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Cited by 20Substance Abuse Treatment and OutcomesNeurotransmitter Receptor Influence on BehaviorOpioid Use Disorder Treatment

Treating alcohol dependence with an abuse and misuse deterrent formulation of sodium oxybate: Results of a randomised, double-blind, placebo-controlled study

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Guiraud, Julien, Addolorato, Giovanni, Aubin, Henri-Jean, Batel, Philippe, de Bejczy, Andrea, Caputo, Fabio, Goudriaan, Anna E., Gual, Antoni +9 more·2021·European Neuropsychopharmacology
DOI 10.1016/j.euroneuro.2021.06.003
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Abstract

Sodium oxybate (SMO) has been approved in Italy and Austria for the maintenance of abstinence in alcohol dependent (AD) patients. Although SMO is well tolerated in AD patients, cases of abuse and misuse have been reported outside the therapeutic setting. Here we report on a phase IIb double-blind, randomized, placebo-controlled trial for the maintenance of abstinence in AD patients with a new abuse and misuse deterrent formulation of SMO. A total of 509 AD patients were randomized to 12 weeks of placebo or one of four SMO doses (0.75, 1.25, 1.75 or 2.25 g t.i.d.) followed by a one-week medication-free period. The primary endpoint was the percentage of days abstinent (PDA) at end of treatment. An unexpectedly high placebo response (mean 73%, median 92%) was observed. This probably compromised the demonstration of efficacy in the PDA, but several secondary endpoints showed statistically significant improvements. A post-hoc subgroup analysis based on baseline severity showed no improvements in the mild group, but statistically significant improvements in the severe group: PDA: mean difference +15%, Cohen's d = 0.42; abstinence: risk difference +18%, risk ratio = 2.22. No safety concerns were reported. Although the primary endpoint was not significant in the overall population, several secondary endpoints were significant in the intent-to-treat population and post-hoc results showed that treatment with SMO was associated with a significant improvement in severe AD patients which is consistent with previous findings. New trials are warranted that take baseline severity into consideration.

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  • In an RCT involving 509 patients with AUD, a new formulation of GHB was assessed for abstinence maintenance; the primary endpoint and percentage of days abstinent did not differ between groups, but significant improvements were observed in several secondary measures, with post-hoc analysis showing increased abstinence in severe AUD patients and no safety concerns.

    “In an RCT involving 509 patients with AUD, a new formulation of GHB was assessed for abstinence maintenance. The primary endpoint and the percentage of days abstinent did not differ between groups. However, significant improvements were observed in several secondary measures. Post-hoc analysis highlighted a notable benefit in severe AUD patients, showing increased abstinence. The study reported no”

    From A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder (2024) · cites this paper as [61]

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  1. European Medicines Agency, 2019. Guideline on the in- vestigation of subgroups in confirmatory clinical tri- als. EMA/CHMP/539146/2013. Available at: https: //www.ema.europa.eu/en/documents/scientific-guideline/ guideline-investigation-subgroups-confirmatory-clinical-trials _ en.pdf Accessed March 5, 2021. · DOI
  2. Higgins, J. , Thomas, J. , Chandler, J. , Cumpston, M. , Li, T. , Page, M. , Welch, V. , 2020. Cochrane Handbook for Systematic Reviews of Interventions, version 6.1, Second edition Cochrane book series. Wiley-Blackwell updated September 2020ed, .

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Authors
Guiraud, J., Addolorato, G., Aubin, H.-J., Batel, P., de Bejczy, A., Caputo, F., Goudriaan, A. E., Gual, A., Lesch, O., Maremmani, I., Perney, P., Poulnais, R., Raffaillac, Q., Soderpalm, B., Spanagel, R., Walter, H., & van den Brink, W.
Affiliations
  • Amsterdam Neuroscience (NL)
  • Agostino Gemelli University Polyclinic (IT)
  • Inserm (FR)
  • University of Ferrara (IT)
  • Hospital Clínic de Barcelona (ES)
  • Medical University of Vienna (AT)
  • University of Pisa (IT)
  • Heidelberg University (DE)
Corresponding author
Guiraud, Julien
ORCID
Venue
European Neuropsychopharmacology
Publisher
Elsevier BV
Published
2021-11
Volume
52
Pages
18-30
ISSN
0924-977X (ISSN-L)
DOI
10.1016/j.euroneuro.2021.06.003
OpenAlex
W3180244763
Cited by
20
References
55
Citations by year
2026: 1 · 2025: 2 · 2024: 6 · 2023: 5 · 2022: 6
FWCI
3.06
Type
journal article
Language
en
Open access
Licence
Locations
  • European Neuropsychopharmacology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • VU Research Portal (publishedVersion, other-oa)
  • Pure Amsterdam UMC (acceptedVersion, cc-by-nc-sa)
  • HAL (submittedVersion, cc-by-nc-sa)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, cc-by-nc-nd)
Topics
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
Keywords
sodium oxybate, alcoholism, placebo response, treatment severity
MeSH terms
Ethanol, Alcoholism, Austria, Double-Blind Method, Humans, Sodium Oxybate, Treatment Outcome

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