Efficacy and safety of VNS therapy or continued medication management for treatment of adults with drug-resistant epilepsy: systematic review and meta-analysis

Sarah Batson,Francesca Barion,Joanna Murphy,Rohit Shankar,Jane Boggs,Joan Conry,Stephen Mitchell,Vanessa Danielson,Rodney Radtke

doi:10.1007/s00415-022-10967-6

Abstract

Vagus nerve stimulation (VNS) Therapy® is an adjunctive neurostimulation treatment for people with drug-resistant epilepsy (DRE) who are unwilling to undergo resective surgery, have had unsuccessful surgery or are unsuitable for surgery. A systematic review and meta-analysis were conducted to determine the treatment effects of VNS Therapy as an adjunct to anti-seizure medications (ASMs) for the management of adults with DRE. A literature search was performed in August 2020 of the Medline®, Medline® Epub Ahead of Print, Embase, and the Cochrane library databases. Outcomes examined included reduction in seizure frequency, seizure freedom, ASM load, discontinuations, and serious adverse events (SAEs). Comparators included best medical practice, ASMs, low-stimulation or sham VNS Therapy. Four RCTs and six comparative observational studies were identified for inclusion. Against comparators, individuals treated with VNS had a significantly better odds of experiencing a ≥ 50% reduction in seizure frequency (OR: 2.27 [95% CI 1.47, 3.51]; p = 0.0002), a ≥ 75% reduction in seizure frequency (OR: 3.56 [95% CI 1.59, 7.98]; p = 0.002) and a reduced risk for increased ASM load (risk ratio: 0.36 [95% CI 0.21, 0.62]; p = 0.0002). There was no difference in the odds of discontinuation or the rate of SAEs between VNS versus comparators. This meta-analysis demonstrated the benefits of VNS Therapy in people with DRE, which included improvement in seizure frequency without an increase in the rate of SAEs or discontinuations, thereby supporting the consideration of VNS Therapy for people who are not responding to ASMs and those unsuitable or unwilling to undergo surgery.

Highlights

Epilepsy is a common neurological condition, affecting approximately 50 million people globally [1]
38 Vagus nerve stimulation (VNS) Therapy studies did not meet eligibility criteria for inclusion in this meta-analysis; 10 studies were identified for inclusion (Fig. 1)
This systematic review and meta-analysis demonstrated that in people with drug-resistant epilepsy (DRE), adjunctive high-stimulation VNS Therapy resulted in statistically significant reductions in seizure frequency without increasing the rate of serious adverse events (SAEs) or discontinuations when compared with adjunctive low-stimulation VNS Therapy/anti-seizure medications (ASMs)/best medical practice

Summary

Introduction

Epilepsy is a common neurological condition, affecting approximately 50 million people globally [1]. At least 30% exhibit drug-resistant epilepsy (DRE) and continue to suffer seizures despite treatment [2]. People with DRE experience significantly more comorbidities, including depression, seizure-related injuries, and neurological deficits than those without epilepsy or with epilepsy that responds to treatment [4, 5], and have significantly higher mortality risk [6, 7]. People with DRE have substantially higher healthcare costs than those who are seizure-free, including costs associated with medical investigations, treatment costs, emergency room visits, hospitalisations, and outpatient care [18,19,20]. People with DRE frequently report feeling stigmatised because of their epilepsy [11]

Methods

Results

Conclusion