POST-TRAUMATIC EPILEPSY: CLINICAL EFFICACY OF ANTICONVULSANT THERAPY AND THE ROLE OF THE “ACCESSIBLE MEDICINES” PROGRAM

Abstract

Post-traumatic epilepsy (PTE) represents one of the most severe complications of traumatic brain injury (TBI), particularly in the context of armed conflict, where the incidence of penetrating and blast-related brain injuries has significantly increased. According to the literature, the risk of PTE following severe TBI ranges from 7% to 39%, and exceeds 57% after penetrating TBI. PTE accounts for approximately 20% of acquired epilepsy cases and 5% of all epilepsy cases overall. The condition often follows a chronic course, substantially impairing patients’ quality of life, leading to disability among the working-age population, and imposing a considerable socio-economic burden on healthcare systems. Despite advances in neurology and pharmacotherapy, effective prevention and treatment of PTE remain challenging, primarily due to the lack of reliable biomarkers for predicting seizure onset and the limited efficacy of existing anticonvulsant drugs (ACDs) in preventing late-onset PTE. This study aimed to evaluate, based on international clinical trials, scientific publications, and domestic clinical observations, the clinical efficacy and safety of anticonvulsant drugs of different generations in the prevention and treatment of post-traumatic epilepsy in patients with TBI. Additionally, the study assessed the impact of Ukraine’s national “Affordable Medicines” program on the accessibility of modern pharmacotherapy and its influence on real-world clinical practice. The research utilized data from international scientific databases, analytical and clinical publications, as well as official regulatory documents issued by the Ministry of Health of Ukraine–specifically, the State Register of Medicinal Products (as of September 2025) and the list of medicines included in the “Affordable Medicines” reimbursement program (as of July 1, 2025). The study employed methods of information retrieval, generalization, comparative analysis, marketing analysis (examining medicines by manufacturer, dosage form, and market availability), and systematic analysis of aggregated data from scientific, clinical, and regulatory sources. The analysis revealed that levetiracetam is the optimal first-line agent for the prevention of early post-traumatic seizures (within 7 days after TBI), demonstrating a favorable efficacy and safety profile. Phenytoin and carbamazepine are effective only in preventing early–but not late–seizures, thus their use is limited to the acute phase. Prophylactic administration of ACDs during the acute period of TBI does not prevent the development of chronic PTE. Newergeneration drugs (e.g., lacosamide, lamotrigine) show potential neuroprotective and antiseizure effects; however, their role in PTE prophylaxis requires further investigation through randomized controlled trials. Within the “Affordable Medicines” program, 6 international nonproprietary names (INNs) of ACDs are available (35% of all ACDs registered in Ukraine), predominantly in tablet form. Ukrainian manufacturers dominate the production of carbamazepine, whereas lamotrigine and levetiracetam are more widely represented by international companies (from Greece, India, and North Macedonia). Significant variations in patient co-payments were observed even for identical INNs, depending on the manufacturer, dosage form, strength, and pack size. Notably, certain formulations–such as dispersible lamotrigine tablets and all strengths of levetiracetam–are available with zero co-payment, enhancing treatment adherence. Levetiracetam emerges as the most optimal initial therapy for PTE due to its proven clinical efficacy, safety, and full financial accessibility under the “Affordable Medicines” program. While the program ensures basic access to essential ACDs, its limitations–covering only 35% of registered INNs–and substantial price discrepancies among therapeutically equivalent products highlight the need for program expansion and the implementation of unified pricing policies. Given the chronic nature of PTE and the necessity for long-term pharmacotherapy, financial accessibility is a critical determinant of treatment adherence and therapeutic success. Therefore, prioritizing zero co-payment formulations (e.g., dispersible lamotrigine and all levetiracetam strengths) is both clinically and economically justified in real-world practice.