VNS is used adjunctively primarily for the treatment of certain intractable seizure disorders. In 2005 the FDA approved its use for treatment refractory depression.
However, despite its approval and the endorsement by the American Psychiatric Association, its use has been limited because in the only randomized controlled trial, which is considered the gold standard of scientific studies, VNS failed to perform any better than placebo. In this case the study included a placebo group of patients who had VNS implanted but not activated. (For further information regarding the ongoing debate about VNS, see vnsdepression.com.)
Implanting the device is performed as an outpatient procedure. An incision is made in the upper left chest and the generator is placed under the left clavicle, similar to a pacemaker. Another incision is made in the left neck where the surgeon places the generator leads around the left branch of the vagus nerve. The generator then sends electrical signals to the leads at regular intervals similar to a pacemaker, stimulating the vagus nerve. The left vagus nerve is used because the right vagus nerve stimulates the heart; cardiac effects are thus minimized. The theory behind VNS is that signals are sent via the vagus nerve back to the brain, which affect various areas of the brain, as well as neurotransmitter systems that play a role in mood and seizure control. Obviously, there are immediate risks associated with the surgery and potential complications resulting from that, as well as placing a foreign object in the body. But the most significant risk has been the development of obstructive sleep apnea. This occurs because the laryngeal nerves are also stimulated, which can cause the larynx to constrict. Additional side effects include hoarseness (the most common), coughing, and sore throat. Other nonspecific symptoms have been reported, including stomach upset, nausea and vomiting, shortness of breath, headache, and numbness. Finally, although the left vagus nerve has significantly fewer effects on the heart, there can still be cardiac-related adverse effects, such as reversible bradycardia (slowed pulse).
DBS is the most invasive procedure of the three described and is still not FDA approved. It is similar to VNS in that it uses a pacemaker that periodically stimulates an area of the brain, but instead of doing so indirectly by wrapping leads around the vagus nerve, the leads are placed directly in specific brain regions. DBS has shown clear benefits to patients with Parkinson's disease and other movement disorders. The FDA has approved it for these conditions. More recently, it has been used in treatment-resistant depression as well as chronic pain with some success. As in VNS, the pacemaker is placed under the clavicle. The leads then run up under the skin of the neck, behind the ear, and under the scalp. This is performed under general anesthesia. Then, under local anesthesia a small diameter hole is drilled in the skull, allowing the lead to enter the brain. For Parkinson's disease, essential tremor, and other movement disorders, lead placement is fairly standardized. It is important that the patient be awake for this part of the procedure for the surgeon to receive feedback from the patient regarding the success of lead placement. Currently, there is limited evidence for the FDA to grant approval for the use of DBS in depression. In 2005 research demonstrated its effectiveness when the leads were placed in the frontal cortex of the brains of six depressed patients, with four responding positively. The effects were immediate. Researchers are also investigating other brain regions. As with any invasive procedure the potential side effects are significant but, in this instance, include any surgical procedures involving the brain, including bleeding, infection, and swelling. Lead placement can also inadvertently create new problems for the individual. There can be significant cognitive and emotional side effects associated with improper lead placement. These can include the very conditions one is attempting to treat, such as depression, but also compulsive behaviors and psychosis have been reported.