Prescribing cascades in community-dwelling adults: a systematic review

Problem

Potentially inappropriate prescribing (PIP) is common among patients with polypharmacy and increases the risk for adverse drug reactions (ADRs). Several prescribing indicator sets exist to reduce PIP but these do not address prescribing cascades. Prescribing cascades occur when a medication is used to treat an ADR to another medication and are an important aspect to consider when characterising problematic polypharmacy. The aim of this systematic review is to identify and collate an exhaustive list of published prescribing cascades in community-dwelling adults.

Approach

This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and pre-registered with PROSPERO [CRD42021243163]. A systematic search of Medline (Ovid), EMBASE, PsycINFO, CINAHL and the Cochrane Library was conducted from inception to end of March 2021. Grey literature searches were conducted using Open Grey, MedNar, Dart Europe and the Turning Research Into Practice (TRIP) databases. Inclusion criteria were: population-community-dwelling adults (≥18 years); risk-prescription medication with the potential to cause side effects; outcomes-initiation of a new medicine to ‘treat’ or to reduce the risk of an ADR; study type-prospective and retrospective cohort studies, case-control and case series studies. Title and abstract screening, full-text screening, data extraction and quality assessment was conducted independently by two reviewers. Two reviewers independently assessed study quality using the relevant Joanna Briggs Institute Critical Appraisal Checklist. A narrative synthesis is currently in progress.

Findings

The electronic database search yielded 15,588 papers. A further 51 titles were retrieved from forward and backward citation searches. A total of 98 papers were included in the narrative synthesis. The majority of studies (n=91) were hypothesis-driven or examined a predefined list of medications as potentially initiating a cascade. Seven studies conducted exploratory analyses to identify potential new prescribing cascade signals. The drug classifications most commonly identified as initiating a cascade were nervous system and cardiovascular system medications. The most common ADR symptoms investigated included depression, Parkinsonism or extra-pyramidal side effects (EPS), oedema and urinary incontinence. Drug classifications most commonly initiated in response to an ADR included antidepressants, anti-Parkinson drugs, diuretics and drugs for urinary frequency. Commonly investigated cascades included the calcium channel blocker-loop diuretic and anticholinesterase-drugs for urinary frequency cascades.

Consequences

Prescribing cascades occur for many drug classifications, with nervous system and cardiovascular system medications commonly identified as both triggers and outcomes of potential prescribing cascades. Identification of the most frequently reported prescribing cascades in the literature can support prescribers to intervene to prevent the development of prescribing cascades in the future. Potential ADRs should form part of the differential diagnosis prior to initiating new medications to treat emergent symptoms among those already prescribed pharmacotherapy.