What Are the Pros and Cons of Vagus Nerve Stimulation for Depression?

The vagus nerve stimulator (VNS) is a miniature implantable device that is used to assist in the treatment of drug-refractory epilepsy and depression. Usually consists of a pulse generator, a spiral electrode, a flexible lead, and an external control device. The pulse generator is placed in the subcutaneous tissue below the left midclavicular line. The spiral electrode is wrapped around the vagus nerve. The flexible wire is buried in the subcutaneous tunnel. The spiral electrode and the pulse generator are connected. The external control device is used to set the stimulation parameters. After the stimulation parameters are set, the vagus nerve is stimulated by intermittently transmitting current pulses through a pulse generator. The vagus nerve excitement is transmitted to the solitary nucleus and is then transmitted to different regions of the brain to achieve the purpose of treating neurological diseases.

Chinese name: Vagus nerve stimulator

Foreign name: VNS

1. Vagus nerve stimulator 1. Mechanism of vagus nerve action

The vagus nerve is the tenth cranial nerve. It is produced in the medulla oblongata and carries both afferent and efferent fibers. The vagus nerve afferent fibers connect to the solitary nucleus and are connected to other brain regions of the central nervous system. Although it is currently unknown how vagal nerve stimulation regulates emotions and seizures, researchers have proposed including changes in the release of norepinephrine projected from the solitary beam onto the blue spot, and increasing the inhibition of GABA levels associated with vagus nerve stimulation. Reticulate activation system inhibits abnormal cortical activity and other mechanisms.

2. Vagus nerve stimulator 2. Development history

In 1997, the US Food and Drug Administration (FDA) approved the use of vagus nerve stimulator (VNS) as an adjuvant treatment for drug-refractory epilepsy. In 2005, the FDA approved the use of VNS to treat refractory depression.

Although the American Psychiatric Association has approved the use of vagus nerve stimulators for the treatment of intractable depression, the approval is still controversial. According to Dr. John Rush, deputy chairman of the Department of Psychiatry, University of Texas Southwestern Medical Center, the results of the vagus nerve stimulator trial show that 40% of patients have improved by more than 50% according to the Hamilton Depression Scale (References Should be listed last). Many other studies have also proven that the vagus nerve stimulator is effective in the treatment of depression. However, the results of these clinical studies have not been followed up and compared in patients without equipment. In the only randomized controlled trial, VNS did not show a significant increase in efficacy compared to patients with implanted devices without turning on stimulation (should be listed last in the reference).

Charles E. Donovan wrote "Getting Out of the Black Hole-A Guide for Patients with Vagus Nerve Stimulation and Depression" in a Research Experimental Research Project on Vagus Nerve Stimulation for Refractory Depression (Are there articles? Should write this article's main Viewpoints should be listed last in the references)

3. Vagus nerve stimulator 3. Stimulation method

1 Vagus nerve stimulator 1) direct vagus nerve stimulation

This is currently the only widely used method for vagus nerve stimulation treatment, which requires surgical implantation of the vagus nerve stimulator. The vagus nerve stimulator manufactured by Cyberonics is composed of a pulse signal generator, a lead system with electrodes, and a fixing clip that fixes the lead to the vagus nerve. Among them, the pulse signal generator is packaged in a titanium case, the size of which is equivalent to a pocket watch, and uses a lithium battery as an energy source. The battery life of a pulse signal generator ranges from 1 to 16 years, depending on the strength of the transmitted signal, pulse width, time interval for nerve stimulation, and frequency of stimulation.

Cyberonics' vagus nerve stimulators are typically implanted as an outpatient procedure. The surgical procedure is as follows: Make an incision in the upper left corner of the chest, and implant the pulse signal generator into a small "bag" of the left chest under the clavicle. Make a second incision in the neck so that the surgeon can access the vagus nerve. The surgeon then wound a wire around the left branch of the vagus nerve and connected the electrodes to the generator. Once successfully implanted, the pulse signal generator sends electrical pulses to the vagus nerve at regular intervals. Because the right vagus nerve affects heart function, stimulating it will damage the heart, so it can only stimulate the left vagus nerve.

Currently, only NCP systems from Cyberonics Co., Ltd. are available for VNS therapy. In addition, Neurotech in Belgium and BioControl Medical in Israel developed VNS systems for the treatment of heart failure and other diseases. And domestic Beijing Pinchi Medical Equipment Co., Ltd. has also launched VNS for drug refractory in Beijing Tiantan Hospital, Second Affiliated Hospital of Zhejiang University Medical College, Qilu Hospital of Shandong University, General Hospital of Shenyang Military Region, and First Hospital of Jilin University Clinical trials of epilepsy. Internationally, some companies are also testing and developing other "wearable" VNS devices. These devices use percutaneous stimulation methods without implantation. They are used in conjunction with transcutaneous electrical nerve stimulators (TENS) that are commonly used for pain management. Similar.

2t-VNS Vagus nerve stimulator 2) percutaneous vagus nerve stimulation (t-VNS)

This method can stimulate the vagus nerve without surgery, and uses electrical pulses to stimulate parts of the vagus nerve branch that have skin characteristics, such as the ear. It should be noted that the turbinates have also been the target of percutaneous vagal nerve stimulation (t-VNS) (the reference should be listed last).

4. Vaginal nerve stimulator 4. Treatment of other diseases of vagus nerve stimulation

Kevin J. Tracey found that by inhibiting the production of proinflammatory cytokines, the vagus nerve stimulator can suppress inflammation. Thus vagus nerve stimulation can be used to treat inflammatory diseases such as arthritis, colitis, ischemia, myocardial infarction, and congestive heart failure. The action potential transmitted in the vagus nerve activates the inflammatory reflex exit arm, a neural circuit focused on the spleen to inhibit TNF and other pro-inflammatory cytokines produced by macrophages. This outgoing arc is also known as the cholinergic anti-inflammatory pathway. Since this strategy aims to inhibit the release of TNF and other pro-inflammatory cytokines, vagus nerve stimulation can be used instead of anti-inflammatory antibodies to treat inflammation.

A study published in Science in 2011 (Sept 15, 2011 DOI: 10.1126 / science.1209985) demonstrated that the presence of T cells synthesized by spleen acetylcholine due to vagus nerve stimulation can inhibit the inflammatory response / TNF- .

5. Vagus nerve stimulator 5. Other uses

Because the vagus nerve is associated with many different functions and brain regions, researchers are conducting research on the treatment of vagus nerve stimulators in other diseases. These diseases include: various anxiety disorders, Alzheimer's disease, migraine, fibromyalgia, obesity, tinnitus, alcohol addiction, atrial fibrillation, autism, binge eating disorder, burning-induced organ dysfunction, chronic heart failure , Chronic refractory hiccup, sick personality disorder, coronary artery disease, infant severe myoclonic epilepsy (also known as Dravet syndrome, a type of refractory epilepsy syndrome), sudden dizziness or weakness, heat stroke , Ruptured intestinal epithelial barrier, childhood diffuse slow spines-slow wave epilepsy encephalopathy (also known as Lennox-Gastaut syndrome, a special epilepsy syndrome), emotional disorders in the elderly, myocarditis, multiple sclerosis, obsessive-compulsive Disease, peripheral arterial occlusive disease, postoperative cognitive dysfunction in elderly patients, Rasmussen encephalitis, severe mental illness, sepsis, transient focal cerebral ischemia, traumatic hemorrhagic shock, traumatic brain injury, visceral pain response, emotional memory, etc. .

Other brain stimulation techniques used to treat depression include electrical shock therapy (ECT) and transcranial microcurrent stimulation therapy (CES). Research on deep brain stimulation for depression is ongoing; transcranial magnetic stimulation (TMS) for depression and epilepsy; UCLA is conducting research on trigeminal nerve stimulation (TNS) for epilepsy.

6. Vagus nerve stimulator 6. Side effects

1 Vagus nerve stimulator 1) Heart disease

Lead testing during device implantation has been reported to cause arrhythmias and delayed cardiovascular adverse effects.

2 Vagus nerve stimulator 2) sleep apnea

Studies have shown that patients with vagus nerve stimulator (VNS) implants intermittently reduce respiratory flow during sleep. This appears to be due to the increased control of the vagus nerve over the heartbeat. Clinically significant sleep apnea associated with the vagus nerve stimulator (VNS) has been found in pediatric and adult patient populations. Most patients treated with VNS have increased postoperative apnea hypopnea index (AHI). Approximately one-third of patients have mild obstructive sleep apnea, and a few patients have severe obstruction associated with VNS. Sleep apnea. The following measures can usually be used to reduce the adverse effects of obstruction: reduce the frequency and intensity of VNS stimulation; enable patients to use non-recumbent position during sleep; use positive airway pressure ventilation.

It is also important to screen for obstructive sleep apnea (OSA) symptoms in patients with epilepsy with VNS implants, as adequate treatment of undiagnosed and treated OSA symptoms may better control epilepsy.

For patients with obstructive sleep apnea (OSA) due to implantation of the vagus nerve stimulator (VNS), implantation of the vagus nerve stimulator is risky. Therefore, clinical screening for the appearance of OSA symptoms is needed after surgery. Continuous positive airway pressure (CPAP) is a feasible treatment for patients with OSA after VNS implantation. Other options include increasing the duration or frequency of stimulation of the vagus nerve stimulator. With more and more OSA phenomena and the increase in the number of patients undergoing surgery, it is very important to properly diagnose and treat the symptoms of obstructive sleep apnea caused by implantation of vagus nerve stimulators.

Symptoms such as loud snoring, intermittent apnea, behavioral changes, fatigue, or drowsiness after surgery will alert patients and their families that they may have obstructive sleep apnea. But these phenomena are not easy to find, so sleep studies (diagnostic polysomnography) are usually needed to diagnose the occurrence of obstructive sleep apnea. In fact, the majority of patients are children with related cognitive deficits, making it more difficult to diagnose OSA symptoms without sleep studies (which should be listed last in the reference).

The vagus nerve stimulator can cause superior and recurrent laryngeal nerve stimulation, and can produce speech changes (66%), cough (45%), pharyngitis (35%), sore throat (28%), hoarseness (very rare), and obvious symptoms Laryngeal muscle spasms and upper airway obstructions (rare). In addition, muscle tension may increase during the stimulation period (probably in the upper body). Since the left vagus nerve's cardiac outgoing fibers decrease proportionally, placing the vagus nerve stimulator on this side may reduce the arrhythmia caused by vagus nerve stimulation, but it cannot control the reversible bradyarrhythmia well. Other nonspecific symptoms include headache, nausea, vomiting, indigestion, dyspnea, and paresthesia (which should be listed last in the reference).

Randomized controlled trials of vagal nerve stimulators in the United States in the treatment of epilepsy have shown that one-third of patients using a particular vagal nerve stimulator have an increased number of seizures, of which 17% have increased by more than 25 percentage points. In each study, patients increased by more than 100 percent. In the E05 study, the range rose to 234 percentage points, while in the E04 study, the maximum range even rose to 680 percentage points.