The misattribution of an adverse drug reaction (ADR) as a symptom or illness can lead to the prescribing of additional medication, referred to as a prescribing cascade. The aim of this systematic review is to identify published prescribing cascades in community‐dwelling adults. A systematic review was reported in line with the PRISMA guidelines and pre‐registered with PROSPERO. Electronic databases (Medline [Ovid], EMBASE, PsycINFO, CINAHL, Cochrane Library) and grey literature sources were searched. Inclusion criteria: community‐dwelling adults; risk‐prescription medication; outcomes‐initiation of new medicine to “treat” or reduce ADR risk; study type‐cohort, cross‐sectional, case‐control, and case‐series studies. Title/abstract screening, full‐text screening, data extraction, and methodological quality assessment were conducted independently in duplicate. A narrative synthesis was conducted. A total of 101 studies (reported in 103 publications) were included. Study sample sizes ranged from 126 to 11 593 989 participants and 15 studies examined older adults specifically (≥60 years). Seventy‐eight of 101 studies reported a potential prescribing cascade including calcium channel blockers to loop diuretic ( n = 5), amiodarone to levothyroxine ( n = 5), inhaled corticosteroid to topical antifungal ( n = 4), antipsychotic to anti‐Parkinson drug ( n = 4), and acetylcholinesterase inhibitor to urinary incontinence drugs ( n = 4). Identified prescribing cascades occurred within three months to one year following initial medication. Methodological quality varied across included studies. Prescribing cascades occur for a broad range of medications. ADRs should be included in the differential diagnosis for patients presenting with new symptoms, particularly older adults and those who started a new medication in the preceding 12 months.

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Adverse drug events (ADEs) and adverse drug reactions (ADRs) are leading causes of iatrogenic injury, which can result in emergency department (ED) visits or admissions to inpatient wards. The aim of this systematic review and meta-analysis was to provide up-to-date estimates of the prevalence of (preventable) drug-related ED visits and hospital admissions, as well as the type and prevalence of implicated ADRs/ADEs and drugs. A literature search of studies published between January 2012 and December 2021 was performed in PubMed, Medline, EMBASE, Cochrane Library, and Web of Science. Retrospective and prospective observational studies investigating acute admissions to EDs or inpatient wards due to ADRs or ADEs in the general population were included. Meta-analyses of prevalence rates were conducted using generalized linear mixed models (GLMM) with the random-effect method. Seventeen studies reporting ADRs and/or ADEs were eligible for inclusion. The prevalence rates of ADR- and ADE-related admissions to EDs or inpatient wards were estimated at 8.3% ([95% CI, 6.4–10.7%]) and 13.9% ([95% CI, 8.1–22.8%]), respectively, of which almost half (ADRs: 44.7% [95% CI: 28.1; 62.4]) and more than two thirds (ADEs: 71.0% [95% CI, 65.9–75.6%]) had been classified as at least possibly preventable. The ADR categories most frequently implicated in ADR-related admissions were gastrointestinal disorders, electrolyte disturbances, bleeding events, and renal and urinary disorders. Nervous system drugs were found to be the most commonly implicated drug groups, followed by cardiovascular and antithrombotic agents. Our findings demonstrate that ADR-related admissions to EDs and inpatient wards still represent a major and often preventable health care problem. In comparison to previous systematic reviews, cardiovascular and antithrombotic drugs remain common causes of drug-related admissions, while nervous system drugs appear to have become more commonly implicated. These developments may be considered in future efforts to improve medication safety in primary care.

Background: The misattribution of an adverse drug reaction (ADR) as a symptom or illness can lead to the prescribing of additional medication, referred to as a prescribing cascade. The aim of this systematic review is to identify published prescribing cascades in community-dwelling adults. Methods: Systematic review reported in line with the PRISMA guidelines and pre-registered with PROSPERO. Electronic databases (Medline (Ovid), EMBASE, PsycINFO, CINAHL, Cochrane Library) and grey literature sources were searched. Inclusion criteria: Community-dwelling adults; Risk-prescription medication; Outcomes-initiation of new medicine to ‘treat’ or reduce ADR risk; Study type-cohort, cross-sectional, case-control and case-series studies. Title/abstract screening, full-text screening, data extraction and methodological quality assessment was conducted independently in duplicate. A narrative synthesis was conducted. Results: A total of 101 studies (reported in 103 publications) were included. Study sample sizes ranged from 126 to 11,593,989 participants and 15 studies examined older adults specifically (≥60 years). Seventy-eight of 101 studies reported a potential prescribing cascade including calcium channel blockers to loop diuretic (n=5), amiodarone to levothyroxine (n=5), inhaled corticosteroid to topical antifungal (n=4), antipsychotic to anti-Parkinson drug (n=4), and acetylcholinesterase inhibitor to urinary incontinence drugs (n=4). Identified prescribing cascades occurred within three months to one year following initial medication. Methodological quality varied across included studies. Conclusion and implications: Prescribing cascades occur for a broad range of medications. ADRs should be included in the differential diagnosis for patients presenting with new symptoms, particularly older adults and those who started a new medication in the preceding 12 months. Word count: 245