VNS devices are used to treat drug-resistant epilepsy and treatment-resistant major depressive disorder. Specifically, it is used for treatment-resistant focal epilepsy. As of 2017 the efficacy of VNS for TR-MDD was unclear.
Adverse events
For the treatment of epilepsy generally the left vagus nerve is stimulated at mid-cervical region. The adverse effects of this stimulation include cardiac arrest, bradycardia, voice alteration and hoarseness, cough, shortness of breath, pain, a tingling sensation, nausea, and headache; difficulty swallowing has also been reported as common, as well as sleepiness. In randomized controlled trials for epilepsy conducted in the United States, one-third of the subjects had some type of an increase in seizures, with 17 percent having greater than a 25 percent increase, some had 100 percent increase or more.
Mechanism of action
As of 2017 little was understood about exactly how vagal nerve stimulation modulates mood and seizure control. The vagus is the tenth cranial nerve and arises from the medulla; it carries both afferent and efferent fibers. The afferent vagal fibers connect to the nucleus of the solitary tract which in turn projects connections to other locations in the central nervous system. Proposed mechanisms include an anti-inflammatory effect, as well as changes in monoamines.
Devices and procedures
The device consists of a generator the size of a matchbox that is implanted under the skin below the person’s collarbone. Lead wires from the generator are tunnelled up to the patient’s neck and wrapped around the left vagus nerve at the carotid sheath, where it delivers electrical impulses to the nerve. Implantation of the VNS device is usually done as an out-patient procedure. The procedure goes as follows: an incision is made in the upper left chest and the generator is implanted into a little "pouch" on the left chest under the collarbone. A second incision is made in the neck, so that the surgeon can access the vagus nerve. The surgeon then wraps the leads around the left branch of the vagus nerve, and connects the electrodes to the generator. Once successfully implanted, the generator sends electric impulses to the vagus nerve at regular intervals. The left vagus nerve is stimulated rather than the right because the right plays a role in cardiac function such that stimulating it could have negative cardiac effects. The "dose" administered by the device then needs to be set, which is done via a magnetic wand; the parameters adjusted include current, frequency, pulse width, and duty cycle. "Wearable" devices are being tested and developed that involve transcutaneous stimulation and do not require surgery. Electrical impulses are targeted at the aurical, at points where branches of the vagus nerve have cutaneous representation; such devices had been tested in clinical trials for treatment resistant major depressive disorder as of 2017.
History
In 1997, the US Food and Drug Administration's neurological devices panel met to consider approval of an implanted vagus nerve stimulator for epilepsy, requested by Cyberonics. The FDA approved an implanted VNS for TR-MDD in 2005. In April 2017, the FDA cleared marketing of a handheld noninvasive vagus nerve stimulator, called "gammaCore" and made by ElectroCore LLC, for episodic cluster headaches, under the de novo pathway. In January 2018, the FDA cleared a new use of that device, for the treatment of migraine pain in adults under a 510 based on the de novo clearance.
Controversy
Although the use of VNS for TRD has been endorsed by the American Psychiatric Association, the FDA's approval of VNS for TRD remains controversial. According to Dr. A. John Rush, vice chairman for research in the Department of Psychiatry at the University of Texas Southwestern Medical Center at Dallas, results of the VNS pilot study showed that 40 percent of the treated patients displayed at least a 50 percent or greater improvement in their condition, according to the Hamilton Depression Rating Scale. Many other studies concur that VNS is indeed efficacious in treating depression. However, these findings do not take into account improvements over time in patients without the device. In the only randomized controlled trial VNS failed to perform any better when turned on than in otherwise similar implanted patients whose device was not turned on.
As of 2015 VNS devices were being developed that were not implanted, but rather transmitted signals through the skin, known as transcutaneous vagus nerve stimulation. Electrical impulses are targeted at the auricle of the ear at points where branches of the vagus nerve are close to the surface. It is non-invasive and based on the rationale that there is vagus nerve distribution on the surface of the ear. tVNS is being studied for stroke and the treatment of depression.
