Consumption patterns and factors associated with inappropriate prescribing of benzodiazepines in Primary Health Care settings.

BACKGROUND: Benzodiazepines are frequently prescribed to treat anxiety and insomnia, but long-term use has been associated with the development of dependence, tolerance, and cognitive decline, especially among older adults. This study aimed to investigate the pattern of consumption and factors associated with inappropriate prescribing of benzodiazepines in primary health care. METHODS: This is a cross-sectional analytical study, using dispensing records of diazepam, clonazepam, and nitrazepam from public pharmacies in a Brazilian municipality between 2018 and 2022. Metrics for benzodiazepine consumption were DDD (Defined Daily Dose) and DDD/1000PD (per 1000 population per day). Long-term/prolonged benzodiazepine use was defined as consuming at least 90 DDD and at least 2 dispensations per year. To ascertain associations between long-term use and predictor variables, a multivariate logistic regression model was utilized. FINDINGS: A total of 40402 participants were included, with an average age of 55 years (SD = 0.30), 38.5% were older aged. Diazepam and nitrazepam exceeded the daily dose recommended. There was a reduction in diazepam consumption during the study period, as calculated by DDD/1.000PD, while the consumption of other benzodiazepines remained stable. However, a significant increase in diazepam consumption is noted when considering the last decade. Prolonged use was observed in 29.1% of participants, with a significant prevalence among the older people (34.8% of them were long-term users) and advancing age was identified as a risk factor for long-term use. Higher PDDs were also associated with long-term use and aging. Participants who used different benzodiazepines during the period had a higher risk of prolonged use. CONCLUSIONS: These results provide insights into the prevalence of problematic utilization of benzodiazepines in primary health care. Authorities and health care providers must take steps to encourage gradual cessation of prolonged benzodiazepine prescriptions and the embrace of suitable strategies for addressing anxiety and insomnia within primary health care settings.

Comparison of the recovery quality between remimazolam and propofol after general anesthesia: systematic review and a meta-analysis of randomized controlled trials.

Introduction: To evaluate the recovery quality between remimazolam and propofol after general anesthesia surgery. Methods: We included eligible randomized controlled trials (RCTs) in EMBASE, PubMed, Cochrane Central, Scopus, and Web of Science up to June 26, 2024 for comparison the recovery quality of remimazolam and propofol after general anaesthesia. The primary outcomes were the total Quality of Recovery-15 (QoR-15) and five dimensions of QoR-15 on postoperative day 1 (POD1). Secondary outcomes were adverse events, the Quality of Recovery-40 (QoR-40) on POD1, and the intraoperative and postoperative time characteristics. Results: Thirteen RCTs with a total of 1,305 patients were included in this meta-analysis. Our statistical analysis showed that remimazolam group had higher QoR-15 score on POD1, with no significant difference (Mean Difference (MD) = 1.24; 95% confidence interval (CI), [-1.67-4.15]; I2 = 75%; P = 0.41). In the five dimensions of QoR-15, remimazolam group was superior to propofol group in terms of physical independence (MD = 0.79; 95% CI [0.31-1.27]; I2 = 0%; P = 0.001). Remimazolam group was lower than propofol group in incidence of hypotension (Risk Ratio (RR) = 0.48; 95% CI [0.40-0.59]; I2 = 14%; P < 0.00001), bradycardia (RR = 0.18; 95% CI [0.08-0.38]; I2 = 0%; P < 0.0001) and injection pain (RR = 0.03; 95% CI [0.01-0.12]; I2 = 48%; P < 0.00001), respectively. The intraoperative and postoperative time characteristics and the QoR-40 were similar in the two groups. Conclusions: Our analysis showed that the recovery quality of the remimazolam group after general anaesthesia was similar to propofol group, while the incidence of adverse events was low in remimazolam group. As a potential anesthetic, remimazolam can be used in place of propofol for surgical general anesthesia.

Therapeutic Effects, Side Effects, and Adverse Effects of Neuropsychiatric Drugs in the Context of Treating Cancer-Related Anorexia With Olanzapine and Mirtazapine.

Drugs have actions that may be classified as therapeutic effects and side effects; side effects are actions that do not contribute to therapeutic benefit. Some side effects are neutral; others, experienced as undesirable or unpleasant, are recorded as adverse effects. Some drug actions are therapeutic for some disorders and adverse for others; or therapeutic during acute illness and adverse during maintenance treatment. As an example, anticholinergic action may be adverse when a tricyclic antidepressant is used to treat depression but therapeutic when the drug is used to treat irritable bowel syndrome with diarrhea. In clinical practice, side or adverse effects of a drug may be leveraged to manage troublesome symptoms. As an example, the sedative effect of a low dose of trazodone may be useful for some patients with insomnia. With this background, studies have examined whether the increase in appetite and weight associated with olanzapine and mirtazapine may be effective against anorexia and cachexia associated with cancer and cancer chemotherapy. The subject is important because cachexia may be present in 30%-50% of patients with cancer (with higher prevalence in patients with more advanced cancer) and because the presence of cachexia is associated with a higher risk of disease progression and mortality. Many randomized controlled trials (RCTs) have examined pharmacologic interventions such as progestins, corticosteroids, anamorelin, and medical cannabis for cancer related cachexia; most results have been disappointing. A recent RCT found that olanzapine (2.5 mg/d for 12 weeks) improved appetite, weight, other nutritional parameters, and quality of life in patients with locally advanced or metastatic cancer treated with chemotherapy. Another RCT, however, found that mirtazapine (30 mg/d for 8 weeks) brought no nutritional or anthropometric gain in patients with cancer and anorexia. It is concluded that olanzapine but not mirtazapine merits further investigation in patients with cancer who have anorexia and cachexia.

Evaluation of Clinical Correlation between Insulin Resistance and Antipsychotic Drug Therapy in Patients with Schizophrenia.

BACKGROUND: Treatment with different antipsychotics can lead to various metabolic side effects in patients with psychosis, impacting long-term prognosis. This study aimed to compare the changes and clinical efficacy of insulin resistance in patients treated with olanzapine and ziprasidone. METHOD: A retrospective analysis was conducted on the clinical data of 80 patients with schizophrenia. The patients were divided into olanzapine treatment group and ziprasidone treatment group. Parameters including body weight, body mass index (BMI), fasting plasma glucose (FPG), fasting plasma insulin (FPI), cholesterol (CHO), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), insulin resistance index, and Positive and Negative Syndrome Scale (PANSS) scores were recorded and compared before and after treatment. RESULTS: BMI, FPG, FPI, homeostatic model assessment of insulin resistance (HOMA-IR), CHO, TG and LDL in both groups were significantly higher than before treatment (p < 0.05). These parameters were significantly higher in the olanzapine group than in the ziprasidone group (p < 0.05). The level of HDL in both groups was significantly decreased after treatment, and the level of HDL in the olanzapine group was significantly lower than that in the ziprasidone group after treatment (p < 0.05). After treatment, the total score and score of PANSS in both groups were significantly lower than before treatment (p < 0.05). After treatment, there was no significant difference in total score and PANSS score between both groups (p > 0.05). The incidence of insulin resistance (IR) was significantly higher in the olanzapine group compared to the ziprasidone group (χ2 = 4.021, p < 0.05). In the IR group, BMI, FPG, FPI, TG, and LDL levels were higher than in the non-IR group (p < 0.05). Multivariate analysis indicated that BMI, FPG, FPI, TG, and LDL were independent risk factors for IR (odd ratio (OR) >1, p < 0.05). CONCLUSIONS: Treatment with olanzapine and ziprasidone improves clinical symptoms in patients with schizophrenia, but increases the risk of insulin resistance. The metabolic side effects of olanzapine are more pronounced.

Incident Benzodiazepine and Z-Drug Use and Subsequent Risk of Serious Infections.

BACKGROUND AND OBJECTIVES: Animal studies have suggested a link between benzodiazepine and related Z-drug (BZDR) use and immune dysfunction. Corresponding evidence in humans is limited and focuses mainly on pneumonia. This study aimed to assess the association of incident BZDR use with subsequent development of serious infections. METHODS: This Swedish register-based study included a population-based demographically matched cohort, a co-twin control cohort, and an active comparator cohort. Out of 7,362,979 individuals aged below 65 years who were BZDR naïve by 2007, 713,896 BZDR recipients with incident dispensation of any BZDRs between 2007 and 2019 were 1:1 matched to 713,896 nonrecipients from the general population; 9197 BZDR recipients were compared with their 9298 unexposed co-twins/co-multiples; and 434,900 BZDR recipients were compared with 428,074 incident selective serotonin reuptake inhibitor (SSRI) recipients. The outcomes were identified by the first inpatient or specialist outpatient diagnosis of serious infections in the National Patient Register, or death from any infections recorded as the underlying cause in the Cause of Death Register. Cox proportional hazards regression models were fitted and controlled for multiple confounders, including familial confounding and confounding by indication. To study a possible dose-response association, the cumulative dosage of BZDRs dispensed during the follow-up was estimated for each BZDR recipient and modeled as a time-varying exposure with dose categories in tertiles [≤ 20 defined daily doses (DDDs), > 20 DDDs ≤ 65, and > 65 DDDs). The risk of infections was assessed in BZDR recipients within each category of the cumulative BZDR dosage compared to their demographically matched nonrecipients. RESULTS: In the demographically matched cohort (average age at incident BZDR use 42.8 years, 56.9% female), the crude incidence rate of any serious infections in BZDR recipients and matched nonrecipients during 1-year follow-up was 4.18 [95% confidence intervals (CI) 4.13-4.23] and 1.86 (95% CI 1.83-1.89) per 100 person-years, respectively. After controlling for demographic, socioeconomic, clinical, and pharmacological confounders, BZDR use was associated with 83% relative increase in risk of any infections [hazard ratio (HR) 1.83, 95% CI 1.79-1.89]. The risk remained increased, although attenuated, in the co-twin cohort (HR 1.55, 95% CI 1.23-1.97) and active comparator cohort (HR 1.33, 95% CI 1.30-1.35). The observed risks were similar across different types of initial BZDRs and across individual BZDRs, and the risks increased with age at BZDR initiation. We also observed a dose-response association between cumulative BZDR dosage and risk of serious infections. CONCLUSIONS: BZDR initiation was associated with increased risks of serious infections, even when considering unmeasured familial confounding and confounding by indication. The exact pathways through which BZDRs may affect immune function, however, remain unclear. Further studies are needed to explore the neurobiological mechanisms underlying the association between BZDR use and serious infections, as it can lead to safer therapeutic strategies for patients requiring BZDR.

Potentially inappropriate medication on communitydwelling older adults: Longitudinal analysis using the International Mobility in Aging Study. / Medicación potencialmente inapropiada en adultos mayores de la comunidad: análisis longitudinal del estudio IMIAS

Introduction: Medications are a fundamental part of the treatment of multiple pathologies. However, despite their benefits, some are considered potentially inappropriate medications for older people given their safety profile. Epidemiological data differences related to potentially inappropriate medications make it difficult to determine their effects on elderly people. Objective: To estimate the prevalence and types of potentially inappropriate medications using the 2019 Beers Criteria® in a cohort of adults older than 65 years. Materials and methods: We performed an observational, multicenter, retrospective, longitudinal study of a four-year follow-up of potentially inappropriate medications in community-dwelling older adults. Results: We followed 820 participants from five cities for four years (2012-2016) and evaluated them in three different moments (m1 = 2012, m2 = 2014, and m3 = 2016). The average age was 69.07 years, and 50.9% were women. The potentially inappropriate medication prevalence in the participants was 40.24%. The potentially inappropriate medications' mean among the studied subjects in the first moment was 1.65 (SD = 0.963), in the second was 1.73 (SD = 1.032), and in the third was 1.62 (SD = 0.915). There were no statistical differences between measurements (Friedman test, value = 0.204). The most frequent potentially inappropriate medications categories were gastrointestinal (39.4%), analgesics (18.8%), delirium-related drugs (15.4%), benzodiazepines (15.2%), and cardiovascular (14.2%). Conclusions: About half of the population of the community-dwelling older adults had prescriptions of potentially inappropriate medications in a sustained manner and without significant variability over time. Mainly potentially inappropriate medications were gastrointestinal and cardiovascular drugs, analgesics, delirium-related drugs, and benzodiazepines.

Introducción. Los fármacos son parte fundamental del tratamiento de múltiples enfermedades. Sin embargo, a pesar de sus beneficios, algunos se consideran medicamentos potencialmente inapropiados en adultos mayores, dado su perfil de seguridad. Las diferencias en los datos epidemiológicos relacionados con los medicamentos potencialmente inapropiados dificultan el establecimiento de sus efectos en adultos mayores. Objetivo. Estimar la prevalencia longitudinal y los tipos de medicamentos potencialmente inapropiados, utilizando los criterios Beers® del 2019 en una cohorte de adultos mayores de 65 años. Materiales y métodos. Se realizó un estudio observacional, multicéntrico, retrospectivo y longitudinal, de cuatro años de seguimiento de los medicamentos potencialmente inapropiados en adultos mayores de la comunidad. Resultados. Se evaluaron 820 participantes de cinco ciudades durante cuatro años (2012 a 2016) en tres momentos (m1: 2012, m2: 2014 y m3; 2016). La edad promedio fue de 69,07 años y el 50,9 % eran mujeres. La prevalencia de medicamentos potencialmente inapropiados en los participantes fue del 40,24 %. El promedio de estos medicamentos entre los sujetos estudiados en el primer momento fue de 1,65 (DE = 0,963), en el segundo fue de 1,73 (DE = 1,032) y en el tercero fue de 1,62 (DE = 0,915). No hubo diferencias estadísticas entre las mediciones (prueba de Friedman, p = 0,204). Las categorías de los medicamentos potencialmente inapropiados más frecuentes fueron: gastrointestinales (39,4 %), analgésicos (18,8 %), relacionados con delirium (15,4 %), benzodiacepinas (15,2 %) y cardiovasculares (14,2 %). Conclusiones. En cerca de la mitad de la población de adultos mayores de la comunidad, se prescribieron medicamentos potencialmente inapropiados de manera sostenida y sin variabilidad importante en el tiempo. Los más recetados fueron aquellos para tratar malestares gastrointestinales y cardiovasculares, analgésicos, para el delirium y benzodiacepinas.

Remimazolam in General Anesthesia: A Comprehensive Review of Its Applications and Clinical Efficacy.

Remimazolam is a novel ultra-short-acting benzodiazepine with a unique pharmacokinetic profile that makes it an attractive option for use in general anesthesia. This review paper provides an in-depth analysis of remimazolam's applications in the field of general anesthesia, focusing on its pharmacological properties, clinical efficacy, safety profile, and potential advantages compared to other anesthetic agents. Remimazolam acts on GABAa receptors, offering rapid onset and recovery times due to its unique metabolic pathway involving tissue esterases. Clinical trials have demonstrated its efficacy in procedural sedation and general anesthesia, showing a favorable safety profile with minimal cardiovascular and respiratory depression. Compared to traditional anesthetics such as propofol, remimazolam presents distinct advantages, including predictable pharmacokinetics, reduced risk of prolonged sedation, and a reliable safety margin. These attributes position remimazolam as a promising agent in various clinical settings. The purpose of this review is to synthesize current evidence on remimazolam and discuss its potential to improve clinical outcomes in anesthesia practice.

Incidence of Adverse Events Using Flumazenil in Patients With Iatrogenic Benzodiazepine Delirium: A Retrospective Study.

BACKGROUND: Flumazenil is a competitive benzodiazepine (BZD) antagonist most used for treating delirium in BZD overdoses. Since its introduction, many have expressed concerns about its safety secondary to the risk of inducing BZD withdrawal and refractory seizures. STUDY QUESTION: What is the incidence of adverse drug events after the administration of flumazenil in patients with suspected iatrogenic BZD delirium? STUDY DESIGN: This is a retrospective cross-sectional study of patients from a single center from 2010 to 2013. Patients experiencing delirium after receiving BZDs in the hospital were included if they had a bedside toxicology consult and were administered flumazenil. Patients were excluded if they were given BZDs for ethanol withdrawal or if they did not have mental status documentation before and after flumazenil administration. Descriptive statistics were calculated. MEASURES AND OUTCOMES: The primary outcome was the incidence of adverse drug events after flumazenil administration. The secondary outcome was the efficacy of flumazenil determined by the patient's mental status. RESULTS: A total of 501 patient records were reviewed, and 206 patients were included in the final analysis. Of those patients, 172 (83.5%) experienced an objective improvement in their mental status within 1 hour after flumazenil administration. A total of 5 patients experienced adverse events (2.4%), 95% confidence interval (0.78, 5.54). Of these, 3 patients experienced minor agitation or restlessness without pharmacologic intervention. Two patients experienced moderate agitation or restlessness that resolved with haloperidol or physostigmine administration. No patients had a reported seizure, 95% confidence interval (0.0, 1.77). CONCLUSIONS: Flumazenil seems to be a safe and effective intervention for the reversal of delirium secondary to iatrogenic BZD administration.

Comparative efficacy and safety of olanzapine and risperidone in the treatment of psychiatric and behavioral symptoms of Alzheimer's disease: Systematic review and meta-analysis.

OBJECTIVES: Olanzapine and risperidone have emerged as the most widely used drugs as short-term prescription in the treatment of behavioral disturbances in dementia. The present systematic review and meta-analysis was hence performed to investigate the effectiveness and safety profile of olanzapine and risperidone in the treatment of behavioral and psychological symptoms of dementia (BPSD), aiming to provide updated suggestion for clinical physicians and caregivers. DESIGN: Prospective controlled clinical studies were included, of which available data was extracted. Outcomes of BEHAVE-AD scores with the variation of grades, specific behaviors variables, as well as safety signals were pooled for the analysis by odds rates and weighted mean differences, respectively. DATA SOURCES: Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang. ELIGIBILITY CRITERIA: Prospective, controlled clinical studies, conducted to compare the effectiveness and safety profile of olanzapine and risperidone in the treatment of BPSD. DATA EXTRACTION AND SYNTHESIS: Interested data including baseline characteristics and necessary outcomes from the included studies were extracted independently by 2 investigators. BEHAVE-AD scale was adopted to assess the efficacy in the present study. All behaviors were evaluated at the time of the initiation of the treatment, as well as the completion of drugs courses. Adverse events were assessed with the criteria of Treatment Emergent Symptom Scale, or Coding Symbols for a Thesaurus of Adverse Reaction Terms dictionary. Weighted mean difference was used for the pooled analysis. RESULTS: A total of 2427 participants were included in the present meta-analysis. Comparative OR on response rate, and remarkable response rate between olanzapine and risperidone was 0.65 (95% CI: 0.51-0.84; P = .0008), and 0.62 (95% CI: 0.50-0.78; P < .0001), respectively. There were statistical differences observed by olanzapine on the improvement of variables including delusions (WMD, -1.83, 95% CI, -3.20, -0.47), and nighttime behavior disturbances (WMD, -1.99, 95% CI, -3.60, -0.38) when compared to risperidone. CONCLUSION: Our results suggested that olanzapine might be statistically superior to risperidone on the reduction of BPSD of Alzheimer's disease, especially in the relief of delusions and nighttime behavior disturbances. In addition, olanzapine was shown statistically lower risks of agitation, sleep disturbance, and extrapyramidal signs.

Etomidate Combined with Propofol versus Remimazolam for Sedation in Elderly Patients During Gastrointestinal Endoscopy: A Randomized Prospective Clinical Trial.

Purpose: Remimazolam is a novel short-acting benzodiazepine used for sedation and general anesthesia. This study aimed to evaluate the efficacy and safety of remimazolam besylate in elderly patients who underwent diagnostic gastrointestinal endoscopy. Patients and Methods: A total of 120 patients aged 60-75 years were randomly allocated to one of two groups. Remifentanil 0.3µg/kg was used for analgesia. Patients were administered remimazolam besylate 7 mg (R group) or etomidate 0.1 mg/kg combined with 1% propofol 0.5 mg/kg (EP group) for induction, supplemental repeated doses were given as needed. Some time metrics, vital signs, adverse events were evaluated. Patients' Mini-cog score and recovery questionnaires were compared. Results: Compared to the EP group, the induction time was slightly longer in the R group (1.50 VS 1.15 minutes) (P<0.05), the time spent in the post-anesthesia care unit (PACU) was shorter (15.17 VS 17.40 minutes) (P<0.05). Compare with EP group, SBP was lower in R group at T15 and T25 time point, but heart rate was higher in T2, T3, T5 (P< 0.05). The Mini-Cog score was higher after the procedure (2.83 VS 2.58) (P<0.05). The incidence of respiratory adverse events was higher in the EP group than R group (18.3% VS 5.0%, P < 0.05). The most common adverse event in R group was hiccups. The sedation satisfaction rate and degree of amnesia were higher in the R group (66.7% VS 11.7%) (P < 0.05), and the effect on patient's life within 24 hours was lower (12.0% VS 30.5%) (P < 0.05). Conclusion: The safety and efficacy of remimazolam besylate are not inferior to those of etomidate combined with propofol, rendering it a safe option for sedation during gastrointestinal endoscopy in ASA I-II elderly patients, but care should be taken to monitor the occurrence of hiccups.

Concomitant use of antidepressants and benzodiazepines during pregnancy and associated risk of congenital malformations: a population-based cohort study in Taiwan.

BACKGROUND: Despite the frequent co-administration of antidepressants and benzodiazepines, the association between such concomitant use during pregnancy and the risk of congenital malformations remains inadequately explored. This study aims to examine the association between concomitant use of antidepressants and benzodiazepines during the first trimester and organ-specific congenital malformations. METHODS: We conducted a population-based cohort study using Taiwan's National Birth Certificate Application database, the Maternal and Child Health database, and Taiwan's National Health Insurance database. Pregnant people aged 15-50 years with singleton births between Jan 1, 2004, and Dec 31, 2018, were included. Use of antidepressants and benzodiazepines was defined as at least one prescription during the first trimester, and concomitant use was defined as the overlapping prescription of both drugs with an overlapping prescription period. The primary outcomes were overall congenital malformations and eight organ-specific malformations, consisting of the nervous system, heart, respiratory system, oral cleft, digestive system, urinary system, genital system, and limb malformations. Logistic regression models with propensity score fine stratification weighting approach were used to control for measured confounders. Analyses controlling for confounding by indication and sibling comparison analyses were done to address unmeasured confounders. No individuals with lived experience participated in the research or writing process. FINDINGS: The cohort included 2 634 021 singleton pregnancies, and 8599 (0·3%) individuals were concomitant users of antidepressants and benzodiazepines during the first trimester (mean age at delivery was 31·8 years [SD 5·2] for pregnancies with exposure to antidepressants and benzodiazepines vs 30·7 years [SD 4·9] for pregnancies without exposure). All study participants were female, and information about ethnicity was not available. Absolute risk of overall malformations was 3·81 per 100 pregnancies with exposure, compared with 2·87 per 100 pregnancies without exposure. The propensity score-weighted odds ratios (weighted ORs) did not suggest an increased risk for overall malformations (weighted OR 1·10, 95% CI 0·94-1·28), heart defects (1·01, 0·83-1·23), or any of the other organ-specific malformations, except for digestive system malformations, for which the weighted OR remained statistically significant after adjustment (1·63, 1·06-2·51). The absence of an increased risk for overall congenital malformations associated with concomitant use of antidepressants and benzodiazepines was supported by the analyses controlling for confounding by indication and sibling-matched comparisons. INTERPRETATION: The findings of this study suggest that the concomitant use of antidepressants and benzodiazepines during the first trimester is not associated with a substantial increase in risk for most malformation subtypes. However, considering other potential adverse effects of using both medications concomitantly, a thorough assessment of the risks and benefits is crucial for clinical decision making. FUNDING: National Science and Technology Council.

Prevalence and clinical correlates of benzodiazepine use in the patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a serious and disabling condition characterized by abnormal mood changes. Clinical guidelines for depression treatment recommend antidepressant medications, with benzodiazepines acting as short-term synergists. However, little is currently known about the prevalence and associated clinical risk factors of benzodiazepine use among Chinese patients with MDD. This study aimed to explore the prevalence and clinical risk factors associated with benzodiazepine use in this population. METHODS: A total of 2742 patients with MDD (males/females = 816/1926, aged 14-60 years) participated in this cross-sectional observational study. General information and psychosis assessments were collected online. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), anxiety symptoms using the Generalized Anxiety Disorder-7 (GAD-7), and sleep problems and suicidal tendencies using the third and ninth items of the PHQ-9. Multivariable logistic regression analysis models were employed to identify factors associated with benzodiazepine use. RESULTS: The prevalence of benzodiazepine use among patients with MDD was 42.9 %. Among these patients, 99.6 % used a single benzodiazepine, with oxazepam being the most frequently prescribed. Age, severity of sleep problems, depressive symptoms, and anxiety symptoms were significantly correlated with benzodiazepine use (all P < 0.001). LIMITATIONS: The cross-sectional design of this study precludes establishing causal relationships. CONCLUSION: Our findings indicate a high prevalence of benzodiazepine use among Chinese patients with MDD. Factors such as severe depressive symptoms, anxiety symptoms, age, and sleep problems appear to be associated with benzodiazepine use. These results underscore the importance of vigilance regarding benzodiazepine use in patients with MDD.

Onset of Prolonged High-Potency Benzodiazepine Use Among ICU Survivors: A Nationwide Cohort Study.

OBJECTIVES: Exposure to critical illness and intensive care may lead to long-term psychologic and physical impairments. To what extent ICU survivors become prolonged users of benzodiazepines after exposure to critical care is not fully explored. This study aimed to describe the extent of onset of prolonged high-potency benzodiazepine use among ICU survivors not using these drugs before admission, identify factors associated with this use, and analyze whether such usage is associated with increased mortality. DESIGN: Retrospective cohort study. SETTING: Sweden, including all registered ICU admissions between 2010 and 2017. PATIENTS: ICU patients surviving for at least 3 months, not using high-potency benzodiazepine before admission, were eligible for inclusion. INTERVENTIONS: Admission to intensive care. MEASUREMENTS AND MAIN RESULTS: A total of 237,904 patients were screened and 137,647 were included. Of these 5338 (3.9%) became prolonged users of high-potency benzodiazepines after ICU discharge. A peak in high-potency benzodiazepine prescriptions was observed during the first 3 months, followed by sustained usage throughout the follow-up period of 18 months. Prolonged usage was associated with older age, female sex, and a history of both somatic and psychiatric comorbidities, including substance abuse. Additionally, a longer ICU stay, a high estimated mortality rate, and prior consumption of low-potency benzodiazepines were associated with prolonged use. The risk of death between 6 and 18 months post-ICU admission was significantly higher among high-potency benzodiazepine users, with an adjusted hazard ratio of 1.8 (95% CI, 1.7-2.0; p < 0.001). No differences were noted in causes of death between users and nonusers. Conclusions: Despite the lack of evidence supporting long-term treatment, prolonged usage of high-potency benzodiazepines 18 months following ICU care was notable and associated with an increased risk of death. Considering the substantial number of ICU admissions, prevention of benzodiazepine misuse may improve long-term outcomes following critical care.

Remimazolam vs. propofol for general anaesthesia in elderly patients: a meta-analysis with trial sequential analysis.

BACKGROUND: Elderly patients comprise an increasing proportion of patients undergoing surgery, and they require special attention due to age-related physiological changes. Propofol is the traditional agent for anaesthesia, and recently, remimazolam, a novel ultra-short-acting benzodiazepine, has emerged as an alternative to propofol in general anaesthesia. OBJECTIVES: We aim to compare remimazolam vs . propofol for general anaesthesia in elderly patients regarding hypotension, induction characteristics, haemodynamics and recovery outcomes. DESIGN: Meta-analysis with sensitivity and trial sequential analyses (TSA) to assess inconsistencies. Risk ratios and mean differences with 95% confidence intervals (95% CIs) were computed using a random effects model. Subgroups and meta-regression according to anaesthesia methods were also performed. DATA SOURCES: We systematically searched MEDLINE, Embase and Cochrane for randomised controlled trials (RCTs) up to January 1, 2024. ELIGIBILITY CRITERIA: Patients at least 60 years old, comparing remimazolam vs . propofol for general anaesthesia. RESULTS: Eleven RCTs (947 patients) were included. Compared with propofol, remimazolam was associated with lower postinduction and intra-operative hypotension (RR 0.41, 95% CI 0.27 to 0.62, P  < 0.001) and incidence of bradycardia (risk ratio 0.58, 95% CI 0.34 to 0.98, P  = 0.04), with a higher heart rate ( P  = 0.01). The incidence of injection pain was lower ( P  < 0.001), but remimazolam was associated with a longer time to loss of consciousness ( P  < 0.001) and a higher bispectral index at loss of consciousness ( P  = 0.04). No differences were found for mean arterial pressure, emergence time, extubation time and incidence of emergence agitation. The TSA was consistent and achieved the required information size for hypotension. CONCLUSIONS: Remimazolam significantly reduced the risk of hypotension, bradycardia and injection pain, despite an increase in the time to loss of consciousness. Remimazolam appears to be an effective and well tolerated alternative to propofol in elderly patients undergoing general anaesthesia.

Adolescent Use, Diversion Sources, and Perceived Procurement Difficulty of Prescription Medications.

This study examines trends in medical use, nonmedical use, diversion sources, and perceived procurement difficulty of prescription medications for nonmedical use among US adolescents.

Benzodiazepine use in relation to long-term dementia risk and imaging markers of neurodegeneration: a population-based study.

BACKGROUND: Benzodiazepine use is common, particularly in older adults. Benzodiazepines have well-established acute adverse effects on cognition, but long-term effects on neurodegeneration and dementia risk remain uncertain. METHODS: We included 5443 cognitively healthy (MMSE ≥ 26) participants from the population-based Rotterdam Study (57.4% women, mean age 70.6 years). Benzodiazepine use from 1991 until baseline (2005-2008) was derived from pharmacy dispensing records, from which we determined drug type and cumulative dose. Benzodiazepine use was defined as prescription of anxiolytics (ATC-code: N05BA) or sedative-hypnotics (ATC-code: N05CD) between inception of pharmacy records and study baseline. Cumulative dose was calculated as the sum of the defined daily doses for all prescriptions. We determined the association with dementia risk until 2020 using Cox regression. Among 4836 participants with repeated brain MRI, we further determined the association of benzodiazepine use with changes in neuroimaging markers using linear mixed models. RESULTS: Of all 5443 participants, 2697 (49.5%) had used benzodiazepines at any time in the 15 years preceding baseline, of whom 1263 (46.8%) used anxiolytics, 530 (19.7%) sedative-hypnotics, and 904 (33.5%) used both; 345 (12.8%) participants were still using at baseline assessment. During a mean follow-up of 11.2 years, 726 participants (13.3%) developed dementia. Overall, use of benzodiazepines was not associated with dementia risk compared to never use (HR [95% CI]: 1.06 [0.90-1.25]), irrespective of cumulative dose. Risk estimates were somewhat higher for any use of anxiolytics than for sedative-hypnotics (HR 1.17 [0.96-1.41] vs 0.92 [0.70-1.21]), with strongest associations for high cumulative dose of anxiolytics (HR [95% CI] 1.33 [1.04-1.71]). In imaging analyses, current use of benzodiazepine was associated cross-sectionally with lower brain volumes of the hippocampus, amygdala, and thalamus and longitudinally with accelerated volume loss of the hippocampus and to a lesser extent amygdala. However, imaging findings did not differ by type of benzodiazepines or cumulative dose. CONCLUSIONS: In this population-based sample of cognitively healthy adults, overall use of benzodiazepines was not associated with increased dementia risk, but potential class-dependent adverse effects and associations with subclinical markers of neurodegeneration may warrant further investigation.

Remimazolam-Induced Anaphylaxis and Cardiovascular Collapse: A Narrative Systematic Review of Eleven Cases.

Background and Objectives: Remimazolam, a novel benzodiazepine, is used for procedural sedation and general anesthesia due to its rapid onset and short duration of action. However, remimazolam-induced anaphylaxis (RIA) is a rare but severe complication. This study aimed to analyze RIA characteristics, focusing on cardiovascular collapse, and provide guidelines for safe remimazolam use. Methods: This study conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Research articles retrieved from PubMed on 26 May 2023, using the keywords 'remimazolam AND anaphylaxis' were evaluated based on the inclusion criteria of being written in English and aligning with the World Allergy Organization criteria for anaphylaxis, while studies not meeting these criteria were excluded. All published articles up to the search date were included without any date restrictions. The review analyzed factors such as age, sex, type of anesthesia, remimazolam dose (bolus/continuous), allergic symptoms and sign, epinephrine use, serum tryptase levels, and skin prick tests. Results: Among eleven cases, the mean age was 55.6 ± 19.6 years, with 81.8% male. Hypotension (81.8%) was the most common symptom, followed by bradycardia (54.5%) and desaturation (36.4%). Two patients experienced cardiac arrest. Serum tryptase levels confirmed anaphylaxis in ten cases. Epinephrine was the primary treatment, with intravenous doses ranging from 0.1 mg to 0.3 mg. Conclusions: Vigilance is crucial when administering remimazolam, adhering to recommended dosages, and promptly treating RIA with epinephrine. Further research is needed to understand the risk factors and refine the management strategies. Guidelines for safe remimazolam use are proposed.

Comparison emergence of sedation, using dexmedetomidine and remimazolam, in spinal anaesthesia - double blinded randomized controlled trial.

Background: Continuous intravenous infusion of remimazolam may be suitable for sedation in patients undergoing regional anaesthesia. However, there have been no studies comparing remimazolam and dexmedetomidine for this purpose. This study compared emergence from sedation between dexmedetomidine and remimazolam following continuous intravenous infusion in patients undergoing spinal anaesthesia. Methods: This double-blinded, randomised controlled trial assessed the sedative effects of dexmedetomidine and remimazolam. Following spinal anaesthesia, patients were sedated using continuous intravenous infusion of either dexmedetomidine (D group) or remimazolam (R group).The D group received dexmedetomidine administered at 6 mL/kg/h (6 µg/kg/h) for 10 minutes, followed by 1 mL/kg/h (1 µg/kg/h). The R group received remimazolam administered at 6 mL/kg/h (6 mg/kg/h) for 10 minutes, followed by 1 mL/kg/h (1 mg/kg/h). Sedation levels were evaluated using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. The time to reach MOAA/S ≤ 3 from the start of drug infusion and the time to reach MOAA/S = 5 from the end of infusion were recorded. Hemodynamic parameters and respiratory rate were also monitored. Results: The R group reached MOAA/S ≤ 3 significantly faster than the D group during induction of sedation (4 ± 1 minutes and 11 ± 3 minutes, respectively, p < 0.001). The R group also reached MOAA/S = 5 significantly faster than the D group during emergence from sedation (11 ± 3 minutes and 16 ± 5 minutes, respectively, p < 0.001). Both groups maintained stable hemodynamic parameters and respiratory rate without any significant differences, although the mean heart rate was significantly lower in the D group than in the R group after the start of infusion. Conclusion: Remimazolam demonstrated significantly faster induction of and emergence from sedation compared to dexmedetomidine, with no significant differences in haemodynamics or respiratory depression.

Prescription Patterns and Predisposing Factors of Benzodiazepine and Z-Hypnotic Use During Pregnancy: A Nationwide Cohort Study.

PURPOSE: The use of benzodiazepines and Z-hypnotics during pregnancy has raised significant concerns in recent years. However, there are limited data that capture the prescription patterns and predisposing factors in use of these drugs, particularly among women who have been long-term users of benzodiazepines and Z-hypnotics before pregnancy. METHODS: This population-based cohort study comprised 2 930 988 pregnancies between 2004 and 2018 in Taiwan. Women who were dispensed benzodiazepines or Z-hypnotics during pregnancy were identified and further stratified into groups based on their status before pregnancy: long-term users (with a supply of more than 180 days within a year), short-term users (with a supply of less than 180 days within a year), and nonusers. Trends in the use of benzodiazepines or Z-hypnotics and concomitant use with antidepressants or opioids were assessed. Logistic regression models were utilized to identify factors associated with use of these drugs during pregnancy, and interrupted time series analyses (ITSA) were employed to evaluate utilization patterns of these drugs across different pregnancy-related periods. RESULTS: The overall prevalence of benzodiazepine and Z-hypnotic use was 3.5% during pregnancy. Among prepregnancy long-term users, an upward trend was observed. The concomitant use of antidepressants or opioids among exposed women increased threefold (from 8.6% to 23.1%) and sixfold (from 0.3% to 1.7%) from 2004 to 2018, respectively. Women with unhealthy lifestyle behaviors, such as alcohol abuse (OR 2.48; 95% CI, 2.02-3.03), drug abuse (OR 10.34; 95% CI, 8.46-12.64), and tobacco use (OR 2.19; 95% CI, 1.96-2.45), as well as those with psychiatric disorders like anxiety (OR 6.99; 95% CI, 6.77-7.22), insomnia (OR 15.99; 95% CI, 15.55-16.45), depression (OR 9.43; 95% CI, 9.07-9.80), and schizophrenia (OR 21.08; 95% CI, 18.76-23.69), and higher healthcare utilization, were more likely to use benzodiazepines or Z-hypnotics during pregnancy. ITSA revealed a sudden decrease in use of benzodiazepines and Z-hypnotics after recognition of pregnancy (level change -0.55 percentage point; 95% CI, -0.59 to -0.51). In contrast, exposures to benzodiazepines and Z-hypnotics increased significantly after delivery (level change 0.12 percentage point; 95% CI, 0.09 to 0.16). CONCLUSIONS: In this cohort study, an increased trend of benzodiazepine and Z-hypnotic use during pregnancy among prepregnancy long-term users, as well as concomitant use with antidepressants or opioids were found. The findings have highlighted the existence of various risk factors associated with the use of these drugs during pregnancy. Utilization patterns varied across different stages of pregnancy, highlighting the need for prescription guidelines and educational services for women using these drugs during pregnancy.