Purpose: To investigate: (1) the cross-sectional association between polypharmacy, hyperpolypharmacy and presence of prefrailty or frailty; (2) the risk of incident prefrailty or frailty in persons with polypharmacy, and vice versa. Methods: A systematic review and meta-analysis was performed according to PRISMA guidelines. We searched PubMed, Web of Science, and Embase from 01/01/1998 to 5/2/2018. Pooled estimates were obtained through random effect models and Mantel–Haenszel weighting. Homogeneity was assessed with the I ² statistic and publication bias with Egger’s and Begg’s tests. Results: Thirty-seven studies were included. The pooled proportion of polypharmacy in persons with prefrailty and frailty was 47% (95% CI 33–61) and 59% (95% CI 42–76), respectively. Increased odds ratio of polypharmacy were seen for prefrail (pooled OR = 1.52; 95% CI 1.32–1.79) and frail persons (pooled OR = 2.62, 95% CI 1.81–3.79). Hyperpolypharmacy was also increased in prefrail (OR = 1.95; 95% CI 1.41–2.70) and frail (OR = 6.57; 95% CI 9.57–10.48) persons compared to robust persons. Only seven longitudinal studies reported data on the risk of either incident prefrailty or frailty in persons with baseline polypharmacy. A significant higher odds of developing prefrailty was found in robust persons with polypharmacy (pooled OR = 1.30; 95% CI 1.12–1.51). We found no papers investigating polypharmacy incidence in persons with prefrailty/frailty. Conclusions: Polypharmacy is common in prefrail and frail persons, and these individuals are also more likely to be on extreme drug regimens, i.e. hyperpolypharmacy, than robust older persons. More research is needed to investigate the causal relationship between polypharmacy and frailty syndromes, thereby identifying ways to jointly reduce drug burden and prefrailty/frailty in these individuals. Prospero registration number: CRD42018104756.

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Poor adherence to treatment regimens has long been recognized as a substantial roadblock to achieving better outcomes for patients. Non-adherence to medications affects the quality and length of life and has been associated with negative health outcomes and increasing healthcare costs. The problem of non-adherence is particularly troublesome in older patients who are affected by multiple chronic diseases and for this reason receive multiple treatments. To date, no single intervention strategy has been shown to be effective in improving adherence across all patients, conditions, and settings. Between September and October 2014, a group of experts in geriatrics, pharmacology, epidemiology, and public health applied a modified RAND appropriateness method to reach a consensus on the possible best interventions to improve adherence in older individuals. Seven interventions were identified, classified based on their target (patient, therapy,
and public health/society): (1) Comprehensive Geriatric Assessment, (2) patient (and caregiver) education to improve patient empowerment, (3) optimization of treatment, (4) use of adherence aids, (5) physician and other
healthcare professionals’ education, (6) adherence assessment, (7) facilitating access to medicine by service integration. For each intervention, experts assessed (a) target population, (b) health professionals potentially involved in
the intervention, (c) strategies/instruments needed for implementation, and (d) time of the intervention. Interventions that target adherence must combine different approaches targeting the complex aspects of older adults in
a holistic approach. Tackling non-adherence, with its complexity, requires a multi-stakeholder patient-centred approach acting in a defined framework of interactions in which the different players may provide different services
but are integrated with one another.@en