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The Medical Letter on Drugs and... Aug 2023
Topics: Humans; Anxiety Disorders
PubMed: 37516898
DOI: 10.58347/tml.2023.1682a -
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 -
Orvosi Hetilap Sep 2023Alcohol withdrawal syndrome is one of the most important consequences of alcohol use disorder, a complex neuropsychiatric disorder, which is firstly treated in... (Review)
Review
Alcohol withdrawal syndrome is one of the most important consequences of alcohol use disorder, a complex neuropsychiatric disorder, which is firstly treated in non-specific and secondly in psychiatric/addictive in- or outpatient units. On the other hand, alcohol withdrawal syndrome is one of the most important outcomes of the severity of alcohol use disorder, further, it can lead to the development of alcohol-related seizure and delirium tremens. Hence, early recognition and optimal treatment of alcohol withdrawal syndrome have a critical importance. Therefore, the main goal of the present review was - by systematically summarizing the scientific data published during the past two decades - to form a unique diagnostic and therapeutic algorithm. During the recognition and the course of alcohol withdrawal syndrome, the Clinical Institute Withdrawal Assessment for Alcohol, Revised scale, while in the risk assessment the Prediction of Alcohol Withdrawal Severity Scale are the recommended psychometric tools. Benzodiazepines are the key elements of the pharmacotherapy of alcohol withdrawal syndrome. Many studies have evaluated that diazepam, chlordiazepoxide, lorazepam and oxazepam with distinct indications have sufficient evidence in the treatment of alcohol withdrawal syndrome. However, in the past few years some authors have recommended the importance of non-benzodiazepine medications. The efficacy of propofol, phenobarbital, carbamazepin, oxcarbamazepin and alpha-2 receptor agonists in the treatment of alcohol withdrawal syndrome have been revealed. Furthermore, it has been evaluated that benzodiazepines are recommended in the treatment of alcohol-related seizure and delirium tremens. In the present review, our aim was to construct a unique, up-to-date diagnostic and therapeutic algorithm by summarizing the related papers published during the past two decades. Hence this scheme may be useful in the optimal treatment of patients diagnosed with alcohol use disorder and it could help to conduct further clinical researches. Orv Hetil. 2023; 164(38): 1487-1496.
Topics: Humans; Alcoholism; Substance Withdrawal Syndrome; Alcohol Withdrawal Seizures; Alcohol Withdrawal Delirium; Benzodiazepines
PubMed: 37742220
DOI: 10.1556/650.2023.32847 -
Nature Communications Apr 2024Between 30% and 70% of patients with breast cancer have pre-existing chronic conditions, and more than half are on long-term non-cancer medication at the time of...
Between 30% and 70% of patients with breast cancer have pre-existing chronic conditions, and more than half are on long-term non-cancer medication at the time of diagnosis. Preliminary epidemiological evidence suggests that some non-cancer medications may affect breast cancer risk, recurrence, and survival. In this nationwide cohort study, we assessed the association between medication use at breast cancer diagnosis and survival. We included 235,368 French women with newly diagnosed non-metastatic breast cancer. In analyzes of 288 medications, we identified eight medications positively associated with either overall survival or disease-free survival: rabeprazole, alverine, atenolol, simvastatin, rosuvastatin, estriol (vaginal or transmucosal), nomegestrol, and hypromellose; and eight medications negatively associated with overall survival or disease-free survival: ferrous fumarate, prednisolone, carbimazole, pristinamycin, oxazepam, alprazolam, hydroxyzine, and mianserin. Full results are available online from an interactive platform ( https://adrenaline.curie.fr ). This resource provides hypotheses for drugs that may naturally influence breast cancer evolution.
Topics: Humans; Female; Breast Neoplasms; Cohort Studies; Comorbidity; Simvastatin
PubMed: 38580683
DOI: 10.1038/s41467-024-47002-3 -
International Journal of Molecular... Sep 2023In this study, atomistic simulations were carried out to study the difference in the adsorption process between two similar molecules, diazepam and oxazepam, on...
In this study, atomistic simulations were carried out to study the difference in the adsorption process between two similar molecules, diazepam and oxazepam, on Na-montmorillonite. Kinetic and XRD measurements showed a contrasting adsorption mechanism of these two molecules, differing only by the presence/absence of methyl and hydroxyl groups, with a larger adsorption amount and intercalation for the oxazepam. The structural characterization of these molecules was investigated through DFT calculations and showed the vicinity of hydroxyl and carbonyl groups for only the chair conformation of oxazepam compared to the boat conformation. Classical molecular dynamics simulations of diazepam and the two forms of oxazepam on the external surface of Na-montmorillonite highlighted the better coordination of the oxazepam-chair conformation, compared to its boat counterpart and diazepam. This has been confirmed through DFT calculations, from which a coordination energy that is greater by 10 kcal·mol is observed. This strongly suggests that the experimentally observed intercalation of oxazepam occurs only in the chair form because of the strong coordination with the Na cation present in the Na-Mt interlayer. Classical MD simulations of the intercalated oxazepam chair molecule in the Na-Mt interlayer allowed the evaluation of the interlayer spacing d001, which was in very good agreement with the experimental XRD measurement.
Topics: Clay; Bentonite; Adsorption; Oxazepam; Diazepam
PubMed: 37834226
DOI: 10.3390/ijms241914781 -
Addiction (Abingdon, England) Oct 2023The aim of this study was to present the first nation-wide, systematic, repeated assessment of doctor-shopping (i.e. visiting multiple physicians to be prescribed the...
AIMS
The aim of this study was to present the first nation-wide, systematic, repeated assessment of doctor-shopping (i.e. visiting multiple physicians to be prescribed the same drug) during 10 years for more than 200 psychoactive prescription drugs in the 67 million inhabitants in France.
DESIGN
This was a nation-wide, repeated cross-sectional study.
SETTING AND PARTICIPANTS
Data are from the French National Health Data System in 2010, 2015 and 2019 for 214 psychoactive prescription drugs (i.e. anaesthetics, analgesics, antiepileptics, anti-Parkinson drugs, psycholeptics, psychoanaleptics, other nervous system drugs and antihistamines for systemic use).
MEASUREMENTS
The detection and quantification of doctor-shopping relied upon an algorithm that detects overlapping prescriptions from repeated visits to different physicians. We used two doctor-shopping indicators aggregated at population level for each drug dispensed to more than 5000 patients: (i) the quantity doctor-shopped, expressed in defined daily doses (DDD), which measures the total quantity doctor-shopped by the study population for a given drug; and (ii) the proportion doctor-shopped, expressed as a percentage, which standardizes the quantity doctor-shopped according to the use level of the drug.
FINDINGS
The analyses included approximately 200 million dispensings to approximately 30 million patients each year. Opioids (e.g. buprenorphine, methadone, morphine, oxycodone and fentanyl), benzodiazepines and non-benzodiazepine hypnotics (Z-drugs) (e.g. diazepam, oxazepam, zolpidem and clonazepam) had the highest proportions doctor-shopped during the study period. In most cases, the proportion and the quantity doctor-shopped increased for opioids and decreased for benzodiazepines and Z-drugs. Pregabalin had the sharpest increase in the proportion doctor-shopped (from 0.28 to 1.40%), in parallel with a sharp increase in the quantity doctor-shopped (+843%, from 0.7 to 6.6 DDD/100 000 inhabitants/day). Oxycodone had the sharpest increase in the quantity doctor-shopped (+1000%, from 0.1 to 1.1 DDD/100 000 inhabitants/day), in parallel with a sharp increase in the proportion doctor-shopped (from 0.71 to 1.41%). Detailed results for all drugs during the study period can be explored interactively at: https://soeiro.gitlab.io/megadose/.
CONCLUSIONS
In France, doctor-shopping occurs for many drugs from many pharmacological classes, and mainly involves opioid maintenance drugs, some opioids analgesics, some benzodiazepines and Z-drugs and pregabalin.
Topics: Prescription Drug Misuse; Prescription Drugs; Cross-Sectional Studies; Psychotropic Drugs; France; Humans; Office Visits
PubMed: 37203878
DOI: 10.1111/add.16261 -
Pharmaceutics Feb 2024Benzodiazepines (BZDs) such as oxazepam are commonly prescribed depressant drugs known for their anxiolytic, hypnotic, muscle relaxant, and anticonvulsant effects and...
Benzodiazepines (BZDs) such as oxazepam are commonly prescribed depressant drugs known for their anxiolytic, hypnotic, muscle relaxant, and anticonvulsant effects and are frequently used in conjunction with other illicit drugs including cannabis. Oxazepam is metabolized in an enantiomeric-specific manner by glucuronidation, with S-oxazepam metabolized primarily by UGT2B15 and R-oxazepam glucuronidation mediated by both UGT 1A9 and 2B7. The goal of the present study was to evaluate the potential inhibitory effects of major cannabinoids, Δ-tetrahydrocannabinol (THC) and cannabidiol (CBD), and major THC metabolites, 11-hydroxy-Δ-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Δ-tetrahydrocannabinol (11-COOH-THC), on the UGT-mediated metabolism of R- and S-oxazepam. The cannabinoids and metabolites were screened as inhibitors of R- and S-oxazepam glucuronidation in microsomes isolated from HEK293 cells overexpressing individual UGT enzymes (rUGTs). The IC values were determined in human liver microsomes (HLM), human kidney microsomes (HKM), and rUGTs and utilized to estimate the nonspecific, binding-corrected K (K) values and predict the area under the concentration-time curve ratio (AUCR). The estimated K values observed in HLM for S- and R-oxazepam glucuronidation by CBD, 11-OH-THC, and THC were in the micromolar range (0.82 to 3.7 µM), with the K values observed for R-oxazepam glucuronidation approximately 2- to 5-fold lower as compared to those observed for S-oxazepam glucuronidation. The mechanistic static modeling predicted a potential clinically significant interaction between oral THC and CBD with oxazepam, with the AUCR values ranging from 1.25 to 3.45. These data suggest a pharmacokinetic drug-drug interaction when major cannabinoids like CBD or THC and oxazepam are concurrently administered.
PubMed: 38399297
DOI: 10.3390/pharmaceutics16020243