Anticholinergic medicines use among older adults before and after initiating dementia medicines

Narayan, Sujita W.; Pearson, Sallie‐Anne; Litchfield, Melisa; Couteur, David G. Le; Buckley, Nicholas A.; McLachlan, Andrew J.; Zoëga, Helga

doi:10.1111/bcp.13976

Cited by 12 publications

(15 citation statements)

References 38 publications

(88 reference statements)

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“…Over 30% of patients with prodromal dementia are current users of anticholinergic drugs [340]. Chronic exposure to these products alters behavior and deteriorates cognition and psychomotor function in a dose-dependent fashion [341][342][343]. The pharmacogenetic genotyping of detoxification systems may help to predict risks in susceptible subjects [55].…”

Section: Further Considerationsmentioning

confidence: 99%

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Cacabelos

2020

IJMS

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Symptomatic interventions for patients with dementia involve anti-dementia drugs to improve cognition, psychotropic drugs for the treatment of behavioral disorders (BDs), and different categories of drugs for concomitant disorders. Demented patients may take >6–10 drugs/day with the consequent risk for drug–drug interactions and adverse drug reactions (ADRs >80%) which accelerate cognitive decline. The pharmacoepigenetic machinery is integrated by pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes redundantly and promiscuously regulated by epigenetic mechanisms. CYP2D6, CYP2C9, CYP2C19, and CYP3A4/5 geno-phenotypes are involved in the metabolism of over 90% of drugs currently used in patients with dementia, and only 20% of the population is an extensive metabolizer for this tetragenic cluster. ADRs associated with anti-dementia drugs, antipsychotics, antidepressants, anxiolytics, hypnotics, sedatives, and antiepileptic drugs can be minimized by means of pharmacogenetic screening prior to treatment. These drugs are substrates, inhibitors, or inducers of 58, 37, and 42 enzyme/protein gene products, respectively, and are transported by 40 different protein transporters. APOE is the reference gene in most pharmacogenetic studies. APOE-3 carriers are the best responders and APOE-4 carriers are the worst responders; likewise, CYP2D6-normal metabolizers are the best responders and CYP2D6-poor metabolizers are the worst responders. The incorporation of pharmacogenomic strategies for a personalized treatment in dementia is an effective option to optimize limited therapeutic resources and to reduce unwanted side-effects.

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Section: Further Considerationsmentioning

confidence: 99%

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Cacabelos

2020

IJMS

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“…An Australian investigation into this same prescribing cascade found 36 cases over 4 years of study in a population of 4393 older adults with dementia (0.8% of their cohort compared to our finding of 0.2%). In the Australian study nearly half of the cases of the prescribing cascade had each medication prescribed by a different prescriber [ 54 ]. We did not capture data on prescriber so are unable to determine if different prescribers was a factor in our examination.…”

Section: Discussionmentioning

confidence: 99%

An examination of three prescribing cascades in a cohort of older adults with dementia

et al. 2021

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Background Prescribing cascades are a source of inappropriate prescribing for older adults with dementia. We aimed to study three prescribing cascades in older Nova Scotians with dementia using administrative databases. Methods Cohort entry for Nova Scotia Seniors’ Pharmacare Program beneficiaries was the date of dementia diagnosis. Prescription drug dispensing data was extracted for inciting medication and second treatment (cholinesterase inhibitor and bladder anticholinergic, metoclopramide and Parkinson’s disease medication, or calcium channel blocker (CCB) and diuretic) over the six-year period April 1, 2009 to March 31, 2015. In three separate analyses, dispensing an inciting medication signaled a look back of 365 days from the date of first dispensing to confirm that the second treatment was started after the inciting medication. The prescribing cascade was considered when the second treatment was started within 180 days of the inciting treatment. Sex differences in the prescribing cascade were tested using t-tests or chi square tests as appropriate. Both univariate (unadjusted) and multivariate (adjusted) logistic regression (adjusted for age, rurality, and sex) and Cox proportional hazards regression was used to identify risk factors for the prescribing cascade. Results From March 1, 2005 to March 31, 2015, 28,953 Nova Scotia Seniors' Pharmacare beneficiaries with dementia (NSSPBD) were identified. There were 60 cases of bladder anticholinergics following cholinesterase inhibitors, 11 cases of Parkinson’s disease medication following metoclopramide, and 289 cases of a diuretic following CCB in the cohort. Regression analysis demonstrated that risk of bladder anticholinergics following cholinesterase inhibitors and diuretics following CCBs were associated with female sex. Cox regression suggested that bladder anticholinergics were less often used by those on cholinesterase inhibitors and did not identify CCB use as leading more frequently to diuretic use. Conclusions The combination of diuretics following CCB was the most common prescribing cascade and bladder anticholinergics following cholinesterase inhibitors the second most common. However, exposure to the inciting medications did not increase risk of exposure to the second treatments. Combinations of bladder anticholinergics following cholinesterase inhibitors and diuretics following CCBs were more common for women raising concern that women may be at increased risk of these prescribing cascades.

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“…An Australian investigation into this same prescribing cascade found 36 cases over 4 years of study in a population of 4,393 older adults with dementia (0.8% of their cohort compared to our nding of 0.2%). In the Australian study nearly half of the cases of the prescribing cascade had each medication prescribed by a different prescriber (45). This highlights the importance of encouraging a single prescriber, ideally each person's primary care provider, to oversee treatment choices.…”

Section: Discussionmentioning

confidence: 99%

An examination of three prescribing cascades in a cohort of older adults with dementia

Trenaman

Bowles²,

Kirkland

et al. 2021

Preprint

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Background Prescribing cascades are a source of inappropriate prescribing for older adults with dementia. We aimed to study three prescribing cascades in older Nova Scotians with dementia using administrative databases. Methods Cohort entry for Nova Scotia Seniors’ Pharmacare Program beneficiaries was at the date of dementia diagnosis. Prescription drug dispensation data was extracted for inciting medication and second treatment (cholinesterase inhibitor and bladder anticholinergic, metoclopramide and Parkinson’s disease medication, or calcium channel blocker (CCB) and diuretic) over the six-year period from April 1, 2009 to March 31, 2015. In three separate analyses, dispensation of an inciting medication signaled a look back of 365 days from the date of first dispensation to confirm that the second treatment was started after the inciting medication. The prescribing cascade was considered when second treatment was started within 180 days of the inciting treatment. Sex differences in the prescribing cascade were tested using t-tests or chi square tests as appropriate. Both univariate (unadjusted) and multivariate (adjusted) logistic regression (adjusted for age, rurality, and sex) and Cox proportional hazards regression was used to identify risk factors for the prescribing cascade. Results In the period from March 1, 2005 to March 31, 2018 28,953 Nova Scotia Seniors Pharmacare beneficiaries with dementia (NSSPBD) were identified. There were 60 cases of bladder anticholinergics following cholinesterase inhibitors, 11 cases of Parkinson’s disease medication following metoclopramide, and 289 cases of a diuretic following CCB. Regression analysis demonstrated that risk of bladder anticholinergics following cholinesterase inhibitors and diuretics following CCBs were associated with female sex. Cox regression analyses suggested that bladder anticholinergics were less often used by those on cholinesterase inhibitors but did not identify CCB use as leading more frequently to diuretic use. Conclusions Of the three prescribing cascades investigated, diuretics following CCB was the most common and bladder anticholinergics following cholinesterase inhibitors the second most common. Both these prescribing cascades were more common for women suggesting clinicians need increased attention to monitor for prescribing cascades among women.

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Anticholinergic medicines use among older adults before and after initiating dementia medicines

Cited by 12 publications

References 38 publications

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

An examination of three prescribing cascades in a cohort of older adults with dementia

An examination of three prescribing cascades in a cohort of older adults with dementia

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