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We, therefore, aimed to evaluate the comparative performance of pharmacotherapies for AW.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Six databases were searched for randomized clinical trials through November 2021. Trials were included after a blinded review by two independent reviewers. Outcomes included incident seizures, delirium tremens, AW severity scores, adverse events, dropouts, dropouts from adverse events, length of hospital stay, use of additional medications, total benzodiazepine requirements, and death. Effect sizes were pooled using frequentist random\u2010effects network meta\u2010analysis models to generate summary ORs and Cohen's <jats:italic>d<\/jats:italic> standardized mean differences (SMDs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Across the 149 trials, there were 10\u2009692 participants (76% male, median 43.5\u2009years old). AW severity spanned mild (<jats:italic>n<\/jats:italic>\u2009=\u200932), moderate (<jats:italic>n<\/jats:italic>\u2009=\u200951), and severe (<jats:italic>n<\/jats:italic>\u2009=\u200966). Fixed\u2010schedule chlormethiazole (OR,\u00a00.16; 95% CI, 0.04\u20130.65), fixed\u2010schedule diazepam (OR,\u00a00.16; 95% CI, 0.04\u20130.59), fixed\u2010schedule lorazepam (OR\u2009=\u20090.19; 95% CI, 0.08\u20130.45), fixed\u2010schedule chlordiazepoxide (OR\u2009=\u20090.21; 95% CI, 0.08\u20130.53), and divalproex (OR\u2009=\u20090.22; 95% CI, 0.05\u20130.86) were superior to placebo at reducing incident AW seizures. However, only fixed\u2010schedule diazepam (OR,\u00a00.19; 95% CI, 0.05\u20130.76) reduced incident delirium tremens. Oxcarbazepine (d\u2009=\u2009\u22123.69; 95% CI, \u22126.21 to \u22121.17), carbamazepine (d\u2009=\u2009\u22122.76; 95% CI, \u22124.13 to \u22121.40), fixed\u2010schedule oxazepam (d\u2009=\u2009\u22122.55; 95% CI, \u22124.26 to \u22120.83), and \u03b3\u2010hydroxybutyrate (d\u2009=\u2009\u22121.80; 95% CI, \u22123.35 to \u22120.26) improved endpoint Clinical Institute Withdrawal Assessment for Alcohol\u2010Revised scores over placebo. Promazine and carbamazepine were the only agents significantly associated with greater dropouts because of adverse events. The quality of evidence was downgraded because of the substantial risk of bias, heterogeneity, inconsistency, and imprecision.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although some pharmacotherapeutic modalities, particularly benzodiazepines, appear to be safe and efficacious for reducing some measures of alcohol withdrawal, methodological issues and a high risk of bias prevent a consistent estimate of their comparative performance.<\/jats:p><\/jats:sec>","DOI":"10.1111\/add.15853","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T05:50:30Z","timestamp":1645595430000},"page":"2591-2601","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Comparative efficacy and safety of pharmacotherapies for alcohol withdrawal: a systematic review and network meta\u2010analysis"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3490-314X","authenticated-orcid":false,"given":"Anees","family":"Bahji","sequence":"first","affiliation":[{"name":"Department of Psychiatry University of Calgary  Calgary AB Canada"},{"name":"British Columbia Centre for Substance Use  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2413-9133","authenticated-orcid":false,"given":"Paxton","family":"Bach","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Substance Use  Vancouver BC Canada"},{"name":"Department of Medicine University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlon","family":"Danilewitz","sequence":"additional","affiliation":[{"name":"Ontario Shores Centre for Mental Health Sciences, Whitby  ON Canada"},{"name":"Department of Psychiatry University of Toronto  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Crockford","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Calgary  Calgary AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nady","family":"el\u2010Guebaly","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Calgary  Calgary AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Devoe","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Calgary  Calgary AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2535-1427","authenticated-orcid":false,"given":"Richard","family":"Saitz","sequence":"additional","affiliation":[{"name":"Department of Community Health Sciences, School of Public Health Boston University School of Public Health  Boston MA USA"},{"name":"Department of Medicine Boston University School of Medicine and Boston Medical Center  Boston MA USA"},{"name":"Clinical Translational Science Institute Boston University  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,15]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"RahmanA PaulM.Delirium Tremens. 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