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Objective: This study compares substance use by medical specialty among resident physicians., Method: The authors estimated the prevalence of substance use of 11 medical specialties from a national sample of 1,754 U.S. resident physicians., Results: Emergency medicine and psychiatry residents showed higher rates of substance use than residents in other specialties. Emergency medicine residents reported more current use of cocaine and marijuana, and psychiatry residents reported more current use of benzodiazepines and marijuana. Contrary to recent concerns, anesthesiology residents did not have high rates of substance use. Family/general practice, internal medicine, and obstetrics/gynecology were not among the higher or lower use groups for most substances. Surgeons had lower rates of substance use except for alcohol. Pediatric and pathology residents were least likely to be substance users., Conclusions: The authors' previous research indicates that residents overall have lower rates of substance use than their age peers in society. Yet resident substance use patterns do differ by specialty. Residents in some specialties are more likely to use specific classes of drugs, to use a greater number of drug classes, and to be daily users of alcohol or cigarettes.

Background Remimazolam, an ultra-short-acting anesthetic with flumazenil as a reversal agent, typically facilitates patient awakening postoperatively. However, our case reveals an unusual occurrence: despite flumazenil initially restoring consciousness, re-sedation due to remimazolam ensued six hours later. Case A 65-year-old woman underwent total intravenous general anesthesia with remimazolam and remifentanil during the 140-min surgery. Despite an initially smooth recovery, she progressively became drowsy upon transfer to the general ward, eventually reaching a stuporous state. Multiple interventions, including opioid reversal (intravenous patient-controlled analgesia discontinuation, and naloxone administration) were attempted. Neurological consultation revealed no issues; however, immediate improvement after flumazenil administration suggested remimazolam's involvement. The patient was discharged without complications. Conclusions This case challenges our understanding of remimazolam's dynamics, emphasizing the necessity for vigilant post-anesthesia monitoring, even in seemingly low-risk cases. It advocates for standardized response protocols to promptly manage unforeseen events and ensure patient safety.

Midazolam is generally effective and safe to be widely used in the management of seizures, procedural sedation, and anxiolytic. However, paradoxical reactions, though rare, present clinical challenges. Flumazenil is the preferred option for reversing the reactions. Additionally, ketamine, physostigmine, and haloperidol have been successfully used to counteract the adverse effects (AEs). Herein, we report an 11-year-old girl with epilepsy who was brought to the emergency department with a breakthrough seizure. Approximately 10 minutes after a midazolam administration, she developed increased agitation, confusion, uncontrollable crying, and excessive random movements. Despite receiving 4 doses of flumazenil, no improvement was observed. However, the AEs ceased following the administration of ketamine. This report may increase awareness of the uncommon AEs and equip clinicians to effectively handle such occurrences.

Background: The practice of palliative sedation continues to raise ethical questions among people, which in turn leads to its varied acceptance and practice across regions. As part of the Palliative Sedation European Union (EU) project, the aim of the present study was to determine the perceptions of palliative care experts regarding the practice of palliative sedation in eight European countries (The Netherlands, Belgium, Germany, UK, Italy, Spain, Hungary, and Romania). Methods: A specifically designed survey, including questions on the most frequently used medications for palliative sedation, their availability per countries and settings, and the barriers and facilitators to the appropriate practice of palliative sedation was sent to expert clinicians involved and knowledgeable in palliative care in the indicated countries. A purposive sampling strategy was used to select at least 18 participating clinicians per consortium country. Descriptive statistical analysis was conducted on the survey data. Results: Of the 208 expert clinicians invited to participate, 124 participants completed the survey. Midazolam was perceived to be the most frequently used benzodiazepine in all eight countries. 86% and 89% of expert clinicians in Germany and Italy, respectively, perceived midazolam was used "almost always", while in Hungary and Romania only about 50% or less of the respondents perceived this. Levomepromazine was the neuroleptic most frequently perceived to be used for palliative sedation in the Netherlands, Spain, Germany, and the United Kingdom. Between 38- 86% of all eight countries´ expert clinicians believed that opioid medications were "almost always" used during palliative sedation. The perceived use of IV hydration and artificial nutrition "almost always" was generally low, while the country where both IV hydration and artificial nutrition were considered to be "very often" given by a third of the expert clinicians, was in Hungary, with 36% and 27%, respectively. Conclusions: Our study provides insight about the differences in the perceived practice of medication during palliative sedation between eight European countries. In countries where palliative care services have been established longer perceptions regarding medication use during palliative sedation were more in line with the recommended European guidelines than in Central and Eastern European countries like Romania and Hungary. [ABSTRACT FROM AUTHOR]

Background: Benzodiazepines (BZDs) are widely prescribed for anxiety disorders. However, the long-term implications on mental health remain uncertain, especially the potential association between chronic BZD use and subsequent diagnosis of mood and substance use disorders (SUDs). Method: We conducted a 5-year retrospective cohort study by analyzing the TriNetX database, a real-time electronic medical record network. The study population was defined as patients aged 18–65 with anxiety disorders (ICD-10-CM: F40-F48). We employed propensity score matching to pair a BZD-exposed cohort (≥12 BZD prescriptions) with a BZD-unexposed control cohort. The outcomes were defined as depressive disorders, bipolar disorders, and SUDs. We employed Kaplan-Meier analyses to assess the survival probability over five years following diagnosis and BZD exposure; log-rank test to obtain the hazard ratio (HR) with 95 % confidence interval (CI). Results: We identified and matched 76,137 patients in the study and control cohorts. Compared to the control cohort, the BZD-exposed group exhibited significantly higher risks of being diagnosed with depressive disorders (HR, 2.64; 95 % CI, 2.59–2.68), bipolar disorders (HR, 4.39; 95 % CI, 4.15–4.64), overall substance use disorders (HR, 3.00; 95 % CI, 2.92–3.08), alcohol use disorder (HR, 3.38; 95 % CI, 3.20–3.57), stimulant use disorder (HR, 3.24; 95 % CI, 2.95, 3.55), cannabis use disorder (HR, 2.93; 95 % CI, 2.75–3.11), inhalant use disorder (HR, 4.14; 95 % CI, 3.38–5.06), and nicotine use disorder (HR, 2.72; 95 % CI, 2.63–2.81). Conclusion: Our findings demonstrate a concerning association between BZD use and an increased risk of being diagnosed with various mood disorders and SUDs.

Sleep is an essential activity for the survival of mammals. Good sleep quality helps promote the performance of daily functions. In contrast, insufficient sleep reduces the efficiency of daily activities, causes various chronic diseases like Alzheimer's disease, and increases the risk of having accidents. The GABAergic system is the primary inhibitory neurotransmitter system in the central nervous system. It transits the gamma-aminobutyric acid (GABA) neurotransmitter via GABAA and GABAB receptors to counterbalance excitatory neurotransmitters, such as glutamate, noradrenaline, serotonin, acetylcholine, orexin, and dopamine, which release and increase arousal activities during sleep. Several studies emphasized that dysfunction of the GABAergic system is related to insomnia, the most prevalent sleep-related disorder. The GABAergic system comprises the GABA neurotransmitter, GABA receptors, GABA synthesis, and degradation. Many studies have demonstrated that GABA levels correlate with sleep quality, suggesting that modulating the GABAergic system may be a promising therapeutic approach for insomnia. In this article, we highlight the significance of sleep, the classification and pathology of insomnia, and the impact of the GABAergic system changes on sleep. In addition, we also review the medications that target the GABAergic systems for insomnia, including benzodiazepines (BZDs), non-BZDs, barbiturates, GABA supplements, and Chinese herbal medicines.

Cannabis, derived from Cannabis sativa plants, is a prevalent illicit substance in the United States, containing over 400 chemicals, including 100 cannabinoids, each affecting the body’s organs differently upon ingestion. Cannabis hyperemesis syndrome (CHS) is a gut–brain axis disorder characterized by recurring nausea and vomiting intensified by excessive cannabis consumption. CHS often goes undiagnosed due to inconsistent criteria, subjective symptoms, and similarity to cyclical vomiting syndrome (CVS). Understanding the endocannabinoid system (ECS) and its dual response (pro-emetic at higher doses and anti-emetic at lower doses) is crucial in the pathophysiology of CHS. Recent research noted that type 1 cannabinoid receptors in the intestinal nerve plexus exhibit an inhibitory effect on gastrointestinal motility. At the same time, the thermoregulatory function of endocannabinoids might explain compulsive hot bathing in CHS patients. The prevalence of cannabis CHS is expected to rise as legal restrictions on its recreational use decrease in several states. Education and awareness are vital in diagnosing and treating CHS as its prevalence increases. This comprehensive review explores the ECS’s involvement, CHS management approaches, and knowledge gaps to enhance understanding of this syndrome.

Introduction: Alcohol dependence is an increasing and pervasive problem. Alcohol Withdrawal Syndrome (AWS) is a cluster of symptoms that occur in alcohol-dependent individuals after cessation or reduction of alcohol consumption. However, studies on the clinicoepidemiological profile of patients with AWS and treatment patterns in India are scarce. Aim: To assess the treatment patterns during hospitalisation and after discharge in Indian patients with AWS. Materials and Methods: A retrospective observational study was conducted using data from 1000 patients with AWS who were admitted to nine addiction centres across India. Data from medical charts from the previous five years were collected over six months, from January to June 2022. The study included patients of either sex, aged ≥18 years at the time of data collection, who had been hospitalised for AWS symptoms and had ≥3 months of documented follow-ups. The primary endpoints of the study were the most commonly used medications and their dose titrations in the treatment of AWS, as well as the duration of treatment in the hospital and post-discharge. Key secondary endpoints included the socio-demographic profile of patients, common comorbidities, common signs and symptoms, the association between prescription patterns of Benzodiazepines (BZDs) and liver enzyme levels, and the average duration of hospital stay. Continuous variables were summarised as mean and Standard Deviation (SD), while categorical variables were summarised as frequency and percentages. Levels of serum Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), γ-Glutamyl Transferase (GGT), and bilirubin were recorded from the source data, if available, and the association with the use of chlordiazepoxide and lorazepam was analysed using the Chi-square test. Results: The mean±SD age of the 1000 enrolled patients was 41.4±9.6 years, with the majority (n=997; 99.7%) being males. BZDs were the mainstay pharmacotherapy, with lorazepam (n=686; 68.6%) and chlordiazepoxide (n=482; 48.2%) being the two most commonly prescribed BZDs during hospitalisation. During post-discharge treatment, 57.0% (n/N=74/130) of patients received lorazepam, while 52.0% (n/N=67/130) received chlordiazepoxide. Frequently used drug regimens during hospitalisation included fixed doses of chlordiazepoxide {25 mg twice a day (BID:143/482; 29.7%), 20 mg thrice a day (TID:103/482; 21.4%), or 25mg TID (87/482; 18.0%)}, or lorazepam {2 mg TID (188/686; 27.4%), 2 mg BID (183/686; 26.7%), or 2 mg once a day (OD;175/686; 25.5%)}. Commonly observed signs and symptoms included tremors (n=567; 56.7%), irritability (n=539; 53.9%), and agitation (n=500; 50.0%). Depression (n=182; 18.2%) and anxiety (n=136; 13.6%) were the most commonly reported co-morbidities. Among the patients, only 13.4% (86/641) had an AST/ALT ratio >2, and 12.9% (44/340) had AST and GGT levels >2× Upper Limit of Normal (ULN). There was no significant difference in these patients between those receiving and not receiving chlordiazepoxide (p>0.05). The mean±SD duration of hospitalisation was 23.1±18.97 days, while the mean±SD duration of treatment during hospitalisation and post-discharge was 22.3±16.36 days and 71.6±52.3 days, respectively. Conclusion: The two most commonly prescribed drugs during hospitalisation and post-discharge were the BZDs, lorazepam and chlordiazepoxide. Fixed-dose regimens of chlordiazepoxide at 25 mg BID or TID, or 20 mg TID, and lorazepam at 2 mg TID, BID, or OD were frequently used during hospitalisation.

Biological matrices are typically used in forensic toxicological or pharmacological analysis: mainly blood, vitreous humor or urine. However, there are many cases in which crimes are a consequence of drug intoxication or drug abuse and they are not closed because over the months or years the samples become altered or decomposed. A dried blood stains test (DBS-MS) has recently been proposed to be used in drug toxicology when blood is found at a crime scene. This test could help an investigator to reveal what a person had consumed before the perpetration of the crime. In order to check the possibilities of this test, we analyzed several dried blood stains located on a cotton fabric. Therefore, the aim of this study was to determine if the analysis of a dried blood spot located on a cotton fabric could be an alternate source of obtaining toxicological results, particularly regarding benzodiazepines. We splashed blood stains on cotton fabric with different concentrations of the following benzodiazepines: alprazolam, bromazepam, clonazepam, diazepam and lorazepam, which were dried for 96 h and subsequently quantified by high-performance liquid chromatography coupled mass spectrometry (HPLC-MS). Our results show that it is possible to identify several benzodiazepines contained in a cotton fabric blood stain; consequently, this method may add another sample option to the toxicological analysis of biological vestiges found at a crime scene.

Objective To investigate the protective effect of remimazolam on cerebral nerves in a rat model of cerebral ischemia/reperfusion injury and its mechanism. Methods A total of 50 male Sprague-Dawley rats were randomly divided into sham-operation group (Sham group), cerebral ischemia/reperfusion group (I/R group), I/R+remimazolam (RE) group, I/R+RE+LY294002 (LY) group, and I/R+LY group. Neurological deficit score was used to evaluate the degree of neurological dysfunction. After arterial blood samples and brain tissue pathological sections were collected from the rats in each group, 2,3,5-trip-henyltetrazolium chloride staining was performed for the brain tissue sections to calculate cerebral infarct volume ratio; ELISA was used to measure the serum levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α); Western blotting was used to measure the relative expression levels of protein kinase B (AKT), phosphorylated AKT (p-AKT), nuclear factor-kappa B p65 (NF-κB p65), and phosphorylated NF-κB p65 (p-NF-κB p65) in brain tissue, and then immunofluorescence assay was used to measure the expression level of p-NF-κB p65 inside and outside the nucleus of cells in brain tissue. Results There were significant differences between these groups in cerebral infarct volume ratio, neurological deficit score, the serum levels of IL-6, IL-1β, and TNF-α, the relative expression levels of p-AKT and p-NF-κB p65, p-AKT/AKT ratio, and p-NF-κB p65/NF-κB p65 ratio (F=72.41-654.90,P

Concurrent opioid and benzodiazepine users are at increased risk of overdose death, compared to opioid-only users. The objective of this study was to understand recent time trends in opioid and benzodiazepine concurrent use, misuse, and schedule-I drug use, and how these differ by age, sex and geographic region. Commercial, United States medical insurance claims data and urine drug test results from 2013 to 2019 were used to study the outcomes of concurrent use (n = 756,258), schedule-I drug use (n = 746,672) and prescription misuse (n = 452,523). Drug use outcomes were studied at quarterly time points for each year.Data analysis included joinpoint regression models to estimate quarterly drug use rates, determined by positive urine tests for corresponding drug categories, and was conducted from November 2021 through January 2022. Concurrent use decreased from 19.3% to 9.8%, misuse generally decreased from 75.6% to 55.1%, and schedule-I use increased from 8.9% to 13.8%, from 2013 to 2019. Concurrent use decreased at greater rates after 2016, after the Centers for Disease Control and Food and Drug Administration guidelines against concurrent use were released, while schedule-I use increased, notably after the 2014 hydrocodone reschedule. This indicates a potential shift from prescription use to non-prescribed drug use, where most affected groups included males, younger individuals, and those residing in Northeastern regions.Study results support public health initiatives focused on policy that increases access to multimodal pain management and substance use disorder management programs—critical steps in preventing patients from seeking non-prescribed drugs for self- medicating due to pain or addiction.

Resumen: El objetivo principal del tratamiento para los trastornos de ansiedad es aliviar síntomas, prevenir recaídas y evitar secuelas. Se debe plantear un enfoque terapéutico integral (psicosocial, biológico y farmacológico).Los antidepresivos y los ansiolíticos son los pilares del tratamiento farmacológico.En la prescripción los pacientes deben ser informados de los objetivos terapéuticos, la duración y los posibles efectos secundarios. Hay que considerar la edad, tratamiento previo, tolerancia, embarazo y efectos secundarios.En España existe un aumento incesante en la prescripción y consumo de antidepresivos y ansiolíticos: los datos de la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) confirman que el consumo de antidepresivos en España ha pasado de 26,5 DHD (dosis diaria definida por 1.000 habitantes/día) en el año 2000 a 79,5 DHD en el año 2013, representando un incremento de 200%. Y respecto a los ansiolíticos, la DHD se ha incrementado de 50,88 en 2012, a 58,09 en 2022. Abstract: The main objective of the treatment for anxiety disorders is to relieve symptoms, prevent relapse and avoid sequels. An integral therapeutic approach most be considered (psychosocial, biologic and pharmacologic). The antidepressants and anxiolytics are the mainstay pharmacological treatment. When the prescription is made, the patient must be informed of therapeutic objectives, duration and possible side effects. Age, previous treatment, tolerance, pregnancy and side effects most be considered. In Spain there is a high rate of prescription and consume of antidepressants and anxiolytics: the data of “Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)” support that the consume of antidepressants in Spain has passed from 26.5 DHD (Daily doses per 1000 habitants/Dose per day per 1000 habitants) in the year 2000 to 79.5 DHD in the year 2013; translating and increment of 200%. Regarding the anxiolytics the DHD has increased from 50.88 in 2012 to 58.09 in 2022.

AbstractBackground Benzodiazepine-positive overdoses increased between 2019 and 2021 in Tennessee. We sought to determine the changes in the number and characteristics of prescription and illicit benzodiazepine-positive fatal drug overdoses during this period.Materials and Methods A statewide study was conducted to determine changes in the number and characteristics of benzodiazepine-positive drug overdose decedents using 2019–2021 data from the Tennessee State Unintentional Drug Overdose Reporting System. The analyses were limited to Tennessee residents aged ≥ 18 years. A benzodiazepine-positive overdose was defined as any benzodiazepine on toxicology, regardless of the presence of other substances. Frequencies were generated to compare demographics, circumstances, prescription history, and toxicology between 2019 and 2021 for illicit and prescription benzodiazepine-positive fatal overdoses.Results Between 2019 and 2021, 1666 benzodiazepine-positive unintentional or undetermined fatal drug overdoses out of 5916 total overdoses that occurred among adult Tennessee residents with available toxicological information. Prescription benzodiazepines were identified in 80.7% of deaths, whereas illicit benzodiazepines were identified in 12.0% of deaths. Many decedents had an anxiety disorder (45.5%), while over half of all decedents had a history of substance use disorder (52.3%). Most benzodiazepine-positive overdoses involved fentanyl (71.3%).Conclusions This analysis can inform local and regional public health workers to implement focused prevention and intervention efforts for people with co-occurring mental health conditions and substance use disorders to curb overdose epidemics among persons using benzodiazepines in Tennessee. Public health campaigns should focus on educating people on appropriate prescription medication use and the dangers of obtaining substances illicitly. Given the high proportion of opioids in this population, further education also is needed on the dangers of polysubstance drug use. The differences between prescription and illicit benzodiazepine-positive fatal overdoses indicate the need to develop substance-specific prevention and treatment strategies.

Abstract Background and Aims Communicating information about the risks and benefits of benzodiazepines so that it is meaningful to the patient has not been previously described. This study aims to determine patient preferences regarding information received before initiating a benzodiazepine. Methods An online survey was distributed through social media and advertisements to Canadians ≥18 years old over a 6‐month period (May–Oct 2022) to collect participant's rating of importance of statements and factors about the risk and benefits of benzodiazepines before initiating treatment using a 10‐point Likert‐type scale. Treatment preferences based on efficacy and risk information were also elicited. The survey was developed and pilot‐tested in collaboration with an advisory committee of individuals with lived and living experience with benzodiazepine use. Results Thirty‐seven participants responded to the survey (mean age 30 years old, 81.1% identified as female). The majority of respondents had a history of anxiety (83.8%) or insomnia (32.4%), and 10 (27.0%) respondents had used a benzodiazepine. Patient counseling related to withdrawal symptoms of benzodiazepines, risk of harm in combination with other sedating agents, risk of physical and psychological dependence, and risk of effects on cognition were rated high in the importance of receiving this information before starting a benzodiazepine relative to efficacy endpoints, such as improvement in sleep parameters. When provided with information about the chance of efficacy and risk of harm, 100% would have selected cognitive behavioral therapy as the best treatment option. The most frequently reported source of medication information where patients have sought information was from the internet (25.0%), followed by doctors (21.9%) and pharmacists (18.8%). Conclusions This study identified patient important factors and statements viewed as important to communicate before initiating a benzodiazepine. The findings of this survey study will help inform decision‐making when considering treatment options for managing anxiety or insomnia.

Introduction: Benzodiazepines are commonly prescribed but often misused, leading to dependence and withdrawal symptoms. Increased worldwide prescriptions raise adverse effects and overdose concerns, especially for the elderly. Caution is needed in prescribing and considering alternative treatments to minimize risks. Aim: Narrative literature review of potential atrial fibrillation mechanism of action induced by discontinuation of benzodiazepines. Materials and methods: Database PubMed was searched using the combination of keywords – “Benzodiazepine AND atrial fibrillation OR peripheral benzodiazepine receptors”, “history of benzodiazepines”, “benzodiazepines mechanism of action”, “benzodiazepines indications”, “benzodiazepines adverse effects” and “benzodiazepines withdrawal effects”. Non-full-text and non-English scientific publications were removed. A total of 31 publication was included. Discussion: Benzodiazepines (BZDs) were synthesized in 1955 and initially considered less toxic than barbiturates. They interact with GABA-A receptors, causing hyperpolarization and inhibitory effects in the central nervous system. BZDs are used to treat various clinical disorders, but long-term use can lead to adverse effects and withdrawal symptoms. There is evidence that genetic diversity can influence the response to BZDs through GABA receptors. The interaction between benzodiazepines and peripheral benzodiazepine receptors may influence calcium ion channels, affecting cardiac action potential and contractility, and discontinuation of these medications can potentially contribute to atrial fibrillation. Additionally, benzodiazepines may directly affect calcium channels, causing antiarrhythmic effects and vasodilation. Conclusion: In summary, benzodiazepines, once considered safer sedatives, now raise concerns about misuse, dependence, and withdrawal symptoms. While there is a potential link between discontinuing benzodiazepines and atrial fibrillation through mechanisms involving peripheral benzodiazepine receptors and cardiac calcium channels, causality remains uncertain and multifaceted. Further research is needed to clarify these mechanisms, and healthcare providers should exercise caution in long-term benzodiazepine prescriptions while exploring alternative treatment strategies to mitigate risks.

Resumen: El consumo de benzodiacepinas en nuestro medio ha aumentado en los últimos años debido al incremento en los trastornos de salud mental por motivo de la pandemia de COVID-19; sin embargo, los datos ya mostraban un incremento previo no solamente en España, sino a nivel mundial. Las causas detectadas son la falta de tiempo, las inercias del médico y el paciente, la falta de conocimiento en el manejo de su retirada, entre otras. La mayoría de las prescripciones se realizan en el contexto de la atención primaria. Por ello, también debería de ser el espacio en el que se deberían de realizar las deprescripciones. Este artículo analiza las causas del incremento en el consumo de benzodiacepinas, el momento en el que se deberían de retirar, las estrategias para poder llevar a cabo un correcta retirada y las estrategias comunitarias llevadas a cabo en España que han contribuido a disminuir su consumo. Abstract: The consumption of benzodiazepines in our environment has increased in recent years due to the increase in Mental Health disorders caused by the COVID-19 pandemic. However, the data already showed a previous increase not only in Spain but worldwide. The causes detected are the lack of time, the inertia of the doctor and the patient or the lack of knowledge in the management of its withdrawal. Most prescriptions are made in the Primary Care context. For this reason, it should also be the space in which the deprescriptions should be carried out. This article analyzes the causes of the increase, the moment in which they should be withdrawn, the strategies to be able to carry out a correct withdrawal and community strategies carried out in Spain that have contributed to reducing their consumption.

Background: Benzodiazepines are regularly prescribed to treat patients in alcoholic withdrawal. After analyzing pharmacology of benzodiazepines, diazepam is faster metabolized and concentrated in the liver, as an active metabolite whereas lorazepam is metabolized in liver by conjugation and excreted in urine. lorazepam being a drug of choice used in patients with deranged liver functions is needed to be compared with that of diazepam. The objective of the study is the comparasion of two benzodiazepines in treatment of alcohol dependence syndrome in Nepal. Material and Methods: This was a prospective, open label study carried out in Department of Psychiatry, Nobel Medical College and Teaching Hospital, Biratnagar. 50 patients (25 in each) aged between 25 to 65 years diagnosed as alcohol dependent admitted and grouped in either diazepam or lorazepam alternatively. The doses prescribed to the diazepam group and lorazepam group are 30 mg/day and 8 mg/day respectively in divided doses. For both the treatment groups, the dose was tapered every alternate day for 10 days. The Clinical Institute Withdrawal Assessment Alcohol Scale Revised (CIWA-Ar) scale was used for withdrawal symptoms scoring on the baseline and day 10. Lab Investigations were performed but were not a part of the study. Results: Out of the Fifty patients included in the study, at day 0, the mean CIWA-Ar scores were similar in both the treatment groups: 24.38±5.03 in the diazepam group and 24.79±6.42 in the lorazepam group. There was a significant intragroup decrease in the CIWA-Ar scores measured from Day 0 to the end of 10 days (p

Benzodiazepines (BZDs) are indicated for the short-term treatment of chronic insomnia disorder, since real-world use of them in large doses for a long time could cause serious side effects. Patients with long-term use of BZDs are prone to BZDs tolerance and dependence, but sudden withdrawal from BZDs can lead to rebound and withdrawal symptoms, resulting in difficulty in withdrawal. We reviewed recent studies about the withdrawal from long-term use of BZDs in chronic insomnia disorder patients, focusing on the overview of BZDs, timing and strategy of withdrawal, and treatment of withdrawal symptoms. Our review will contribute to enriching the ideas of appropriately discontinuing BZDs in chronic insomnia disorder patients with long-term use of BZDs.

Benzodiazepines (BZDs) and Z-drugs are commonly prescribed medications for anxiety and sleep disorders. This review examines their efficacy, associated risks, and alternative treatment options. BZDs enhance the activity of gamma-aminobutyric acid (GABA), reducing anxiety, while Z-drugs selectively target GABA-A receptors' alpha-1 subunits for sedative effects. Despite their effectiveness, both drug classes carry the risk of addiction, physical and psychological dependence, and withdrawal symptoms. Side effects, such as drowsiness, dizziness, and cognitive impairment, are also associated with their use. Recent studies indicate that chronic use of BZDs and Z-drugs may lead to cognitive impairment and an increased risk of dementia in older adults. Furthermore, individual factors, dosage, duration of use, and drug interactions can affect their efficacy. Prescribing trends show a decline in benzodiazepine prescriptions and an increase in Z-drug use due to perceived safety advantages. However, evidence suggests that Z-drugs carry similar risks of adverse effects and addiction potential as benzodiazepines. Healthcare professionals should carefully assess patients before prescribing these drugs and monitor their use to prevent dependence and addiction. Brief interventions, patient education, drug withdrawal support, and cognitive behavioral therapy have shown effectiveness in reducing long-term benzodiazepine and Z-drug use. Alternative treatments, including cognitive behavioral therapy and relaxation techniques, should be considered, particularly for patients with a history of addiction or those at high risk of addiction. In conclusion, the risk of addiction, withdrawal symptoms, and adverse effects associated with benzodiazepines and Z-drugs necessitates cautious prescribing and the exploration of alternative treatment options.

New clinical reports have recently been published on tofisopam—an anxiolytic drug currently registered as a benzodiazepine—after a long break in this research area. Neurobiological studies concerning its properties, which differ from those of benzodiazepines, are underway. The analyses presented in this study aimed to compare the effects of tofisopam, diazepam, and a placebo in the treatment of anxiety symptoms. A total of 66 outpatients (43 women and 23 men) with generalized anxiety disorder aged 19 to 74 years (M = 41.4; SD = 13.2) were randomized in three groups receiving (1) tofisopam (50 mg three times a day), (2) diazepam (5 mg three times a day), or (3) a placebo for 2 weeks. Then, throughout a 2-week washout period, the patients were monitored for withdrawal symptoms. During the last 2 weeks, the effects of tofisopam (50 mg three times a day) and diazepam (5 mg three times a day) were compared (crossover design). The mean improvement on the Hamilton Anxiety Rating Scale was significantly higher in both the tofisopam and diazepam groups compared to the placebo group. There were no significant differences between the effects of diazepam and tofisopam, whereas adverse effects and withdrawal symptoms occurred less frequently in the tofisopam group. Tofisopam did not impair cognitive abilities, and related withdrawal symptoms resembled those of the placebo. If larger future studies corroborate these findings, tofisopam should be classified as a homophtalazine.

The aim of this retrospective analysis is to determine the most frequently prescribed medications for the treatment of NREM parasomnias and evaluate reported outcomes. We performed a retrospective chart review of all patients with NREM parasomnia diagnosed within Brigham and Women’s Hospital (BWH) clinics examining the date of diagnosis, date of starting therapy, comorbidities, type of medication prescribed, and the reported change in symptoms or side effects at follow-up visits. From 2012 to 2019, 110 patients (59 females, 51 male) at BWH clinics received a diagnosis of NREM parasomnia, including sleepwalking and night terrors. The mean age was 44. Comorbidities included obstructive sleep apnea (OSA) (46%), periodic limb movement syndrome (PLMS) (13%), insomnia (19%), Restless leg syndrome (RLS) (9%), epilepsy (4%), and REM behavior disorder (RBD) (9%). Initial treatment strategies include behavioral and safety counseling only (34%), pharmacological treatment (29%), treatment of any comorbidity (28%), and combined treatment of any of the above (9%). Improvement was reported with: treatment of OSA (n = 23 52% reported improvement), melatonin (n = 8, improvement reported by 88%.,benzodiazepine (n = 7, improvement reported by 57%). Treating comorbid conditions is a frequent treatment strategy, often associated with symptom improvement. The pharmacologic treatment most commonly included melatonin and benzodiazepines. Comprehensive management should include behavioral and safety recommendations, assessment of comorbid conditions, and individually tailored pharmaceutical treatment.

As tranquilizers, benzodiazepines have a wide range of clinical uses. Recently, there has been a significant rise in the number of novel psychoactive substances, including designer benzodiazepines. Flubromazolam(8-bromo-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazeZpine) is a triazolo-analogue of flubromazepam. The most common effects noted by recreational users include heavy hypnosis and sedation, long-lasting amnesia, and rapid development of tolerance. Other effects included anxiolysis, muscle-relaxing effects, euphoria, loss of control, and severe withdrawals. Clonazolam, or 6-(2-chlorophenyl)-1-methyl-8-nitro-4H-[1,2,4]triazolo[4,3-α]-[1,4]-benzodiazepine, is a triazolo-analog of clonazepam. It is reported to be over twice as potent as alprazolam. Deschloroetizolam (2-Ethyl-9-methyl-4-phenyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine) is part of the thienodiazepine drug class, which, like benzodiazepines, stimulates GABA-A receptors. Meclonazepam ((3S)-5-(2-chlorophenyl)-3-methyl-7-nitro-1,3-dihydro-1,4-benzodiazepin-2-one) is a designer benzodiazepine with additional anti-parasitic effects. Although it has proven to be an efficacious therapy for schistosomiasis, its sedative side effects have prevented it from being marketed as a therapeutic agent. The use of DBZs has been a subject of multiple recent clinical studies, likely related to increasing presence and availability on the internet drug market and lack of regulation. Many studies have aimed to identify the prevalence of DBZs and their effects on those using them. This review discussed these designer benzodiazepines and the dangers and adverse effects that the clinician should know.

Chronic pain is one of the main leading causes of disability in the world at present. A variety in the symptomatology, intensity and duration of this phenomenon has led to an ever-increasing demand of pharmacological treatment and relief. This demand for medication, ranging from well-known groups, such as antidepressants and benzodiazepines, to more novel drugs, was followed by a rise in safety concerns of such treatment options. The validity, frequency, and diversity of such concerns are discussed in this paper, as well as their possible effect on future prescription practices. A specific caution is provided towards the psychological safety and toll of these medications, regarding suicidality and suicidal ideation. Most significantly, this paper highlights the importance of pharmacovigilance and underscores the necessity of surveillance programs when considering chronic pain medication.

Catatonia is a syndrome that has been associated with several mental illness disorders but that has also presented as a result of other medical conditions. Schizophrenia and other psychiatric disorders such as mania and depression are known to be associated with catatonia; however, several case reports have been published of certain medical conditions inducing catatonia, including hyponatremia, cerebral venous sinus thrombosis, and liver transplantation. Neuroleptic Malignant Syndrome and anti-NMDA receptor encephalitis are also prominent causes of catatonia. Patients taking benzodiazepines or clozapine are also at risk of developing catatonia following the withdrawal of these medications—it is speculated that the prolonged use of these medications increases gamma-aminobutyric acid (GABA) activity and that discontinuation may increase excitatory neurotransmission, leading to catatonia. The treatment of catatonia often involves the use of benzodiazepines, such as lorazepam, that can be used in combination therapy with antipsychotics. Definitive treatment may be found with electroconvulsive therapy (ECT). Aberrant neuronal activity in different motor pathways, defective neurotransmitter regulation, and impaired oligodendrocyte function have all been proposed as the pathophysiology behind catatonia. There are many clinical challenges that come with catatonia and, as early treatment is associated with better outcomes, it becomes imperative to understand these challenges. The purpose of this manuscript is to provide an overview of these challenges and to look at clinical studies regarding the pathophysiology, diagnosis, and treatment of as well as the complications and risk factors associated with catatonia.

Benzodiazepines (BZDs) are among one of the most widely prescribed drug classes in the United States. BZDs are a class of psychoactive drugs known for their depressant effect on the central nervous system (CNS). They quickly diffuse through the blood–brain barrier to affect the inhibitory neurotransmitter GABA and exert sedative effects. Related to their rapid onset and immediate symptom relief, BZDs are used for those struggling with sleep, anxiety, spasticity due to CNS pathology, muscle relaxation, and epilepsy. One of the debilitating side effects of BZDs is their addictive potential. The dependence on BZDs generally leads to withdrawal symptoms, requiring careful tapering of the medication when prescribed. Regular use of BZDs has been shown to cause severe, harmful psychological and physical dependence, leading to withdrawal symptoms similar to that of alcohol withdrawal. Some of these withdrawal symptoms can be life threatening. The current treatment for withdrawal is through tapering with clonazepam. Many drugs have been tested as a treatment for withdrawal, with few proving efficacious in randomized control trials. Future research is warranted for further exploration into alternative methods of treating BZD withdrawal. This call to action proves especially relevant, as those seeking treatment for BZD dependence and withdrawal are on the rise in the United States.

Background: There is a growing number of service users looking to discontinue use of psychiatric medicines. Tapering is the recommended approach for reducing and/or discontinuing the use of psychiatric medicines. This involves gradually reducing the dose over time to minimise the potential for withdrawal symptoms. However, many uncertainties exist regarding the process of reducing and stopping psychiatric medicines. This study will use a James Lind Alliance Priority Setting Partnership to determine the Top 10 unanswered questions and uncertainties about reducing and stopping psychiatric medicines. Methods: The Priority Setting Partnership will be conducted using the James Lind Alliance methodology. It will involve seven stages: (i) creating an international Steering Group of representatives from key stakeholder groups that will include people with lived experience of taking and/or stopping psychiatric medicines, family members, carers/supporters and healthcare professionals, and identifying potential partners to support key activities (e.g. dissemination); (ii) gathering uncertainties about reducing and stopping psychiatric medicines from key stakeholders using an online survey; (iii) data processing and summarising the survey responses; (iv) checking the summary questions against existing evidence and verifying uncertainties; (v) shortlisting the questions using a second online survey; (vi) determining the Top 10 research questions through an online prioritisation workshop; (vii) disseminating results. Conclusions: This study will use a Priority Setting Partnership to generate a Top 10 list of research questions and uncertainties about reducing and stopping psychiatric medicines. This list will help to guide future research and deliver responsive and strategic allocation of research resources, with a view to ultimately improving the future health and well-being of individuals who are taking psychiatric medicines.

The purpose of this paper is a systematic review of articles and research in the context of drugs used and suicide in elderly patients. Suicide in the elderly may be much more frequent than in the younger population. In addition to factors such as mental illness, dementia, deteriorating health, or problems with adapting to old age, the impact of chronic and reliever medications in this age group should also be considered. The greatest challenge of pharmacotherapy in the elderly is polypharmacy, drug interactions, different metabolism, pharmacokinetics and pharmacodynamics of the drugs used, as well as the side effects appearing in chronic therapy. In elderly patients, strong groups of drugs such as benzodiazepines and opioids are used extensively and sometimes too often. These drugs can cause addiction and overdose. Prescribing benzodiazepines alone carries a high risk of suicide. On the other hand, opioids often lead to addiction and abuse of these drugs, which may be associated with the development of respiratory depression. According to estimates by the Centers for Disease Control and Prevention (CDC), suicide accounts for approximately 7% of all opioid overdose deaths. Therapy should be carefully selected with regard to the use of other medications, drug interactions, and possible dependence and drug abuse by patients.The use of some classes of drugs in the elderly requires increased vigilance and control in the context of depression and episodes of suicide attempts. Drugs such as B blockers, digitalis glycosides, NSAIDs, opioids, ACEIs, calcium channel blockers, corticosteroids, diuretics, levodopa, and benzodiazepines can cause symptoms of depression. Older people are more susceptible to side effects of drugs, for example because of polypharmacy and the chronicity of treatment.

Abstract Background Catatonia is a clinical syndrome characterized by psychomotor disruption, which often goes undiagnosed. Most reports have focused on interventions and outcomes for catatonia in younger people and those with schizophrenia. The clinical characteristics and course of catatonia in old age are poorly understood. We present a report of an older person whose catatonia was refractory to extensive treatment, and we identify important implications for the management of catatonia in old age. Case presentation We describe a 73-year-old white man with longstanding autistic spectrum disorder who presented with symptoms of depression. Following a period of diagnostic uncertainty and failure to improve with antidepressant medication, a lorazepam challenge yielded an abrupt improvement in presentation. The patient was treated extensively with lorazepam, zolpidem, and electroconvulsive therapy during his 16-month hospital admission, but his catatonia ultimately proved refractory to treatment. Conclusions Catatonia should be considered promptly as a differential diagnosis in older people presenting with atypical features of functional mental illness. Although partial improvement of catatonic features was achieved using benzodiazepines and electroconvulsive therapy, these were not sustained in our patient. We identified comorbid autistic spectrum disorder, prolonged duration of catatonia, and sensitivity to benzodiazepines as important factors in prognostication in old age.

Background: In the context of a recovery-oriented approach to mental healthcare, the role of psychotropic medication over extended or indefinite periods is increasingly being called into question. To minimise the risks of withdrawal symptoms and relapse, it is crucial that service users who want to discontinue psychotropic medication are supported throughout the tapering process. However, in the absence of effective interventions and supports, service users are increasingly relying on online resources for guidance and support. To date, the evidence base for mobile phone applications (‘apps’) and app-based interventions supporting discontinuation of psychotropic use has not been examined. This scoping review aims to examine the content, underpinning evidence base and impact of available mobile phone apps and app-based interventions to support psychotropic tapering. Methods: A scoping review will be conducted using the Joanna Briggs Institute guidance and results will be reported using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses extension for Scoping Reviews (PRISMA-ScR) guideline. Several electronic databases (MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, ACM and IEEE Xplore) will be searched from 2008 onwards. Searches of the major app stores will also be conducted, specifically Apple's App Store (iOS) and Google Play Store (Android). Following screening, key information will be extracted from the included studies and apps. Identified apps will be coded using the Behaviour Change Technique (BCT) Taxonomy. The findings will be described using narrative synthesis. Conclusions: This scoping review will provide a broad overview of available apps to support psychotropic tapering, including a summary of their content using the BCT Taxonomy. The review findings will guide future research relating to the development, implementation and evaluation of app-based interventions to support the tapering of psychotropic medication.

Abstract We report a case of concurrent ingestion of Clonazepam and Amlodipine in a 25‐year‐old man, in a second attempt to take his life, which resulted in unconsciousness, hypotension, and hypokalemia. The clinical and/or biochemical presentation varied from the individual pattern when ingested. In the scarcity of consensus recommendations, supportive treatment helped.

Introduction: Cancer patients are usually subjected to numerous surgeries during their course of treatment. Recent studies suggest that anesthetic drugs such as propofol, benzodiazepines, and opioids are linked to cognitive impairment.Aim: The aim of the study was to show and compare the cognitive function of oncology patients who have undergone surgery and have been sedated with propofol, fentanyl and benzodiazepines.Materials and methods: In order to determine whether the cognition of oncological patients is being impaired, a mini-mental state examination (MMSE) test was obtained 6 to 24 hours pre- and postoperatively for the duration of one month from 8 eligible oncological patients and 7 non-oncological ones. Afterwards, the data were statistically processed with SPSS version 25.0 (Chicago, Ill. the USA).Results: The analysis shows that there is statistically significant difference in the preoperative MMSE scores between oncological and non-oncological patients. Conclusions: Oncological patients compound a sensitive group for cognitive dysfunction, and indeed, MMSE test could be useful for cognitive evaluation. The present sample, however, is small, and the results could not be generalized. Therefore a more extensive study is needed.

Background: As many patients view conventional antidepressants and anxiolytics negatively, it is not surprising that the willingness to apply these treatments is far from ideal, thus posing a critical barrier in promoting an effective and durable treatment. Aim: The present study aimed to explore patients' attitudes toward conventional and herbal treatments for depression and anxiety, while considering cultural and demographic factors, to further elucidate the antecedes that putatively determine the treatment's outcome. Methods: During June 2017, a cross-sectional survey was conducted using stratified sampling from a large-scale Israeli volunteer online panel. The final sample included 591 Jewish Israeli adults that reported they were suffering from depression or anxiety. Results: A heterogeneous range of attitudes toward treatment was found: for example, a large group of patients did not utilize prescription medications (39%), a professional consultation (12.9%), or any form of treatment (17.4%). Interestingly, these patients were significantly more likely to support naturally-derived treatments and were less concerned with scientific proof. Further, adverse effects were demonstrated as a prominent factor in the choice of treatment. A higher incidence of adverse effects was associated with an increased willingness to consider an alternative herbal treatment. Noteworthy attitudes were found in orthodox-Jewish individuals, who showed similar consultation rates, but utilized more psychological, rather than pharmacological treatments. Conclusions: It is proposed that patients' perspectives and cultural backgrounds are needed to be taken into consideration during the clinical assessment and choice of treatment. The findings imply that a particular emphasis should be placed on patients that discard conventional pharmacological options and on distinct cultural aspects. Several recommendations for revising the current policy are advocated to promote more culturally-informed and patient-oriented care. [ABSTRACT FROM AUTHOR]

Objective To establish a method using supramolecular solvent and gas chromatography-tandem mass spectrometry （GC-MS/MS） to analyze 9 benzodiazepines in urines. Methods Urine samples containing 9 benzodiazepines reference substance were subjected to liquid-liquid extractions with supramolecular solvent, which consisted of tetrahydrofuran and 1-hexanol. The solvent layer was evaporated to dryness by stream of nitrogen. The residue was reconstituted with methanol, and GC-MS/MS analysis was performed on it. The way of data collection was multiple reaction monitoring （MRM） mode; internal standard method was employed for quantification. Results In urine samples, when the range of mass concentration was 1- 100 ng/mL for diazepam, midazolam, flunitrazepam and clozapine, 5- 100 ng/mL for lorazepam and alprazolam, 2-100 ng/mL for nitrazepam and clonazepam, and 0.2-100 ng/mL for estazolam, respectively, good linearities were obtained, correlation coefficients were 0.999 1-0.999 9, the lower limits of the quantifications ranged from 0.2 to 5 ng/mL, the extraction recovery rates were 81.12%- 99.52%. The intra-day precision［relative standard deviation（RSD）］and accuracy（bias）were lower than 9.86% and 9.51%, respectively; the inter-day precision（RSD）and accuracy（bias）were lower than 8.74% and 9.98% , respectively. Nine drugs in urine samples showed good stability at ambient temperature and -20 ℃ within 15 days. The mass concentrations of alprazolam in urine samples obtained from 8 volunteers who took alprazolam tablets orally within 8-72 h after ingestions ranged from 6.54 to 88.28 ng/mL.

The post-mortem toxicological findings may be misinterpreted, if the drug undergoes substantial post-mortem redistribution. As alprazolam is one of the most frequently evaluated drug for legal/forensic reasons in drug-related fatalities, we studied possible changes in alprazolam distribution after death in a rat model. Rats were sacrificed 30 minutes after alprazolam administration. Blood and tissue samples from 8 animals per sampling time were collected at 0, 2, 6, and 24 h after death. The experimental samples were assayed for alprazolam using validated UHPLC-PDA method. Median blood alprazolam concentrations increased approximately 2 times compared with ante-mortem levels due to the redistribution during early post-mortem phase and then slowly decreased with a half-life of 60.7 h. The highest alprazolam tissue concentrations were found in fat and liver and the lowest levels were observed in lungs and brain. The median amount of alprazolam deposited in the lungs was relatively stable over the 24-h post-mortem period, while in heart, liver and kidney the deposited proportion of administered dose increased by 43–48% in comparison with ante-mortem values indicating continuous accumulation of alprazolam into these tissues. These results provide evidence needed for the interpretation of toxicological results in alprazolam-related fatalities and demonstrate modest alprazolam post-mortem redistribution.

Abstract Background With antidepressants (ADs) having minimal therapeutic effects during the initial weeks of treatment, benzodiazepines (BZDs) are concomitantly used to alleviate depressive symptoms of insomnia or anxiety. However, with mortality risks associated with this concomitant use yet to be examined, it remains unclear as to whether this concomitant therapy offers any benefits in treating depression. Methods We conducted a population-based cohort study using South Korea’s nationwide healthcare database from 2002 to 2017. Of 2.6 million patients with depression, we identified 612,729 patients with incident depression and newly prescribed ADs or BZDs, by excluding those with a record of diagnosis or prescription within the 2 years prior to their incident diagnosis. We classified our study cohort into two discrete groups depending on the type of AD treatment received within 6 months of incident diagnosis—AD monotherapy and AD plus BZD (AD+BZD) therapy. We matched our study cohort in a 1:1 ratio using propensity scores to balance baseline characteristics and obtain comparability among groups. The primary outcome was all-cause mortality, and patients were followed until the earliest of outcome occurrence or end of the study period. We conducted multivariable Cox proportional hazards regression analysis to estimate adjusted hazards ratios (HRs) with 95% confidence intervals (CIs) for the risk of mortality associated with AD+BZD therapy versus AD monotherapy. Results The propensity score-matched cohort had 519,780 patients with 259,890 patients in each group, where all baseline characteristics were well-balanced between the two groups. Compared to AD monotherapy, AD+BZD therapy was associated with an increased risk of all-cause mortality (adjusted HR, 1.04; 95% CI, 1.02 to 1.06). Conclusions Concomitantly initiating BZDs with ADs was associated with a moderately increased risk of mortality. Clinicians should therefore exercise caution when deciding to co-prescribe BZDs with ADs in treating depression, as associated risks were observed.

The management of patients with Alzheimer’s disease (AD) is one of the urgent problems of modern medicine, however, not only general practitioners, but also neurologists in our country are not sufficiently aware of modern methods of AD therapy, which largely determines the errors in patient management. The disease is rarely diagnosed, patients are often observed with an erroneous diagnosis of chronic cerebrovascular disease (chronic cerebral ischemia, discirculatory encephalopathy) and do not receive the necessary treatment. It is relatively rare for AD patients to receive advice on non-drug therapies that include cognitive stimulation, cognitive training, regular physical activity, and antioxidant-rich nutrition. Anti dementic agents are rarely prescribed to patients: acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine, an NMDA receptor blocker. Only a relatively small percentage of people who developed Alzheimer’s disease receive effective antidement therapy. This may be due to the fact that AD is not diagnosed or is diagnosed at more advanced stages of the disease when antidement therapy is not so effective, or that doctors do not have sufficient knowledge about antidement drugs and, finally, that the price of drugs is relatively high and the prescribing process for preferential provision of drugs is rather complicated. Unfortunately, antipsychotics and benzodiazepines are often unreasonably prescribed to patients with AD, the use of which impairs cognitive functions. The article presents a clinical observation of a relatively young patient with AD, who was followed up for a long time with an erroneous diagnosis of discirculatory encephalopathy. The issues of optimizing the management of AD patients in our country are discussed, and the data of the Cochrane review on the use of donepezil at different stages of the disease are analyzed.

Background and Aim: Opioid and benzodiazepine family drugs are concurrently used in various patients. Considering the respiratory depressant effects of both classes, in this study, we investigated the effect of coadministration of morphine and several widely used benzodiazepines in the clinic on the rate of respiratory depression in rats. Methods & Materials: Seventy adult male Wistar rats were randomly divided into 10 groups; morphine, midazolam, diazepam, lorazepam, alprazolam, morphine-midazolam, morphine-diazepam, morphine-lorazepam, and morphine-alprazolam. Respiration signal was recorded using whole-body plethysmography 15 minutes after the intraperitoneal injection of the drugs. The respiratory pattern was examined using several parameters; the mean value of inter-breath interval and the respiratory rate, as well as the coefficient of variation and sample entropy analysis of inter-breath interval. Ethical Considerations: This study was approved by the Ethics Committee of Arak University of Medical Sciences (Code: IR.ARAKMU.REC.1397.327). Results: Analyzing respiratory data revealed that injecting the anxiolytic dose of alprazolam, and the combination of morphine-alprazolam and morphine-midazolam, altered the respiratory pattern. Such changes were associated with a decrease in the number of breaths and an increase in the inter-breath interval in the explored test animals, compared with the controls. The obtained data also indicated that morphine-midazolam injection increased the variability of the breathing pattern; such an alternation was associated with increased irregularity and decreased coefficient of variation of the inter-breath interval. Conclusion: The present research results suggested that the short-term injection of morphine-midazolam changes the respiratory pattern more severely than morphine combined with other benzodiazepines.

Alcohol withdrawal syndrome (AWS) is the most common and well-known condition occurring after intentional or unintentional cessation or decreasing heavy drinking. Approximately 5-10% of these people are suffering from serious medical and psychiatric problems, withdrawal seizures, perceptual disturbances, and delirium tremens. Despite acute medical conditions with the high mortality of severe AWS, proper management could decrease the severity and mortality of AWS. The Clinical Institute withdrawal assessment for alcohol-revised version is a valid, reliable, and sensitive instrument for assessing the clinical course and the treatment monitoring of alcohol withdrawal. Benzodiazepine is the pharmacotherapy of choice for alcohol withdrawal. Diazepam or lorazepam treatment is best initiated early in the course of alcohol withdrawal to prevent progression to more severe withdrawal. There are three strategies for the pharmacotherapy of AWS. After the treatment of AWS, most patients should be managed or treated by the continuing care, including the psychosocial treatments, community-based management, and programs for preventing recurrence of AWS.

Представлен обзор современных публикации, посвященных применению бензодиазепиновых транквилизаторов при лечении пациентов с синдромом отмены алкоголя (СОА). Симптомы СОА проявляются более чем у 50 употребляющих алкоголь пациентов, которые нуждаются в медикаментозном лечении. Бензодиазепины являются препаратами выбора при лечении СОА, протекающего с аффектом тревоги, страха и эмоциональнои напряженности. Однако терапия нередко оказывается неэффективнои, а у части пациентов развиваются дозозависимые нежелательные лекарственные реакции (НЛР), что снижает эффективность терапии даннои категории больных. Цель исследования систематизация научных данных о применении бензодиазепинов при лечении пациентов с СОА. Задачи: проанализировать публикации, посвященные применению бензодиазепиновых транквилизаторов при лечении пациентов с СОА обобщить результаты фармакоэпидемиологических исследовании по изучению частоты встречаемости неэффективных случаев терапии транквилизаторами СОА и случаев развития дозозависимых НЛР проанализировать причины, способные оказывать влияние на индивидуаль ныи ответ терапии бензодиазепинами, ухудшая ее эффективность и безопасность. Выводы: на показатели эффективности и безопасности терапии бензодиазепиновыми транквилизаторами могут оказывать влияние индивидуальные особенности пациента, как связанные с клиникои СОА, так и обусловленные полиморфизмом генов, кодирующих элементы фармакокинетики и фармакодинамики лекарственных средств. Материал и методы исследования: в качестве материала исследования использовались репрезентативные базы данных по поиску научных источников PubMed и Google Scholar. Поиск литературы проводился в период с 2010 по 2019 г. В качестве инструментов поиска использо вались следующие слова и сочетания: alcohol withdrawal, AWS, benzodiazepines, BDZ, diazepam, lorazepam, alcoholism, alcohol addiction, alcohol dependence, alcohol abuse, alcohol use disorder.

Abstract Background The risks of harms from opioids increase substantially at high doses, and high-dose prescribing has increased in primary care. However, little is known about what leads to high-dose prescribing, and studies exploring this have not been synthesized. We, therefore, systematically synthesized factors associated with the prescribing of high-dose opioids in primary care. Methods We conducted a systematic review of observational studies in high-income countries that used patient-level primary care data and explored any factor(s) in people for whom opioids were prescribed, stratified by oral morphine equivalents (OME). We defined high doses as ≥ 90 OME mg/day. We searched MEDLINE, Embase, Web of Science, reference lists, forward citations, and conference proceedings from database inception to 5 April 2019. Two investigators independently screened studies, extracted data, and appraised the quality of included studies using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. We pooled data on factors using random effects meta-analyses and reported relative risks (RR) or mean differences with 95% confidence intervals (CI) where appropriate. We also performed a number needed to harm (NNTH) calculation on factors when applicable. Results We included six studies with a total of 4,248,119 participants taking opioids, of whom 3.64% (n = 154,749) were taking high doses. The majority of included studies (n = 4) were conducted in the USA, one in Australia and one in the UK. The largest study (n = 4,046,275) was from the USA. Included studies were graded as having fair to good quality evidence. The co-prescription of benzodiazepines (RR 3.27, 95% CI 1.32 to 8.13, I 2 = 99.9%), depression (RR 1.38, 95% CI 1.27 to 1.51, I 2 = 0%), emergency department visits (RR 1.53, 95% CI 1.46 to 1.61, I 2 = 0%, NNTH 15, 95% CI 12 to 20), unemployment (RR 1.44, 95% CI 1.27 to 1.63, I 2 = 0%), and male gender (RR 1.21, 95% CI 1.14 to 1.28, I 2 = 78.6%) were significantly associated with the prescribing of high-dose opioids in primary care. Conclusions High doses of opioids are associated with greater risks of harms. Associated factors such as the co-prescription of benzodiazepines and depression identify priority areas that should be considered when selecting, identifying, and managing people taking high-dose opioids in primary care. Coordinated strategies and services that promote the safe prescribing of opioids are needed. Study registration PROSPERO, CRD42018088057

Alprazolam (ALP), a benzodiazepine (BDZ) used to treat anxiety, panic, and sleep disorders, is one of the most prescribed psychotropic drugs worldwide. The side effects associated with long-term (mis)use of ALP have become a major challenge in pharmacotherapy, emphasizing the unmet need to further investigate their underlying molecular mechanisms. Prolonged BDZ exposure may induce adaptive changes in the function of several receptors, including the primary target, gammaaminobutyric acid receptor type A (GABAAR), but also other neurotransmitter receptors such as glutamatergic. The present study investigated the potential effects of prolonged ALP treatment on components of glutamatergic neurotransmission, with special emphasis on N-Methyl-D-aspartate receptor (NMDAR) in the hippocampus of adult male Wistar rats. The study revealed behavioral changes consistent with potential onset of tolerance and involvement of the glutamatergic system in its development. Specifically, an increase in NMDAR subunits (NR1, NR2A, NR2B), a decrease in vesicular glutamate transporter 1 (vGlut1), and differential modulation of excitatory amino acid transporters 1 and 2 (EAAT1/2, in vivo and in vitro) were observed, alongside a decrease in α1-containing GABAAR following the treatment. By describing the development of compensatory actions in the glutamatergic system, the present study provides valuable information on neuroadaptive mechanisms following prolonged ALP intake.

В настоящеи статье рассмотрены доказательные исследования, посвященные проблеме диагностики, патофизиологии и терапии кататонии. Кататоническии синдром (Кс) представлен широким спектром двигательных, речевых и поведенческих нарушении и на текущии момент рассма- тривается как полиэтиологичное состояние, имеющее в основе формирования как психиатрические, так и непсихиатрические причины. новые исследования показывают, что среди психических расстроиств Кс наиболее часто встречается при биполярном расстроистве, в то время как при шизофрении он наблюдается существенно реже. Рассмотрены различные терапевтические подходы к Кс, среди которых методами первого выбора являются бензодиазепины и электросудорожная терапия.

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Benzodiazepines and “Z-drugs” (BZD/Z) are overprescribed in many countries. This study evaluates their consumption in a social security sector health insurance provider with national coverage in Argentina. With a descriptive and observational approach, outpatient dispensations of BZD/Zs were analyzed for people over 18 years old from April 2020 to March 2021, disaggregated by sex, age, active ingredient, and half-life. An annual prevalence of use of 11.6% was found among the 431,445 adult affiliates, with higher rates in women and in those over age 60. Overall consumption of BZD/Zs was 77.6 defined daily doses (DDD) per 1000 enrollee-days. The average user received 5.1 annual dispensations and the equivalent of 1.4 DDD for each day of the year. BZD/Zs with long half-life were the most used. We found high levels of BZD/Z consumption and for longer periods than recommended. It is necessary to improve the quality of consumption and reduce the negative impact of inappropriate use of these drugs among treated individuals.

Abstract Background Substance use, alcohol use, and smoking use have all been associated with burn injury. Few studies have investigated associations with substances, alcohol, smoking, inhalational only burns, and patient outcomes. The purpose of the study was to identify risk factors for pulmonary failure in patients suffering inhalation injury, focusing on the impact of substance, alcohol, and cigarette use. Methods This is a single-center retrospective analysis of 115 patients admitted to the Johns Hopkins Bayview Burn Center with inhalational injury from January 1, 2010, through September 30, 2018. Patients were excluded if they were under the age of 18 years or had burn involvement of the skin > 5%. Primary outcome variables measured were if patients were intubated, length of total time intubated, substance use, alcohol use, and smoking use. Secondary outcome variables measured were types of substances used (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, codeine/morphine), total number of substances used, intensive care unit (ICU) length of stay (LOS), hospital LOS, secondary complications, and patient mortality. Analysis was performed with Fisher’s exact test and the Mann-Whitney U test. A sub-group analysis for each substance, alcohol, smoking, and control sub-group was compared to its respective sub-group without substance, alcohol, smoking, and control within the no intubation and intubation group. A sub-group analysis of substance use, alcohol use, smoking use, and control was further analyzed with binomial logistic regression within the intubation group. Results Following inhalation injury, 50/115 (43%) patients required intubation. Forty-two of the 50 (84%) patients intubated had substance use (p

Background: In view of the high prevalence of poisoning with antipsychotics, antidepressants, and benzodiazepines, the aim of this study was to compare the cardiovascular complications of poisoning with antipsychotic and antidepressant drugs with or without benzodiazepines. Methods: In this case-control study, 120 patients poisoned with psychiatric drugs were divided into two groups of case (with benzodiazepine) and control (without benzodiazepine). Demographic and clinical features as well as cardiac complications of patients were extracted from their files at the time of admission to the emergency department, and then the data were analyzed. Findings: There was no significant difference between the groups in terms of demographic information, poisoning way, drug type, duration of hospitalization, pupil size, hemodynamic data, electrocardiography findings, and outcomes (P > 0.05). Conclusion: Poisoning with antidepressants and antipsychotics, when combined with benzodiazepines, led to a decreased level of consciousness than those who did not take benzodiazepine. Meanwhile, hemodynamic symptoms, changes in electrocardiography, vital signs, nervous system status, and even the outcome of patients in the benzodiazepine group were not significantly different from those who did not take this drug.

Background: Benzodiazepines (BZDs) are very often inappropriately prescribed drugs. The aim of this study is to analyse physicians' prescribing patterns for BZD in Republic of Srpska, and to assess to what extent primary diagnosis determine the dose and the length of use of BZDs. Methods: A retrospective analysis of the physicians' prescription habits based on the database of Family Medicine Information Systems of Republic of Srpska, as well as on data from patient's medical record were performed. Patients' socio-demographic and clinical characteristics, including the data on the type and dose of BZDs prescribed, were recorded and evaluated. Results: BZDs were mostly prescribed for anxiety disorders (30.05%), for depressive disorders (17.54%), and for anxiety-depressive disorders (10.86%). A significant amount of BZDs was prescribed for non-psychiatric diagnoses (23.81%). Patients suffering from psychotic disorders were taking the highest dose of BZD and for the longest periods of time (p

Chronic insomnia is a fairly common condition affecting one-fourth of the clinical population. It has been variously defined and is related to a large number of conditions. A thorough assessment of the patient presenting with chronic insomnia is of vital importance for the treatment. Treatment consists of modifying sleep habits to reduce autonomic and cognitive factors and education about healthier sleep practice. Drug treatment should be reserved for the short-term alleviation of insomnia. Appropriate treatment of chronic insomnia improves the quality of life. The prevention of insomnia consists of a balance of rest, recreational exercise in combination with stress management and a healthy diet.

Introduction: The co-association of benzodiazepines and opioids is associated with an increased risk of overdose, death, and poorer psychosocial prognosis. The aim of this study is to characterize the prevalence, pattern of use, and primary clinical outcomes in benzodiazepines users in a public opioid maintenance treatment unit. Material and Methods: We conducted a cross-sectional study involving 236 patients treated with opioid substitutes (methadone and buprenorphine). We conducted a descriptive, bivariable, and multivariable analysis to determine clinical differences between benzodiazepines users and non-users. Results: The prevalence of consumption of benzodiazepines was 25.4% (60). The benzodiazepines were obtained with a medical prescription (49.8%) or on the black market (42.6%). The most prescribed benzodiazepine was diazepam (29.1%), and the main reasons were to relieve insomnia (27.7%) or anxiety (26.9%) and to enhance the psychoactive effects of other drugs (19.7%). Regarding the clinical outcomes, we highlight: a very high prevalence of hepatitis C (51.7%); severe ongoing consumption of psychoactive drugs (73.7%); and a high rate of depression and anxiety (> 60%), significantly higher in the benzodiazepines-user group. In the multivariable analysis of benzodiazepine use, we found alcohol consumption (OR 0.482; IC 95% 0.247, 0.238) had a negative association and having hepatitis C (OR 2.544, IC 95% 1.273, 5.084) or anxiety symptoms (OR 5.591; IC 95% 2.345, 13.326) had positive associations. Discussion: Our results suggest the BZD users had a complex drug addiction problem and underline the importance of adequately addressing BZD use, contemplating psychological and psychiatric approach in this particular population. Conclusion: Past or current use of benzodiazepines is associated with poor clinical and psychiatric outcomes. A multidisciplinary approach with a focus on infectious diseases and mental health is critical in order to enhance the treatment effectiveness and overall prognosis.

Narcolepsy is a neurological disorder characterised by cataplexy, sleep paralysis and excessive daytime sleepiness. The literature on dental managements of patients with narcolepsy is lacking with no set guidelines for dental practitioners. A 31-year-old female presented to the dental office with a dull pain related to the maxillary left lateral incisor with Grade 2 mobility and isolated 8 mm periodontal pocket. In addition, there was loss of buccal gingiva with radiographic changes suggestive of caries and fractured crown. The patient had a history of narcolepsy with cataplexy and hypertension controlled with bisoprolol and desvenlafaxine in addition to clonazepam 1 mg/day as needed to prevent episodes of cataplexy. Patient was asked to take 2 mg clonazepam and 600 mg ibuprofen one hour before procedure. The maxillary left lateral incisor was extracted atraumatically and an immediate implant combined with allogenic bone graft and collagen membrane was placed. The procedure was uneventful, and patient left conscious and stable. After three months, the implant was restored with porcelain fused-to-metal crown and followed-up for six months without any complications. This is the first case describing a narcolepsy patient who successfully received a dental implant without developing a cataplexy episode. Clonazepam prophylaxis may be considered prior to dental procedures for similar situations.