Comparative Effectiveness of Monotherapy versus Combination Therapy in Seizure Management: A Prospective Observational Study

Abstract

Epilepsy is a chronic neurological disorder characterized by recurrent, unprovoked seizures that significantly impact physical, psychological, and social well-being. Effective seizure management is critical to reducing morbidity, mortality, and economic burden. Antiepileptic drugs (AEDs) constitute the mainstay of therapy, administered as monotherapy or combination therapy depending on seizure type, severity, and patient response. Monotherapy is preferred as initial treatment due to lower adverse effect profiles and ease of adherence, yet a considerable proportion of patients require combination therapy to achieve seizure control. This prospective observational study was conducted at Yashoda Multispeciality Hospital, India, from November 2024 to April 2025, involving 102 adult patients with epilepsy. Patients were categorized into monotherapy (n=31) and combination therapy (n=71) groups. Demographic, clinical, and treatment data were collected, including seizure frequency, adverse events, and treatment adherence. Findings demonstrated complete seizure control in 56% of the cohort, partial control in 25%, and poor control in 19%. Combination therapy exhibited a 72% improvement rate, markedly higher than the 28% observed in monotherapy, suggesting enhanced efficacy in patients not responsive to single-drug regimens. Adverse events were more frequent with polytherapy but were generally mild and manageable. These results underscore the importance of individualized therapy selection, balancing efficacy, tolerability, and quality of life. Observational real-world data such as these provide critical insights for optimizing epilepsy management and highlight the need for larger, multicentre studies to further refine treatment protocols, including the optimal timing for transitioning from monotherapy to combination therapy.