Comparison of Clomethiazole and Diazepam in the Treatment of Alcohol Withdrawal Syndrome in Clinical Practice

Sychla, Hannah; Gründer, Gerhard; Lammertz, Sarah E.

doi:10.1159/000480380

Cited by 20 publications

(9 citation statements)

References 36 publications

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“…Compared with the blank control group, three lt14a groups showed significant differences ( P < .01, P < .001). Diazepam could significantly prolong the pentobarbital‐induced sleep time ( P < .001), which was consistent with its clinical effect 19 . According to previous studies, 10,20 the effective analgesic concentration of lt14a was 1 mg/kg.…”

Section: Resultssupporting

confidence: 78%

Acute toxicity and micronucleus test of conotoxin lt14a in mice

Qiang

Zhang

Zhou

2021

Basic Clin Pharma Tox

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Conotoxins, which target ion channels or neurotransmitter receptors with high specificity, are valuable in drug development for pain, epilepsy and other neurological diseases. However, the toxicology of conotoxins is rarely reported. In this study, we primarily researched parts of the pharmacological and toxicological properties of an analgesic conotoxin lt14a. Three doses of lt14a (1, 5 and 10 mg/kg) could prolong the pentobarbital‐induced sleep time of mice and showed no significant effect on the spontaneous locomotor activity of mice. Three doses of lt14a (50, 100 and 200 mg/kg) did not increase micronucleus rate in the micronucleus test. In addition, three doses of lt14a (200, 500 and 1000 mg/kg) showed no pathological change on the heart or brain of mice in the acute toxicity test. The high dose of lt14a (1000 times the effective analgesic dose) had a certain damaging effect on the liver and lung according to serological detection and histopathology. As part of the preclinical studies, our results provide acute toxicity and mutagenicity evaluation of the promising analgesic conotoxin lt14a.

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Section: Resultssupporting

confidence: 78%

Acute toxicity and micronucleus test of conotoxin lt14a in mice

Qiang

Zhang

Zhou

2021

Basic Clin Pharma Tox

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“…Spironolactone, a mineralocorticoid receptor antagonist, reduced alcohol use in both rats and humans in a recent study 59 . Clomethiazole, a GABA receptor antagonist, also showed effect of treatment for alcohol withdrawal syndrome 60 . Future clinical trials may use the evidence from this drug-repurposing analysis to prioritize drugs for further study.…”

Section: Discussionmentioning

confidence: 99%

Multi-ancestry study of the genetics of problematic alcohol use in >1 million individuals

Zhou

Kember

Deak

et al. 2023

Preprint

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Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. To improve our understanding of the genetics of PAU, we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals. We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine-mapping improved the identification of likely causal variants. Prioritizing genes through gene expression and/or chromatin interaction in brain tissues identified multiple genes associated with PAU. We identified existing medications for potential pharmacological studies by drug repurposing analysis. Cross-ancestry polygenic risk scores (PRS) showed better performance in independent sample than single-ancestry PRS. Genetic correlations between PAU and other traits were observed in multiple ancestries, with other substance use traits having the highest correlations. The analysis of diverse ancestries contributed significantly to the findings, and fills an important gap in the literature.

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“…The sedative‐hypnotic chlormethiazole has been used widely in managing AW outside of North America [87]. However, its greater side effect burden, narrower therapeutic window, and potential withdrawal with abrupt discontinuation have lessened enthusiasm for its use [88].…”

Section: Discussionmentioning

confidence: 99%

Comparative efficacy and safety of pharmacotherapies for alcohol withdrawal: a systematic review and network meta‐analysis

et al. 2022

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Background and Aims: There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of pharmacotherapies for AW.Methods: 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-effects network meta-analysis models to generate summary ORs and Cohen's d standardized mean differences (SMDs).Results: Across the 149 trials, there were 10 692 participants (76% male, median 43.5 years old). AW severity spanned mild (n = 32), moderate (n = 51), and severe (n = 66). Fixed-schedule chlormethiazole (OR, 0.16; 95% CI, 0.04-0.65), fixed-schedule diazepam (OR, 0.16; 95% CI, 0.04-0.59), fixed-schedule lorazepam (OR = 0.19; 95% CI, 0.08-0.45), fixed-schedule chlordiazepoxide (OR = 0.21; 95% CI, 0.08-0.53), and divalproex (OR = 0.22; 95% CI, 0.05-0.86) were superior to placebo at reducing incident AW seizures. However, only fixed-schedule diazepam (OR, 0.19; 95% CI, 0.05-0.76) reduced incident delirium tremens. Oxcarbazepine (d = −3.69; 95% CI, −6.21 to −1.17), carbamazepine (d = −2.76; 95% CI, −4.13 to −1.40), fixed-schedule oxazepam (d = −2.55; 95% CI, −4.26 to −0.83), and γ-hydroxybutyrate (d = −1.80; 95% CI, −3.35 to −0.26) improved endpoint Clinical Institute Withdrawal Assessment for Alcohol-Revised 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.Conclusions: 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.

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Comparison of Clomethiazole and Diazepam in the Treatment of Alcohol Withdrawal Syndrome in Clinical Practice

Cited by 20 publications

References 36 publications

Acute toxicity and micronucleus test of conotoxin lt14a in mice

Acute toxicity and micronucleus test of conotoxin lt14a in mice

Multi-ancestry study of the genetics of problematic alcohol use in >1 million individuals

Comparative efficacy and safety of pharmacotherapies for alcohol withdrawal: a systematic review and network meta‐analysis

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