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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: It is unclear how primary care physicians manage insomnia after the introduction of novel hypnotics such as orexin receptor antagonists and melatonin receptor agonists. This Web-based questionnaire survey aimed to examine treatment strategies for insomnia in Japanese primary care practice. Methods: One-hundred-and-seventeen primary care physicians were surveyed on the familiarity of each management option for insomnia on a binary response scale (0 = "unfamiliar"; 1 = "familiar") and how they managed insomnia using a nine-point Likert scale (1 = "I never prescribe/perform it"; 9 = "I often prescribe/perform it"). Physicians who were unfamiliar with a management option were deemed to have never prescribed or performed it. Results: Regarding medication, most physicians were familiar with novel hypnotics. Suvorexant was the most used hypnotic, followed by lemborexant and ramelteon. These novel hypnotics averaged 4.8–5.4 points and 4.0–4.7 points for sleep onset and sleep maintenance insomnia, respectively. By contrast, most benzodiazepines were seldom used below two points. Regarding psychotherapy, only approximately 40% of the physicians were familiar with cognitive behavioral therapy for insomnia (CBT-I) and they rarely implemented it, at an average of 1.5–1.6 points. More physicians were familiar with single-component psychotherapies (i.e., relaxation, sleep restriction therapy, and stimulus control) compared to CBT-I, and 48–74% of them implemented it slightly more often, with scores ranging from 2.6 to 3.4 points. Conclusion: This study suggests that Japanese primary care physicians seldom use CBT-I to treat insomnia. In addition, they use novel sleep medications more frequently than benzodiazepines in terms of pharmacotherapy. The use and availability of CBT-I in Japanese primary care might be facilitated by: educating primary care physicians, implementing brief or digital CBT-I, and/or developing collaborations between primary care physicians and CBT-I specialists. [ABSTRACT FROM AUTHOR]

Effective treatments for major depressive disorder (MDD) have long been needed. One hypothesis for the mechanism of depression involves a decrease in neuroactive steroids such as allopregnanolone, an endogenous positive allosteric modulator of the γ-aminobutyric acid-gated chloride channel (GABAA) receptor. In our previous study, we discovered that allopregnanolone, not diazepam, exhibited antidepressant-like effects in the social interaction test (SIT) of social defeat stress (SDS) model mice. However, the dynamics of neuronal activity underlying the antidepressant-like effect remain unknown. In the current study, we conducted local field potentials (LFPs) recordings from the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) during the SIT to elucidate the relationship between the antidepressant-like effect and neuronal oscillation. We discovered that allopregnanolone has antidepressantlike effects in the SIT of SDS model mice by decreasing intervals of repetitive social interaction (inter-event intervals), resulting in increase of total social interaction time. We also found that theta and beta oscillation increased in BLA at the onset of social interaction following administration of allopregnanolone, which differed from the effects of diazepam. Theta and beta power in BLA within the social interaction zone exhibited a positive correlation with interaction time. This increase of theta and beta power was negatively correlated with inter-event intervals. Regarding theta-band coordinated activity between the BLA and mPFC, theta power correlation decreased at the onset of social interaction with the administration of allopregnanolone. These findings suggest that theta activity in BLA following social interaction and the reduced theta-band coordinated activity between the BLA and mPFC are implicated in social interaction, which is one of the antidepressant behaviors. These differences in neural activity could elucidate the distinctive mechanism underlying antidepressant-like effects of neuroactive steroids, as opposed to benzodiazepines. [ABSTRACT FROM AUTHOR]

Summary Insomnia is a common feature of depression; however, depression treatment guidelines provide limited recommendations regarding hypnotic drugs. Few studies have thoroughly investigated the use of hypnotic drugs in depression. In this cohort study using national Swedish registers, we included all patients ≥18 years with incident unipolar depression during 2007–2017. Patients were followed for 3 years, noting the annual and quarterly prevalence of hypnotic drug use from prescription fills. Prevalence ratios (PR) comparing 2017 to 2007 were calculated with 95% confidence intervals (CI). A total of 222,077 patients with depression were included (mean age 41 years, 59% women). In the year following diagnosis, 44.1% used any hypnotic drug in 2017, compared with 46.7% in 2007 (PR 0.94, 95% CI 0.92–0.97). The most commonly used drugs were Z‐drugs (zopiclone, zolpidem, and zaleplon) with a prevalence of 27.6% in 2017 and 35.6% in 2007 (PR 0.78, 95% CI 0.75–0.80). Melatonin use increased sharply to 12.0% in 2017 from 0.4% in 2007 (PR 28.9, 95% CI 23.5–35.7). Hypnotic drug use was most prevalent in the first two quarters after diagnosis; however, after 3 years, the quarterly prevalence was still 19.2%. Hypnotics were more common among women, older patients, those with somatic comorbidities, more severe depression, or a history of suicide attempt. Evidence from this large register‐based study demonstrates that hypnotics were used to a large extent in depression in Sweden 2007–2017. Z‐drugs use declined and melatonin use increased dramatically. Hypnotic drug use remained high even 3 years after diagnosis. [ABSTRACT FROM AUTHOR]

3,4-Fused pyrrolocoumarins, synthetically prepared or naturally occurring, possess interesting biological properties. In this review, the synthetic strategies for the synthesis of the title compounds are presented along with their biological activities. Two routes are followed for that synthesis. In one, the pyrrole ring is formed from coumarin derivatives, such as aminocoumarins or other coumarins. In the other approach, the pyranone moiety is built from an existing pyrrole derivative or through the simultaneous formation of coumarin and pyrrole frameworks. The above syntheses are achieved via 1,3-dipolar cycloaddition reactions, Michael reaction, aza-Claisen rearrangement reactions, multi-component reactions (MCR), as well as metal-catalyzed reactions. Pyrrolocoumarins present cytotoxic, antifungal, antibacterial, α-glucosidase inhibition, antioxidant, lipoxygenase (LOX) inhibition, and fluorescent activities, as well as benzodiazepine receptor ability. [ABSTRACT FROM AUTHOR]

We designed a robust and efficient greener synthetic protocol to access p-quinone fused 5-substituted-1,4-benzodiazepine scaffolds, a new molecular hybrid, through InCl3 mediated Pictet–Spengler type cycloannulation of 2-amino-3-arylamino-p-quinone and commercially prevalent aldehydes. This protocol would ease access to privileged redox-active p-quinone fused seven-membered frameworks that are difficult to access by other protocols and would find potential applications in biological and electrochemical research. [ABSTRACT FROM AUTHOR]

Introduction and aim. This study investigates the relationship between heart failure (HF) and insomnia, focusing on this two-way association's clinical significance, epidemiology, and management. Material and methods. Literature available in November 2023 was searched using Pubmed, Medline, Google Scholar, and Europe PMC with keywords associated with Heart Failure, Insomnia, and related pharmaceuticals. 69 articles were included. Analysis of the literature. Insomnia is associated with higher mortality and a potential risk of sudden cardiac death, particularly in individuals with HF. Treatment is challenging and side effects can worsen the symptoms of HF. The use of benzodiazepines in HF patients raises concerns about cardiovascular risks, prompting the exploration of other medications like nonbenzodiazepines, antidepressants with sedative effects, and histamine receptor antagonists. On the other hand, HF is also a condition that affects sleep quality. Drugs including ACE-I, beta-blockers, MRA, and SGLT2i are essential for its treatment. Some of them may have an impact on the intensity of insomnia. Conclusion. Considering the impact of insomnia medications on heart failure outcomes and vice versa is necessary. It is important to consider all aspects when treating these two conditions simultaneously. [ABSTRACT FROM AUTHOR]

Background: Data on overuse of diagnostic and therapeutic resources underline their contribution to the decline in healthcare quality. The application of "Do Not Do" recommendations, in interaction with gender biases in primary care, remains to be fully understood. Therefore, this study aims to identify which low-value practices (LVPs) causing adverse events are susceptible to be applied in primary care setting with different frequency between men and women. Methods: A consensus study was conducted between November 1, 2021, and July 4, 2022, in the primary care setting of the Valencian Community, Spain. Thirty-three of the 61 (54.1%) health professionals from clinical and research settings invited, completed the questionnaire. Participants were recruited by snowball sampling through two scientific societies, meeting specific inclusion criteria: over 10 years of professional experience and a minimum of 7 years focused on health studies from a gender perspective. An initial round using a questionnaire comprising 40 LVPs to assess consensus on their frequency in primary care, potential to cause serious adverse events, and different frequency between men and women possibly due to gender bias. A second round-questionnaire was administered to confirm the final selection of LVPs. Results: This study identified nineteen LVPs potentially linked to serious adverse events with varying frequencies between men and women in primary care. Among the most gender-biased and harmful LVPs were the use of benzodiazepines for insomnia, delirium, and agitation in the elderly, and the use of hypnotics without a previous etiological diagnosis. Conclusions: Identifying specific practices with potential gender biases, mainly in mental health for the elderly, contributes to healthcare promotion and bridges the gap in gender inequalities. Trial registration: NCT05233852, registered on 10 February 2022. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic partial hepatectomy inevitably decrease patient immune function. Propofol has been shown to have immunomodulatory effects but is associated with hemodynamic side effects. Despite studies showing a negligible impact of remimazolam tosylate on hemodynamics, it has not been reported for partial hepatectomy patients. Its influence on immune function also remains unexplored. This study sought to investigate the differences in immune function and intraoperative hemodynamics between patients who underwent laparoscopic partial hepatectomy with remimazolam tosylate and those who underwent laparoscopic partial hepatectomy with propofol. Methods: This was a single-center, randomized controlled trial involving 70 patients, who underwent elective laparoscopic partial hepatectomy. The patients were randomly divided into two groups: the remimazolam group (group R) and the propofol group (group P). In this study, the primary outcomes assessed included the patient's immune function and hemodynamic parameters, and the secondary outcomes encompassed the patient's liver function and adverse events. Results: Data from 64 patients (group R, n = 31; group P, n = 33) were analyzed. The differences in the percentages of CD3+, CD4+, CD8+, and NK cells and the CD4+/CD8+ ratio between the two groups were not statistically significant at 1 day or 3 days after surgery. Compared with those in group P, the MAP and HR at T2 and the MAP at T1 in group R were significantly increased(P < 0.05). The differences in HR and MAP at T0, T3, T4, T5, T6, and T7 and HR at T1 between the two groups were not statistically significant. There were no differences in liver function or adverse effects between the two groups, suggesting that remimazolam tosylate is a safe sedative drug(P > 0.05). Conclusion: The effects of remimazolam tosylate on the immune function of patients after partial hepatectomy are comparable to those of propofol. Additionally, its minimal effect on hemodynamics significantly decreases the incidence of hypotension during anesthesia induction, thereby enhancing overall perioperative safety. Trial registration: The trial was registered on May 9, 2022 in the Chinese Clinical Trial Registry, registration number ChiCTR2200059715 (09/05/2022). [ABSTRACT FROM AUTHOR]

Background: Remimazolam is a recently developed, ultrashort-acting benzodiazepine that is used as a general anesthetic. Some cases of remimazolam anaphylaxis have been reported, but its characteristics are not fully understood. We present an interesting case report and review of the literature to better understand remimazolam anaphylaxis. Case presentation: A 75-year-old man scheduled for robot-assisted gastrectomy was administered remimazolam for the induction of general anesthesia. After intubation, low end-expiratory CO2, high airway pressure and concurrent circulatory collapse were observed. Bronchoscopy revealed marked tracheal and bronchial edema, which we diagnosed as anaphylaxis. The patient suffered cardiac arrest after bronchoscopy but recovered immediately with intravenous adrenaline administration and chest compressions. We performed skin prick tests for the drugs used during induction except for remimazolam, considering the high risk of systemic adverse reactions to remimazolam. We diagnosed remimazolam anaphylaxis because the skin prick test results for the other drugs used during anesthesia were negative, and these drugs could have been used without allergic reactions during the subsequent surgery. Furthermore, this patient had experienced severe anaphylactic-like reactions when he underwent cardiac surgery a year earlier, in which midazolam had been used, but it was not thought to be the allergen at that time. Based on these findings, cross-reactivity to remimazolam and midazolam was suspected. However, the patient had previously received another benzodiazepine, brotizolam, to which he was not allergic, suggesting that cross-reactivity of remimazolam may vary among benzodiazepines. In this article, we reviewed the 11 cases of remimazolam anaphylaxis that have been described in the literature. Conclusions: Remimazolam is an ultrashort-acting sedative; however, it can cause life-threatening anaphylaxis. In addition, its cross-reactivity with other benzodiazepines is not fully understood. To increase the safety of this drug, further research and more experience in its use are needed. [ABSTRACT FROM AUTHOR]

AbstractAn increasing number of new psychoactive substances (NPS), such as designer benzodiazepines, are becoming available on the recreational drug market. These are new unregistered substances and thereby an attempt to evade legislation. Often there is very limited clinical information available regarding these NPS, which could result in undesirable clinical outcomes in the management of intoxications, dependencies and withdrawals following NPS use. In this case report we describe a 23-year-old woman, who was admitted to our residential addiction care facility for the detoxification of the designer benzodiazepine bromazolam. Her daily use of 6 mg bromazolam was converted to 20 mg diazepam. Although we expected a higher dose would have been needed, 20 mg was sufficient and was tapered without complications. This case report demonstrates the safe conversion of 6 mg of bromazolam to 20 mg of diazepam by combining the use of fixed-dose and symptom-triggered-dose regimens. More clinical data is necessary to formulate advisory management for the detoxification of bromazolam and other designer benzodiazepines. [ABSTRACT FROM AUTHOR]

Background: Delirium is a common neuropsychiatric syndrome without an FDA-approved treatment. Commonly used modalities show little improvement in outcomes; therefore, prevention efforts are imperative. Abnormalities in the sleep/wake cycle have been linked to delirium, and melatonin has been proposed to replace the hypothesized low levels of endogenous melatonin and restore sleep/wake cycle synchronization. Objectives: The primary objective of this study was to evaluate the association between melatonin, benzodiazepines (BZDs) or zolpidem (ZLP), and the use of as-needed antipsychotics and BZDs for delirium in noncritically ill adult patients. Methods: This was a multicenter retrospective cohort study of noncritically ill adult patients admitted to two separate health systems from August 2012 to December 2018 receiving either melatonin or nonmelatonin medications (ZLP or BZDs) for sleep. The coprimary endpoint was the proportion of patients receiving a pro re nata (PRN) antipsychotic or BZD 5 days from the patient's first dose of melatonin, BZD, or ZLP. Secondary outcomes included evaluation of the coprimary outcome in patients 65 years of age or older, total number of PRN antipsychotic and BZD doses, and length of stay. Results: Two hundred and twenty-five patients were included in the final analysis. Administration of BZD or ZLP was associated with a higher risk of subsequent BZD administration as compared with melatonin (OR 2.78, 95% CI 1.2–1.87) and ZLP (OR 2.78, 95% CI 1.25–6.17). BZD or ZLP had no impact on PRN antipsychotic use compared with melatonin (OR 1.09, 95% CI 0.51–2.35) and ZLP (OR 1.16, 95% CI 0.56–2.4). Conclusion: Melatonin use was found to be associated with a significant decrease in PRN BZD use in noncritically ill patients hospitalized on general floors; however, there was no observed association with overall PRN antipsychotic use. These results suggest that using melatonin may help decrease utilization of medications commonly used to manage delirium. [ABSTRACT FROM AUTHOR]

The coexistence of psychiatric disorders and cardiovascular diseases represents a complex clinical challenge, often necessitating the concurrent use of medications from both therapeutic categories. While these medications are essential for managing their respective pathologies, their combined use can lead to interactions that may affect treatment outcomes and patient safety. Understanding the interactions between psychotropic drugs and those used in cardiovascular diseases is crucial for healthcare professionals to optimize therapeutic regimens and minimize potential adverse effects. This article aims to explore the various types of interactions between psychotropic and cardiovascular medications, analyze their underlying mechanisms, evaluate the clinical implications, and propose strategies to reduce risks and optimize treatment outcomes. By understanding these interactions, healthcare professionals can enhance clinical decision-making and provide safer and more effective pharmacotherapy for patients with complex medical needs. [ABSTRACT FROM AUTHOR]

Introduction: Alcohol and substance use are increasing in older adults, many of whom have depression, and treatment in this context may be more hazardous. We assessed alcohol and other substance use patterns in older adults with treatment‐resistant depression (TRD). We examined patient characteristics associated with higher alcohol consumption and examined the moderating effect of alcohol on the association between clinical variables and falls during antidepressant treatment. Methods: This secondary and exploratory analysis used baseline clinical data and data on falls during treatment from a large randomized antidepressant trial in older adults with TRD (the OPTIMUM trial). Multivariable ordinal logistic regression was used to identify variables associated with higher alcohol use. An interaction model was used to evaluate the moderating effect of alcohol on falls during treatment. Results: Of 687 participants, 51% acknowledged using alcohol: 10% were hazardous drinkers (AUDIT‐10 score ≥5) and 41% were low‐risk drinkers (score 1–4). Benzodiazepine use was seen in 24% of all participants and in 21% of drinkers. Use of other substances (mostly cannabis) was associated with alcohol consumption: it was seen in 5%, 9%, and 15% of abstainers, low‐risk drinkers, and hazardous drinkers, respectively. Unexpectedly, use of other substances predicted increased risk of falls during antidepressant treatment only in abstainers. Conclusions: One‐half of older adults with TRD in this study acknowledged using alcohol. Use of alcohol concurrent with benzodiazepine and other substances was common. Risks—such as falls—of using alcohol and other substances during antidepressant treatment needs further study. Key points: Approximately half of older adults with treatment‐resistant depression acknowledged drinking alcoholAmong drinkers, 24% were also using benzodiazepine and 10% were using other substances like cannabisUse of other substances (mostly cannabis) was associated with alcohol consumption [ABSTRACT FROM AUTHOR]

Aim: Knowledge of risk factors may provide strategies to reduce the high burden of delirium in intensive care unit (ICU) patients. We aimed to compare the risk of delirium after deep sedation with propofol versus midazolam in ICU patients. Methods: In this prospective cohort study, ICU patients who were in an unarousable state for ≥24 h due to continuous sedation with propofol and/or midazolam were included. Patients admitted ≤24 h, those with an acute neurological disorder and those receiving palliative sedation were excluded. ICU patients were assessed daily for delirium during the 7 days following an unarousable state due to continuous sedation. Results: Among 950 included patients, 605 (64%) subjects were delirious during the 7 days after awaking. The proportion of subsequent delirium was higher after midazolam sedation (152/207 [73%] patients) and after both propofol and midazolam sedation (257/377 [68%] patients), compared to propofol sedation only (196/366 [54%] patients). Midazolam sedation (adjusted cause‐specific hazard ratio [adj. cause‐specific HR] 1.32, 95% confidence interval [CI] 1.05‐1.66) and propofol and midazolam sedation (adj. cause‐specific HR 1.29, 95% CI 1.06‐1.56) were associated with a higher risk of subsequent delirium compared to propofol sedation only. Conclusion: This study among sedated ICU patients suggests that, compared to propofol sedation, midazolam sedation is associated with a higher risk of subsequent delirium. This risk seems more apparent in patients with high cumulative midazolam intravenous doses. Our findings underpin the recommendations of the Society of Critical Care Medicine Pain, Agitation/sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep (disruption) guidelines to use propofol over benzodiazepines for sedation in ICU patients. [ABSTRACT FROM AUTHOR]

β‐Phenyl‐γ‐aminobutyric acid (phenibut) is an analog of the inhibitory neurotransmitter γ‐aminobutyric acid (GABA) that was first synthesized in Russia in the early 1960s. It is marketed as a nootropic (smart drug) to improve cognitive performance, and to treat generalized and social anxiety, insomnia, and alcohol withdrawal. The use of phenibut is legal in the USA and it is widely available online without a prescription. Increased public awareness of phenibut has led to a growing number of reports of acute intoxication and withdrawal. In this review, we describe the pharmacology of phenibut, the presentation and management of acute intoxication, and regulatory issues, placing particular emphasis on the treatment of acute withdrawal, for which there are no comparative studies. Among 29 cases of phenibut withdrawal, patients were successfully treated with baclofen, benzodiazepines, and phenobarbital, as individual agents or in various combinations. Ancillary medications included antipsychotics, dexmedetomidine, gabapentin, and pregabalin. After stabilization, a number of patients did well on baclofen tapers, whereas others were weaned off benzodiazepines or phenobarbital. Phenobarbital may be preferred over baclofen, or used as an added agent, in patients at risk for seizures. As long as phenibut remains legal, cases of phenibut intoxication and withdrawal are likely to increase. As urine or plasma drug screening for phenibut is not widely available, it is vital that clinicians obtain a detailed medication history in patients presenting to the emergency department with nonspecific symptoms that may represent phenibut intoxication or withdrawal. Further, clinicians may wish to consult an addiction specialist or toxicologist in these situations. [ABSTRACT FROM AUTHOR]

Background: Holocaust survivors (HS) experience higher rates of physiological and psychological morbidities, increasing their vulnerability to perioperative complications. Limited information exists regarding their perioperative neurocognitive disorders. This study aimed to assess the rates of preoperative cognitive impairment, postoperative delirium, and other complications among HS aged 75+ undergoing elective surgery. Methods: This is a single‐center retrospective cohort study that analyzed prospectively collected data. All surgical patients born before 1945 who underwent elective noncardiac surgery at a tertiary hospital in Israel during 2020–2021 were included. The HS group was identified through the hospital's information system. Preoperative cognitive impairment was assessed using the Mini‐Cog test. Postoperative delirium was defined as a combined outcome, which included a positive 4A's‐Test (4AT) result during the postanesthesia care unit stay up to the second postoperative day, a positive 3‐Minute Diagnostic Confusion Assessment Method (3D‐CAM) test administered by the geriatric team, and identification through the medical records using the Chart‐based Delirium Identification Instrument (CHART‐DEL). We used multivariable regression to assess the risk factors for postoperative delirium. Results: Out of 1332 eligible patients, 422 (32%) were HS, while the others served as controls. Both groups had a similar rate of preoperative cognitive impairment (24%, p = 0.89) and postoperative delirium (16%, p = 0.95). HS exhibited a higher risk of the composite adverse events (24% vs. 20%, p = 0.05, aOR [95% CI] 1.3 [1.0–1.7]), driven mainly by falls during hospitalization (4% vs. 2%, p = 0.03, aOR 2.1 [1.1–4.1]). HS patients were more likely to be childless (33% vs. 11%, p = 0.001) and had higher rates of chronic antidepressant and benzodiazepine use. Conclusions: HS achieving longevity do not face increased risks of preoperative cognitive impairment and postoperative delirium. However, special care is still warranted due to their elevated rate of other complications during hospitalization. [ABSTRACT FROM AUTHOR]

The use of benzodiazepines is strongly associated with an increased risk of traffic accidents due to their side effects of sedation and drowsiness, which can significantly impair driving performance. The main aim of our study was to investigate the trend of benzodiazepine use over nine years (2015–2023) in a population of 15,988 subjects who had their license suspended for driving under the influence (DUI) of alcohol or drugs. Among the 15,988 users accessed to our laboratory, 924 tested positive for at least one benzodiazepine. An increase in the number of positive-testing users was observed in the period 2015–2018, followed by a slight decrease in 2019. Overall, the trend of benzodiazepine use was stable over the next four years (2020–2023), with the highest incidence in 2022. The most common benzodiazepines, and/or metabolites, found in urine samples were α-OH-alprazolam (28.66%; n = 366) and oxazepam (27.25%; n = 348). Several cases of mixed positivity were observed in the study population. The main substances taken with benzodiazepines were cocaine and Δ9-tetrahydrocannabinol. Our findings suggest that people taking benzodiazepines should be monitored, as these have a relevant impact on driving ability in addition to significant interindividual differences in the behavioral effects of benzodiazepines on driving performance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Tetanus is a life-threatening, vaccine-preventable disease caused by an endotoxin produced by Clostridium tetani. We report a case of severe tetanus in an adult male with a history of intravenous drug use. The patient presented with a 1-day history of inability to open his jaw and a right lower extremity necrotic wound. Initial management consisted of tetanus toxoid, human tetanus immunoglobulin, antimicrobials and intermittent lorazepam. Due to progressive symptoms, wound debridement and placement of an advanced airway in the operating room ensued. Episodes of tetany were associated with fever, autonomic instability, acute desaturations and preemptive ventilator triggering despite maximum doses of continuous propofol and midazolam. Neuromuscular blockade with cisatracurium was added, resulting in control of tetany. Despite initial control, NMB could not be weaned due to recurrent spasms. Intravenous dantrolene was therefore sought as an alternative antispasmodic. Following an initial load, patient was successfully liberated from cisatracurium. Dantrolene was therefore converted to enteral to facilitate gradual down-titration of intravenous sedatives with subsequent conversion to oral benzodiazepines. After a prolonged hospital course, the patient was able to be discharged home. Dantrolene was thus effectively utilized as an adjunctive antispasmodic agent to facilitate liberation from cisatracurium and continuous sedation. [ABSTRACT FROM AUTHOR]

Simple Summary: In the last days and weeks of life, many patients with cancer develop delirium with fluctuating confusion, altered levels of consciousness, hallucinations, restlessness, and, sometimes, agitation, which fluctuate over time. This condition can be very distressing for the patient and their family. In this article, the authors reviewed different treatments for delirium in patients receiving palliative care. Previous studies have shown that certain medications, such as neuroleptics and benzodiazepines, may be helpful in controlling the terminal agitation associated with end-of-life delirium. However, further research is needed to confirm these findings and find new treatment options to address this challenging issue. End-of-life delirium affects a vast majority of patients before death. It is highly distressing and often associated with restlessness or agitation. Unlike delirium in other settings, it is considered irreversible, and non-pharmacologic measures may be less feasible. The objective of this review is to provide an in-depth discussion of the clinical trials on delirium in the palliative care setting, with a particular focus on studies investigating pharmacologic interventions for end-of-life delirium. To date, only six randomized trials have examined pharmacologic options in palliative care populations, and only two have focused on end-of-life delirium. These studies suggest that neuroleptics and benzodiazepines may be beneficial for the control of the terminal restlessness or agitation associated with end-of-life delirium. However, existing studies have significant methodologic limitations. Further studies are needed to confirm these findings and examine novel therapeutic options to manage this distressing syndrome. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of concomitant use of benzodiazepines on the efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with treatment-resistant major depressive disorder (TR-MDD). Methods: This is a retrospective study comparing rTMS treatment outcomes between patients taking benzodiazepines (n = 59) and those who were not (n = 136). Participants completed the HAM-A, HAM-D17, MADRS and ZUNG at baseline and at the end of treatment. Results: Patients taking benzodiazepines during rTMS treatment did not show any difference in partial response, response or remission rates compared to patients not treated with benzodiazepines. There was a significant decrease (p <.0001) in depression and anxiety scores from baseline to post-treatment among both groups. Conclusions: Concomitant benzodiazepine treatment had no effect on the efficacy of rTMS treatment of TRD, contrary to previous research. [ABSTRACT FROM AUTHOR]

New psychoactive substances (NPS), like pyrrolidinophenones, are still very present on the illegal drug market. The presented study reports on two members of this substance group, α-pyrrolidinohexanophenone (α-PHP) and α-pyrrolidinoisohexanophenone (α-PiHP), which occurred in forensic routine cases in the last 6 years. α-PHP could be detected predominantly by a validated liquid chromatography–tandem mass spectrometry (LC–MS-MS) method in 33 authentic human plasma samples and α-PiHP in 8. α-PHP concentrations ranged from ca. 0.75 to 128 µg/L (mean: 23.2, median: 16.3) and α-PiHP concentrations from 7.33 to 118 µg/L (mean: 44.7, median: 33.7, quantified via α-PHP). Individuals were predominantly male and middle aged. As different studies have shown, some pyrrolidinophenones are able to cause aggressive behavior. Therefore, we set out to investigate the relation of α-PHP and α-PiHP plasma concentrations and the behavior of the consumers, reported by police and medical experts. Part of the subjects showed aggressive behavior, including agitation and restlessness. Lethargic and unremarkable behavior might be explained by co-consumption of other drugs, such as opiates/opioids, benzodiazepines, pregabalin or alcohol as well as by drug tolerance and subacute effects of stimulants. Multi-drug use could be detected in all cases; also stimulating substances and multiple different pyrrolidinophenones were determined. Nevertheless, users of α-PHP and α-PiHP showed a tendency to act aggressively, possibly triggered by a high selectivity for dopamine transporter inhibition. In accordance, committed offenses were often violent crimes. This might be considered in terms of toxicological assessment of criminal responsibility and driving ability. [ABSTRACT FROM AUTHOR]

In status epilepticus (SE), "time is brain." Currently, first‐line therapy consists of benzodiazepines (BDZs) and SE is classified by the response to treatment; stage 2 or established SE is defined as "BDZ‐resistant SE." Nonetheless, this classification does not always work, especially in the case of prolonged convulsive SE, where many molecular changes occur and γ‐aminobutyric acid signaling becomes excitatory. Under these circumstances, BDZ therapy might not be optimal, and might be possibly detrimental, if given alone; as the duration of SE increases, so too does BDZ resistance. Murine models of SE showed how these cases might benefit more from synergistic combined therapy from the start. The definition of Stage 1 plus is suggested, as a stage requiring combined therapy from the start, which includes prolonged SE with seizure activity going on for >10 min, the time that marks the disruption of receptor homeostasis, with increased internalization. This specific stage might require a synergistic approach from the start, with a combination of first‐ and second‐line treatment. [ABSTRACT FROM AUTHOR]

Introduction: Catatonia, a psychomotor disorder characterized by diverse clinical signs, including stupor and mutism, remains elusive in its causes and a challenge to diagnose. Moreover, it is often underrecognized due to its resemblance to disorders of consciousness. However, when diagnosing catatonia, an antipsychotic medication may exacerbate the condition. The first‐line treatment typically includes benzodiazepines and/or electroconvulsive therapy (ECT). Case Report: A 60‐year‐old woman with systemic lupus erythematosus (SLE) and epilepsy presented with catatonic stupor. Despite stable treatment, she experienced an acute deterioration in consciousness, requiring hospitalization. Her condition improved markedly following a benzodiazepine challenge, as documented on EEG. This improvement was short‐lived, but a second benzodiazepine challenge restored her from E1V1M1 (stupor) to E4V5M6 within minutes, as documented by a video recording. The patient was treated with lorazepam 1.5 mg/day orally and did not experience further relapses. Discussion: The diagnosis of catatonia had been based on her scores on the Bush‐Francis Catatonia Rating Scale (BFCRS; Screening, 6/14; Severity, 19), despite meeting only two DSM‐5 criteria for catatonia (stupor and mutism). The diagnosis was supported by EEG and video documentation, excluding other potential differential diagnoses such as nonconvulsive status epilepticus and encephalopathy. Additional quantitative EEG analyses indicated that benzodiazepine administration increased brainwide alpha and beta band power significantly, suggesting that the benzodiazepine normalized attention, consciousness, and long‐range synchronization. This report additionally emphasizes the significance of video recordings in managing catatonia, and it helps in accurately tracking symptoms, documenting comprehensively, and improving patient understanding, which is crucial for treatment adherence. [ABSTRACT FROM AUTHOR]

The article offers information on the use of trazodone for insomnia and other sleep disturbances, highlighting its common prescription despite being an off-label use. Topics include the challenges of non-pharmacological options like cognitive behavioral therapy for insomnia (CBT-I) in rural areas, the limitations of sleep hygiene education, and the need for immediate sleep solutions in some cases.

Aging is often associated with an increasing number of comorbidities that warrant use of multiple drugs which increases the use of potentially inappropriate medications (PIMs), drug–drug interactions (DDIs) and drug‐related problems (DRPs). The aim is to assess the prevalence of polypharmacy, PIMs, DDIs and DRPs among Faroese residents aged ≥90 years. In this population‐based cross‐sectional study, 494 individuals ≥90 years were invited and 298 (60%) participated. A pharmacist‐led medication review was performed based on self‐information, electronic patient journal and the Faroese Prescription Registry. The prevalence of polypharmacy was 74% with no sex‐difference. Approximately 60% of participants used PIMs, primarily benzodiazepines and proton pump inhibitors, the latter being a frequently implicated medication in DRPs. Opioid use was low compared with other Nordic studies. DRPs were observed for 79% with discrepancies in the medication lists as the most common cause, and DDIs were identified for 47% of participants, mostly moderately clinically relevant DDIs. In conclusion, the medication use among the oldest old Faroese resembled that in other Nordic countries with a high prevalence of polypharmacy and use of PIMs, especially PPIs and benzodiazepines. However, no sex‐difference was noted in medication use and the use of opioids was low. [ABSTRACT FROM AUTHOR]

The American Journal of Physiology: Lung Cellular & Molecular Physiology is seeking papers on the topic of "Opioids and Respiratory Depression" in response to the opioid health crisis. The call for papers aims to address the dangerous side effect of respiratory depression caused by opioid overdose. The journal encourages researchers and healthcare professionals to submit articles and reviews related to breathing regulation and the detrimental consequences of opioids. The document is a list of references cited in an article discussing the prediction of opioid-induced respiratory depression using continuous capnography and oximetry, including studies on the effects of opioids on breathing, sleep-disordered breathing, risk factors, and the neurobiology of respiratory control. [Extracted from the article]

Purpose: Prior research has noted treatment inequalities in the care of rural veterans with posttraumatic stress disorder (PTSD). This project sought to increase the delivery, or reach, of recommended PTSD treatments in 2 rural health care systems of the Department of Veterans Affairs (VA) using implementation facilitation. Methods: The quality improvement project involved 6 months of facilitation to 2 low‐reach PTSD clinics within 2 VA health care systems. The clinics were matched to a control clinic at another regional system similar in reach, rurality, and patient volume. We compared the delivery of evidence‐based psychotherapies (EBPs) for PTSD at 3 timepoints: baseline, 6 months, and 1 year using difference‐in‐difference effect estimation. Facilitators and barriers of EBP reach were identified through interviews with clinic staff and informed specific implementation plans. We also measured reductions in benzodiazepine prescriptions and polypharmacy to determine the impact of an academic detailing intervention aimed at improving PTSD prescribing practices at the 2 sites. Findings: EBP reach at 6 months more than doubled in the 2 PTSD clinics that received facilitation, while our control clinic experienced a decrease in EBP reach (DID = 24.6; SE = 6.71%). Both intervention clinics identified similar administrative barriers to the delivery of EBPs, offering useful information for improvement at other rural clinics. The use of academic detailing as part of our facilitation intervention further appears to have positively impacted care. Conclusions: In this preliminary work, facilitation is a promising strategy for increasing the delivery of PTSD EBPs to veterans seen in under‐resourced rural VA clinics. [ABSTRACT FROM AUTHOR]

Objective: We aimed to examine the factors associated with treatment outcomes in patients with Alzheimer's disease (AD) after 1 year of acetylcholinesterase inhibitors (AChEI) treatment. Method: We obtained electronic medical records from a medical center in Southern Taiwan between January 2015 and September 2021. Participants aged ≥60 who were newly diagnosed with AD and had been prescribed AChEIs were included. Cognitive assessments were performed before the AChEIs were prescribed and at the 1 year follow‐up. Cognition progressors were defined as a Mini‐Mental State Examination decline of >3 or a Clinical Dementia Rating decline of ≥1 after 1 year of AChEI treatment. The relationship between the baseline characteristics and cognitive status after follow‐up was investigated using logistic regression analysis after adjusting for potential confounders. Results: A total of 1370 patients were included in our study (mean age, 79.86 ± 8.14 years). After adjustment, the body mass index (BMI) was found to be significantly lower in the progressor group [adjusted odds ratio (AOR): 0.970, 95% confidence intervals (95% CIs): 0.943 to 0.997, P = 0.033]. The usage of antipsychotics was significantly higher in the progressor group (AOR: 1.599, 95% CIs: 1.202 to 2.202, P = 0.001). The usage of benzodiazepine receptor agonists also tended to be significantly higher in the progressor group (AOR: 1.290, 95% CIs: 0.996 to 1.697, p = 0.054). Conclusion: These results suggest that patients with AD who receive 1 year of AChEI treatment and have a lower BMI or concurrent treatment with antipsychotics and benzodiazepine receptor agonists are more likely to suffer from cognitive decline. [ABSTRACT FROM AUTHOR]

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Simple Summary: Seizures are commonly noted in dogs and cats and should prompt immediate veterinary assessment and care in first time seizure patients or patients with multiple or ongoing seizures. All animals presenting for seizures should be evaluated to ensure they are not in imminent danger of death, to confirm that the episode noted at home was a seizure, and to look for the underlying causes of seizures. In certain situations, animals with seizures require immediate anticonvulsant medications and possibly in-hospital therapy and monitoring. This review presents a stepwise approach for veterinarians evaluating patients presenting for seizures. Seizures are a common presentation seen in small animal practices. Seizures require prompt management including initial interventions for triage, stabilization, and treatment with first-line anticonvulsant (AC) drugs like benzodiazepines. Concurrently, ruling out metabolic or extracranial causes with point-of-care diagnostics can help guide further diagnostics and treatments. Analysis of the history and a physical exam are also necessary to rule out common "look-alikes" that require specific diagnostic workup and treatments. Typically, causes of seizures can be grouped into intracranial and extracranial causes, with the latter being easier to diagnose with commonly available tests. This review presents a systematic approach to the diagnosis and treatment of single seizures, cluster seizures, and status epilepticus in dogs and cats. [ABSTRACT FROM AUTHOR]

Background and Objectives: Gabapentin has shown promise as a potential agent for the treatment of alcohol withdrawal syndrome. We aimed to evaluate the effectiveness of gabapentin as a benzodiazepine-sparing agent in patients undergoing alcohol withdrawal treatment in all the hospitals of a large tertiary healthcare system. Materials and Methods: Medical records of patients admitted to the hospital for alcohol withdrawal management between 1 January 2020 and 31 August 2022 were reviewed. Patients were divided into two cohorts: benzodiazepine-only treatment who received benzodiazepines as the primary pharmacotherapy and gabapentin adjunctive treatment who received gabapentin in addition to benzodiazepines. The outcomes assessed included the total benzodiazepine dosage administered during the treatment and the length of hospital stay. The statistical models were calibrated to account for various factors. Results: A total of 4364 patients were included in the final analysis. Among these, 79 patients (1.8%) received gabapentin in addition to benzodiazepines, and 4285 patients (98.2%) received benzodiazepines only. Patients administered gabapentin required significantly lower average cumulative benzodiazepine dosages, approximately 17.9% less, compared to those not receiving gabapentin (median 2 mg vs. 4 mg of lorazepam equivalent dose (p < 0.01)). However, there were no significant differences in outcomes between the two groups. Conclusions: Our findings demonstrate that using gabapentin with benzodiazepine was associated with a reduction in the cumulative benzodiazepine dosage for alcohol withdrawal. Considering gabapentin as an adjunctive therapy holds promise for patients with comorbidities who could benefit from reducing benzodiazepine dose. This strategy warrants further investigation. [ABSTRACT FROM AUTHOR]

Purpose: Medicines are often prescribed to workers with musculoskeletal disorders (MSDs) and injuries to relieve pain and facilitate their recovery and return to work. However, there is a growing concern that prescription medicines may have adverse effects on work function. This scoping review aimed to summarize the existing empirical evidence on prescription medicine use by workers with MSD or injury and its relationship with work-related outcomes. Methods: We identified studies through structured searching of MEDLINE, EMBASE, PsycINFO, CINAHL Plus, Scopus, Web of Science and Cochrane library databases, and via searching of dissertations, theses, and grey literature databases. Studies that examined the association between prescription medicine and work-related outcomes in working age people with injury or MSDs, and were published in English after the year 2000 were eligible. Results: From the 4884 records identified, 65 studies were included for review. Back disorders and opioids were the most commonly studied musculoskeletal conditions and prescription medicines, respectively. Most studies showed a negative relationship between prescription medicines and work outcomes. Opioids, psychotropics and their combination were the most common medicines associated with adverse work outcomes. Opioid prescriptions with early initiation, long-term use, strong and/or high dose and extended pre- and post-operative use in workers' compensation setting were consistently associated with adverse work function. We found emerging but inconsistent evidence that skeletal muscle relaxants and non-steroidal anti-inflammatory drugs were associated with unfavorable work outcomes. Conclusion: Opioids and other prescription medicines might be associated with adverse work outcomes. However, the evidence is conflicting and there were relatively fewer studies on non-opioid medicines. Further studies with more robust design are required to enable more definitive exploration of causal relationships and settle inconsistent evidence. [ABSTRACT FROM AUTHOR]

ObjectiveThe study aimed to evaluate Zolpidem and Benzodiazepines prescription and dispensing data in private pharmacies in Brazil from 2014 to 2021. Methods: This retrospective cohort study was carried out with retrospective open data from the Brazilian Federal Government from January 2014 to August 2021 containing medicines registered in the National Controlled Products Management System (SNGPC).ResultsBetween January 2014 and August 2021, a total of 32,441,392 sales of thirteen drugs from the z-drug and benzodiazepine classes used to treat sleep disorders were recorded in Brazil. Throughout the entire period, clonazepam emerged as the most popular drug, accounting for 29.8% of total sales. Alprazolam followed in second place with 20.6% of sales, while zolpidem came in third with 14.4%. The normal-release form of zolpidem was consistently the highest-selling variant during the evaluation period. However, the fast-acting-release form exhibited the most significant growth, indicated by a noticeable upward trend in sales since 2020. In contrast, the extended-release form of zolpidem remained stable over the years.ConclusionThe increased sales of zolpidem in Brazilian private pharmacies raise concerns about potential misuse and dependence on this drug mainly for the treatment of insomnia. The epidemic of sleeping pills arises in a scenario of expectancy of short-term amelioration of symptoms, with no correspondence in best clinical practice. Education and counseling for both healthcare professionals and the general population are essential to address this growing health concern and ensure the safe and appropriate use of medications for sleep disorders.

Background: Acute poisoning is a major medical emergency that translates into morbidity and mortality across all age groups, it is a potentially preventable cause of illness and death. This study was carried out to assess the epidemiological information of acute poisoning among the general population presented to the three campuses of a private tertiary care teaching hospital in Karachi, Pakistan. Method: The cross-sectional study was conducted at three campuses of a private tertiary care teaching hospital, Dr. Ziauddin Hospital in Karachi, comprising of records from January 1, 2018, to December 31, 2022, of patients reporting acute poisoning. These records were accessed after getting approval from the Ethical review committee. Consecutive sampling technique was applied while data was collected. All cases of acute poisoning reporting to the emergency department with complete records were included. While data of those with any other diagnosis or incomplete record were excluded. Descriptive analysis was performed for quantitative variables. For categorical data frequency and percentages were extracted. The chi-square test was used to associate categorical variables. P value less than 0.05 was taken as statistically significant. Results: The total number of cases was n=518 out of which n=235 (45.4%) were males while n=283 (54.6%) were females and the maximum number of cases n=111 (21.4%) were associated with Benzodiazepines followed by insecticide poisoning and ingestion of rodenticides. Conclusions: The most susceptible groups to acute poisoning were found to be women and children. A prevalent agent that caused toxicity was benzodiazepines; the biggest number of cases occurred in April, while the lowest number occurred in December. The year 2020 was linked to the highest number of cases.

ObjectiveTo compare the efficacy of intranasal (IN) and intramuscular (IM) administrations of azaperone (3 mg kg−1), midazolam (0. 3 mg kg−1), and ketamine (7 mg kg−1) combination (AMK) in pigs. Study design: Randomized clinical trial. Animals: sixteen adult male pigs, immunocastrated, of mixed lineage.MethodsIn phase I, these animals were randomly assigned to intranasal (GIN, n = 8) and intramuscular (GIM, n = 8) groups for arterial blood sample collection at 10, 20, 30, 45, 60, and 90 min after AMK administrations for gas and electrolyte analysis. In phase II, performed 1 week after phase I, the 16 pigs were allocated to both groups (GIM, n = 16/GIN, n = 16) and submitted to the same chemical restraint (CR) protocol, with a 96-h interval between administrations. Behavioral parameters (degree of CR, muscle relaxation, loss of postural reflex, and sound stimulus response) and vital parameters (pulse rate, respiratory rate, oxygen saturation, and rectal temperature) were evaluated after recumbency (Trec) and at 5, 15, 30, 45, 60, and 90 min after administrations. In addition, the latency period and duration of CR were determined.ResultsLatency to recumbency and duration of CR in GIN were shorter. CR scores did not vary between groups. Muscle relaxation was more intense in GIN at Trec. An initial tachycardia was observed, followed by a reduction in heart rate from T5 to T90 in both treatments (p < 0.05). The respiratory rate was higher at T45, T60, and T90 in GIN compared to baseline. Rectal temperature reduced in GIM from T45 onwards. PaCO2t elevated at T90 in the GIM (p < 0.05) and there was an incidence of mild hypoxemia in 47% of the animals in the GIM.Conclusions and clinical relevanceIN administration was as effective as IM administration in promoting safe chemical restraint, with minimal changes in homeostasis, with a shorter duration and latency period.

Background A nationwide register-based cohort study from Finland including 48 124 incident benzodiazepines and related drug (BZDR) users aged 18–65 years who initiated use in 2006 and were not dispensed BZDRs during 2004–2005. The follow-up was 5 years or until death, whichever occurred first. Aims To investigate sociodemographic and clinical factors associated with high-dose use of BZDRs (i.e. Z-drugs) among new BZDR users. Method The temporal BZDR dose was calculated as a point estimate every 6 months after initiation as defined daily doses (DDDs) per day, based on the PRE2DUP method (an approach based on mathematical modelling of personal drug purchasing behaviours). Sociodemographic and clinical factors associated with dose categories were studied using multinomial logistic regression. Results During the 5-year follow-up, very high-dose BZDR use was observed in 7.4% (n = 3557) and medium high-dose use in 25.5% (n = 12 266) of the users (corresponding to ≥30 mg and 10–29 mg in diazepam equivalents, respectively). Very high-dose use was more common among men compared with women (10.9% versus 4.6%). Very high-dose use patterns were especially observed in younger age groups (18- to 25-year-olds). Compared with oxazepam, initiating BZDR use with clonazepam (adjusted odds ratio 3.86, 95% CI 3.24–4.60), diazepam (2.05, 1.78–2.36) or alprazolam (1.76, 1.52–2.03) was associated with increased odds for very high-dose use. Both medium high-dose and very high-dose BZDR use were associated with a lower level of education. In all, 58% of very high-dose use occurred in BZDR users who received their first prescription from general practitioners. Conclusions Clinicians should be aware of the dose escalation risk especially when prescribing diazepam, alprazolam or clonazepam for psychiatric indications. If BZDRs are needed, our findings suggest favouring oxazepam.

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.

Benzodiazepines (BDZs) are psychotropic drugs that are often used to treat anxiety, including in older people. It is known that BDZs are sometimes prescribed inappropriately or used for longer than allowed by the guidelines. As a result, BDZs may be associated with tolerance symptoms, cognitive impairment, and confusion, especially when taken by geriatric patients. On the other hand, chronic anxiety is also known to be associated with cognitive decline in older age. This review analyzes the effects of inappropriate consumption of BDZs over a long period of time in older adults and proposes therapeutic alternatives to combat anxiety symptoms in the older adults.

Objective Methods Results Conclusion To highlight the detection of xylazine and nitrazolam in conjunction with benzimidazole opioids (nitazenes) and other novel benzodiazepines in a cluster of patients after putative heroin use.Deidentified clinical and analytical data were gathered from patients enrolled in the Emerging Drugs Network of Australia system.In December 2023, three adults presented to the ED with sedation following putative use of heroin. Toxicological analysis of blood samples identified xylazine, protonitazene, metonitazene, bromazolam and nitrazolam. Local health authorities subsequently issued an alert.This is the first signal of xylazine and nitrazolam use in Australia. These results demonstrate toxico‐surveillance programmes with analytical confirmation of drugs are invaluable in monitoring illicit drug use. [ABSTRACT FROM AUTHOR]