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CNS Drugs Feb 2017Benzodiazepines ameliorate or prevent the symptoms and complications of moderate to severe alcohol withdrawal, which can include autonomic hyperactivity, agitation,... (Comparative Study)
Comparative Study Review
Benzodiazepines ameliorate or prevent the symptoms and complications of moderate to severe alcohol withdrawal, which can include autonomic hyperactivity, agitation, combativeness, hallucinations, seizures, delirium, and death. The benzodiazepines most commonly used for this purpose are lorazepam, chlordiazepoxide, oxazepam, and diazepam. It is widely asserted that no member of this group is superior to the others for treatment of alcohol withdrawal. However, of these, diazepam has the shortest time to peak effect, which facilitates both rapid control of symptoms and accurate titration to avoid over-sedation. Furthermore, diazepam and its active metabolite, desmethyldiazepam, have the longest elimination half-lives, so their levels decrease in a gradual, self-tapering manner, resulting in a smoother withdrawal, i.e., a lower incidence and severity of both breakthrough symptoms and rebound phenomena, including a possibly decreased seizure risk. Importantly, the fear of increased risk of over-sedation with diazepam compared with other benzodiazepines is based on a misunderstanding of its pharmacokinetics and is unfounded. Similarly, the notion that diazepam should be avoided in patients with liver disease and elderly patients to avoid prolonged over-sedation is based on no more than conjecture. In fact, there is clinical evidence that diazepam is safe for the treatment of alcohol withdrawal in these patients when administered using a simple symptom-based approach. There is one instance in which diazepam should not be used: when intramuscular administration is the only option, the lipophilicity of diazepam can result in slow absorption-either lorazepam or, when rapid control of symptoms is required, midazolam should be used. The comparative pharmacokinetics of the benzodiazepines used in the treatment of alcohol withdrawal together with a comprehensive review of the literature on their use strongly suggest that diazepam should be the preferred benzodiazepine for the treatment of patients experiencing moderate to severe alcohol withdrawal under most circumstances.
Topics: Alcohol Withdrawal Delirium; Alcohol Withdrawal Seizures; Benzodiazepines; Diazepam; Half-Life; Humans; Hypnotics and Sedatives; Severity of Illness Index
PubMed: 28101764
DOI: 10.1007/s40263-016-0403-y -
The Medical Letter on Drugs and... Aug 2023
Topics: Humans; Anxiety Disorders
PubMed: 37516898
DOI: 10.58347/tml.2023.1682a -
Deutsches Arzteblatt International Jan 2023The term potentially inadequate medication (PIM) is used to describe substances that may be unsuitable for use inthe elderly and should be avoided. The PRISCUS list,...
BACKGROUND
The term potentially inadequate medication (PIM) is used to describe substances that may be unsuitable for use inthe elderly and should be avoided. The PRISCUS list, published in 2010, was the first catalog of PIM designed for the Germandrug market to become adopted in practice. While 24% of German patients aged ≥ 65 years were prescribed at least one PIMper year in 2009, the proportion in 2019 was only 14.5%.
METHODS
In a three-round Delphi process, experts from clinical practice and research evaluated whether selected substancesare PIM for the elderly. The participants were provided with dedicated literature including systematic reviews carried out for theparticular purposes of this project.
RESULTS
Fifty-nine persons took part in the Delphi process and, in addition, contributed comments and therapeutic alternatives.Altogether, 187 substances were classed as PIM. One hundred thirty-three of the substances now listed were not in the originalPRISCUS list: these include some oral antidiabetics, all of the selective COX-2 inhibitors, and moderately long acting benzodiazepinessuch as oxazepam. For some other substances, e.g., proton pump inhibitors (PPI), the advisability of treatment formore than 8 weeks was considered as potentially inappropriate, as was the use of ibuprofen in doses >1200 mg/day and formore than 1 week without PPI. Risperidone for more than 6 weeks is also PIM.
CONCLUSION
The new, greatly extended PRISCUS list must now be validated in epidemiological and prospective studies and itspracticability in routine daily use must be verified.
Topics: Aged; Humans; Prospective Studies; Hypoglycemic Agents; Ibuprofen; Proton Pump Inhibitors
PubMed: 36507719
DOI: 10.3238/arztebl.m2022.0377 -
Addiction (Abingdon, England) Oct 2022There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Adult; Alcohol Withdrawal Delirium; Alcoholism; Benzodiazepines; Carbamazepine; Diazepam; Female; Humans; Male; Network Meta-Analysis; Seizures; Substance Withdrawal Syndrome
PubMed: 35194860
DOI: 10.1111/add.15853 -
European Journal of Clinical... Sep 2023To compare the efficacy and safety of non-benzodiazepines (non-BZDs) to benzodiazepines (BZDs) in the treatment of alcohol withdrawal syndrome (AWS). (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Humans; Alcoholism; Benzodiazepines; Ethanol; Lorazepam; Substance Withdrawal Syndrome; Randomized Controlled Trials as Topic
PubMed: 37380897
DOI: 10.1007/s00228-023-03523-2