OBJECTIVE: The Drug Burden Index (DBI) calculates a person\'s exposure to anticholinergic and sedative medications. We aimed to review randomized controlled trials (RCTs) of deprescribing interventions that reported the DBI as an outcome, their characteristics, effectiveness in reducing the DBI, and impact on other outcomes.
METHODS: Systematic review with meta-analysis.
METHODS: RCTs of deprescribing interventions where the DBI was measured as a primary or secondary outcome in humans within any setting were included.
METHODS: Electronic databases, citation indexes, and gray literature were searched from April 1, 2007, to September 1, 2023. Quality was assessed using the Cochrane risk-of-bias tool.
RESULTS: Of 1721 records identified, 9 met the inclusion criteria. Six interventions were delivered by pharmacists and 3 were delivered by pharmacists/nurses or pharmacists/geriatricians. All interventions required at least intermediate-level skills and involved multiple components and target groups. Studies were conducted in the community (n = 5), nursing homes (n = 2), and hospitals (n = 2). The mean or median age was ≥75 years and most participants were women in all studies. Most (n = 6) studies were underpowered. The follow-up period ranged from 3 to 12 months. Three studies reported a lower DBI in the intervention group compared with control: 1 pharmacist independent prescriber-delivered in nursing homes (adjusted rate ratio, 0.83; 95% CI, 0.74 to 0.92), 1 pharmacist/nurse practitioner-delivered in hospital (adjusted mean difference (MD), -0.28; 95% CI, -0.51 to -0.04), and 1 geriatrician/pharmacist-delivered in hospital (MD, -0.28; 95% CI, -0.52 to -0.04). Meta-analysis showed no difference in the change in DBI between control and intervention groups in the community including nursing homes (MD, -0.03; 95% CI, -0.08 to 0.01) or hospital setting (MD, -0.19; 95% CI, -0.45 to 0.06). Interventions had inconsistent effects on cognition and no effect on other reported outcomes.
CONCLUSIONS: RCTs of deprescribing interventions had no significant impact on reducing DBI or improving outcomes. Further suitably powered studies are required.

BACKGROUND: Anticholinergic and sedative medications affect cognition among older adults. The Drug Burden Index (DBI) is a validated measure of exposure to these medications, with higher DBI scores indicating higher drug burden. This ancillary analysis investigated the association between DBI and cognition assessed by the Modified Mini-Mental State Examination (3MS) and the Digit Symbol Substitution Test (DSST).
METHODS: The Health, Aging, and Body Composition Study was a prospective study of community-dwelling adults aged 70-79 years at enrollment. Using data from years 1, 5, and 10, DBI was calculated using medication data per participant. Linear mixed modeling was used to assess cross-sectional and longitudinal effects of DBI on 3MS and DSST. Adjusted models included biological sex, race, education level, APOE status, and death. Sensitivity analyses included testing the strength of the associations for each year and testing attrition due to death as a possible confounding factor via Cox-Proportional Hazard models.
RESULTS: After adjustment, DBI was inversely associated with 3MS and DSST scores. These associations became stronger in each subsequent year. Neither DBI at year 1 nor within-person change in DBI were predictive of longitudinal declines in either cognitive measure. Sensitivity analyses indicated that DBI, 3MS, and DSST were associated with a greater risk of attrition due to death.
CONCLUSIONS: Results suggest that in years when older adults had a higher DBI scores, they had significantly lower global cognition and slower processing speed. These findings further substantiate the DBI as a useful pharmacological tool for assessing the effect of medication exposure.

OBJECTIVE: Frailty is common in older people and is associated with increased use of healthcare services and ongoing use of multiple medications. This study provides insights into the healthcare cost structure of a frail group of older adults in Aotearoa, New Zealand. Furthermore, we investigated the relationship between participants\' anticholinergic and sedative medication burden and their total healthcare costs to explore the viability of deprescribing interventions within this cohort.
METHODS: Healthcare cost analysis was conducted using data collected during a randomized controlled trial within a frail, older cohort. The collected information included participant demographics, medications used, frailty, cost of service use of aged residential care and outpatient hospital services, hospital admissions, and dispensed medications.
RESULTS: Data from 338 study participants recruited between 25 September 2018 and 30 October 2020 with a mean age of 80 years were analyzed. The total cost of healthcare per participant ranged from New Zealand $15 (US dollar $10) to New Zealand $270 681 (US dollar $175 943) over 6 months postrecruitment into the study. Four individuals accounted for 26% of this cohort\'s total healthcare cost. We found frailty to be associated with increased healthcare costs, whereas the drug burden was only associated with increased pharmaceutical costs, not overall healthcare costs.
CONCLUSIONS: With no relationship found between a patient\'s anticholinergic and sedative medication burden and their total healthcare costs, more research is required to understand how and where to unlock healthcare cost savings within frail, older populations.

The Drug Burden Index (DBI) measures an individual\'s total exposure to anticholinergic and sedative medications. This systematic review aimed to investigate the association of the DBI with clinical and prescribing outcomes in observational pharmaco-epidemiological studies, and the effect of DBI exposure on functional outcomes in pre-clinical models.
A systematic search of nine electronic databases, citation indexes and gray literature was performed (April 1, 2007-December 31, 2022). Studies that reported primary data on the association of the DBI with clinical or prescribing outcomes conducted in any setting in humans aged ≥18 years or animals were included. Quality assessment was performed using the Joanna Briggs Institute critical appraisal tools and the Systematic Review Centre for Laboratory animal Experimentation risk of bias tool.
Of 2382 studies screened, 70 met the inclusion criteria (65 in humans, five in animals). In humans, outcomes reported included function (n = 56), cognition (n = 20), falls (n = 14), frailty (n = 7), mortality (n = 9), quality of life (n = 8), hospitalization (n = 7), length of stay (n = 5), readmission (n = 1), other clinical outcomes (n = 15) and prescribing outcomes (n = 2). A higher DBI was significantly associated with increased falls (11/14, 71%), poorer function (31/56, 55%), and cognition (11/20, 55%) related outcomes. Narrative synthesis was used due to significant heterogeneity in the study population, setting, study type, definition of DBI, and outcome measures. Results could not be pooled due to heterogeneity. In animals, outcomes reported included function (n = 18), frailty (n = 2), and mortality (n = 1). In pre-clinical studies, a higher DBI caused poorer function and frailty.
A higher DBI may be associated with an increased risk of falls and decreased function and cognition. Higher DBI was inconsistently associated with increased mortality, length of stay, frailty, hospitalization or reduced quality of life. Human observational findings with respect to functional outcomes are supported by preclinical interventional studies. The DBI may be used as a tool to identify older adults at higher risk of harm.

The cumulative effect of drugs with anticholinergic properties may pose a significant risk in the post-discharge period of patients who have undergone elective cardiac surgery. The aim of this study was to investigate the association between anticholinergic burden and 6-month postdischarge mortality in older cardiac surgery patients.
This study performed a retrospective longitudinal analysis of patients undergoing elective cardiac surgery at a tertiary care centre from January 2021 to January 2022. The Deyo-Charlson comorbidity index (D-CCI) was used to estimate the burden of comorbidities. The anticholinergic burden was assessed using the Anticholinergic Cognitive Burden scale (ACB) and Drug Burden Index (DBI) scale. All-cause postdischarge mortality was determined from electronic medical records.
A total of 255 older adults who had undergone elective cardiac surgery and had been followed up for at least 6 months were included in this study. Approximately 12.5% (n = 32) of older patients died within 6 months of discharge. In multivariate Cox regression analysis, ACB (HR:1.31, 95%CI:1.10-1.56 p = 0.01) and DBI (HR:2.08, 95%CI:1.27-3.39 p = 0.01) showed significantly increased risk of 6-month postdischarge mortality after adjusting for several possible confounders (age, gender, D-CCl, and American Society of Anaesthesiologists (ASA) score). Overall event-free survival differed significantly between patients undergoing cardiac surgery based on anticholinergic burden according to the group-stratified ACB and DBI scales (χ2: 5.907, log-rank test, p = 0.015 and χ2: 15.389, log-rank test, p < 0.001 respectively).
The anticholinergic burden is associated with 6-month all-cause post-discharge mortality in older cardiac surgery patients. A deprescribing approach should be considered, especially for older adults in the perioperative period.
The trial was retrospectively registered at ClinicalTrials.gov. Identifier: NCT05312684 Registered on 5 April 2022.

Falls are the most common medication-related safety event in older adults. Deprescribing fall risk-increasing drugs (FRIDs) may mitigate fall risk. This study assesses the effects of an innovative deprescribing program in reducing FRID burden and falls-related acute visits over 1 year.
The Falls Assessment of Medications in the Elderly (FAME) Program is a pilot deprescribing program designed to improve medication safety in Veterans aged ≥65, screening positive for high fall risk at the Durham Veterans Affairs Health Care System. Central case finding and electronic case reviews with deprescribing recommendations were completed by an interdisciplinary team, forwarded to prescribers for approval, then implemented during follow-up telephone visits by FAME team. Primary outcome was change in FRID burden calculated by modified Drug Burden Index (DBI) at 1 year and an exploratory outcome was 1-year fall-related acute visits.
Overall, 472 patients (236 intervention cases, 236 matched controls) were included in the study. Of the 236 patients receiving a FAME deprescribing plan, 147 had recommendations approved by prescriber and patient. In the intention-to-treat analysis, the 1-year change in modified DBI was -0.15 (95% CI -0.23, -0.08) in the intervention cohort and -0.11 (-0.21, -0.00) in the matched control cohort (p = 0.47). The odds of increasing DBI by a clinically important threshold of 0.5 was significantly lower in the FAME cohort (OR 0.37, 0.21, 0.66). Fall-related acute events occurred in 6.3% of patients in the intervention group versus 11.0% in control patients over a one-year period (p = 0.10).
The program was associated with a significantly lower odds of further increasing FRID burden at 1 year compared to matched controls. An electronic case review and telephone counseling program has the potential to reduce drug-related falls in high-risk older adults.

OBJECTIVE: To determine DBI and its relationship with polypharmacy and pharmacotherapeutic complexity (PC) in a cohort of PLWH over 50 years of age at follow-up of pharmacotherapy in a tertiary hospital.
METHODS: Observational and retrospective study that included PLWH in active antiretroviral treatment over 50 years of age who have been followed up in outpatient pharmacy services. Pharmacotherapeutic complexity was estimated through Medication Regimen Complexity Index (MRCI). Collected variables included comorbidities, current prescriptions and its classification according to anticholinergic and sedative activity and associated risk of falls.
RESULTS: Studied population included 251 patients (85.7% men; median age: 58 years, interquartile range: 54-61). There was a high prevalence of high DBI scores (49.2%). High DBI was significantly correlated with a high PC, polypharmacy, psychiatric comorbidity and substances abuse (p<0.05). Among sedative drugs, the most prescribed were anxiolytic drugs (N05B) (n=85), antidepressant drugs (N06A) (n=41) and antiepileptic drugs (N03A) (n=29). For anticholinergic drugs, alpha-adrenergic antagonist drugs (G04C) were the most prescribed (n=18). Most frequent drugs associated with risk of falls were anxiolytics (N05B) (n=85), angiotensin-converting enzyme inhibitors (C09A) (n=61) and antidepressants (N06A) (n=41).
CONCLUSIONS: The DBI score in older PLWH is high and it is related to PC, polypharmacy, mental diseases and substance abuse as is the prevalence of fall-related drugs. Control of these parameters as well as the reduction of the sedative and anticholinergic load should be included in the lines of work in the pharmaceutical care of people living with HIV+.

(1) Background: Anticholinergic and sedative drugs (ASDs) contribute to negative health outcomes, especially in the frail population. In this study, we aimed to assess whether frailty increases with anticholinergic burden and to evaluate the effects of medication reviews (MRs) on ASD regimens among patients attending an acute care for the elderly (ACE) unit. (2) Methods: A cohort study was conducted between June 2019 and October 2020 with 150 consecutive patients admitted to our ACE unit. Demographic, clinical, and pharmacological data were assessed. Frailty score was determined using the Frail-VIG index (FI-VIG), and ASD burden was quantified using the drug burden index (DBI). In addition, the MR was performed using the patient-centered prescription (PCP) model. We used a paired T-test to compare the DBI pre- and post-MR and univariate and multivariate regression to identify the factors associated with frailty. (3) Results: Overall, 85.6% (n = 128) of participants showed some degree of frailty (FI-VIG > 0.20) and 84% (n = 126) of patients received treatment with ASDs upon admission (pre-MR). As the degree of frailty increased, so did the DBI (p < 0.001). After the implementation of the MR through the application of the PCP model, a reduction in the DBI was noted (1.06 ± 0.8 versus 0.95 ± 0.7) (p < 0.001). After adjusting for covariates, the association between frailty and the DBI was apparent (OR: 11.42, 95% (CI: 2.77-47.15)). (4) Conclusions: A higher DBI was positively associated with frailty. The DBI decreased significantly in frail patients after a personalized MR. Thus, MRs focusing on ASDs are crucial for frail older patients.

Comprehensively investigate prescribing in usual care of hospitalized older people with respect to polypharmacy; potentially inappropriate medications (PIMs) according to Beers criteria; and cumulative anticholinergic and sedative medication exposure calculated with Drug Burden Index (DBI). Specifically, to quantify exposure to these measures on admission, changes between admission and discharge, associations with adverse outcomes and medication costs.
Established new retrospective inpatient cohort of 2000 adults aged ≥75 years, consecutively admitted to 6 hospitals in Sydney, Australia, with detailed information on medications, clinical characteristics and outcomes. Conducted cross-sectional analyses of index admission data from cohort.
Cohort had mean (standard deviation) age 86.0 (5.8) years, 59% female, 21% from residential aged care. On admission, prevalence of polypharmacy was 77%, PIMs 34% and DBI > 0 in 53%. From admission to discharge, mean difference (95% confidence interval) in total number of medications increased 1.05 (0.92, 1.18); while prevalence of exposure to PIMs (-3.8% [-5.4, -2.1]) and mean DBI score (-0.02 [-0.04, -0.01]) decreased. PIMs and DBI score were associated with increased risks (adjusted odds ratio [95% confidence interval]) of falls (PIMs 1.63 [1.28, 2.08]; DBI score 1.21[1.00, 1.46]) and delirium (PIMs 1.76 [1.38, 1.46]; DBI score 1.42 [1.19, 1.71]). Each measure was associated with increased risk of adverse drug reactions (polypharmacy 1.42 [1.19, 1.71]; PIMs 1.87 [1.40, 2.49]; DBI score 1.90 [1.55, 2.15]). Cost (AU$/patient/hospital day) of medications contributing to PIMs and DBI was low ($0.29 and $0.88).
In this large cohort of older inpatients, usual hospital care results in an increase in number of medications and small reductions in PIMs and DBI, with variable associations with adverse outcomes.

Introduction: Anticholinergic and sedative medication is prescribed for various conditions in older patients. While the general association between anticholinergic and sedative medication and impaired functioning is well established, its specific role in older individuals with vertigo, dizziness, and balance disorders (VDB) is still incompletely understood. The objective of this study was to investigate, whether an exposure to anticholinergic and sedative medication is associated with lower generic and lower vertigo-specific functioning in older patients with VDB. Methods: Data originates from the longitudinal multicenter study MobilE-TRA with two follow-ups, conducted from 2017 to 2019 in two German federal states. Exposure to anticholinergic and sedative medication was quantified using the drug burden index (DBI). Generic functioning was assessed by the Health Assessment Questionnaire Disability Index, appraising the amount of difficulties in performing activities of daily living (ADL). Vertigo-specific functioning was measured using the Vestibular Activities and Participation (VAP) questionnaire, assessing patient-reported functioning regarding activities of daily living that are difficult to perform because of their propensity to provoke VDB (Scale 1) as well as immediate consequences of VDB on activities and participation related to mobility (Scale 2). Longitudinal linear mixed models were applied to assess the association of exposure to anticholinergic and sedative medication at baseline and the level of generic and vertigo-specific functioning status over time. Results: An overall of 19 (7 from Bavaria) primary care physicians (mean age = 54 years, 29% female) recruited 158 (59% from Bavaria) patients with VDB (median age = 78 years, 70% female). Anticholinergic and sedative medication at baseline was present in 56 (35%) patients. An exposure to anticholinergic and sedative medication at baseline was significantly associated with lower generic functioning [Beta = 0.40, 95%-CI (0.18; 0.61)] and lower vertigo-specific functioning [VAP Scale 1: Beta = 2.47, 95%-CI (0.92; 4.02)], and VAP Scale 2: Beta = 3.74, 95%-CI [2.23; 5.24]). Conclusion: Our results highlight the importance of a close monitoring of anticholinergic and sedative medication use in older patients with VDB. When feasible, anticholinergic and sedative medication should be replaced by equivalent alternative therapies in order to potentially reduce the burden of VDB.