Abstract
Epilepsy is a chronic neurological disorder characterized by recurrent, unprovoked seizures that affect approximately 50 million people worldwide. Despite the availability of numerous anti-seizure medicines (ASMs), about 30% of people develop drug-resistant epilepsy (DRE), defined as failure to achieve sustained seizure freedom after trials of two appropriately chosen and tolerated ASM regimens. This population faces significantly reduced quality of life, increased mortality risks, and substantial socioeconomic burdens due to frequent hospitalizations and limited employability.For these treatment-resistant cases, neurostimulation therapies have emerged as promising alternatives to conventional pharmacotherapy. Among these, vagus nerve stimulation (VNS) has become one of the most widely used neurostimulation techniques since approved in 1997. Clinical studies demonstrated that VNS provides meaningful clinical benefits, with approximately 50-60% of patients achieving over 50% reduction in seizure frequency within 12-24 months after implantation. Beyond seizure control, VNS has been associated with improved mood, cognition, and quality of life measures. The therapy is particularly valuable for patients not candidates for resective surgery.This paper presents a comprehensive cost-effectiveness analysis of VNS in DRE by reviewing relevant literature. We examine three key economic dimensions: (1) direct medical costs (including device implantation and maintenance), (2) indirect societal costs (such as productivity loss), and (3) long-term economic benefits. Our analysis reveals that in published papers mostly from developed countries, while VNS requires initial investment, it demonstrated remarkable long-term cost-effectiveness. The therapy significantly reduces healthcare utilization, medication costs, and socioeconomic burdens associated with uncontrolled epilepsy. Furthermore, we identify critical factors influencing cost-effectiveness and propose evidence-based optimization strategies to enhance the value proposition of VNS therapy for diverse healthcare systems and selected patients.