Polypharmacy, Potential Drug–Drug Interactions and Medication Non-Adherence in Patients with Multiple Sclerosis: A Longitudinal Study

INTRODUCTION: Multiple sclerosis (MS) is a chronic neuroinflammatory disease affecting approximately 2.9 million people worldwide. Disease-modifying therapies for MS effectively lower the risk of relapses and delay disability progression, but the increasing medication burden and ongoing adherence challenges complicate disease management. An improved understanding of predictors of medication-related risks is essential to optimize long-term safety, treatment effectiveness, and quality of life in patients with MS. METHODS: In this longitudinal observational study, 206 adults with MS or clinically isolated syndrome were enrolled, of whom 175 completed the 5-year follow-up assessment. Sociodemographic, clinical, and comprehensive medication data were collected at baseline and follow-up through structured interviews and review of medical records. Polypharmacy was defined as the concurrent use of ≥ 5 medications. Potential drug-drug interactions (pDDIs) were systematically identified using the DrugBank database, and medication non-adherence was defined based on patient self-reported missed medication. RESULTS: Over the 5-year follow-up period, the prevalence of polypharmacy increased from 53.1% to 62.3% (p = 0.024), and pDDI exposure rose from 67.4% to 81.1% (p < 0.001), mainly driven by the greater use of drugs for comorbid conditions and dietary supplements. In contrast, monthly medication non-adherence remained stable (25.7% to 27.3%, p = 0.855). Major interactions accounted for 7.1% of all identified pDDIs. Older age, disability pension status, higher disability levels, coexisting medical conditions, and lower educational attainment were associated with polypharmacy and the presence of pDDIs, whereas non-adherence was linked to prior non-adherent behavior and inpatient care at baseline. CONCLUSION: Over time, the prevalence of polypharmacy and pDDIs increased in patients with MS, whereas medication non-adherence emerged as a largely independent risk domain. Polypharmacy and the presence of pDDIs were mainly associated with aging- and disability-related factors, whereas medication non-adherence was more difficult to predict. Our findings emphasize the need for regular medication monitoring that considers both prescribed and non-prescribed drugs, alongside individualized adherence support to mitigate distinct medication-related risks in long-term MS care.