Network-Based, Cross-Sectional Analysis of Drug-Related Problems Reveals a Strong Association of Possible Inappropriate Medication and Clinical Outcomes in Romanian Elderly Nursing Home Residents

Background/Objectives: Polypharmacy is common in elderly nursing home residents (NHR), due to the high prevalence of chronic diseases. This practice increases the risk of clinically significant drug–drug interactions (DDIs) with serious consequences for patient health and safety. The objective of this study was to evaluate the prevalence of DDIs using the UpToDate Drug–Drug Interaction Checker, potentially inappropriate medication (PIM, as defined by the STOPP-START criteria), and their association with major clinical outcomes. Methods: Demographic data, clinical history and detailed medication records of 275 patients from Romania were collected. Potentially inappropriate medications were identified using 16 selected criteria from the 2023 STOPP/START guidelines. Statistical analysis was performed using GraphPad, R, and Python, involving Chi-squared and Fisher’s exact tests with Benjamini–Hochberg correction, linear regression, and drug-interaction network analysis to characterise interaction frequency and severity. Results: Detailed medical histories over the past year were available for 76 patients. The mean number of drugs prescribed was 9.61 ± 4.47 drugs, with an average of 10.68 ± 10.54 potential interactions per patient. The primary clinical outcome was associated with not respecting certain STOPP-START recommendations (p < 0.01). Overall, 33.1% of NHRs utilised herbal supplements, resulting in a total of 76 potential herb–drug interactions. Conclusions: The results suggest a potential impact of DDIs on clinical outcomes, underscoring the need for further studies to clarify causality. The use of STOPP/START recommendations and deprescribing could lead to better tolerability and smaller drug-related burden in the institutionalised, elderly population.