Anticholinergic Adverse Effects Research Articles

Adverse effects associated with long-term use of anticholinergics amongst older adults with intellectual disability: a longitudinal cohort study

Abstract Introduction Intellectual disability defined as “a condition characterized by significant limitation in both intellectual functioning and adaptive behaviour that originates before the age of 22”.[1] Older adults with intellectual disability are exposed to high anticholinergic burden, due to the high prevalence of neurological and mental health diseases compared to the general older adult population. The long-term use of anticholinergics is associated with adverse effects such as decline in physical function, cognitive function and higher risk of dementia and Alzheimer disease in the general population. However, a recent scoping review found that there are no longitudinal studies examining adverse effects associated with long-term use of anticholinergics amongst older adults with intellectual disability.[2] Aim To examine adverse effects associated with long-term use of medication with anticholinergic activity among older adults with intellectual disability. Methods This study examined older adults with intellectual disability aged 40 or over, who participated in wave 1 (2010-11) (W1) and wave 4 (2019-20) (W4) in the Intellectual Disability Supplement to the Irish Longitudinal Study on Aging (IDS-TILDA). Anticholinergic burden was quantified using the Anticholinergic Cognitive Burden (ACB) Scale. Participants were categorised into three groups based on their total ACB score: no exposure (ACB = 0), mild exposure (ACB 1-4) and high exposure (ACB = 5+). Logistic regression used to examine adverse effects reported at W4 associated with ACB score captured at W1. Reported anticholinergic adverse effects were constipation, falls, edentulous, Barthel Index for activity of daily livings, mental health conditions and dementia/Alzheimer’s. The logistic regression model was adjusted for age, gender, level of intellectual disability, residence, epilepsy, and polypharmacy excluding anticholinergic medications. Results 506 people with intellectual disability participated and 487 (96.24%) provided medication data at both waves. At W1, 30% had no exposure (ACB=0), 40% had mild exposure (ACB = 1-4) and 30% had high ACB score (ACB = 5+). At W4, there was an increase by 5% of those with mild ACB and a reduction of 1.5% and 3.5% in those with no exposure and high ACB exposure respectively. Participants with high ACB score at W1, were significantly associated with falls (OR = 1.97, 95% CI 1.20-3.54), reporting mental conditions (OR = 14.78, 95% CI 7.84 - 27.86) and dementia, Alzheimer’s or taking anti-dementia drugs (N06D) (OR = 0.21, 95% Cl 0.07 - 0.67) at W4, compared to those with no anticholinergic exposure. Conclusion The long-term use of anticholinergics was associated with physical and mental adverse effects, and therefore the possibility of anticholinergic deprescribing should be explored and examined to enhance appropriate medicine use among older adults with intellectual disability. This is the first study examined the impact of long-term anticholinergic use among this population. However, further anticholinergic adverse effects should be addressed in future such as decline in cognitive function and frailty.

Disentangling drug contributions: anticholinergic burden in older adults linked to individual medications: a cross-sectional population-based study

BackgroundMedications with potent anticholinergic properties have well-documented adverse effects. A high cumulative anticholinergic burden may arise from the concurrent use of multiple medications with weaker anticholinergic effects. We sought to identify patterns of high anticholinergic burden and associated patient characteristics.MethodsWe identified patients aged ≥ 65 who filled ≥ 1 medication with anticholinergic adverse effects in 2019 and had a cumulative Anticholinergic Burden score (ACB) ≥ 4 (i.e., high anticholinergic burden) in a large US health insurer. We classified patients based on how they attained high burden, as follows: 1) only filling strong or moderate anticholinergic medications (i.e., ACB = 2 or 3, “moderate/strong”), 2) only filling lightly anticholinergic medications (i.e., ACB = 1, “light/possible”), and 3) filling any combination (“mix”). We used multinomial logistic regression to assess the association between measured patient characteristics and membership in the three anticholinergic burden classifications, using the moderate/strong group as the referent.ResultsIn total, 83,286 eligible patients with high anticholinergic burden were identified (mean age: 74.3 years (SD:7.1), 72.9% female). Of these, 4.5% filled only strong/moderate anticholinergics, 4.3% filled only light/possible anticholinergics, and the rest filled a mix (91.2%). Within patients in the mixed group, 64.3% of medication fills were for light/possible anticholinergics, while 35.7% were for moderate/strong anticholinergics. Compared with patients in the moderate/strong anticholinergics group, patients filling only light/possible anticholinergics were more likely to be older (adjusted Odds Ratio [aOR] per 1-unit of age: 1.06, 95%CI: 1.05–1.07), less likely to be female (aOR: 0.56, 95%CI: 0.50–0.62 vs. male), more likely to have comorbidities (e.g., heart failure aOR: 3.18, 95%CI: 2.70–3.74 or depression aOR: 1.20, 95%CI: 1.09–1.33 vs. no comorbidity), and visited fewer physicians (aOR per 1-unit of change: 0.98, 95%CI: 0.97–0.98). Patients in the mixed group were older (aOR per 1-unit of age: 1.02, 95%CI: 1.02–1.03) and less likely to be female (aOR: 0.89, 95%CI: 0.82–0.97 vs. male) compared with those filling moderate/strong anticholinergics.ConclusionMost older adults accumulated high anticholinergic burden through a combination of light/possible and moderate/strong anticholinergics rather than moderate/strong anticholinergics, with light/possible anticholinergics being the major drivers of overall anticholinergic burden. These insights may inform interventions to improve prescribing in older adults.

Clinical pharmacist-led assessment and management of anticholinergic burden and fall risk in geriatric patients

BackgroundThe aim of this study was to examine the risk of fall with the surrogate outcome of the Aachen Falls Prevention Scale and to assess the clinical pharmacist interventions in order to minimize anticholinergic drug burden and associated risk of fall according to a fall risk assessment scale in the older adults.MethodsPatients who admitted to the geriatric outpatient clinic of a university hospital and taking at least one anticholinergic drug were evaluated both retrospectively and prospectively as groups of different patients by the clinical pharmacist. Patients’ anticholinergic burden was assessed using the Anticholinergic Cognitive Burden Scale. For fall risk assessment, the Aachen Falls Prevention Scale was also administered to each patient whose anticholinergic burden was determined in the prospective phase of the study.ResultsA total of 601 patients were included. Risk of falls increased 2.50 times in patients with high anticholinergic burden (OR (95% CI) = 2.503 (1.071–5.852); p = 0.034), and the existing history of falls increased the risk of high anticholinergic burden 2.02 times (OR (95%CI) = 2.026 (1.059–3.876); p = 0.033). In addition, each unit increase in the fall scale score in the prospective phase increased the risk of high anticholinergic burden by 22% (p = 0.028). Anticholinergic burden was significantly reduced as a result of interventions by the clinical pharmacist in the prospective phase (p = 0.010).ConclusionOur study revealed that incorporating a clinical pharmacist in the handling of geriatric patients aids in the detection, reduction, and prevention of anticholinergic adverse effects.

Anticholinergic Burden and Xerostomia in Critical Care Settings.

Although previous studies have established the association of medications with anticholinergic adverse effects and xerostomia, anticholinergic burden and xerostomia in critical care settings are poorly characterized. The objective of this study was to determine the impact of medication burdens associated with anticholinergic adverse effects, particularly the occurrence of xerostomia (dry mouth) in a critical care setting. In addition, this study explored the correlation between the timing of the first instance of xerostomia and the administration timing of medication known to have anticholinergic adverse effects. A retrospective case-control study was used with the MIMIC (Medical Information Mart for Intensive Care) III database. The MIMIC-III clinical database is a publicly available, deidentified, health-related database with more than 40 000 patients in critical care units from 2001 to 2012. Cases of xerostomia (n = 1344) were selected from clinical notes reporting "dry mouth," "xerostomia," or evidence of pharmacological treatment for xerostomia; control (n = 4032) was selected using the propensity analysis with 1:3 matching on covariates (eg, age, sex, race, ethnicity, and length of stay). The anticholinergic burden was quantified as the cumulative effect of anticholinergic activities using the Anticholinergic Burden Scale. Anticholinergic burden significantly differed between xerostomia patients and control subjects (P = .04). The length of stay was a statistically significant factor in xerostomia. The probability of developing the symptom of xerostomia within 24 hours was .95 (95%) for patients of xerostomia. Anticholinergic Burden Scale is associated with xerostomia in the critical care setting, particularly within 24 hours after admission. It is crucial to carefully evaluate alternative options for medications that may have potential anticholinergic adverse effects. This evaluation should include assessing the balance between the benefits and harms, considering the probability of withdrawal reactions, and prioritizing deprescribing whenever feasible within the initial 24-hour period.

Pharmcokinetic and pharmacodynamic considerations for the anticholinergic burden scale of drugs.

Older adults frequently have many systemic diseases that require treatment with multiple drugs, and thus anticholinergic adverse effect by polypharmacy is a significant concern in the management of older adults. The accuracy of the anticholinergic burden rating may be increased by considering pharmacokinetic and pharmacodynamic factors such as biophase drug concentrations, the pharmacologically active metabolites formed after drug administration, and muscarinic receptor-mediated effects. Therefore, a pharmacological evidence-based burden scale that considers pharmacokinetic and pharmacodynamic factors is expected to be a more optimal tool for precisely assessing the anticholinergic burden, specifically risk reductions in anticholinergic adverse events in the poly-medicated elderly. Geriatr Gerontol Int 2024; 24: 81-87.

Comparative safety of antimuscarinics versus mirabegron for overactive bladder in Parkinson disease

BackgroundOveractive bladder (OAB) is a common non-motor symptom of Parkinson disease (PD), often treated with antimuscarinics or beta-3 agonists. There is lack of evidence to guide OAB management in PD. ObjectivesTo assess the comparative safety of antimuscarinics versus beta-3 agonists for OAB treatment in PD. MethodsWe employed a new-user, active-comparator cohort study design. We included Medicare beneficiaries age ≥65 years with PD who were new users of either antimuscarinic or beta-3 agonist. The primary outcome was any acute care encounter (i.e., non-elective hospitalization or emergency department visit) within 90 days of OAB drug initiation. The main secondary outcome was a composite measure of acute care encounters for anticholinergic related adverse events (AEs). Matching on high-dimensional propensity score (hdPS) was used to address potential confounding. We used Cox proportional hazards models to examine the association between OAB drug category and outcomes. We repeated analyses for 30- and 180-day follow-up periods. ResultsWe identified 27,091 individuals meeting inclusion criteria (mean age: 77.8 years). After hdPS matching, antimuscarinic users had increased risks for any acute care encounter (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.12–1.37) and encounters for anticholinergic related AEs (HR 1.18, 95% CI 1.04–1.34) compared to beta-3 agonist users. Similar associations were observed for sensitivity analyses. ConclusionsAmong persons with PD, anticholinergic initiation was associated with a higher risk of acute care encounters compared with beta-3 agonist initiation. The long-term safety of anticholinergic vs. beta-3 agonist therapy in the PD population should be evaluated in a prospective study.

Anticholinergics: Adverse effects

Nurses should be aware of the more than 600 medications with potentially adverse anticholinergic effects.

Depression in dementia with Lewy bodies: a critical update.

Depression with an estimated prevalence of 35% is a frequent manifestation of dementia with Lewy bodies (DLB), having negative effects on cognitive performance and life expectancy, yet the underlying neurobiology is poorly understood and most likely heterogeneous. Depressive symptoms in DLB can occur during the clinical course and, together with apathy, is a common prodromal neuropsychiatric symptom of this neurocognitive disorder in the group of Lewy body synucleinopathies. There are no essential differences in the frequency of depression in DLB and Parkinson disease-dementia (PDD), while its severity is up to twice as high as in Alzheimer disease (AD). Depression in DLB that is frequently underdiagnosed and undertreated, has been related to a variety of pathogenic mechanisms associated with the basic neurodegenerative process, in particular dysfunctions of neurotransmitter systems (decreased monoaminergic/serotonergic, noradrenergic and dopaminergic metabolism), α-synuclein pathology, synaptic zinc dysregulation, proteasome inhibition, gray matter volume loss in prefrontal and temporal areas as well as dysfunction of neuronal circuits with decreased functional connectivity of specific brain networks. Pharmacotherapy should avoid tricyclic antidepressants (anticholinergic adverse effects), second-generation antidepressants being a better choice, while modified electroconvulsive therapy, transcranial magnetic stimulation therapy and deep brain stimulation may be effective for pharmacotherapy-resistant cases. Since compared to depression in other dementias like Alzheimer disease and other parkinsonian syndromes, our knowledge of its molecular basis is limited, and further studies to elucidate the heterogeneous pathogenesis of depression in DLB are warranted.

Anticholinergic burden in older adults with psychiatric illnesses: A cross-sectional study

ObjectivesWe aimed in this study to determine the extent of exposure to anticholinergic drugs in older adults with psychiatric illnesses using the anticholinergic cognitive burden (ACB) scale and to identify the factors associated with anticholinergic drugs use and higher ACB scores. MethodsA cross-sectional study was conducted in the psychogeriatric division of an elderly care hospital. The study sample comprised all inpatients, aged ≥65 years, and diagnosed with psychiatric illness. ResultsAnticholinergic drugs use was reported in 117 (79.6 %) patients, 76 (51.7 %) had an ACB score ≥ 3. Schizophrenia [OR = 5.4 (95 % CI 1.1–10.2), p = 0.02], anemia [OR = 2.2 (95 % CI 1.54–7.89), p = 0.01], and anticholinergic adverse effects [OR = 2.8 (95 % CI 1.12–7.07), p = 0.04] were significantly associated with a higher likelihood of using anticholinergic drugs. The odds of having an ACB score ≥ 3 over an ACB score = 0 were significantly increased by schizophrenia [OR = 4.9 (95 % CI 1.65–8.02), p = 0.01], anemia [OR = 1.32 (95 % CI 1.90–6.90), p = 0.02], and polypharmacy [OR = 1.74 (95 % CI 1.10–2.40), p = 0.04], while they were significantly decreased by age [OR = 0.86 (95 % CI 0.78–0.96), p < 0.001]. Patients with cognitive impairment were less likely than those without cognitive impairment to have an ACB score ≥ 3 over an ACB score = 0. ConclusionsOur study revealed that older adults with psychiatric illnesses were exposed to high anticholinergic burden.

Anticholinergic adverse effects and oral health

Anticholinergic adverse effects and oral health

Safety and tolerability of KarXT (xanomeline–trospium) in a phase 2, randomized, double-blind, placebo-controlled study in patients with schizophrenia

KarXT combines xanomeline, an M1/M4 preferring muscarinic agonist with no direct D2 receptor antagonism, with the peripherally restricted anticholinergic trospium. In EMERGENT-1 (NCT03697252), a 5-week, randomized, double-blind, placebo-controlled, phase 2 study in inpatients with schizophrenia, KarXT met the primary efficacy endpoint, numerous secondary endpoints, and was generally well tolerated. Here, we conducted additional post hoc analyses of safety and tolerability data of KarXT from EMERGENT-1 with a particular focus on adverse events (AEs) that may be associated with muscarinic receptor agonism (nausea or vomiting) or antagonism (dry mouth or constipation). A total of 179 patients received at least one dose of either KarXT (n = 89) or placebo (n = 90) and were included in the analyses. KarXT was associated with a low overall AE burden. The majority of procholinergic and anticholinergic AEs with KarXT were mild, occurred in the first 1−2 weeks of treatment, and were transient with a median duration ranging from 1 day for vomiting to 13 days for dry mouth. No patients in either treatment group discontinued the study due to any procholinergic or anticholinergic AEs. Incidence of somnolence/sedation AEs with KarXT were low and similar to those in the placebo group. KarXT was associated with no significant or clinically relevant changes in body weight, metabolic parameters, or vital signs. KarXT was generally well tolerated with an AE profile consistent with the activity of xanomeline–trospium at muscarinic receptors.

Tricyclic Antidepressants in Nociceptive and Neuropathic Pain: A Review of Their Analgesic Properties in Combination With Opioids.

Objectives: To determine the efficacy and safety of commonly prescribed tricyclic antidepressants (TCAs) as analgesics for nociceptive and neuropathic pain in combination with opioids. Data Sources: A comprehensive literature review was conducted with the assistance of a medical reference librarian on PubMed, MEDLINE, Scopus, and Web of Science using the following search terminology: "Amitriptyline" OR "Doxepin" OR "Desipramine" OR "Imipramine" OR "Nortriptyline" OR "Clomipramine" OR "Trimipramine" AND "Analgesia." Reports of adult patients who received any TCA as an adjunctive analgesic to opioids were included. Study Selection and Data Extraction: A total of 293 results were obtained from the initial database inquiries, following which exclusion criteria were applied and 6 articles were included in this review. Three of the reports detailed the use of TCAs in the perioperative setting, whereas the remaining 3 evaluated their effect on different etiologies of neuropathic pain. Data Synthesis: Tricyclic antidepressants were found to have modest, yet not insignificant, independent analgesic properties, although the ability to provide pain relief was relegated to a select few agents. Desipramine has the most data available for use in nociceptive, postoperative pain through its ability to potentiate and prolong the analgesic effects of opioids and was not associated with adverse drug effects. Conclusions: The efficacy of TCAs for neuropathic pain was not corroborated by this review, and the anticholinergic adverse effects associated with this drug class were found to be significant. Further research is needed to quantify the efficacy of TCAs in the management of nociceptive pain.

A study on prescriptions contributing to the risk of high anticholinergic burden in adults with intellectual disabilities: retrospective record linkage study

BackgroundPeople with intellectual disabilities may face a disproportionate risk of experiencing high anticholinergic burden, and its negative sequalae, from a range of medications, and at younger ages than the general population, but there has been little previous study. Our aim was to determine the source of anticholinergic burden from prescribed medication.MethodsRetrospective matched observational study using record linkage. Adults with (n = 4,305), and without (n = 12,915), intellectual disabilities matched by age-, sex- and neighbourhood deprivation. The main outcome measure was the prescription of long-term (approximately 12 months use) anticholinergic medications overall (classified according to the Anticholinergic Risk Scale [ARS]), by drug class, individual drugs, and polypharmacy.ResultsAdults with n = 1,654 (38.4%), and without n = 3,047 (23.6%), intellectual disabilities were prescribed medications long-term with anticholinergic effects. Of those on such drugs, adults with intellectual disabilities were most likely to be on central nervous system (62.6%), gastrointestinal (46.7%), and cardiovascular (28.4%) medications. They were prescribed more central nervous system, gynaecological/urinary tract, musculoskeletal, and respiratory medications, and less cardiovascular, infection, and endocrine medications than their matched comparators. Regardless of age, sex, or neighbourhood deprivation, adults with intellectual disabilities had greater odds of being prescribed antipsychotics (OR = 5.37 [4.40–6.57], p < 0.001), antiepileptics (OR = 2.57 [2.22–2.99], p < 0.001), and anxiolytics/hypnotics (OR = 1.28 [1.06–1.56], p = 0.012). Compared to the general population, adults with intellectual disabilities were more likely to be exposed to overall anticholinergic polypharmacy (OR = 1.48 [1.33–1.66], p < 0.001), and to psychotropic polypharmacy (OR = 2.79 [2.41–3.23], p < 0.001).ConclusionsAdults with intellectual disabilities are exposed to a greater risk of having very high anticholinergic burden through polypharmacy from several classes of medications, which may be prescribed by several different prescribers. There is a need for evidence-based recommendations specifically about people with intellectual disabilities with multiple physical and mental ill-health conditions to optimise medication use, reduce inappropriate prescribing and adverse anticholinergic effects.

Synthesis and preliminary biological evaluation of gabactyzine, a benactyzine-GABA mutual prodrug, as an organophosphate antidote

Organophosphates (OPs) are inhibitors of acetylcholinesterase and have deleterious effects on the central nervous system. Clinical manifestations of OP poisoning include convulsions, which represent an underlying toxic neuro-pathological process, leading to permanent neuronal damage. This neurotoxicity is mediated through the cholinergic, GABAergic and glutamatergic (NMDA) systems. Pharmacological interventions in OP poisoning are designed to mitigate these specific neuro-pathological pathways, using anticholinergic drugs and GABAergic agents. Benactyzine is a combined anticholinergic, anti-NMDA compound. Based on previous development of novel GABA derivatives (such as prodrugs based on perphenazine for the treatment of schizophrenia and nortriptyline against neuropathic pain), we describe the synthesis and preliminary testing of a mutual prodrug ester of benactyzine and GABA. It is assumed that once the ester crosses the blood–brain-barrier it will undergo hydrolysis, releasing benactyzine and GABA, which are expected to act synergistically. The combined release of both compounds in the brain offers several advantages over the current OP poisoning treatment protocol: improved efficacy and safety profile (where the inhibitory properties of GABA are expected to counteract the anticholinergic cognitive adverse effects of benactyzine) and enhanced chemical stability compared to benactyzine alone. We present here preliminary results of animal studies, showing promising results with early gabactyzine administration.

Anticholinergics in Older Adults- Avoid, Replace and Monitor

Many medicines have varying degrees of anticholinergic activity. Some of these drugs, particularly those with intermediate or low activity, are not commonly known to possess anticholinergic properties. Regardless of their anticholinergic potency, when used concurrently, they could collectively contribute to the anticholinergic burden in elderly patients. While most of the adverse effects from the anticholinergic burden are reversible upon withdrawal of the anticholinergics, some of the adverse effects on the central nervous system (CNS) may be permanent. Fortunately, for most of the indications for strong anticholinergics, safer alternatives, both non-pharmacological and pharmacological, are available. Therefore, strong anticholinergic should be avoided, especially in older patients already on multiple drugs with anticholinergic activity. This is particularly relevant to those with comorbidities that would put them at risk for the adverse anticholinergic effects. If the use of a drug with strong anticholinergic activity is necessary for an older patient, it should be given at the lowest effective dose for the shortest possible period. Last but not least, the risks and benefits of the drug should be reviewed regularly in a timely manner.

Real-World Safety and Efficacy of Glycopyrronium Bromide in Japanese Patients with COPD: A 52-Week Post-Marketing Surveillance.

To evaluate the long-term safety and efficacy of glycopyrronium (GLY) in patients with COPD in a real-world setting in Japan. This 52-week, multicentre, post-marketing surveillance conducted in Japan, between February 2013 and August 2019, included patients using GLY for the first time for the relief of airway obstructive disorder-related symptoms. Safety outcomes included incidence of adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs), serious ADRs (SADRs) and priority variables included cardiovascular/cerebrovascular (CCV) AEs and anticholinergic AEs during the 52-week period. Safety outcomes were also assessed in elderly patients. Efficacy outcomes included physician's global assessment, COPD assessment test (CAT) and lung function test. Of the 1,331 patients registered for this surveillance, safety and efficacy outcomes were evaluated in 1,277 patients. In the safety analysis population, the incidence of AEs was 15.51%, SAEs 4.70%, ADRs 5.01% and SADRs 0.31%. The CCV AEs and anticholinergic AEs were reported by 0.70% and 2.58% patients, respectively. Physician's global assessment showed that the overall response rate at the last assessment was 70%. The mean (95% CI) CAT scores decreased from the start of treatment to Week 52 with GLY, (-6.2 [-7.0 to -5.4]). Lung function in terms of trough FEV1 and FVC improved over time from the start of GLY to Week 52. GLY demonstrated an acceptable long-term safety profile with no new safety concerns in a real-life setting. It demonstrated improvement in lung function and symptom control in Japanese COPD patients.

Sofpironium bromide: an investigational agent for the treatment of axillary hyperhidrosis

ABSTRACT Introduction In recent years, increased knowledge about pathophysiology of primary hyperhidrosis has led to novel therapeutic advances. Topical and systemic anticholinergic agents have been proven beneficial in reducing sweat production in primary axillary hyperhidrosis (PAH), although their use is limited by the increased likelihood of systemic anticholinergic drug reactions, particularly regarding systemic agents. Areas covered This paper provides an overview of pharmaceutical characteristics, efficacy and safety data from phase II and III clinical trials on sofpironium bromide (SB), a topical anticholinergic agent that has been employed for the treatment of PAH and has already received its first approval in Japan for the treatment of PAH in the form of 5% gel formulation. Expert opinion The retrometabolic drug design of topical SB presents distinct advantages, by limiting systemic absorption and therefore development of anticholinergic adverse events. This along with the popularity of the non-greasy gel formulation is expected to increase compliance. However, this therapy still offers a temporary control of PAH, compared to sympathectomy or device-based treatments, such as microwave thermolysis. Hence, physicians should balance the effectiveness against adverse events of each therapeutic modality and use a personalized approach based on patient’s needs.

Analysis of anticholinergic adverse effects using two large databases: The US Food and Drug Administration Adverse Event Reporting System database and the Japanese Adverse Drug Event Report database.

IntroductionAnticholinergic adverse effects (AEs) are a problem for elderly people. This study aimed to answer the following questions. First, is an analysis of anticholinergic AEs using spontaneous adverse drug event databases possible? Second, what is the main drug suspected of inducing anticholinergic AEs in the databases? Third, do database differences yield different results?MethodsWe used two databases: the US Food and Drug Administration Adverse Event Reporting System database (FAERS) and the Japanese Adverse Drug Event Report database (JADER) recorded from 2004 to 2020. We defined three types of anticholinergic AEs: central nervous system (CNS) AEs, peripheral nervous system (PNS) AEs, and a combination of these AEs. We counted the number of cases and evaluated the ratio of drug–anticholinergic AE pairs between FAERS and JADER. We computed reporting odds ratios (RORs) and assessed the drugs using Beers Criteria®.ResultsConstipation was the most reported AE in FAERS. The ratio of drug–anticholinergic AE pairs was statistically significantly larger in FAERS than JADER. Overactive bladder agents were suspected drugs common to both databases. Other drugs differed between the two databases. CNS AEs were associated with antidementia drugs in FAERS and opioids in JADER. In the assessment using Beers Criteria®, signals were detected for almost all drugs. Between the two databases, a significantly higher positive correlation was observed for PNS AEs (correlation coefficient 0.85, P = 0.0001). The ROR was significantly greater in JADER.ConclusionsThere are many methods to investigate AEs. This study shows that the analysis of anticholinergic AEs using spontaneous adverse drug event databases is possible. From this analysis, various suspected drugs were detected. In particular, FAERS had many cases. The differences in the results between the two databases may reflect differences in the reporting countries. Further study of the relationship between drugs and CNS AEs should be conducted.

Anticholinergic Exposure in Elderly Complex Chronic Patients: A Cross-Sectional Study.

Elderly patients with multiple chronic conditions are closely linked to polymedication, a condition that is also highly associated with the presence of adverse effects, such as those observed by anticholinergic activity. Anticholinergic burden is defined in a very variable way and is described inconsistently using different scores and providing different interpretations of the risk of suffering from anticholinergic adverse effects. The objective is to analyse the anticholinergic risk exposure in elderly complex chronic patients. A observational multicentre study was performed for a cohort of complex chronic patients over 65 years who received treatment with at least one drug with anticholinergic activity. Anticholinergic exposure was assessed using ten scales included in the Anticholinergic Burden Calculator. 473 patients were recruited, being 67.7% with excessive polypharmacy. 80 was the total number of anticholinergic drugs with any scale, with a median of 2 drugs with anticholinergic activity per patient (IQR=2). Three scales evaluated more than 70% of the patients (Chew: 79.1%; Drug Burden Index (DBI): 77.8%; Anticholinergic Cognitive Burden (ACB): 75.9%). The percentage of different drugs with anticholinergic properties evaluated ranged from 13.8% (Anticholinergic Burden Classification (ABC)) to 57.5% (DBI) and anticholinergic drugs prescriptions oscillated from 14% (Anticholinergic Risk Scale (ARS)) to 53.3% (DBI). 71.1% of patients were at risk (moderate and high risk) according to DBI vs. 9.7% by ARS at the opposite side. Important differences of anticholinergic risk in patients with excessive polypharmacy were in ACB, ABC and DBI scales. This study has highlighted clear differences between the scales used. DBI seems to be the scale that identifies a higher number of elderly chronic complex patients at risk of developing anticholinergic adverse effects.

Real-world Safety and Efficacy of Indacaterol/Glycopyrronium in Japanese Patients with Chronic Obstructive Pulmonary Disease: A 52-week Post-marketing Surveillance.

Objective To evaluate the long-term safety and efficacy of indacaterol/glycopyrronium (IND/GLY) in patients with chronic obstructive pulmorary disease (COPD) in a real-world setting in Japan. Methods This 52-week, multicentre, post-marketing surveillance conducted in Japan between December 2013 and August 2019 included patients using IND/GLY for the first time to relieve airway obstructive disorder-related symptoms. Safety outcomes included the incidence of adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs), and serious ADRs during the 52-week period. The incidence of priority variables, including cardiovascular/cerebrovascular (CCV) AEs, β-adrenergic-related or anticholinergic AEs and cough, was also assessed. Safety outcomes were also evaluated in elderly patients. Efficacy outcomes included a physician's global assessment, COPD assessment test (CAT) and lung function test. Results Of the 1,167 patients registered, 1,108 were included in the safety and efficacy analysis. In the safety analysis population, the incidence of AEs was 13.54%, that of SAEs was 4.69%, that of ADR was 3.61%, and that of serious ADRs was 0.36% over 52 weeks. CCV AEs, β-adrenergic-related and anticholinergic AEs and cough were reported as 2.62%, 1.99% and 0.63%, respectively. The physician's global assessment showed that the overall response rate at the last assessment was 74.19%. The mean (95% confidence interval) CAT scores decreased from the start of treatment to Week 52 with IND/GLY [-6.9 (-7.8 to -6.1)]. The lung function (FEV1 and FVC) improved over time from the start of IND/GLY to Week 52. Conclusion IND/GLY demonstrated a good long-term safety profile in a real-world setting in Japanese patients with COPD, with beneficial effects in terms of the lung function and symptoms in clinical use.