The VNS consists of a generator, typically implanted in the chest, and an electrode surgically fastened to the left vagus nerve. In addition, an external handheld magnet may be used if the patient senses an aura or to stop a seizure already in progress.
In 1997, VNS received US Food and Drug Administration (FDA) approval for the adjunctive treatment of refractory seizures in patients older than 12 years. In 2005, the VNS was approved for the treatment of chronic or recurrent depression in patients older than 18 years.
VNS may also have a beneficial effect on mood in patients with epilepsy in addition to its antiepileptic effect. The mechanism of action of VNS is uncertain, but may be related to metabolic activation of brain stem, limbic, or thalamic structures.
To date, the VNS is the only FDA-approved medical device for the treatment of epilepsy. However, other approaches, such as deep-brain stimulation of the anterior nucleus of the thalamus, responsive neurostimulation, trigeminal nerve stimulation, and transcranial magnetic stimulation, are in development.
A randomized, multicenter, clinical trial (Study E03) of 114 patients with partial seizures demonstrated a mean seizure reduction of 31% and a 50% seizure reduction in 39% of patients. A second randomized trial (Study E05) of 254 patients with intractable partial seizures demonstrated an average reduction in seizure frequency of 28% in the high-stimulation group vs a 15% reduction in the low-stimulation (pseudo-placebo) group (P = .04). These results are modest, but similar to those obtained with new antiepileptic drugs in phase 3 trials. Unlike antiepileptic drugs, VNS efficacy appears to improve over time.
Adverse Effects of VNS
Compared with antiepileptic drugs, VNS has a completely different side effect profile. Adverse effects are related to the surgical implantation of the generator, which may result in discomfort and deep or superficial infection. The lead attached to the vagus nerve is subject to breakage. In addition, the electrical stimulation in the neck may be uncomfortable and result in cough, hoarseness, or a feeling of shortness of breath. On the other hand, VNS does not cause sedation or adverse cognitive effects, which are often limiting factors with antiepileptic drug treatment.
Neurostimulation by the VNS occurs at prespecified, continuous intervals (eg, 30 seconds on, 5 minutes off). In addition, the patient may trigger additional stimulation on demand by holding a magnet over the implanted device. Magnet-activated stimulation may abort, diminish, or terminate a seizure.
A retrospective analysis of seizure data collected from the E03 trial demonstrated an increased likelihood of improved seizure control (aborted and decreased) after magnet activation (P = .0479). In the E04 trial, 31% of patients were able to diminish seizures and 22% of patients terminated seizures, but 47% reported no effect with the magnet. The magnet may offer psychological benefits to patients by providing some sense of control over seizures when they occur.
Years ago, I enrolled 5 of my patients with intractable epilepsy in the open-label E04 VNS safety trial. None of the patients became seizure-free, although as a group they experienced a modest benefit in seizure reduction. One college student did not like the stimulator and insisted that it be removed, even though he had not allowed adequate time for us to assess its therapeutic effects. The other 4 patients continued to use the VNS.