Risk Of Benzodiazepine Use Research Articles

Associations of benzodiazepine use with cognitive ability and age-related cognitive decline.

It remains uncertain whether long-term use of benzodiazepines is associated with age-related cognitive decline, and if cognitive ability in early life is the driver of any association. This study examines the association of cognitive ability in young adulthood with later use of benzodiazepines and explores whether the use of benzodiazepines during adult life is associated with cognitive decline in late midlife. The study samples include cognitive tests on the Børge Priens Prøve (BPP) from the conscription board examination (age 19 years) from 335 513 men born 1949-1961 and data from re-examinations of 5183 men 44 years later. Cognitive decline was defined as the difference between scores at the conscription board and the re-examination. Information on purchases of benzodiazepines was obtained from the Danish National Prescription Registry, 1995-2022. Associations were analysed using Cox proportional hazards and linear regression. In total, 120 911 (36%) men purchased benzodiazepines during a follow-up of 20 years. Lower cognitive scores in young adulthood were associated with a higher risk of initiating benzodiazepines (hazard ratio [95% CI] = 0.71[0.68-0.75]). Men with the highest cumulative use of benzodiazepines had larger cognitive decline (β-coefficient [95% CI] = -1.66 [-2.09 to -1.23] BPP scores) compared with never users. Current benzodiazepine users showed a larger cognitive decline than never users (β-coefficient [95% CI] = -2.42[-3.18 to -1.66] BPP scores) and this partially explained the above association. These estimates for cognitive decline were relatively small and may lack clinical relevance. Low cognitive ability increases the risk of benzodiazepine use in adulthood and cognitive decline is more pronounced in those with the highest benzodiazepine use compared with never-use, but the difference lacks clinical significance.

Dose–response association of benzodiazepine use and development of deep vein thrombosis

Benzodiazepines have sedative effects that cause reduced activity in users and may increase the risk of deep vein thrombosis. However, few studies have examined this potential risk of benzodiazepine use. This study examined the association between benzodiazepine use and the risk of deep vein thrombosis (DVT) in adults in Taiwan using a longitudinal health insurance database. The study population included 12,546 individuals with DVT and 50,184 matched controls. Results showed that benzodiazepine use was associated with an increased risk of DVT occurrence (adjusted odds ratio [aOR]: 1.66; 95 % CI, 1.54–1.79; P <0.001), with a dose-response relationship. Patients with a higher defined daily dose had a higher risk of DVT, with ORs of 1.65-, 2.09-, and 2.16-fold higher for those with an average benzodiazepine dose of <0.5, 0.5–0.9, or ≥1 (DDD/day), respectively, compared to nonbenzodiazepine users. Stratification by age, sex, and follow-up duration yielded similar results. This study highlights the need to evaluate the association and benefits of benzodiazepine prescription to decrease the risk of DVT development.

Use of benzodiazepines non-compliant with guidelines in patients with psychiatric and non-psychiatric chronic disorders

ObjectiveTo quantify benzodiazepine use non-compliant with guidelines in patients with psychiatric and non-psychiatric chronic diseases and assess the risk of non-recommended use associated with these diseases. MethodA cohort study was conducted in the French health insurance databases, including 254,488 new benzodiazepine users between 2007 and 2014. Psychiatric, cardiovascular, cancer, diabetes and inflammatory diseases were identified. Patients were followed for 2 years. Non-recommended use was defined as excessive treatment duration, use of long half-life drugs in older patients and concomitant use of several benzodiazepines. Cox models identified the factors associated with non-recommended use. ResultsNon-recommended use was frequent, ranging from 44.9% to 68.1%. It was independently associated with each chronic disease, with a slight increase in patients with chronic inflammatory disease (HR = 1.07; 95%CI 1.03–1.13) or diabetes (HR = 1.09; 1.06–1.12), a higher risk in those with chronic cardiovascular disease (HR = 1.34; 1.31–1.37) or cancer (HR = 1.30; 1.25–1.35) and the highest risk in those with psychiatric disease (HR = 2.04; 2.00–2.09). ConclusionPatients with chronic disease have a high risk of benzodiazepine use leading to a higher exposure than recommended. Prescribers should be aware of the need to comply with the recommendations, especially in these patients who are the most frail and vulnerable to adverse events.

Speaking about pharmacist–physician collaborations to improve patient care

This month’s Pharmacy Today cover story, “Physicians speak: Medicine’s point of view on working with pharmacy,” highlights innovative practices that rely on pharmacist–physician collaborations (page 30). In these practices, pharmacists partner with local physicians to improve care by helping to change opioid prescribing patterns, achieve better outcomes for patients with diabetes and high blood pressure, and more. In this article, John W. Kennedy, MD, chief medical officer for AMGA, said we’ll see more such partnerships that expand traditional professional responsibilities to allow pharmacists to “play an increasing role in outpatient quality care improvement.” Throughout this issue, the most important speaker isn’t the physician or the pharmacist—it’s the patient who is asking for better care who is being heard loud and clear. The types of community-based partnerships described in this issue of Today provide new avenues for pharmacists to improve the lives and outcomes of our patients. When it’s August, it’s time for our annual Special Immunization Section. This August issue includes articles on 10 steps to prepare for influenza season (page 38), immunization registries (page 39), and opportunities to bring patients up to date on recommended immunizations (page 40). This issue also covers a review of OTCs for respiratory symptoms (page 26), soaring insulin prices (page 43), and the risks of benzodiazepine use (page 28). This month’s CPE is on the role of combination therapy or coformulation treatments of type 2 diabetes (page 50). And our Health-System Edition explores the national saline and injectable opioid shortages (page HSE 2). Innovative practice models and pharmacist–physician partnerships are making a difference. On a day-to-day basis, though, patients probably aren’t thinking about these details. They simply know they are receiving excellent and professional care. Because of that, when your patients speak, it is likely they are saying, “Thank you.” Have a great Today!

Patterns of chronic benzodiazepine use in the elderly

Background In several countries, prevalence studies demonstrate that chronic use of BZD in the elderly population is very high. This scenario has reached pandemic proportions for decades and is an important public health problem. Objectives To examine the independent association between chronic benzodiazepine use in depression, anxiety and bipolar disorder, as well as other clinical and sociodemographic factors. Methods This cross-sectional study was developed from a population-based survey and conducted from March, 2011 to December, 2012 using a random sample of 550 elderly people who were enrolled in the Family Health Strategy in Porto Alegre, Brazil. Data was collected from identifying epidemiological and health data (sociodemographic, self-perception health, self-reported diseases, smoking, alcohol and pharmacotherapeutic evaluation) and from the diagnoses of mood and anxiety disorders. Results Elderly patients diagnosed with depression, anxiety, concomitant depression/anxiety and bipolar disorders, and those who were using antidepressants have a higher risk of benzodiazepine use. Individuals who self-reported drinking alcohol had a lower risk of benzodiazepine use. Discussion Benzodiazepines are often used by the elderly for long periods, which has a direct impact on the treatment of mood and anxiety disorders and on vulnerable groups such as the elderly, who may be unnecessarily taking these drugs.

Continued Use of Benzodiazepines in Older Adults.

Benzodiazepine use in older adults has been a highlighted topic of discussion ever since benzodiazepines made an appearance on the Beers Criteria list as potentially inappropriate medications (PIMs). Concern for older adults who take benzodiazepines is substantiated by the potential increased risk of adverse events (eg, falls, fractures, cognitive impairment, and sedation).1,2 Though the levels of benzodiazepine use have decreased over the years, their continued use in older adults is a likely indication of their usefulness in the older adult population.3,4 A study was conducted by Egger et al to determine whether geriatric physicians might prescribe fewer PIMs for their patients than general medical physicians based on the assumption that geriatric physicians are more likely to be aware of the risks involved with prescribing PIMs to older adults. The results showed no difference in the number of PIMs prescribed by geriatric physicians and general physicians.5 These results suggest that providers find that the benefits of benzodiazepines outweigh the risks in many of their patients, despite the number of warnings in the media against benzodiazepine use in older adults. The risks and warnings that persistently appear in the media can be categorized as true risks or ambiguous risks. True risks would include established benzodiazepine-related adverse events that are associated with increased dose and duration of exposure (eg, sedation, falls, and fractures).1,2,5 Some studies show, though, that exposure to short-acting benzodiazepines is not associated with lower risk of adverse events compared to exposure to long-acting benzodiazepines in the older adult patient population.6,7 Benzodiazepine dependency, which can be physiological and/or psychological, however, has been shown to be associated more with continuous administration of long-acting benzodiazepines than with intermittent administration.8 Ambiguous risks refer to adverse events reported to be associated with benzodiazepine exposure, yet cannot be easily separated from confounding factors, including a disease or condition. Recently, a case-control study published in the British Medical Journal raised concerns about the increased risk of Alzheimer’s disease in older adult patients exposed to benzodiazepines.9 Such a warning could be an example of an ambiguous risk. Alzheimer’s disease is difficult to diagnose, and early symptoms (prodromal symptoms) may include anxiety, agitation, and insomnia.9 Without an established diagnosis of Alzheimer’s disease, older adults who complain of anxiety, agitation, and/or insomnia may be prescribed a benzodiazepine. Thus, a study that finds a positive association between use of benzodiazepines and Alzheimer’s disease is more than likely when there is temporal ambiguity (ie, did benzodiazepine use cause Alzheimer’s disease or did the onset of Alzheimer’s cause a need for benzodiazepine use prior to diagnosis). Certainly, clinicians are taught to use sound professional judgment in caring for all patients, and they are trusted to be aware of the benefits and risks associated with benzodiazepine use in older adults. Thus, providers who decide to prescribe a benzodiazepine to an older adult may have determined that a benzodiazepine is the most reasonable drug therapy option available at that point in a patient’s care. Benzodiazepine therapy is commonly used in older adults to treat anxiety and insomnia, but there are other valid medical conditions in older adults that may warrant benzodiazepine therapy, including seizure, alcohol or central nervous system depressant withdrawal, periprocedural anesthesia, palliative care, and agitation.2,8 Despite due diligence from prescribers, issues of duplication and/or inappropriate medication therapy are bound to occur when patients have multiple prescribers and multiple pharmacies. Older adult patients deemed eligible for benzodiazepine therapy should be regularly monitored by pharmacists for frequency of use, inappropriate use, and need for continued use. Physicians have been shown to place great value in the vital role of pharmacists in reviewing patients’ medications and alerting physicians of medication issues.10 It is unlikely that reports about the dangers of benzodiazepine use in older adults will diminish. Providers should be encouraged to continue using professional clinical judgment that weighs all true risks and benefits; reassess the use of benzodiazepines every 6 months based on indication, drug use pattern, and side-effect profile; prescribe the lowest therapeutic dose with the least frequent dosing schedule tolerated; and educate patients/caregivers of the risks of adverse events.8,11 Pharmacists should also continue to educate patients and providers on the true risks of benzodiazepine use, evaluate the various ambiguous risk claims made in literature and media, and monitor medications for duplicate and/or inappropriate therapy.

Benzodiazepine use among mothers of small children: a register-based cohort study.

To compare benzodiazepine (BZD) purchases in different groups of mothers of small children. Prospective population-based cohort study based on the Finnish social and health care registers. Finnish women of child-bearing age. All women who gave birth in 2002 in Finland (n = 54 519). Latent class analysis (LCA) was used to create a typology of mothers according to their substance abuse status, psychiatric disorders and socio-demographic characteristics. The mothers were followed-up yearly for purchases of benzodiazepines, starting 4 years before the child's birth and continuing up to the child's 7th birthday. BZD purchases in different mother groups were compared using negative binomial hurdle models. The five mother types identified by LCA were mothers with substance abuse (1%), mothers with psychiatric disorders (1%), mothers with a risk of social marginalization (11%), mothers with minor social problems (18%) and mothers with no identified problems (69%; the comparison group). Mothers with substance abuse problems had the highest odds of purchasing BZDs [odds ratio OR = 27.5, 95%CI = 22.9-33.0; RR = 20.2, 95%CI = 14.9-27.3. The change in time was similar in all groups: the probability of purchasing and the number of purchases were lowest during pregnancy and the year of the child's birth. In Finland, among mothers of young children, prevalence of benzodiazepine use is reduced during pregnancy and the child's first year, and then increases as the child grows older. Mothers with substance abuse and psychiatric disorders are at particularly high risk of benzodiazepine use.

Reduction of inappropriate benzodiazepine prescriptions among older adults through direct patient education: the EMPOWER cluster randomized trial.

The American Board of Internal Medicine Foundation Choosing Wisely Campaign recommends against the use of benzodiazepine drugs for adults 65 years and older. The effect of direct patient education to catalyze collaborative care for reducing inappropriate prescriptions remains unknown. To compare the effect of a direct-to-consumer educational intervention against usual care on benzodiazepine therapy discontinuation in community-dwelling older adults. Cluster randomized trial (EMPOWER [Eliminating Medications Through Patient Ownership of End Results] study [2010-2012, 6-month follow-up]). Community pharmacies were randomly allocated to the intervention or control arm in nonstratified, blocked groups of 4. Participants (303 long-term users of benzodiazepine medication aged 65-95 years, recruited from 30 community pharmacies) were screened and enrolled prior to randomization: 15 pharmacies randomized to the educational intervention included 148 participants and 15 pharmacies randomized to the "wait list" control included 155 participants. Participants, physicians, pharmacists, and evaluators were blinded to outcome assessment. The active arm received a deprescribing patient empowerment intervention describing the risks of benzodiazepine use and a stepwise tapering protocol. The control arm received usual care. Benzodiazepine therapy discontinuation at 6 months after randomization, ascertained by pharmacy medication renewal profiles. A total of 261 participants (86%) completed the 6-month follow-up. Of the recipients in the intervention group, 62% initiated conversation about benzodiazepine therapy cessation with a physician and/or pharmacist. At 6 months, 27% of the intervention group had discontinued benzodiazepine use compared with 5% of the control group (risk difference, 23% [95% CI, 14%-32%]; intracluster correlation, 0.008; number needed to treat, 4). Dose reduction occurred in an additional 11% (95% CI, 6%-16%). In multivariate subanalyses, age greater than 80 years, sex, duration of use, indication for use, dose, previous attempt to taper, and concomitant polypharmacy (10 drugs or more per day) did not have a significant interaction effect with benzodiazepine therapy discontinuation. Direct-to-consumer education effectively elicits shared decision making around the overuse of medications that increase the risk of harm in older adults. clinicaltrials.gov Identifier: NCT01148186.

Use of Benzodiazepines and Risk of Dementia over a 15-Year Follow-Up Period

Evaluation of: Billioti de Gage S, Bègaud B, Bazin F et al. Benzodiazepine use and risk of dementia: prospective population based study. 345, e6231 (2012). The use of benzodiazepines is highly prevalent in older people. It is well established that benzodiazepines can impair cognitive function. However, it is not clear whether benzodiazepines can cause dementia. Billioti de Gage et al. used three different epidemiological approaches to assess whether benzodiazepine use is associated with incident dementia in a population-based community-dwelling sample of people aged 65 years and older. In the main analysis, benzodiazepine use was associated with a hazard ratio of 1.60 (95% CI: 1.08–2.38) for the development of dementia over a 15-year follow-up period when compared with nonuse of benzodiazepines. The key strengths of the study included the new user design, long-term follow-up, and confirmation of dementia diagnoses by neurologists. The possibility of reverse causation arising from use of benzodiazepines for prodromal symptoms of dementia cannot be excluded. However, this study provides additional evidence about the risks of benzodiazepine use in older people.

Five-Year Trajectories of Long-Term Benzodiazepine Use by Adolescents: Patient, Provider, and Medication Factors

Five-Year Trajectories of Long-Term Benzodiazepine Use by Adolescents: Patient, Provider, and Medication Factors

Benzodiazepine Use Among Patients With Schizophrenia in Taiwan: A Nationwide Population-Based Survey

This study aimed to describe the pattern of benzodiazepine use in a representative sample of patients with schizophrenia in Taiwan. Data from the National Health Insurance Research Database in Taiwan were used to examine the prevalence and indices of benzodiazepine use in 2005. Demographic and clinical characteristics associated with long-term benzodiazepine use (more than 180 days of cumulated prescription in one year) were further explored by multivariate logistic regression analysis. Among the 3,690 patients with schizophrenia, the one-year prevalence rate of benzodiazepine use was 79.2% (N=2,923). Among those who used benzodiazepines, 1,840 (62.9%) were long-term users. Use of benzodiazepines was associated with having a comorbid psychiatric disorder, use of concomitant psychotropic agents, and antipsychotic polypharmacy. Among benzodiazepine users, older age, longer duration of illness, and use of concomitant psychotropic agents were associated with significantly higher odds of being a long-term user. The study showed that benzodiazepine use was highly prevalent among patients with schizophrenia in Taiwan and that a substantial proportion of users (62.9%) were long-term users. Because long-term use was associated with longer duration of illness and with use of concomitant psychotropic medications, long-term users may be at higher risk of neurocognitive side effects caused by benzodiazepines and interactions with other psychotropic medications. Therefore, this group should be closely monitored for drug-drug interactions and the benefits and risks of benzodiazepine use.

Five-Year Trajectories of Long-Term Benzodiazepine Use by Adolescents: Patient, Provider, and Medication Factors

This study sought to understand the stability of and change in benzodiazepine use among incident long-term benzodiazepine users over a five-year period and to investigate predictors of variation in use patterns from adolescence into adulthood. Long-term use was defined as receipt of benzodiazepine prescriptions for 31 or more cumulative days in a calendar year. Data for 1999-2005 were obtained from the National Health Insurance Research Database in Taiwan. Two age groups of incident long-term users in 2000 were identified--1,758 aged 12-15 and 5,265 aged 16-19-and their benzodiazepine prescription records from 2001 to 2005 were retrieved. Group-based trajectory analyses and polytomous logistic regression were performed to evaluate differential risk of benzodiazepine use over time. From 3% to 5% of the incident benzodiazepine users were long-term users. Four distinct groups of users emerged from the five years of study data: occasional, decelerating, accelerating, and chronic users. Overall, one-quarter were accelerating or chronic users. A history of psychosis or epilepsy, prescription by providers from multiple specialties, and receipt of benzodiazepines with a long half-life or mixed indications significantly increased one's risk of becoming a chronic or accelerating user (range of adjusted odds ratios from 2 to 6). Patient characteristics and attributes of service providers and pharmacological agents played significant roles in benzodiazepine use patterns. Prescribers can reduce the risk of long-term use by assessing whether pediatric patients have received benzodiazepines from multiple doctors for various medical conditions.

Benzodiazepine Use Among Patients With Schizophrenia in Taiwan: A Nationwide Population-Based Survey

Benzodiazepine Use Among Patients With Schizophrenia in Taiwan: A Nationwide Population-Based Survey

Use of Benzodiazepines and Benzodiazepine-Related Drugs among 223 Patients with an Acute Hip Fracture in Finland

CNS drugs are a risk factor for falls and fractures among older people. Our aim was to describe the use of benzodiazepines and benzodiazepine-related drugs among patients admitted to two Finnish hospitals as a result of an acute hip fracture, and to analyse the concordance of benzodiazepine findings from different data sources. We studied the use of benzodiazepines and benzodiazepine-related drugs by (i) asking the patient or his/her relatives about his/her use of hypnotics; (ii) checking the patient's medical records; and (iii) analysing for the presence of benzodiazepines in serum and urine. Blood and urine samples were taken at admission. Detection of benzodiazepines in serum and urine was achieved by the fluorescence polarisation method. Concordance in benzodiazepine findings between medical records and laboratory results was estimated by calculating the degree of agreement (kappa) and described graphically using a Venn diagram. A total of 223 patients were enrolled in the study. Of these, 71% were women. The mean age of women was 80.5 years (SD: 10) and of men, 73 years (SD: 12) [p < 0.0001]. Thirty percent of the patients reported that they used hypnotics. Benzodiazepine in serum or urine was detected in 83 (37%) patients. Over half of the patients coming from residential homes (53%) and institutions (54%) were benzodiazepine-positive. For home dwellers the proportion of patients that were benzodiazepine-positive was 29%. In 48% (40/83) of the benzodiazepine-positive patients, the type of benzodiazepine could not be identified because of a lack of drug records regarding benzodiazepines. A total of 113 (51%) patients used benzodiazepines or benzodiazepine-related drugs when both laboratory results and medical drug records were taken into account. Thirty-nine percent of these patients were home dwellers, 69% came from residential care and 76% from institutional care. The concordance between medical records and laboratory results expressed as overlap area was 32% in men and 59% in women, 38% in community-dwelling patients, 63% in residential home patients, and 68% in patients from institutions. Half of patients with an acute hip fracture used benzodiazepines or benzodiazepine-related drugs. The highest prevalences were found in institutional and residential care where it should be well known that the use of CNS drugs increases the risk of hip fracture. Concordance of benzodiazepine findings was moderate in all patients and poorest among men. Concordance was poorer among home dwellers than among those living in residential homes and institutions. Analysing benzodiazepine in serum seems to be the most reliable method for ascertaining benzodiazepine exposure. This laboratory test could be performed routinely when the elderly patient is admitted to hospital because of a fall or, at least, in case of hip fracture. Then, if needed, the patient should be informed about the risks of benzodiazepine use, and further falls and fractures could be prevented.