Abstract
We developed a translational model to evaluate whether polypharmacy (use of ≥5 different medicines) causes adverse geriatric outcomes and whether these are reversible with deprescribing (withdrawal of medicines). Old (23–24 months) male C57BL/6 mice received control diet (no drugs) for eleven weeks, or diet containing therapeutic doses of five commonly used drugs (simvastatin, metoprolol, omeprazole, paracetamol, citalopram) for four weeks, which were gradually withdrawn over the next six weeks. Physical performance was assessed at baseline, four and eleven weeks and transformed into Frailty Intervention Assessment Values (FIAV): sum of standardised values for locomotor activity, rotarod performance and front paw hang. After four weeks, FIAV was unchanged in controls and declined with polypharmacy (p<0.05). At week eleven FIAV remained unchanged in controls and improved but did not return to baseline in the polypharmacy/deprescribing group. This model can assess the effects of polypharmacy on geriatric outcomes and provides opportunities to investigate mechanisms.