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Background and Objective: Benzodiazepines (including zolpidem and zopiclone) are often associated with higher-than-recommended intake and durations of use, especially in older adults. The objective of this study was to characterize trajectories of benzodiazepine use according to recommended patterns in older adults, and to assess predictors of the risk of developing each of these trajectories., Methods: Using the French Health Insurance database, we constituted a cohort of adults aged ≥ 65 years who initiated benzodiazepines in 2007 and were followed for up to 8 years. Concordance with benzodiazepine use guidelines was assessed on a quarterly basis according to a "concordance-with-guideline score" with values 1-5. Group-based trajectory modeling was then applied as implemented in the Proc Traj procedure in SAS to define guideline-concordant trajectories based on seven baseline patient-centered characteristics: sex, complementary health insurance coverage, treated alcohol and tobacco use disorder, polypharmacy, hospital stay, and registered chronic diseases., Results: Among 5080 new users (64.1% women, median age 74 years), six trajectories of benzodiazepine use were identified. Three, representing 70% of users, were concordant with guidelines, whereas three implied non-concordant benzodiazepine use for part or all of the benzodiazepine use follow-up. Polymedicated patients were more prone to develop chronic non-guideline-concordant initially guideline-concordant use, whereas those with a history of long-term disease and hospitalization were more likely to develop chronic non-guideline-concordant use. The number of prescribers during the first quarter, number of daily defined doses, use of loperamide, and use of psychostimulants were associated with a higher risk of developing an initial and persistent non-guideline-concordant use. Treatment initiation by a psychiatrist, initial use of World Health Organization (WHO) step-2 opioids and non-benzodiazepine anxiolytics or sedatives were associated with a higher risk of late non-guideline-concordant use., Conclusions: Concordance with guidelines varied over time during benzodiazepine use in older adults. A third of these adults will hypothetically follow one of the identified non-guideline-concordant trajectories, consisting of initial and/or late non-guideline concordance. This was associated with modifiable and nonmodifiable factors that clinicians should be aware of for tailoring the monitoring of patients., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Despite the risks associated with their use, benzodiazepines remain used more widely than wisely. In this context, a better understanding of how their patterns of use can be associated with an increased risk of death appears essential. Indeed, the studies that investigated this association so far are inconsistent and question the influence of potential biases., Objective: The objective of this study was to investigate the association of various patterns of benzodiazepine use with all-cause mortality., Methods: A nationwide cohort of non-prevalent benzodiazepine users aged ≥ 65 years was identified using French healthcare insurance system claims databases. Exposure to benzodiazepines considered short-term, chronic (defined as a cumulated ≥ 6-month period over the previous 12 months), ongoing, and discontinued use. Using a Cox model, adjusted hazard ratios for all-cause mortality were estimated according to benzodiazepine patterns of use; exposure and confounders were treated as time-dependent variables., Results: In the cohort of 54,958 individuals aged ≥ 65 years, adjusted hazard ratios for all-cause mortality and benzodiazepines were 2.26 (95% confidence interval 1.96-2.61) for short-term use, 3.86 (3.04-4.90) for chronic use-discontinued, and 3.05 (2.17-4.29) for chronic use-ongoing. At age 80 years, these were 1.62 (1.48-1.79), 2.00 (1.82-2.19) and 1.13 (1.02-1.26), respectively. Adjusted hazard ratios show similar decreases with age for all patterns of benzodiazepine use., Conclusions: These findings confirm the existence of an excess risk of mortality associated with benzodiazepine use and provide pattern- and age-specific estimates. Higher risks were observed for patients aged < 80 years, short-term use, or chronic use recently interrupted. If the two latter can relate to an indication bias, the associations found for ongoing chronic use and short-term use conversely support a potential causal hypothesis.

Purpose: To study trends in incident use of benzodiazepines in France between 2006 and 2012., Methods: A cross-sectional study repeated yearly was conducted using data from the French national healthcare insurance system. New benzodiazepine users were defined as users without any benzodiazepine dispensing in the year prior to the first dispensing of benzodiazepine in each year. Relative changes in incidence of use were calculated with the year 2006 as reference; confidence intervals for changes were estimated using the bootstrap method., Results: Over the study period, the incident use of benzodiazepines decreased from 6.2% to 5.9%; this corresponded to a 5.1% decrease (95%CI: -6.8% to -4.2%) for 2012 compared to 2006. The decrease mainly concerned hypnotics (-15.5%; -21.2% to -15.3%) and appeared more pronounced in people aged 18-44 years. Incident use of anxiolytics remained stable overall during the period (4.0% of the population). Within anxiolytics, incident use of long half-life benzodiazepines (bromazepam, prazepam) decreased in favor of short half-life benzodiazepines (alprazolam, oxazepam). This change concerned patients aged 65-79 and patients aged 80 years and over. Nevertheless, in 2012, nearly one third of incident users aged 65 years and over started a treatment with a long half-life benzodiazepine, mostly bromazepam., Conclusions: A limited decrease in incident benzodiazepine use was observed in France between 2006 and 2012 that concerned only hypnotics. Although congruent with recommendations, this improvement appears insufficient with regard to the level of exposure to these drugs in France. New actions especially targeting anxiolytic benzodiazepine use should be undertaken to consolidate these results. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Purpose: To estimate benzodiazepine prevalence of use and to quantify, in benzodiazepine users, the prevalence of comorbidities and concurrent medications increasing the risk of adverse drug reactions (ADRs)., Methods: Cross-sectional study performed using data from the French national healthcare insurance system. The prevalence of use was estimated by considering as users, patients who had at least one benzodiazepine reimbursement during the year 2013. Patients at increased risk for benzodiazepine ADRs were those who had (i) drug-drug interactions at risk for central nervous system and respiratory depression and (ii) comorbidities at risk for adverse respiratory effects, or for falls or fractures., Results: Overall, the prevalence of benzodiazepine use in 2013 was estimated to be 13.8 %; it was higher among women and increased with age. This prevalence was 10.6 % for anxiolytic benzodiazepines, and 6.1 % for hypnotic benzodiazepines. Approximately half of the benzodiazepine users (48.1 %) were at increased risk for benzodiazepine ADRs; this proportion increased with age. Drug-drug interactions represented the most prevalent condition (39.3 % of benzodiazepine users). The drugs most frequently involved were opioids: analgesics (15.9 %) and antitussives (6.8 %). Overall, 11.3 % of benzodiazepine users had comorbidities at increased risk for adverse respiratory effects (13.9 % in those aged 65-79), and 7.0 % comorbidities at increased risk for falls or fractures (13.4 % in those aged ≥80)., Conclusions: This study found that benzodiazepine use remained high in France, and that roughly half of the users presented with comorbidities and concurrent medications increasing the risk of ADRs. These findings are of concern, given that benzodiazepines are frequently used, and especially among the elderly.

Introduction: Benzodiazepine use has been associated with increased risk of dementia. However, it remains unclear whether the risk relates to short or long half-life benzodiazepines and whether it extends to other psychotropic drugs., Methods: Prospective cohort study among 8240 individuals ≥65, interviewed on medication use. Incident dementia confirmed by an end point committee after a multistep procedure., Results: During a mean of 8 years of follow-up, 830 incident dementia cases were observed. Users of benzodiazepines at baseline had a 10% increased risk of dementia (adjusted hazard ratio [HR], 1.10; 95% confidence interval, 0.90-1.34). However, long half-life (>20 hours) benzodiazepine users had a marked increased risk of dementia (HR = 1.62; 1.11-2.37) compared with short half-life users (HR = 1.05; 0.85-1.30). Users of psychotropics had an increased risk of dementia (HR = 1.47; 1.16-1.86)., Discussion: Results of this large, prospective study show increased risk of dementia for long half-life benzodiazepine and psychotropic use., (Copyright © 2015 Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

The short-term effects of benzodiazepines on memory are well established and are suspected in the long term. Eleven studies have been published so far concerning benzodiazepine use and the risk of dementia disorders; nine of these studies concluded these drugs have a deleterious effect, one found a protective effect, and one (the most recently published) observed no effect. The positive association found in some studies could be due to a reverse causation bias since the main indications for benzodiazepines (e.g. sleep disorders, anxiety) can also be prodromes of dementia disorders. This bias is less likely for treatments started more than 10 years before the diagnosis. Among others, three mechanisms could underlie the potential influence of benzodiazepines on the development of dementia disorders. First, benzodiazepines can decrease beta-site amyloid precursor protein-cleaving enzyme 1 (BACE-1) and γ-secretase activity and slow down the accumulation of Aβ oligomers in the brain. This potential positive effect has never been confirmed; the same is true for the prevention of excitotoxicity through benzodiazepine anti-glutamatergic action. Second, since astrocytes located in the area of amyloid plaques could have gamma-aminobutyric acid (GABA)-secreting activity, patients with pre-dementia lesions could be at increased risk of presenting with more pronounced deleterious cognitive effects of benzodiazepines. Finally, owing to the neural compensation and cognitive reserve concepts, some subjects could cope with initial lesions by using/developing alternative networks. By lowering the brain activation level, benzodiazepines could limit this capacity. In conclusion, it is essential that animal studies explore the mechanistic hypotheses of this association found by most of the pharmacoepidemiological studies conducted on this topic.

Introduction: Several studies have highlighted an increased risk of dementia in benzodiazepine users. As dementia incidence and benzodiazepine use are both high, particularly in the elderly, even a moderate increase in this risk would induce a tremendous number of cases and have a major public health impact., Areas Covered: The aim of this article was to systematically review published observational studies having assessed the relation between benzodiazepine use and dementia, to assess and rank their quality and to provide a balanced opinion about the plausibility of a causal relationship., Expert Opinion: Out of the ten studies retrieved, nine reported an increased risk of dementia in benzodiazepine users. The risk increased with cumulative dose and treatment duration and when long-acting molecules were used. Even if the causal nature of this association remains unproved, the reviewed material provides arguments for evoking a causal link. Further research would be necessary to elucidate the mechanism of this effect, if any, to evaluate the risk of exposure in younger population and the influence of risk factors such as depression. In any case, the body of evidence seems sufficient for avoiding prescriptions or renewals that are not fully justified and indiscriminate long-term use.

Objectives: To investigate the relation between the risk of Alzheimer's disease and exposure to benzodiazepines started at least five years before, considering both the dose-response relation and prodromes (anxiety, depression, insomnia) possibly linked with treatment., Design: Case-control study., Setting: The Quebec health insurance program database (RAMQ)., Participants: 1796 people with a first diagnosis of Alzheimer's disease and followed up for at least six years before were matched with 7184 controls on sex, age group, and duration of follow-up. Both groups were randomly sampled from older people (age >66) living in the community in 2000-09., Main Outcome Measure: The association between Alzheimer's disease and benzodiazepine use started at least five years before diagnosis was assessed by using multivariable conditional logistic regression. Ever exposure to benzodiazepines was first considered and then categorised according to the cumulative dose expressed as prescribed daily doses (1-90, 91-180, >180) and the drug elimination half life., Results: Benzodiazepine ever use was associated with an increased risk of Alzheimer's disease (adjusted odds ratio 1.51, 95% confidence interval 1.36 to 1.69; further adjustment on anxiety, depression, and insomnia did not markedly alter this result: 1.43, 1.28 to 1.60). No association was found for a cumulative dose <91 prescribed daily doses. The strength of association increased with exposure density (1.32 (1.01 to 1.74) for 91-180 prescribed daily doses and 1.84 (1.62 to 2.08) for >180 prescribed daily doses) and with the drug half life (1.43 (1.27 to 1.61) for short acting drugs and 1.70 (1.46 to 1.98) for long acting ones)., Conclusion: Benzodiazepine use is associated with an increased risk of Alzheimer's disease. The stronger association observed for long term exposures reinforces the suspicion of a possible direct association, even if benzodiazepine use might also be an early marker of a condition associated with an increased risk of dementia. Unwarranted long term use of these drugs should be considered as a public health concern., (© Billioti de Gage et al 2014.)

Objective: To evaluate the association between use of benzodiazepines and incident dementia., Design: Prospective, population based study., Setting: PAQUID study, France., Participants: 1063 men and women (mean age 78.2 years) who were free of dementia and did not start taking benzodiazepines until at least the third year of follow-up., Main Outcome Measures: Incident dementia, confirmed by a neurologist., Results: During a 15 year follow-up, 253 incident cases of dementia were confirmed. New use of benzodiazepines was associated with an increased risk of dementia (multivariable adjusted hazard ratio 1.60, 95% confidence interval 1.08 to 2.38). Sensitivity analysis considering the existence of depressive symptoms showed a similar association (hazard ratio 1.62, 1.08 to 2.43). A secondary analysis pooled cohorts of participants who started benzodiazepines during follow-up and evaluated the association with incident dementia. The pooled hazard ratio across the five cohorts of new benzodiazepine users was 1.46 (1.10 to 1.94). Results of a complementary nested case-control study showed that ever use of benzodiazepines was associated with an approximately 50% increase in the risk of dementia (adjusted odds ratio 1.55, 1.24 to 1.95) compared with never users. The results were similar in past users (odds ratio 1.56, 1.23 to 1.98) and recent users (1.48, 0.83 to 2.63) but reached significance only for past users., Conclusions: In this prospective population based study, new use of benzodiazepines was associated with increased risk of dementia. The result was robust in pooled analyses across cohorts of new users of benzodiazepines throughout the study and in a complementary case-control study. Considering the extent to which benzodiazepines are prescribed and the number of potential adverse effects of this drug class in the general population, indiscriminate widespread use should be cautioned against.

Objective: To investigate the prevalence of current use of benzodiazepines (BZDs) and related drugs in the French general population and factors associated with this use., Methods: National cross-sectional telephone survey conducted between 25 April 2001 and 8 May 2001 in a representative sample of non-institutionalized adults of BZD use and duration, prescriber specialty, socio-demographic data and mood and anxiety disorders, using a structured diagnostic interview., Results: The prevalence of current use of BZD was 7.5%. It was higher among women (9.7%) than men (5.2%). It increased with age and was higher in the jobless (10.9). Duration of BZD use was more than 6 months in 75.9% of users and increased with age. Of the 711 (17.7%) subjects with at least one mood or anxiety disorder, 122 (17%) used BZD compared with 180 (5.5%) of the 3296 subjects without mood or anxiety disorders. In multivariate analysis, factors associated with BZD use were age [odds ratio (OR): 3.6; 95% confidence interval (CI) 2.0-5.6], 6.5 (4.1-10.3) and 10.9 (6.9-17.1), respectively, for ages 35-44 years, 45-59 years and over 60 years compared with below 34 years, female gender (OR: 1.7; 95% CI 1.3-2.1), anxiety only (OR: 2.2; 95% CI 1.5-3.2), mood disorder only (OR: 4.4; 95% CI 2.7-7.1) or both mood and anxiety disorders (OR: 8.8; 95% CI 5.9-12.6)., Conclusion: Despite precautions, warnings and attempts to limit use, there remains a high proportion of long-term BZD users in the general French population, especially in the elderly. Our findings add to the weight of opinion that messages concerning proper use of BZDs certainly need to be clarified and amplified.

Background: Benzodiazepines (BZD) are commonly prescribed in the elderly. Persons with dementia may be at a greater risk of adverse reactions of BZD such as cognitive impairment., Objective: To assess the prevalence of BZD use in Alzheimer's disease patients and to examine patient and drug-characteristics associated with this use., Design: Cross-sectional study., Participants: Five thousand community-dwelling and institutionalized patients initiating a treatment with tacrine for a mild to moderate Alzheimer's disease and included in the tacrine-study (Paco cohort)., Measurements: Patient characteristics and BZD use recorded at the inclusion., Main Outcome: Use of BZD during the 3 months prior to inclusion., Results: The 3-month prevalence of ever use of BZD was 20%. After controlling for age and gender, there was a non-significant inverse association between BZD use and a score of Mini-Mental Status Evaluation (MMSE) below 24 (OR: 0.88, 95% CI: 0.71-1.09), and significant inverse association with an increased number of chronic conditions (OR: 0.73, 95% CI: 0.58-0.91). Higher use of BZD was associated with higher level of overall drug consumption (OR: 2.3, 95% CI: 1.97-2.80)., Conclusion: Alzheimer's disease patients are frequently prescribed BZD. A low score of MMSE (< 24) is associated with a decreased use of BZD. These results suggest important differences in BZD use patterns among persons with Alzheimer's disease.

The objective of this article was to examine the possible association between benzodiazepine use and the risk of dementia in the elderly. This was a nested case--control study set in community settings in Bordeaux area, France. The participants were a representative sample of 3,777 elderly persons (65 years of age and older) followed from 1989 to 1997. The main outcome measures were the use of benzodiazepines in incident cases of dementia versus nondemented controls. On the basis of medical and psychological data, 150 patients were diagnosed with dementia according to the criteria of the third revision of the Diagnostic and Statistical Manual of Mental Disorders. Information on benzodiazepine use was obtained by face-to-face interview and visual assessment of patient's medicine chest by a trained neuropsychologist. After controlling for age, gender, education level, living alone, wine consumption, psychiatric history, and depressive symptomatology, ever use of benzodiazepines was associated with a significantly increased risk of dementia [adjusted odds ratio (OR), 1.7; 95% confidence interval, 1.2-2.4]. Former use was associated with a significantly increased risk of dementia (adjusted OR, 2.3; 95% CI,1.2-4.5). No association was found between dementia and the current use of benzodiazepines (adjusted OR, 1.0; 95% CI, 0.6-1.6). Our finding suggest that former use of benzodiazepines could be a risk factor for dementia, but more detailed investigation are needed.

Objectives: The objective of this study was to describe determinants of current and subsequent benzodiazepine use in an elderly population, the Paquid cohort Methods: The study was conducted on a cohort of 2792 community-dwelling subjects 65 years of age or more living in the Gironde department, southwestern France. Benzodiazepine use and its correlates were studied with data collected at inclusion in the cohort. Longitudinal analysis over a 5-year period of follow-up was done to identify baseline predictors of subsequent use. Results: At baseline, prevalence rate of benzodiazepine use was 31.9%. It was associated with female gender [odds ratio (OR)=2.0; 95% confidence interval (CI): 1.66, 2.46], previous psychiatric disease (OR =2.87; 95% CI: 2.31, 3.56), concomitant antidepressant use (OR=2.45; 95% CI: 1.59, 3.78), depressive symptomatology (OR=1.70; 95% CI: 1.28, 2.26), multiple drug use (OR=1.82; 95% CI: 1.50, 2.21), multiple chronic diseases (OR=1.37; 95% CI: 1.12, 1.67) and poor self-perceived health (OR=1.63; 95% CI: 1.33, 2.0). For the 1926 benzodiazepine non-users at inclusion and followed during 5 years, incidence rate of subsequent use was 5.37 per 100 person-years (95% CI: 4.76, 5.98). In multivariate Cox proportional hazards regression analysis, previous psychiatric diseases, poor self-perceived life satisfaction and polymorbidity were significantly associated with subsequent benzodiazepine use. Conclusions: Elderly people are heavy users of benzodiazepines. Independently from mental health status, those in poor health were most at risk of benzodiazepine use. [ABSTRACT FROM AUTHOR]

The article discusses a study that shows an association between benzodiazepine use and the subsequent diagnosis of dementia and presents symptoms that herald the emergence of dementia and lead to benzodiazepine use before dementia is diagnosed.

The article investigates the potential association between long-term use of benzodiazepines and risks of developing Alzheimer's disease among older people. Topics discussed include the correlation between the length of time that a patient has been using the drug and the patient's chances of developing Alzheimer's disease and the experts' warning that benzodiazepine may not be the cause of Alzheimer's disease but may just be an early marker of increased risk.

The article inquires whether the use of benzodiazepines increases the risk of dementia in elderly people. It is revealed that over a 15 year follow-up period, starting treatment with benzodiazepines increased the risk of dementia by about 50 percent compared with non-users. Adjustment for factors strongly associated with starting benzodiazepines or considered to be markers for a prodrome of early dementia did not alter the association.