Prescription cascades associated with acetylcholinesterase inhibitors use: a high-throughput sequence symmetry analysis
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Abstract Background Acetylcholinesterase inhibitors (AChEIs), are commonly prescribed for dementia and can cause adverse drug events that may lead to new prescriptions, known as prescription cascades. We aimed to identify potential AChEI-induced prescription cascades using high-throughput sequence symmetry analysis (SSA). sec3 Methods Patients aged ≥18 years with 365 days of prior observation initiating AChEIs (donepezil, rivastigmine, or galantamine) were identified from the Clinical Practice Research Datalink GOLD (2002–2022). We screened 510 drug classes and 1213 individual ingredients initiated within ±180 days of AChEI initiation (365 days in sensitivity analyses). Crude and adjusted sequence ratios (ASRs) were calculated, and positive signals were reviewed for clinical plausibility. sec4 Results We identified 66 155 AChEI initiators (median age 81 years [IQR 76–85]; 62.8% female). Among ATC classes and individual ingredients, 51 and 46 signals were positive with 28 (55%) and 22 (48%) classified as potential prescription cascades after review. Gastrointestinal drugs showed positive signals including antipropulsives (ASR 1.50 [99% CI 1.28–1.75]), loperamide (ASR 1.52 [1.30–1.77]) and cyclizine (ASR 2.10 [1.72–2.59]). Positive signals were also observed nervous system drugs such as benzodiazepine derivatives (ASR 1.83 [1.55–2.16]) and respiratory drugs including corticosteroids (ASR 1.66 [1.33–2.08]) and glucocorticoids (ASR 1.54 [1.30–1.83]). Most positive signals remaine
Abstract
Abstract Background Acetylcholinesterase inhibitors (AChEIs), are commonly prescribed for dementia and can cause adverse drug events that may lead to new prescriptions, known as prescription cascades. We aimed to identify potential AChEI-induced prescription cascades using high-throughput sequence symmetry analysis (SSA). sec3 Methods Patients aged ≥18 years with 365 days of prior observation initiating AChEIs (donepezil, rivastigmine, or galantamine) were identified from the Clinical Practice Research Datalink GOLD (2002–2022). We screened 510 drug classes and 1213 individual ingredients initiated within ±180 days of AChEI initiation (365 days in sensitivity analyses). Crude and adjusted sequence ratios (ASRs) were calculated, and positive signals were reviewed for clinical plausibility. sec4 Results We identified 66 155 AChEI initiators (median age 81 years [IQR 76–85]; 62.8% female). Among ATC classes and individual ingredients, 51 and 46 signals were positive with 28 (55%) and 22 (48%) classified as potential prescription cascades after review. Gastrointestinal drugs showed positive signals including antipropulsives (ASR 1.50 [99% CI 1.28–1.75]), loperamide (ASR 1.52 [1.30–1.77]) and cyclizine (ASR 2.10 [1.72–2.59]). Positive signals were also observed nervous system drugs such as benzodiazepine derivatives (ASR 1.83 [1.55–2.16]) and respiratory drugs including corticosteroids (ASR 1.66 [1.33–2.08]) and glucocorticoids (ASR 1.54 [1.30–1.83]). Most positive signals remained in sensitivity analysis. sec5 Conclusions These findings suggest potential AChEI-related prescription cascades consistent with gastrointestinal, neuropsychiatric, dermatological and respiratory adverse effects. While findings require further validation, this study demonstrates the utility of high-throughput signal detection to support pharmacovigilance in high-risk populations. sec6 Graphical Abstract Graphical Abstract For image description, please refer to the figure legend and surrounding text. http://www.w3.org/1999/xlink float portrait afag188f1.jpg float ga1 portrait graphical