Abstract
Background: Drugs commonly prescribed for heart rate control may induce adverse drug reactions in Alzheimer patients treated with acetylcholinesterase inhibitors (AChEIs). We have studied use of drugs with a known risk of Torsades de pointes (TdP) and drugs used to treat behavioral and psychological symptoms of dementia, as well as a combination of drugs with a known risk of TdP and drugs with a known heart rate-lowering effect, before and after initiating treatment with AChEIs. Methods: The study applied data from the Norwegian Prescription Database for the period 2004–2016. Prescriptions of concomitant use of drugs in persistent users of AChEIs was studied in a follow-up period from 4 years before to 2 years after AChEI initiation in men and women of two age groups: 37–80 and 81–88 years. Results: A small number of patients were prescribed haloperidol (∼1.5% The second year after AChEI initiation), digoxin/digitoxin (∼3%), and verapamil (∼1.3%), while a substantial proportion of the patients were prescribed betablockers (∼28%) and citalopram/escitalopram (∼17%). During follow-up, up to 6% of the study population were prescribed both betablockers and citalopram/citalopram in addition to AChEIs, a combination that increased over the follow-up period and was observed most frequently in women in the oldest age group. Conclusions: A large proportion (∼44%) of patients treated with AChEIs were prescribed drugs that could cause bradycardic and prolonged time from the start of the Q wave to the end of the T wave (QT interval). Thus, action should be taken to reduce the combination of drugs with risk of bradycardia and prolonged QT interval. Medication review on a regular basis could be an option as an important risk-reducing intervention.
Highlights
Acetylcholinesterase inhibitors (AChEIs) are usually prescribed early in the course of dementia due to Alzheimer’s disease (AD), and patients who respond well may take these drugs for several years (Hernandez et al, 2009)
Treatment with AChEI should be evaluated 90–180 days after initiation according to guidelines; we considered, due to a possible delay, users who continued treatment 8 months (240 days) after initiation as persistent users (Efjestad et al, 2019)
The study population consisted of 11.764 persistent AChEI users aged 37–88 years who initiated treatment between
Summary
Acetylcholinesterase inhibitors (AChEIs) are usually prescribed early in the course of dementia due to Alzheimer’s disease (AD), and patients who respond well may take these drugs for several years (Hernandez et al, 2009). The use of AChEIs has been associated with more than twofold risk of hospitalization due to bradycardia among elderly patients. Those receiving concurrent therapy with negative chronotropic drugs, such as betablockers, digoxin, and verapamil, had an increased risk as well (Park-Wyllie et al, 2009). Drugs commonly prescribed for heart rate control may induce adverse drug reactions in Alzheimer patients treated with acetylcholinesterase inhibitors (AChEIs). We have studied use of drugs with a known risk of Torsades de pointes (TdP) and drugs used to treat behavioral and psychological symptoms of dementia, as well as a combination of drugs with a known risk of TdP and drugs with a known heart rate-lowering effect, before and after initiating treatment with AChEIs
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