Browsing by Subject "Anticholinergic"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Association of the Prescribing of Anticholinergic Medications with Incident Delirium: A Cohort Study
    (Wiley, 2011) Campbell, Noll; Perkins, Anthony; Hui, Siu; Khan, Babar; Boustani, Malaz; Medicine, School of Medicine
    Objectives: To describe the association between anticholinergic medications and incident delirium in hospitalized older adults with cognitive impairment and to test the hypothesis that anticholinergic medications would increase the risk of incident delirium. Design: Observational cohort study. Setting: Urban public hospital in Indianapolis, Indiana. Participants: One hundred forty-seven participants aged 65 and older with cognitive impairment who screened negative for delirium at the time of admission to a general medical ward. Measurements: Cognitive function at the time of admission was assessed using the Short Portable Mental Status Questionnaire (SPMSQ). Anticholinergic medication orders between the time of admission and the final delirium assessment were evaluated. Anticholinergic medication orders were identified using the Anticholinergic Cognitive Burden Scale. Delirium was assessed using the Confusion Assessment Method. Results: Fifty-seven percent of the cohort received at least one order for possible anticholinergic medications, and 28% received at least one order for definite anticholinergic medications. The incident rate for delirium was 22% of the entire cohort. After adjusting for age, sex, race, baseline SPMSQ score, and Charlson Comorbidity Index, the odds ratio (OR) for developing delirium in those with orders for possible anticholinergic medications was 0.33 (95% confidence interval (CI) = 0.10-1.03). The OR for developing delirium among those with orders for definite anticholinergic medications was 0.43 (95% CI = 0.11-1.63). Conclusion: The results did not support the hypothesis that prescription of anticholinergic medications increases the risk of incident delirium in hospitalized older adults with cognitive impairment. This relationship needs to be established using prospective study designs with medication dispensing data to improve the performance of predictive models of delirium.
  • Thumbnail Image
    Item
    Deprescribing in the Pharmacologic Management of Delirium (de-PMD): A Randomized Trial in the Intensive Care Unit
    (Wiley, 2019-04) Campbell, Noll L.; Perkins, Anthony J.; Khan, Babar A.; Gao, Sujuan; Farber, Mark O.; Khan, Sikandar; Wang, Sophia; Boustani, Malaz A.; Medicine, School of Medicine
    OBJECTIVE: Benzodiazepines and anticholinergics are risk factors for delirium in the intensive care unit (ICU). We tested the impact of a deprescribing intervention on short-term delirium outcomes. DESIGN: Multi-site randomized clinical trial SETTING: ICU’s of three large hospitals PARTICIPANTS: Two hundred adults aged ≥ 18 years admitted to an ICU with delirium according to the Richmond Agitation Severity Scale and the Confusion Assessment Method for the ICU (CAM-ICU). Participants had a contraindication to haloperidol (seizure disorder or prolonged QT interval) or preference against haloperidol as a treatment for delirium, and were excluded for serious mental illness, stroke, pregnancy or alcohol withdrawal. Participants were randomized to a deprescribing intervention or usual care. The intervention included electronic alerts combined with pharmacist support to deprescribe anticholinergics and benzodiazepines. MEASUREMENTS: Primary outcomes were delirium duration measured by the CAM-ICU, and severity measured by the Delirium Rating Scale Revised-98 (DRS-R-98) and the CAM-ICU-7; secondary outcomes included adverse events and mortality. RESULTS: Participants had a mean age of 61.8 (standard deviation: 14.3) years, 59% female, and 52% African American with no significant differences in baseline characteristics between groups. No differences between groups were identified in the number exposed to anticholinergics (p=0.219) or benzodiazepines (p=0.566), the median total anticholinergic score (p=0.282), or the median total benzodiazepine dose in lorazepam equivalents (p=0.501). Neither median delirium/coma-free days (p=0.361) nor median change in delirium severity scores (p=0.582 for DRS-R-98; p=0.333 for CAM-ICU-7) were different between groups. No differences in adverse events or mortality were identified. CONCLUSIONS: When added to state-of-the-art clinical services, this deprescribing intervention had no impact on medication use in ICU participants. Given the age of the population, results of clinical outcomes may not be easily extrapolated to older adults. Nonetheless, improved approaches for deprescribing or preventing anticholinergics and benzodiazepines should be developed to determine the impact on delirium outcomes.
  • Thumbnail Image
    Item
    Donepezil Plus Solifenacin (CPC-201) Treatment for Alzheimer's Disease
    (Springer, 2017-04) Chase, Thomas N.; Farlow, Martin R.; Clarence-Smith, Kathleen; Department of Neurology, IU School of Medicine
    Available cholinergic drugs for treating Alzheimer's disease (AD) provide modest symptomatic benefit. We hypothesized that co-administration of a peripheral anticholinergic to reduce dose-limiting adverse effects (AEs) would enable the safe/tolerable use of higher cholinesterase inhibitor doses and thus improve their antidementia efficacy. A modified single-blind, ascending-dose, phase IIa study of donepezil plus solifenacin (CPC-201) lasting 26 weeks was conducted in 41 patients with probable AD of moderate severity. Entry criteria included the use of donepezil at a dose of 10 mg/day during the preceding 3 months. The primary outcome measure was the maximum tolerated dose (MTD) of donepezil achieved (to protocol limit of 40 mg/day) when administered with the anticholinergic solifenacin 15 mg/day. Secondary measures included assessments of cognitive and global function, as well as of AEs. The mean ± SD donepezil MTD increased to 38 ± 0.74 mg/day (median 40 mg/day; p < 0.001); 88% of the study population safely attained this dose at the end of titration. Markedly reduced donepezil AE frequency, especially gastrointestinal, allowed this dose increase. There were no drug-related serious AEs or clinically significant laboratory abnormalities. At 26 weeks, Alzheimer's Disease Assessment Scale Cognitive Component scores in the efficacy evaluable population improved by 0.35 ± 0.85 points over baseline (p < 0.05), an estimated 2.5 ± 0.84 points above 10 mg/day donepezil and 5.4 ± 0.84 points above historic placebo (both p < 0.05). Clinical Global Impression of Improvement scores improved by 0.94 ± 0.20 to 3.1 ± 0.20 points (p < 0.001). The findings suggest that limiting donepezil AEs by co-administration of solifenacin allows the safe administration of substantially higher cholinesterase inhibitors doses that may augment cognitive and global benefits in patients with AD.
  • Thumbnail Image
    Item
    Editorial: Deprescribing and Minimizing Use of Anticholinergic Medications
    (Frontiers Media, 2021-12-15) Soiza, Roy L.; Boustani, Malaz A.; Campbell, Noll L.; Mangoni, Arduino A.; Medicine, School of Medicine
  • Thumbnail Image
    Item
    Multicomponent behavioral intervention to reduce exposure to anticholinergics in primary care older adults
    (Wiley, 2021) Campbell, Noll L.; Holden, Richard J.; Tang, Qing; Boustani, Malaz A.; Teal, Evgenia; Hillstrom, Jennifer; Tu, Wanzhu; Clark, Daniel O.; Callahan, Christopher M.; Medicine, School of Medicine
    Objective: To test the impact of a multicomponent behavioral intervention to reduce the use of high-risk anticholinergic medications in primary care older adults. Design: Cluster-randomized controlled trial. Setting and participants: Ten primary care clinics within Eskenazi Health in Indianapolis. Intervention: The multicomponent intervention included provider- and patient-focused components. The provider-focused component was computerized decision support alerting of the presence of a high-risk anticholinergic and offering dose- and indication-specific alternatives. The patient-focused component was a story-based video providing education and modeling an interaction with a healthcare provider resulting in a medication change. Alerts within the medical record triggered staff to play the video for a patient. Our design intended for parallel, independent priming of both providers and patients immediately before an outpatient face-to-face interaction. Measurement: Medication orders were extracted from the electronic medical record system to evaluate the prescribing behavior and population prevalence of anticholinergic users. The intervention was introduced April 1, 2019, through March 31, 2020, and a preintervention observational period of April 1, 2018, through March 31, 2019, facilitated difference in difference comparisons. Results: A total of 552 older adults had visits at primary care sites during the study period, with mean age of 72.1 (SD 6.4) years and 45.3% African American. Of the 259 provider-focused alerts, only three (1.2%) led to a medication change. Of the 276 staff alerts, 4.7% were confirmed to activate the patient-focused intervention. The intervention resulted in no significant differences in either the number of discontinue orders for anticholinergics (intervention: two additional orders; control: five fewer orders, p = 0.7334) or proportion of the population using anticholinergics following the intervention (preintervention: 6.2% and postintervention: 5.1%, p = 0.6326). Conclusion: This multicomponent intervention did not reduce the use of high-risk anticholinergics in older adults receiving primary care. Improving nudges or a policy-focused component may be necessary to reduce use of high-risk medications.