Vagus nerve stimulation for treatment of partial seizures: 2. Safety, side effects, and tolerability. First International Vagus Nerve Stimulation Study Group.

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 output complications, and impact of the therapy on overall health status. We analyzed the first 67 patients to exist the acute phase of the EO3 VNS trial comparing high (therapeutic) VNS to low (less or noneffective) VNS. Data were collected from case report forms used at each of the four visits during the 12-week baseline and at each of the four visits during the 14-week randomized phase of the trial. No significant complications were reported as a result of the implant procedure. Serious adverse events included 1 patient who experienced direct current to the vagus nerve owing to generator malfunction resulting in left vocal cord paralysis and withdrawal of the patient from the study. No clinically significant effects on vital signs, cardiac function, or gastric function were detected. Side effects associated with VNS in the high group were hoarseness (35.5%), coughing (13.9%), and throat pain (12.9%). In the low group, only hoarseness (13.9%) and throat pain (13.9%) were associated with VNS. These effects generally wrre not considered clinically significant and occurred primarily during the stimulation pulses. No patients discontinued VNS therapy during the acute phase because of side effects associated with normal stimulation. Except for the one instance of a short circuit in the system resulting in a direct current, stimulating system 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 overall health status. Antiepileptic drug (AED) plasma concentrations were not affected by VNS. The implant procedure, stimulating system, and therapy proved safe and tolerable during the study. The high percentage (67 of 68) of patients completing the study reflects patient acceptance and tolerability of this mode of therapy.