Identifying and quantifying potentially problematic prescribing cascades in clinical practice: A mixed-methods study.

Background: A prescribing cascade occurs when medication causes an adverse drug reaction (ADR) that leads to the prescription of additional medication. Prescribing cascades can cause excess medication burden, which is of particular concern in older adults. This study aims to identify and quantify potentially problematic prescribing cascades relevant for clinical practice.

Methods: A mixed-methods study was conducted. First, prescribing cascades were identified through literature search. An expert panel (n = 16) of pharmacists and physicians assessed whether these prescribing cascades were potentially problematic. Next, a cohort study quantified potentially problematic prescribing cascades in adults using Dutch community pharmacy data for the period 2015-2020. Additionally, the influence of multiple medications potentially causing the same ADR was evaluated. Prescription sequence symmetry analysis was used to calculate adjusted sequence ratios (aSRs), adjusting for temporal prescribing trends. An aSR >1.0 indicates the occurrence of a prescribing cascade. In a subgroup analysis, aSRs were calculated for older adults.

Results: Seventy-six prescribing cascades were identified in literature and three were provided by experts. Of these, 66 (83.5%) were considered potentially problematic. A significant positive aSR for the medication sequence was found for 41 (62.1%) of these prescribing cascades. The highest aSR was found for amiodarone potentially causing hypothyroidism treated with thyroid hormones (4.63 [95% confidence interval 4.40-4.85]), based on 565 incident users. The biggest population (n = 34,645) was found for angiotensin converting enzyme-inhibitors potentially causing urinary tract infections treated with antibiotics. Regarding four potential ADRs, the aSRs were higher for people using multiple medications that cause the same ADR as compared to people using only one of those medications. Among older adults the aSRs remained significant for 37 prescribing cascades.

Conclusion: An overview was generated of potentially problematic prescribing cascades relevant for clinical practice. These results can support healthcare providers to intervene and reduce medication burden for older adults.