Prescribing Cascades Can Often Lead to Polypharmacy for Older Adults
Pharmacists play an essential role in helping to identify patients at risk for inappropriate prescribing.
Investigators have identified 5 relevant prescription cascades, underscoring the importance of addressing polypharmacy for older adults with multimorbidity, according to a study published in The Annals of Family Medicine. Prescription cascades refer to a medication being prescribed to prevent or treat an adverse drug reaction to another medication.1
Pharmacists play an essential role in helping to identify patients at risk for inappropriate prescribing. | Image Credit: Rob Byron - stock.adobe.com
“Prescribing cascades are an underresearched area of potentially inappropriate prescribing,” the authors wrote.1 “Our study details the prevalence of 9 clinically relevant potential prescribing cascades, ThinkCascades, in a national prescription database.”
Prescribing cascades can be appropriate when the combination has a positive benefit-risk balance, but if the ratio is negative, it would be inappropriate, explained authors in a separate study published in Deutsches Ärzteblatt International in 2022. Further, it would be potentially inappropriate if there are more suitable treatment alternatives available, such as switching the drug causing the adverse drug reaction.2
“The classification into appropriate versus necessary prescribing cascades ultimately depends on the extent to which their benefits outweigh their risks. However, this has practical implications,” the authors wrote.2 “Whereas the non-use of necessary prescription cascades represents undertreatment (and thus their use should be actively recommended), this is not necessarily true for the non-use of merely appropriate prescribing cascades.”
Prescribing cascading can often cause polypharmacy, which is defined as the regular use of 5 or more medications at the same time, usually for older adults or at-risk younger individuals. Further, polypharmacy is associated with inappropriate prescribing, so it is essential to identify appropriate prescriptions for patients. Pharmacists often play a large role in identifying patients who are more at risk for polypharmacy, as they are the medication experts.3
The investigators of the current study conducted a retrospective observational cohort study, including users of medications of interest—medications hypothesized to cause AE and medications used to treat the AE. They used data from an Irish national database of prescriptions and included patients 65 years or older. Patients were considered incident users, which included use of both medications in each of the 9 Think Cascade dyads from January 1, 2018, to December 31, 2020. The primary outcome was the first dispensing of the maker medication in each dyad, according to the study authors.1
Among a total of 533,464 older adults from 2017 to 2020, there were a total of 46,678,010 index and marker medication prescriptions dispensed, with 35,273,662 prescriptions dispensed during the observation period from 2018 to 2020. The number of incident users of the Think-Cascades medications ranged from 17,078 for α1-receptor blockers to 137,280 for nonsteroidal anti-inflammatory drugs (NSAIDs).1
Investigators found that there were positive associations for 5 dyads, which indicated a likelihood of a marker medication following the initiation of the index medication. This included calcium channel blockers followed by diuretic prescribing, antipsychotics leading to antiparkinsonian agents, benzodiazepines leading to antipsychotic prescribing, selective serotonin reuptake inhibitors or selective norepinephrine reuptake inhibitors leading to sleep agents, and α1-receptor blockers leading to vestibular sedative medication.
However, investigators found that there was a decrease in prescriptions for dyads such as diuretic to overactive bladder medications, benzodiazepine to antidementia agents, and NSAIDs to antihypertensive medication. Lastly, there were no significant associations for urinary anticholinergic and antidementia agents.1
"Further studies are warranted to identify whether effect modification by age, sex, and individual medication can be replicated," the study authors concluded.1 "Nevertheless, prescribing cascades are challenging to identify and confirm and may require clinical process mapping to untangle the medication initiation sequence."
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REFERENCES
1. Doherty AS, Lund LC, Moriarty F, et al. Prescribing cascades among older community-dwelling adults: application of prescription sequence symmetry analysis to a national database in Ireland. Ann Fam Med. 2025;23(4):315-324. Published online July 28, 2025. doi:10.1370/afm.240383
2. Dreischulte T, Shahid F, Muth C, Schmiedl S, Haefeli WE. Prescribing cascades: how to detect them, prevent them, and use them appropriately. Dtsch Arztebl Int. 2022;119(44):745-752. doi:10.3238/arztebl.m2022.0306
3. Varghese D, Ishida C, Patel P, et al. Polypharmacy. [Updated 2024 Feb 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532953/
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