Vagus Nerve Stimulation for Treatment of Partial Seizures: 2. Safety, Side Effects, and Tolerability

Summary: Vagus nerve stimulation (VNS) significantly reduces the frequency of partial seizures in refractory epilepsy patients. We examined the serious adverse events, side effects, and tolerability as they relate to the surgical implant procedure and the stimulating device.We also reviewed potential drug interactions, device out-put complications, and impact of the therapy on overallhealth status. We analyzed the first 67 patients to exit theacute phase of the EO3 VNS trial comparing high (therapeutic) VNS to low (less or noneffective) VNS. Datawere collected from case report forms used at each of thefour visits during the 12-week baseline and at each of thefour visits during the 14-week randomized phase of the trial. No significant complications were reported as a re-sult of the implant procedure. Serious adverse events in-cluded 1 patient who experienced direct current to thevagus nerve owing to generator malfunction resulting inleft vocal cord paralysis and withdrawal of the patientfrom the study. No clinically significant effects on vitalsigns, cardiac function, or gastric function were detected. Side effects associated with VNS in the high group werehoarseness (35.5%), coughing (13.9%), and throat pain(12.9%). In the low group, only hoarseness (13.9%) andthroat pain (13.9%) were associated with VNS. Theseeffects generally were not considered clinically significantand occurred primarily during the stimulation pulses. Nopatients discontinued VNS therapy during the acutephase because of side effects associated with normal stimulation. Except for the one instance of a short circuitin the system resulting in a direct current, stimulatingsystem complications were minor, limited to programming, unscheduled stimulation, and high lead impedance.Patients, investigators, and patient companions rated patients receiving high stimulation as more “improved” than those receiving low stimulation in regards to overallhealth status. Antiepileptic drug (AED) plasma concentrations were not affected by VNS. The implant procedure, stimulating system, and therapy proved safe andtolerable during the study. The high percentage (67 of 68)of patients completing the study reflects patient acceptance and tolerability of this mode of therapy.