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Beyond benzodiazepines: a meta-analysis and narrative synthesis of the efficacy and safety of alternative options for alcohol withdrawal syndrome management

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Abstract

Purpose

To compare the efficacy and safety of non-benzodiazepines (non-BZDs) to benzodiazepines (BZDs) in the treatment of alcohol withdrawal syndrome (AWS).

Methods

For relevant literature, Google Scholar, PubMed, Embase, OVID MEDLINE, EBSCO, Cochrane Central Registry of Controlled Trials, Web of Science, and Scopus were searched. Randomized control trials (RCTs) were included, omitted were nonblinded trials, blinded trials that were not randomized, and open-label studies. The Effective Public Health Practice Project Quality Assessment was used to assess the trial’s quality. A meta-analysis and a narrative synthesis were carried out.

Results

Twenty non-BZDs and five BZDs were investigated in thirty RCTs. Meta-analysis favored gabapentin over chlordiazepoxide and lorazepam (d = 0.563, p < 0.001) and carbamazepine over oxazepam and lorazepam (d = 0.376, p = 0.029), for reducing Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scale scores. Eleven non-BZDs fared better than BZDs for reducing CIWA-Ar, Total Severity Assessment, Selective Severity Assessment, Borg and Weinholdt, and Gross Rating Scale for Alcohol Withdrawal scores. Eight non-BZDs outmatched BZDs regarding autonomic, motor, awareness, and psychiatric symptoms. Sedation and fatigue were prevalent in BZDs, while seizures were prevalent in non-BZDs.

Conclusion

For AWS treatments, non-BZDs are superior to or equally effective as BZDs. Non-BZD adverse events warrant further investigation. Agents that inhibit gated ion channels are promising candidates.

Protocol registration

PROSPERO CRD42022384875.

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D.F. initiated the project and developed the protocol. D.F. and V.K. searched for the articles in databases. D.F. and V.K. screened the titles and extracted the data. D.F. and V.K. reviewed the reference lists of retrieved the articles for additional reports. D.F., V.K., and C.P. reviewed full texts for selection/exclusion. D.F., V.K., and C.P. checked the screening and selection. D.F. and V.K. conducted the risk of the bias assessment. D.F., V.K., and C.P. reviewed the outline. D.F. prepared the tables and figures and drafted the introduction, methods, results sections, and discussion. D.F., V.K., and C.P. reviewed and provided intellectual contributions to the draft manuscript. D.F., V.K., and C.P. approved the final draft.

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Correspondence to Dimy Fluyau.

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Fluyau, D., Kailasam, V.K. & Pierre, C.G. Beyond benzodiazepines: a meta-analysis and narrative synthesis of the efficacy and safety of alternative options for alcohol withdrawal syndrome management. Eur J Clin Pharmacol 79, 1147–1157 (2023). https://doi.org/10.1007/s00228-023-03523-2

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