Prescribing cascades in community‐dwelling adults: A systematic review

Abstract

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.

Prescribing cascades in ambulatory care: A structured synthesis of evidence

“…We performed an analysis of all prescribing cascades identified by our previous systematic review as relevant to ambulatory care, 18 for which one or more confirmatory studies had found a statistically significant association between an index and a marker drug. We limited our analyses to cohort, case–control, or prescription sequence symmetry analyses (PSSA) 19 with pre‐specified hypotheses, and thus excluded both cross‐sectional as well as exploratory studies aiming to identify new signals of prescribing cascades (as opposed to confirming pre‐specified ones) 20 .…”

“…Considering these domains, we differentiated between four levels of evidence (from I = strong to IV = poor) as shown in Table 1.Methodological quality (risk of bias) was assessed for each study using the appropriate Joanna Briggs Institute (JBI)—Critical Appraisal checklist 21 (Box S1). Assessments were conducted by at least two reviewers independently, with disagreements resolved by discussion or consultation of a third reviewer where necessary, as detailed in our previously published systematic review 18 . The quality score of each individual study was calculated, where the cut‐off score for high‐quality study (low risk of bias) was ≥70%, for moderate‐quality study design 50%–69%, and for low‐quality (high risk of bias) study design <50% (Table S1 and S2).…”

“…Assessments were conducted by at least two reviewers independently, with disagreements resolved by discussion or consultation of a third reviewer where necessary, as detailed in our previously published systematic review. 18 The quality score of each individual study was calculated, where the cut-off score for high-quality study (low risk of bias) was ≥70%, for moderate-quality study design 50%-69%, and for low-quality (high risk of bias) study design <50% (Table S1 and S2). 22,23…”

“…Despite the insights from this prior work, 18 our previous goal was primarily to enumerate potential prescribing cascades rather than to systematically assess the evidence supporting them. Here, we grade the strength of evidence from observational studies supporting each cascade and examine whether the adverse event associated with the index drug is described in the product's United States Food and Drug Administration (FDA) label.…”

Prescribing Cascades with Recommendations to Prevent or Reverse Them: A Systematic Review

“…Many prescribing cascades have been described in the literature and several reviews have been published [ 3 , 6 – 8 ]. One of the reviews was limited by including only prescribing cascades that were identified through a prescription sequence symmetry analysis [ 7 ], whereas another review identified prescribing cascades occurring with pain medication [ 6 ] .…”