Conceptualizing multiple drug use in patients with comorbidity and multimorbidity: proposal for standard definitions beyond the term polypharmacy

With older and ageing populations, patients experience multiple chronic diseases at the same time. Individual chronic disease guidelines often recommend pharmacological therapies as a key intervention, resulting in patients being prescribed multiple regular medications for their different diseases. Whilst the term 'polypharmacy' has been applied to the use of multiple medications, there is no consistent definition and this term is now being used all inclusively. To improve both scientific rigor and optimal patient care, it is crucial that a standard terminology is used which reclassifies the term 'polypharmacy' into distinct phenotypes relating to the index chronic disease, additional conditions to the index ('comorbidity') or the experience of multiple chronic conditions at the same time (multimorbidity). Using three exemplar index conditions; heart failure, type 2 diabetes and breast cancer, we propose the reclassification of the term 'polypharmacy' into three distinct phenotypes. First, index drug or multi-index drug therapy, where each index condition creates multiple drug use for that condition; second, co-drug therapy, where addition of other comorbid conditions increases the multiple drug use and may influence the management of the index disease and third, multi drug therapy, where adult population with multimorbidity may be on many drugs. This paper reviews guidelines for the individual exemplars to develop the basis for the new terms and then develops the pharmaco-epidemiology of multiple drug use further by reviewing the evidence on the relationship between the phenotypic classification and important outcomes. The importance of standardising 'polypharmacy' terminology for the scientific agenda and clinical practice is that it relates to an index condition or disease safety outcomes including drug interactions, adverse side effects in hospital admissions and related 'polypill' concept.