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Sodium Oxybate in the Treatment of Alcohol Withdrawal Syndrome: A Randomized Double-Blind Comparative Study versus Oxazepam. The GATE 1 Trial

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Abstract

Background

Benzodiazepines (BDZs) are the gold standard in the treatment of alcohol withdrawal syndrome (AWS). Sodium oxybate (SMO) has been tested as a treatment for AWS with encouraging results. The aim of this phase IV, multicenter, randomized, double-blind, double-dummy study was to evaluate the efficacy of SMO in comparison with oxazepam in the treatment of uncomplicated AWS.

Methods

Alcohol-dependent outpatients (n = 126) affected by uncomplicated AWS according to the Clinical Institute Withdrawal Assessment for Alcohol-revised (CIWA-Ar) scale were enrolled in the study and randomized in two groups: 61 patients received SMO and 65 patients received oxazepam for 10 days. The primary endpoint was the reduction of symptoms of AWS measured by the change in the total CIWA-Ar score from baseline (day 1) to the end of the study (day 10). This study is registered with ClinicalTrials.gov, number: NCT02090504

Results

A significant decrease of the mean total CIWA-Ar score from baseline to the end of the study was found in both the SMO (p < 0.0001) and the oxazepam group (p < 0.0001), with no significant differences between the two treatments (p = 0.21). Treatment with SMO and oxazepam resulted in a marked decrease in the severity of the mean CIWA subscales, i.e. sweating, tremor, and anxiety, with no significant differences between the two treatments. Both drugs were well tolerated and no severe side effects were reported.

Conclusion

SMO is as effective as oxazepam, one of the gold standard BDZs, in the treatment of uncomplicated AWS. Due to its tolerability and absence of significant side effects, SMO may be considered a valid alternative choice in the treatment of AWS.

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Acknowledgments

The authors thank Pierrel Research Italy SPA, particularly Barbara Pierotti for the statistical analysis.

Role of the funding source

This study was supported by CT Pharmaceutical Industries, Sanremo, Italy.

The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Conflict of interest

Fabio Caputo, MD, reports personal fees from D&A Pharma and personal fees from CT Pharmaceutical Industries, Sanremo, during the conduct of the study.

Otto Lesch, MD, reports personal fees from D&A Pharma during the conduct of the study.

Giovanni Addolorato, MD, reports personal fees from Ortho McNeil Janssen Scientific Affairs, LLC, personal fees from D&A Pharma and personal fees from CT Pharmaceutical Industries, during the conduct of the study.

Katrin Skala, MD, Antonio Mirijello, MD, Anna Ferrulli, MD, Henriette Walter, MD do not have any conflicts of interest to declare.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, SS Annunziata Hospital, Cento, Ferrara, Italy

    Fabio Caputo

  2. Department of Clinical Medicine, “G. Fontana” Centre for the Study and Multidisciplinary Treatment of Alcohol Addiction, University of Bologna, Bologna, Italy

    Fabio Caputo

  3. Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria

    Katrin Skala

  4. Alcohol Use Disorders Unit, Department of Internal Medicine, Gemelli Hospital, Catholic University of Rome, Largo Gemelli 8, 00168, Rome, Italy

    Antonio Mirijello, Anna Ferrulli & Giovanni Addolorato

  5. Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria

    Henriette Walter & Otto Lesch

Authors
  1. Fabio Caputo
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  2. Katrin Skala
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  3. Antonio Mirijello
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  4. Anna Ferrulli
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  5. Henriette Walter
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  6. Otto Lesch
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  7. Giovanni Addolorato
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Corresponding author

Correspondence to Giovanni Addolorato.

Additional information

On behalf of the GATE 1 Study Group.

The members of the GATE 1 Study Group are given in the Appendix.

F. Caputo and K. Skala contributed equally to the manuscript.

Appendix

Appendix

The GATE (Gamma Hydroxybutyric Acid in Alcohol-dependence Treatment Efficacy) Study Group

Italy: Alcohol Use Disorders Unit, Department of Internal Medicine, Catholic University of Rome (Vassallo G, Antonelli M, D’Angelo C); Servizio Alcologia, Dipartimento di Medicina Clinica, Università “La Sapienza”, Rome (Ceccanti M); ASS 2 “Isontina”, Dipartimento per le dipendenze, Gorizia, Italy (Spazzapan B); Ufficio Ricerche e Progetti Innovativi su Alcool, altre Dipendenze e Salute Mentale, Trieste, Italy (Poldrugo F); Ospedale di Fidenza (Parma), Italy (Pini LA); “G. Fontana” Centre for the Study and Multidisciplinary Treatment of Alcohol Addiction, Department of Clinical Medicine, University of Bologna (Domenicali M, Bernardi M); Department of Internal Medicine, “SS. Annunziata” Hospital, Cento, Ferrara (Zoli G); Department of Internal Medicine, Catholic University of Rome (Gasbarrini G). Poland: Oddzial terapii uzaleznien alkoholowych Szpital dla Nerwowo i Psychicznie Chorych im. Stanislawa Kryzana, Starogard Gdanski (Djurkowski M); Szpitial Specjalistyczny SP ZOZ Im. J. Babinskiego, Krakow (Filipecka E); Head Department of Prevention and Treatment of Addictions, Institute of Psychiatry and Neurology, Warsaw (Habrat B); Pomeranian Academy of Medicine Department of Psychiatry, Szczecin (Horodnicki J); Klinica Psychiatrii Doroslych II Katedra Choròb Ukladu Nerwowego, Uniwersytet Medyczny w Lodzi, Łódź, Poland (Florkowski A); Szpital Woljewódzki w Piotkowie Trybunalskim, Przychodnia Zdrowia Publicznego, Piotrków Trybunalski, Poland (Grejcz K); Miejski Ośrodek Profilaktyki i Terapii Uzależnień im. bł. R. Chylińskiego, Łódź, Poland (Zblowska H). Germany: Krankenhaus Reinickendorf OB Karl-Bonhoeffer Nervenklinik, Berlin (Platz W); Rheinische Klininiken Dusseldorf Kliniken der Heinrich Heine Universitat Bergische, Dusseldorf (Burtscheidt W); Klinik fur Psychiatrie und Psychoterapie Universitatsklinikum Eppendorf, Hamburg (Holzbach P).

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Caputo, F., Skala, K., Mirijello, A. et al. Sodium Oxybate in the Treatment of Alcohol Withdrawal Syndrome: A Randomized Double-Blind Comparative Study versus Oxazepam. The GATE 1 Trial. CNS Drugs 28, 743–752 (2014). https://doi.org/10.1007/s40263-014-0183-1

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