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JAMA Network Open May 2023Anticholinergic medications to treat overactive bladder (OAB) have been associated with increased risk of cognitive decline, whereas β3-adrenoceptor agonists...
IMPORTANCE
Anticholinergic medications to treat overactive bladder (OAB) have been associated with increased risk of cognitive decline, whereas β3-adrenoceptor agonists (hereafter, β3-agonists) have comparable efficacy and do not carry the same risk. Yet, anticholinergics remain the predominant OAB medication prescribed in the US.
OBJECTIVE
To evaluate whether patient race, ethnicity, and sociodemographic characteristics are associated with receipt of anticholinergic vs β3-agonist OAB medications.
DESIGN, SETTING, AND PARTICIPANTS
This study is a cross-sectional analysis of the 2019 Medical Expenditure Panel Survey, a representative sample of US households. Participants included individuals with a filled OAB medication prescription. Data analysis was performed from March to August 2022.
EXPOSURE
A prescription for medication to treat OAB.
MAIN OUTCOMES AND MEASURES
The primary outcomes were receipt of a β3-agonist or an anticholinergic OAB medication.
RESULTS
An estimated 2 971 449 individuals (mean age, 66.4 years; 95% CI, 64.8-68.2 years) filled prescriptions for OAB medications in 2019; 2 185 214 (73.5%; 95% CI, 62.6%-84.5%) identified as female, 2 326 901 (78.3%; 95% CI, 66.3%-90.3%) self-identified as non-Hispanic White, 260 685 (8.8%; 95% CI, 5.0%-12.5%) identified as non-Hispanic Black, 167 210 (5.6%; 95% CI, 3.1%-8.2%) identified as Hispanic, 158 507 (5.3%; 95% CI, 2.3%-8.4%) identified as non-Hispanic other race, and 58 147 (2.0%; 95% CI, 0.3%-3.6%) identified as non-Hispanic Asian. A total of 2 229 297 individuals (75.0%) filled an anticholinergic prescription, and 590 255 (19.9%) filled a β3-agonist prescription, with 151 897 (5.1%) filling prescriptions for both medication classes. β3-agonists had a median out-of-pocket cost of $45.00 (95% CI, $42.11-$47.89) per prescription compared with $9.78 (95% CI, $9.16-$10.42) for anticholinergics. After controlling for insurance status, individual sociodemographic factors, and medical contraindications, non-Hispanic Black individuals were 54% less likely than non-Hispanic White individuals to fill a prescription for a β3-agonist vs an anticholinergic medication (adjusted odds ratio, 0.46; 95% CI, 0.22-0.98). In interaction analysis, non-Hispanic Black women had an even lower odds of filing a β3-agonist prescription (adjusted odds ratio, 0.10; 95% CI, 0.04-0.27).
CONCLUSIONS AND RELEVANCE
In this cross-sectional study of a representative sample of US households, non-Hispanic Black individuals were significantly less likely than non-Hispanic White individuals to have filled a β3-agonist prescription compared with an anticholinergic OAB prescription. These differences may reflect an inequity in prescribing behaviors promulgating health care disparities. Targeted research should assess the relative contribution of a variety of individual and societal factors.
Topics: Aged; Female; Humans; Cholinergic Antagonists; Cross-Sectional Studies; Drug Prescriptions; Urinary Bladder, Overactive; Healthcare Disparities; Prescriptions; Male
PubMed: 37223899
DOI: 10.1001/jamanetworkopen.2023.15074 -
The Journal of Nutrition, Health & Aging 2021Anticholinergic burden defined by the Anticholinergic Risk Scale (ARS) has been associated with cognitive and functional decline. Associations with health-related...
OBJECTIVES
Anticholinergic burden defined by the Anticholinergic Risk Scale (ARS) has been associated with cognitive and functional decline. Associations with health-related quality of life (HRQoL) have been scarcely studied. The aim of this study was to examine the association between anticholinergic burden and HRQoL among older people living in long-term care. Further, we investigated whether there is an interaction between ARS score and HRQoL in certain underlying conditions.
DESIGN AND PARTICIPANTS
Cross-sectional study in 2017. Participants were older people residing in long-term care facilities (N=2474) in Helsinki.
MEASUREMENTS
Data on anticholinergic burden was assessed by ARS score, nutritional status by Mini Nutritional Assessment, and HRQoL by the 15D instrument.
RESULTS
Of the participants, 54% regularly used ARS-defined drugs, and 22% had ARS scores ≥2. Higher ARS scores were associated with better cognition, functioning, nutritional status and higher HRQoL. When viewing participants separately according to a diagnosis of dementia, nutritional status or level of dependency, HRQoL was lower among those having dementia, worse nutritional status, or being dependent on another person's help (adjusted for age, sex, comorbidities). Significant differences within the groups according to ARS score were no longer observed. However, interactions between ARS score and dementia and dependency emerged.
CONCLUSION
In primary analysis there was an association between ARS score and HRQoL. However, this relationship disappeared after stratification by dementia, nutritional status and dependency. The reasons behind the interaction concerning dementia or dependency remain unclear and warrant further studies.
Topics: Aged; Aged, 80 and over; Cholinergic Antagonists; Cross-Sectional Studies; Female; Humans; Long-Term Care; Male; Quality of Life
PubMed: 33491038
DOI: 10.1007/s12603-020-1493-2 -
Pharmacology Research & Perspectives May 2021Evidence suggests that the prescription of bladder anticholinergics is increasing. Recent studies have accentuated concerns about whether certain prescribed medications...
Evidence suggests that the prescription of bladder anticholinergics is increasing. Recent studies have accentuated concerns about whether certain prescribed medications could increase risk of dementia, including anticholinergic drugs, and specifically anticholinergics used for bladder symptoms. Nevertheless, it can be difficult to draw together the evidence to review the case for possible causation. Recognising this issue in 1965, Bradford-Hill set out nine criteria to help assess whether evidence of a causal relationship could be inferred between a presumed cause and an observed effect. In this commentary, we explore the extent to which associations between anticholinergics and dementia satisfy the Bradford-Hill criteria and examine the potential implications. First, we look at studies that have examined the relationship between anticholinergic drugs with urological properties (bladder drugs) and the onset of dementia, and then present those studies which specifically focus on the cognitive effects of bladder drugs that affect muscarinic receptors in the brain versus the bladder on older people along with suggestions for future research. We also discuss the risks and benefits of these drugs for treating overactive bladder. If it can be shown that certain medications carry a specific risk of dementia, it is possible that initiatives to change prescribing could become a key tool in reducing the risk of dementia and may be easier to implement than some lifestyle changes.
Topics: Cholinergic Antagonists; Dementia; Humans; Risk; Urinary Bladder, Overactive
PubMed: 34087056
DOI: 10.1002/prp2.793 -
BMJ Open Mar 2021The aims of our study were to examine the anticholinergic drug use and to assess the association between anticholinergic burden and cognitive function in the multimorbid... (Observational Study)
Observational Study
Anticholinergic drug burden according to the anticholinergic drug scale and the German anticholinergic burden and their impact on cognitive function in multimorbid elderly German people: a multicentre observational study.
OBJECTIVES
The aims of our study were to examine the anticholinergic drug use and to assess the association between anticholinergic burden and cognitive function in the multimorbid elderly patients of the MultiCare cohort.
SETTING
MultiCare was conducted as a longitudinal cohort study in primary care, located in eight different study centres in Germany.
PARTICIPANTS
3189 patients (59.3% female).
PRIMARY AND SECONDARY OUTCOME MEASURES
Baseline data were used for the following analyses. Drugs were classified according to the well-established anticholinergic drug scale (ADS) and the recently published German anticholinergic burden (German ACB). Cognitive function was measured using a letter digit substitution test (LDST) and a mixed-effect multivariate linear regression was performed to calculate the influence of anticholinergic burden on the cognitive function.
RESULTS
Patients used 1764 anticholinergic drugs according to ADS and 2750 anticholinergics according to the German ACB score (prevalence 38.4% and 53.7%, respectively). The mean ADS score was 0.8 (±1.3), and the mean German ACB score was 1.2 (±1.6) per patient. The most common ADS anticholinergic was furosemide (5.8%) and the most common ACB anticholinergic was metformin (13.7%). The majority of the identified anticholinergics were drugs with low anticholinergic potential: 80.2% (ADS) and 73.4% (ACB), respectively. An increasing ADS and German ACB score was associated with reduced cognitive function according to the LDST (-0.26; p=0.008 and -0.24; p=0.003, respectively).
CONCLUSION
Multimorbid elderly patients are in a high risk for using anticholinergic drugs according to ADS and German ACB score. We especially need to gain greater awareness for the contribution of drugs with low anticholinergic potential from the cardiovascular system. As anticholinergic drug use is associated with reduced cognitive function in multimorbid elderly patients, the importance of rational prescribing and also deprescribing needs to be further evaluated.
TRIAL REGISTRATION NUMBER
ISRCTN89818205.
Topics: Aged; Cholinergic Antagonists; Cognition; Female; Germany; Humans; Longitudinal Studies; Male; Pharmaceutical Preparations
PubMed: 33757948
DOI: 10.1136/bmjopen-2020-044230 -
Schizophrenia Research Apr 2024Schizophrenia is characterized by cognitive impairment affecting everyday functioning. Earlier research has hypothesized that antidepressants may associate with better...
Schizophrenia is characterized by cognitive impairment affecting everyday functioning. Earlier research has hypothesized that antidepressants may associate with better cognitive functioning, but results are mixed. This study explored the association between antidepressant use and cognitive performance in terms of reaction time and visual learning in a clinical sample. In addition, we examined benzodiazepine use and anticholinergic burden. Study participants were drawn from the SUPER-Finland cohort, collected among patients with psychotic illnesses in 2016-2018 throughout Finland (n = 10,410). The analysis included adults with a schizophrenia diagnosis (F20) and results from a cognitive assessment (n = 3365). Information about medications and psychosocial factors were gathered through questionnaire and interview. Cognitive performance was assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB) with two subtests measuring reaction time and visual learning. Almost 36 % of participants used at least one antidepressant. The use of antidepressants in general was not associated with performance in the reaction time and visual learning tasks. However, the use of SNRI antidepressants was associated with a faster reaction time. Benzodiazepine use and a higher anticholinergic burden were associated with poorer performance in both tests. The results strengthen earlier findings that there is no association between antidepressant use in general and cognitive performance in schizophrenia. However, the association of SNRI medications with a faster reaction time warrants further research. Moreover, the results suggest that more attention should be paid to the anticholinergic burden of the medications used by patients with schizophrenia, as well as avoiding continuous benzodiazepine use.
Topics: Adult; Humans; Schizophrenia; Cholinergic Antagonists; Benzodiazepines; Serotonin and Noradrenaline Reuptake Inhibitors; Cognitive Dysfunction; Cognition; Neuropsychological Tests; Antidepressive Agents
PubMed: 38401410
DOI: 10.1016/j.schres.2024.02.025 -
Respiratory Medicine May 2016Exacerbation frequency is related to disease progression, quality of life, and prognosis in COPD. Earlier diagnosis, along with interventions aimed at preventing... (Comparative Study)
Comparative Study Review
BACKGROUND
Exacerbation frequency is related to disease progression, quality of life, and prognosis in COPD. Earlier diagnosis, along with interventions aimed at preventing exacerbations and delaying progression, may help reduce the global burden of disease. Long-acting inhaled bronchodilators are effective at maintaining symptom relief and are recommended as first-choice therapy for more symptomatic patients and those at risk of exacerbation.
METHODS
As prevention of exacerbations is a priority goal in COPD management and a number of different long-acting bronchodilators are available, we conducted a systematic review of exacerbation data from randomized controlled trials (published January 2000 to May 2014) comparing the effect of tiotropium versus placebo and/or other maintenance therapies.
RESULTS
Exacerbations were a primary endpoint in 12 publications (five studies: four comparing tiotropium with placebo; one with active comparator) and a secondary endpoint in 17 publications (seven studies: six comparing tiotropium with placebo; one with active comparator). Overall, tiotropium was associated with a longer time to first exacerbation event and fewer exacerbations (including severe exacerbations/hospitalizations) compared with placebo and long-acting β2-agonists. Tiotropium also showed similar efficacy to glycopyrronium and a fixed long-acting muscarinic antagonist/long-acting β2-agonist combination (glycopyrronium/indacaterol), although not all studies were powered to demonstrate differences in exacerbation outcomes. Exacerbation outcomes were comparable with both formulations of tiotropium (HandiHaler(®) 18 μg/Respimat(®) 5 μg).
CONCLUSIONS
The results of this comprehensive systematic review demonstrate tiotropium is beneficial in reducing exacerbation risk versus placebo or other maintenance treatments.
Topics: Administration, Inhalation; Bronchodilator Agents; Cholinergic Antagonists; Glycopyrrolate; Humans; Indans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quinolones; Randomized Controlled Trials as Topic; Tiotropium Bromide
PubMed: 27109805
DOI: 10.1016/j.rmed.2016.02.012 -
BMJ Open May 2019To estimate the association between cumulative anticholinergic burden and falls and fractures in patients with overactive bladder (OAB).
OBJECTIVE
To estimate the association between cumulative anticholinergic burden and falls and fractures in patients with overactive bladder (OAB).
DESIGN
A retrospective claims-based study (2007-2015) of patients with OAB; outcomes from a subset were contrasted to a non-OAB comparison.
SETTING
United States, commercially and Medicare-insured population.
PARTICIPANTS
154 432 adults with OAB and 86 966 adults without OAB, mean age of 56 years, and 67.9% women.
MAIN OUTCOME MEASURES
Cumulative anticholinergic burden, a unitless value representing exposure over time, was estimated over the 12 months pre-index ('at baseline') and every 6 months post index. Burden was categorised as no burden (0), low burden (1-89), medium burden (90-499) or high burden (500+). Unadjusted rates of falls or fractures were estimated, and the increased risk associated with anticholinergic burden (measured at the closest 6-month interval prior to a fall or fracture) was assessed using a Cox proportional hazards model and a marginal structural model.
RESULTS
Median (IQR) baseline anticholinergic burden was 30 (0.0-314.0) and higher among older (≥65 years, 183 [3.0-713.0]) versus younger (<65 years, 13 [0.0-200.0]) adults. The unadjusted rate of falls or fractures over the period was 5.0 per 100 patient-years, ranging from 3.1 (95% CI 3.0-3.2) for those with no burden, to 7.4 (95% CI 7.1-7.6) for those with high burden at baseline. The adjusted risk of falls and fractures was greater with higher anticholinergic burden in the previous 6 months, with an HR of 1.2 (95% CI 1.2 to 1.3) for low burden versus no burden, to 1.4 (95% CI 1.3 to 1.4) for high versus no burden. Estimates from marginal structural models adjusting for time-varying covariates were lower but remained significantly higher with a higher anticholinergic burden. Rates of falls and fractures were approximately 40% higher among those with OAB (vs those without).
CONCLUSION
Higher levels of anticholinergic burden are associated with higher rates of falls and fractures, highlighting the importance of considering anticholinergic burden when treating patients with OAB.
Topics: Accidental Falls; Aged; Aged, 80 and over; Cholinergic Antagonists; Female; Fractures, Bone; Health Care Costs; Humans; Logistic Models; Male; Medicare; Middle Aged; Quality of Life; Retrospective Studies; Risk Factors; United States; Urinary Bladder, Overactive
PubMed: 31061036
DOI: 10.1136/bmjopen-2018-026391 -
British Journal of Clinical Pharmacology Jul 2023The aim of this study is to estimate the association between anticholinergic burden, general cognitive ability and various measures of brain structural MRI in relatively...
AIMS
The aim of this study is to estimate the association between anticholinergic burden, general cognitive ability and various measures of brain structural MRI in relatively healthy middle-aged and older individuals.
METHODS
In the UK Biobank participants with linked health-care records (n = 163,043, aged 40-71 at baseline), of whom about 17 000 had MRI data available, we calculated the total anticholinergic drug burden according to 15 different anticholinergic scales and due to different classes of drugs. We then used linear regression to explore the associations between anticholinergic burden and various measures of cognition and structural MRI, including general cognitive ability, 9 separate cognitive domains, brain atrophy, volumes of 68 cortical and 14 subcortical areas and fractional anisotropy and median diffusivity of 25 white-matter tracts.
RESULTS
Anticholinergic burden was modestly associated with poorer cognition across most anticholinergic scales and cognitive tests (7/9 FDR-adjusted significant associations, standardised betas (β) range: -0.039, -0.003). When using the anticholinergic scale exhibiting the strongest association with cognitive functions, anticholinergic burden due to only some classes of drugs exhibited negative associations with cognitive function, with β-lactam antibiotics (β = -0.035, P < 0.001) and opioids (β = -0.026, P < 0.001) exhibiting the strongest effects. Anticholinergic burden was not associated with any measure of brain macrostructure or microstructure (P > 0.08).
CONCLUSIONS
Anticholinergic burden is weakly associated with poorer cognition, but there is little evidence for associations with brain structure. Future studies might focus more broadly on polypharmacy or more narrowly on distinct drug classes, instead of using purported anticholinergic action to study the effects of drugs on cognitive ability.
Topics: Middle Aged; Humans; Aged; Cholinergic Antagonists; Cognition; Brain; Central Nervous System Diseases; Neurodegenerative Diseases; Atrophy; Cognitive Dysfunction
PubMed: 36813260
DOI: 10.1111/bcp.15698 -
Clinical Interventions in Aging 2020Overactive bladder syndrome (OAB) is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency incontinence, in the absence of... (Review)
Review
Overactive bladder syndrome (OAB) is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency incontinence, in the absence of urinary tract infection or other obvious pathology. The mainstay of treatment of OAB is anticholinergic/antimuscarinic medication. These drugs block muscarinic receptors throughout the body, not only the bladder, including in the brain, which may lead to cognitive side effects. Anticholinergic load or burden is the cumulative effect of taking drugs that are capable of producing anticholinergic adverse effects. The elderly are more susceptible to these effects, especially as there is increased permeability of the blood brain barrier. The anticholinergic drugs for OAB are able to enter the central nervous system and lead to central side effects. There is increasing evidence that a high anticholinergic load is linked to the development of cognitive impairment and even dementia. Some studies have found an increased risk of mortality. In view of this, care is needed when treating OAB in the elderly. Trospium chloride is a quaternary amine anticholinergic, which has a molecular structure, which theoretically means it is less likely to cross the blood brain barrier and exert central side effects. Alternatively, mirabegron can be used, which is a beta-3 adrenoceptor agonist, which does not add to the anticholinergic load or exert central nervous system side effects. Conservative therapy can be used as an alternative to pharmacological treatment in the form of behavioral modification, fluid management and bladder retraining. Neuromodulation or the use of botox can also be alternatives, but success may be less in the older adult and will require increased hospital attendances.
Topics: Acetanilides; Aged; Behavior Therapy; Benzilates; Blood-Brain Barrier; Cholinergic Antagonists; Cognitive Dysfunction; Female; Humans; Muscarinic Antagonists; Nortropanes; Thiazoles; Urinary Bladder, Overactive
PubMed: 32921995
DOI: 10.2147/CIA.S252852 -
GeroScience Jun 2022Many medications of different indications have a relevant anticholinergic activity. The anticholinergic burden of medication has been shown to have significant effects...
Many medications of different indications have a relevant anticholinergic activity. The anticholinergic burden of medication has been shown to have significant effects on the cognition and the risk for cognitive impairment and dementia particularly in older patients. So far, most of the studies used data from geriatric patients and the effect of the anticholinergic burden on brain structures is still unexplored. Our study aimed to analyze possible associations of hippocampus and cholinergic basal forebrain volumes as vulnerable brain structures for the development of dementia and the anticholinergic burden in a population-based cohort of non-demented participants spanning the adult age range from 21 to 80 years. We analyzed associations between medication-related anticholinergic burden and structural MRI volumes from participants (n = 3087, 52.2% female) of the population-based "Study of Health in Pomerania" (SHIP). Anticholinergic burden was obtained from the current medication plan using the Anticholinergic Burden Scale (ACB). All analyses were adjusted for age, sex, education, and total intracranial volume. We found statistically significant associations between the ACB and the left and right hippocampus volume but not for the basal forebrain cholinergic system. Complementary voxel-based analysis across all participants revealed FWE-corrected (p = < 0.05) clusters in the temporo-parietal regions reaching into frontal areas, showing reduced volumes with higher ACB scores. We identified an association between anticholinergic burden of medication on hippocampal volume suggesting a potential inverse effect of such medication. This association highlights the importance of a careful prescription of medication with anticholinergic activity at any adult age.
Topics: Aged; Aged, 80 and over; Cholinergic Agents; Cholinergic Antagonists; Cognitive Dysfunction; Dementia; Female; Hippocampus; Humans; Male
PubMed: 34940948
DOI: 10.1007/s11357-021-00497-w