development of a rating scale for primary depressive illness.  Br J Soc Clin Psychol. 1967;  6 278-296
    CrossrefPubMedGoogle Scholar
  • 34 Miller WR. Form 90: A structured assessment interview for drinking and related behaviors test manual. In: Mattson ME, Marshall LA, editors NIAAA Project Match Monograph Series. Vol. 5. Rockville: National Institute on Alcoholism and Alcohol Abuse; 1996
    Google Scholar
  • 35 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
  • 36 Samson HH, Harris RA. Neurobiology of alcohol abuse.  TiPS. 1992;  13 206-211
    PubMedGoogle Scholar
  • 37 Ait-Daoud N, Malcolm RJ, Johnson BA. An overview of medications for the treatment of alcohol withdrawal and alcohol dependence with an emphasis on the use of older and newer anticonvulsants.  Addict Behav. 2006;  31 1628-1649
    CrossrefPubMedGoogle Scholar
  • 38 Rogawski MA, Löscher W. The neurobiology of antiepileptic drugs.  Nature Rev Neurosci. 2004;  5 553-564
    CrossrefPubMedGoogle Scholar
  • 39 Biton V. Clinical pharmacology and mechanism of action of zonisamide.  Clin Neuropharmacol. 2007;  30 230-240
    PubMedGoogle Scholar
  • 40 Johnson BA. Progress in the development of topiramate for treating alcohol dependence: from a hypothesis to a proof-of-concept study.  Alcohol Clin Exp Res. 2004;  28 1137-1144
    CrossrefPubMedGoogle Scholar
  • 41 Dodgson SJ, Shank RP, Maryanoff BE. Topiramate as an inhibitor of carbonic anhydrase isoenzymes.  Epilepsia. 2000;  41 (Suppl. 1) S35-S39
    PubMedGoogle Scholar
  • 42 Dessirier JM, Simons CT, Carstens MI. et al . Psychophysical and neurobiological evidence that the oral sensation elicited by carbonated water is of chemogenic origin.  Chem Senses. 2000;  25 277-284
    CrossrefPubMedGoogle Scholar
  • 43 Rubio G, Martínez-Gras I, Manzanares J. Modulation of impulsivity by topiramate: implications for the treatment of alcohol dependence.  J Clin Psychopharmacol. 2009;  29 584-589
    CrossrefPubMedGoogle Scholar

Correspondence

Dr. G. Rubio

Department of Psychiatry

“Doce de Octubre” University

Hospital

Avenida de Córdoba, s/n

28041-Madrid

Spain

Phone: +34-913 908022

Fax: +34-913 908538

Email: grubio.hdoc@ salud.madrid.org

      >