Prescribing Cascades: An Umbrella Review and Updated Systematic Review

Background: Prescribing cascades (PCs) often remain underrecognized, contributing to inappropriate prescribing and increased healthcare burden. Objective: This study aimed to synthesize existing knowledge on reported PCs and identify the medications and adverse drug reactions (ADRs) involved. Methods: An umbrella review was conducted using PubMed, Embase, Cochrane Library, Web of Science, and Scopus (inception-16 July 2025). Systematic and scoping reviews on potential PCs were included. An updated systematic review, using the same databases, was conducted to cover the period from 16 February 2022 (the end date of the search period in the most recent included review) to 16 July 2025 to identify more recent studies. Results: Two systematic and two scoping reviews were included in the umbrella review, for a total of 156 primary studies, and 34 more studies met the inclusion criteria of the updated systematic review. Overall, 84 different ADRs potentially leading to PCs were described. Medications mostly involved in the onset of ADRs leading to PCs were antidepressants, antidementia drugs, antipsychotics, anxiolytics, hypnotics/sedatives, lipid-modifying agents, and antihypertensives. The most frequently reported ADRs belonged to the "psychiatric disorders," "nervous system," and "gastrointestinal disorders" system organ classes. Prescription sequence symmetry analysis (PSSA) emerged as the most used method for PC identification. Conclusions: PCs are an underrecognized driver of inappropriate polypharmacy, especially in older adults, yet current evidence is largely retrospective and heterogeneous. By consolidating available data, our work provides a valuable reference tool for clinicians and researchers. Future efforts should focus on establishing standardized definitions and developing clinical strategies to prevent inappropriate PC use.