Download PDF
Pharmacopsychiatry 2009; 42(5): 175-181
DOI: 10.1055/s-0029-1202264
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

Oxcarbazepine in Combination with Tiaprid in Inpatient Alcohol-withdrawal – a RCT

B. Croissant1 , S. Loeber2 , A. Diehl2 , H. Nakovics2 , F. Wagner3 , F. Kiefer2 , K. Mann2
  • 1Department of Psychiatry, Psychotherapy and Psychosomatics, Teaching Hospital Sigmaringen, University of Tuebingen, Germany
  • 2Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Mannheim, University of Heidelberg, Germany
  • 3Internal Medicine, Diakoniekrankenhaus Mannheim GmbH, Teaching Hospital University of Heidelberg, Germany
Further Information

Publication History

received 09.07.2008 revised 09.12.2008

accepted 17.12.2008

Publication Date:
01 September 2009 (online)

Also available at
    Permissions and Reprints

Abstract

Introduction: Oxcarbazepine (OXC), a derivative of Carbamazepine (CBZ), may represent a solution to metabolic and side effects of CBZ treatment due to the fact that renal excretion is its major route of elimination. The goal of the study is to compare the efficacy and tolerability of OXC/Tiaprid (TIA) combination therapy to the well established Clomethiazole (CLO) therapy in an inpatient setting.

Methods: To investigate the efficacy of OXC/TIA in terms of lower alcohol withdrawal symptoms and better tolerability, 56 alcohol-dependent patients participated in a randomized open-label trial, where OXC/TIA and CLO treatments were compared.

Results: Following admission, we observed that severity of alcohol withdrawal syndrome was comparable between OXC/TIA and CLO-patients. Overall tolerability was good. However, significantly more patients in the OXC/TIA-group (48.1%) displayed no AE compared to the CLO-group (24.1%). We found no significant differences between groups regarding total number of recorded adverse events (AEs).

Discussion: OXC/TIA inpatient therapy proved to be as effective and participants demonstrated the same tolerance as with CLO. In medication-based alcohol withdrawal, OXC/TIA could have the potential to become a promising alternative for alcohol dependent patients unable to undergo inpatient withdrawal therapy with CLO. Our findings further indicate that it could be worthwhile testing OXC/TIA in alcohol withdrawal in daily care units and outpatient settings. This is an important question for national health care services, since outpatient therapy is more and more asked for as alternative to inpatient settings.

References

  • 1 Anton RF, Drobes DJ, Voronin K. et al . Naltrexone effects on alcohol consumption in a clinical laboratory paradigm: temporal effects of drinking.  Psychopharmacology. 2004;  173 ((1–2)) 32-40
    CrossrefPubMedGoogle Scholar
  • 2 Babor TF, Higgins-Biddle JC, Saunders JB, Monteiro MG. AUDIT The Alcohol Use Disorders Identification Test: Guidelines for Use in Primary Care. Second Edition, WHO/MSD/MSB/01.6a 2001
    PubMed
  • 3 Beydoun A, Kutluay E. Oxcarbazepine.  Expert Opin Pharmacother. 2002;  3 59-71
    CrossrefPubMedGoogle Scholar
  • 4 Bock J. Determination of group sizes for biological experiments and controlled clinical trials [Bestimmung des Stichprobenumfangs für biologische Experimente und kontrollierte klinische Studien]. Oldenbourg, München 1998
    PubMed
  • 5 Book SW, Myrick H. Novel anticonvulsants in the treatment of alcoholism.  Expert Opin Investig Drugs. 2005;  14 371-376
    CrossrefPubMedGoogle Scholar
  • 6 Cazzato G, Gioseffi M, Torre P. et al . Prevention and therapy of delirium tremens with tiapride.  Riv Neurol. 1982;  52 379-391
    PubMedGoogle Scholar
  • 7 Croissant B, Grosshans M, Klein O. et al . Scheme-based benzodiazepine detoxification with oxcarbazepine.  Pharmacopsychiatry. 2005;  38 222-223
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Croissant B, Scherle T, Diehl A. et al . Oxcarbazepine in alcohol relapse prevention – A case series.  Pharmacopsychiatry. 2004;  37 306-307
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Croissant B, Diehl A, Klein O. et al . A pilot study of oxcarbazepine versus acamprosate in alcohol-dependent patients.  Alcohol Clin Exp Res. 2006;  30 630-635
    CrossrefPubMedGoogle Scholar
  • 10 Finzen A. Medikamentenbehandlung bei psychischen Störungen. [Medication treatment of mental disorders]. Bonn: Psychiatrie-Verlag 1984
    PubMed
  • 11 Franz M, Dlabal H, Kunz S. et al . Treatment of alcohol withdrawal: tiapride and carbamazepine versus clomethiazol.  Eur Arch Psychiatry Clin Neurosci. 2001;  251 185-192
    CrossrefPubMedGoogle Scholar
  • 12 Furlanut M, Franceschi L, Poz D. et al . Acute oxcarbazepine, benazepril, and hydrochlorothiazide overdose with alcohol.  Ther Drug Monit. 2006;  28 267-268
    CrossrefPubMedGoogle Scholar
  • 13 Glauser TA. Oxcarbazepine in the treatment of epilepsy.  Pharmacotherapy. 2001;  21 904-919
    CrossrefPubMedGoogle Scholar
  • 14 Gonzalez L, Veatch L, Ticku M. et al . Alcohol withdrawal kindling: mechanisms and implications for treatment.  Alcohol Clin Exp Res. 2001;  25 197-201
    PubMedGoogle Scholar
  • 15 Hermann D, Klages E, Croissant B. Oxcarbazepine in outpatient benzodiazepine withdrawal in polytoxicomanic patients during an opiate maintenance therapy.  Psychopharmakotherap. 2005;  12 97-99
    PubMedGoogle Scholar
  • 16 Hillemacher T, Weinland C, Heberlein A. et al . Treatment with clomethiazole is associated with lower rates of premature discharge during alcohol withdrawal.  Pharmacopsychiat. 2008;  41 134-137
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Homberg V, Kowalik A, Schulze-Bonhage A. Ad hoc change from carbamazepine to oxcarbazepine – effectiveness and tolerance.  A retrospective analysis. Nervenarzt. 2001;  72 918-923
    CrossrefPubMedGoogle Scholar
  • 18 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
  • 19 Kosten TR, O’Connor PG. Management of drug and alcohol withdrawal.  N Engl J Med. 2003;  348 1786-1795
    CrossrefPubMedGoogle Scholar
  • 20 Littleton JM, De Witte P, Litten R. et al . Challenges to medications development in treating alcohol dependence: an international perspective.  Alcohol Alcohol. 2004;  39 ((4)) 271-275
    PubMedGoogle Scholar
  • 21 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 Alcohol. 2003;  38 168-175
    PubMedGoogle Scholar
  • 22 Lu BY, Coberly R, Bogenschutz M. Use of oxcarbazepine in outpatient alcohol detoxification.  Am J Addict. 2005;  14 191-192
    CrossrefPubMedGoogle Scholar
  • 23 Majumdar SK. Chlormethiazole: current status in the treatment of the acute ethanol withdrawal syndrome.  Drug Alcohol Depend. 1991;  27 201-207
    CrossrefPubMedGoogle Scholar
  • 24 Malcolm R, Lucht M, Kuehn KU. et al . Double-blind controlled trial comparing carbamazepine to oxazepam treatment of alcohol withdrawal.  Am J Psychiatry. 1989;  146 617-621
    PubMedGoogle Scholar
  • 25 Malcolm R, Myrick H, Brady KT. et al . Update on anticonvulsants for the treatment of alcohol withdrawal.  Am J Addict. 2001;  10 16-23
    PubMedGoogle Scholar
  • 26 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
  • 27 Mann K, Croissant B. Konzepte der Alkoholismustherapie [Concepts of Alcoholism Therapy]. In: Singer MV, Theyssen S, Herausgeber Alkohol und Alkoholfolgekrankheiten. Grundlagen – Diagnostik – Therapie [Alcohol and Alcohol Sequelae. Principles – Diagnostics – Therapy]. Berlin, Heidelberg, New York: Springer 2005: 509-518
    PubMedGoogle Scholar
  • 28 Martinotti G, Nicola M Di, Romanelli R. et al . High and low dosage oxcarbazepine versus naltrexone for the prevention of relapse in alcohol-dependent patients.  Hum Psychopharmacol. 2007;  22 149-156
    CrossrefPubMedGoogle Scholar
  • 29 Martinotti G, Romanelli R, Nicola M Di. et al . Oxcarbazepine at high dosages for the treatment of alcohol dependence.  Am J Addict. 2007;  16 247-248
    CrossrefPubMedGoogle Scholar
  • 30 Mayo-Smith MF. Pharmacological management of alcohol withdrawal.  A meta-analysis and evidence-based practice guideline. JAMA. 1997;  278 144-151
    Google Scholar
  • 31 Murphy DJ, Shaw GK, Clarke I. Tiaprid and Chlormethiazole in alcohol withdrawal: a double-blind trail.  Alcohol Alcohol. 1983;  18 227-237
    PubMedGoogle Scholar
  • 32 Peters DH, Faulds D. Tiapride. A review of its pharmacology and therapeutic potential in the management of alcohol dependence syndrome.  Drugs. 1994;  47 1010-1032
    CrossrefPubMedGoogle Scholar
  • 33 Ponce G, Rodriguez-Jimenez R, Ortiz H. et al . Oxcarbazepine in the prevention of epileptic syndromes in alcohol detoxification.  Rev Neurol. 2005;  40 577-580
    PubMedGoogle Scholar
  • 34 Ritola E, Malinen L. A double-blind comparison of carbamazepine and clomethiazole in the treatment of alcohol withdrawal syndrome.  Acta Psychiatr Scand. 1981;  64 254-259
    CrossrefPubMedGoogle Scholar
  • 35 Schaffer A, Naranjo CA. Recommended drug treatment strategies for the alcoholic patient.  Drugs. 1998;  56 571-585
    CrossrefPubMedGoogle Scholar
  • 36 Schik G, Wedegaertner FR, Liersch J. et al . Oxcarbazepine versus carbamazepine in the treatment of alcohol withdrawal.  Addict Biol. 2005;  10 283-288
    CrossrefPubMedGoogle Scholar
  • 37 Schmidt D, Elger CE. What is the evidence that oxcarbazepine and carbamazepine are distinctly different antiepileptic drugs?.  Epilepsy Behav. 2004;  5 627-635
    CrossrefPubMedGoogle Scholar
  • 38 Seifert J, Peters E, Jahn K. et al . Treatment of alcohol withdrawal: chlormethiazole vs. carbamazepine and the effect on memory performance-a pilot study.  Addict Biol. 2004;  9 43-51
    CrossrefPubMedGoogle Scholar
  • 39 Shaw JM, Kolesar GS, Sellers EM. et al . Development of optimal treatment tactics for alcohol withdrawal. I. Assessment and effectiveness of supportive care.  J Clin Psychopharmacol. 1981;  1 382-387
    CrossrefPubMedGoogle Scholar
  • 40 Soyka M, Morhart-Klute V, Horak M. A combination of carbamazepine/tiapride in outpatient alcohol detoxification. Results from an open clinical study.  Eur Arch Psychiatry Clin Neurosci. 2002;  252 197-200
    CrossrefPubMedGoogle Scholar
  • 41 Soyka M, Schmidt F, Schmidt P. Efficacy and safety of outpatient alcohol detoxification with a combination of tiapride/carbamazepine: additional evidence.  Pharmacopsychiatry. 2006;  39 30-34
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Soyka M, Täschner B, Clausius N. Neuroleptic treatment of alcohol hallucinosis: case series.  Pharmacopsychiatry. 2007;  40 291-292
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 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
  • 44 Thome J, Wiesbeck GA, Vince GH. Carbamazepine in treatment of alcohol withdrawal syndrome – an overview of current research.  Fortschr Neurol Psychiatr. 1994;  62 125-133
    Article in Thieme ConnectPubMedGoogle Scholar
  • 45 Wellington K, Goa KL. Oxcarbazepine: an update of its efficacy in the management of epilepsy.  CNS Drugs. 2001;  15 137-163
    CrossrefPubMedGoogle Scholar
  • 46 Wetterling T, Veltrup C. Diagnostik und Therapie von Alkoholproblemen. Berlin: Springer Verlag 1997
    PubMed
  • 47 Wetterling T, Weber B, Depfenhart M. et al . Development of a rating scale to predict the severity of withdrawal syndrome.  Alcohol Alcohol. 2006;  41 611-615
    PubMedGoogle Scholar

1 Work was conducted at Department of Internal Medicine, Diakoniekrankenhaus Mannheim GmbH, Teaching Hospital University of Heidelberg, Germany.

Correspondence

Prof. K. MannMD 

Department of Addictive Behavior and Addiction Medicine

Central Institute of Mental Health

University of Heidelberg

J 5, 68159 Mannheim

Germany

Phone: +49/621/1703 35 02

Fax: +49/621/1703 35 05

Email: sucht@zi-mannheim.de

      >