A Systematic Review and Meta-analysis on Impact of Suboptimal Use of Antidepressants, Bisphosphonates, and Statins on Healthcare Resource Utilisation and Healthcare Cost

Background: Depression, osteoporosis, and cardiovascular disease impose a heavy economic burden on society. Understanding economic impacts of suboptimal use of medication due to nonadherence and non-persistence (non-MAP) for these conditions is important for clinical practice and health policy-making.

Objective: This systematic literature review aims to assess the impact of non-MAP to antidepressants, bisphosphonates and statins on healthcare resource utilisation and healthcare cost (HRUHC), and to assess how these impacts differ across medication classes.

Methods: A systematic literature review and an aggregate meta-analysis were performed. Using the search protocol developed, PubMed, Cochrane Library, ClinicalTrials.gov, JSTOR and EconLit were searched for articles that explored the relationship between non-MAP and HRUHC (i.e., use of hospital, visit to healthcare service providers other than hospital, and healthcare cost components including medical cost and pharmacy cost) published from November 2004 to April 2021. Inverse-variance meta-analysis was used to assess the relationship between non-MAP and HRUHC when reported for at least two different populations.

Results: Screening 1,123 articles left 10, seven and 13 articles on antidepressants, bisphosphonates, and statins, respectively. Of those, 27 were rated of good quality, three fair and none poor using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. In general, non-MAP was positively associated with HRUHC for all three medication classes and most prominently for bisphosphonates, although the relationships differed across HRUHC components and medication classes. The meta-analysis found that non-MAP was associated with increased hospital cost (26%, p = 0.02), outpatient cost (10%, p = 0.01), and total medical cost excluding pharmacy cost (12%, p<0.00001) for antidepressants, and increased total healthcare cost (3%, p = 0.07) for bisphosphonates.

Conclusions: This systematic literature review is the first to compare the impact of non-MAP on HRUHC across medications for three prevalent conditions, depression, osteoporosis and cardiovascular disease. Positive relationships between non-MAP and HRUHC highlight inefficiencies within the healthcare system related to non-MAP, suggesting a need to reduce non-MAP in a cost-effective way.