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There are numerous definitions of polypharmacy to describe the use of many medications among older adults, but there is a need to clarify if they are purposive and meaningful. By means of a systematic review, we identified definitions of polypharmacy used in multimorbid older adults (≥65 years). We evaluated if the definitions align among the domains of research, clinical practice, and public health and appraised whether concepts of polypharmacy are based on strong foundations. More than 46 definitions of polypharmacy were retrieved from 348 publications (research: n = 243; clinical practice: n = 88; public health: n = 17). Several thresholds based on the number of medications were mentioned. The majority of the publications (n = 202, 58%) used a minimal threshold of five medications. Heterogeneous qualitative definitions were identified, mostly stating that polypharmacy is “more drugs than needed”. There was no significant divergence between domains as to the type of definitions used, although qualitative definitions were more common in clinical practice. Nearly half (n = 156, 47%) of the publications provided no justification for the polypharmacy definition used. The wide variety of definitions for polypharmacy precludes comparisons, appropriate identification and management of polypharmacy in multimorbid older adults. Standardized definitions would allow more coherent judgments regarding the individual and collective stakes of polypharmacy.

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