Medical Policy: 07.01.60
Original Effective Date: November 2000
Reviewed: September 2016
Revised: September 2016
Benefit determinations are based on the applicable contract language in effect at the time the
services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary
based on contract, and individual member benefits must be verified. Wellmark determines medical
necessity only if the benefit exists and no contract exclusions are applicable. This medical
policy may not apply to FEP. Benefits are determined by the Federal Employee Program.
This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
Vagus nerve stimulation (VNS) was initially investigated as a treatment alternative in patients with medically refractory partial-onset seizures for whom surgery is not recommended or for whom surgery has failed. Over time, the use of VNS has expanded to include generalized seizures, and it has been investigated for a range of other conditions.
Seizures are considered paroxysomal disorders (i.e. characterized by abnormal cerebral neuronal discharge) and occur when there is errant electrical discharge activity in the brain. Seizures cause different physical symptoms depending on the location of the electrical activity in the brain. They may be mild to severe, ranging from causing slight tingling sensation or momentary confusion to causing complete loss of consciousness. Classification and subtypes of seizures are commonly diagnosed by electroencephalography (EEG). Seizures are classified as simple partial, complex partial, and generalized onset, and are distinguished on the basis of level of consciousness.
Partial seizures affect only a portion, or one hemisphere of the brain and are subdivided into the following:
Generalized seizures are caused by errant activity in multiple locations or large areas that may involve both the left and the right hemispheres of the brain. This type of seizure has a more complex set of symptoms, with impaired awareness leading to complete loss of consciousness. The subtypes of generalized seizures are usually classed as follows:
Epilepsy is diagnosed in individuals with predisposition for recurrent, unprovoked seizures. During the past 10 years, new medications and surgical techniques have emerged to treat epilepsy. Despite these advantages, 20 percent to 50 percent of individuals with epilepsy have breakthrough seizures or experience adverse effects of anti-seizure medications.
The basic principles of VNS when used as a treatment for epilepsy are the vagal visceral afferents (nerves that convey impulses from sense organs and other receptors to the brain or spinal cord) have diffuse central nervous system projection, and the activation of these pathways has a widespread effect upon neuronal excitability. The exact mechanism of VNS on neuronal excitability is not fully known. Adverse effects of VNS therapy include headache, neck pain, cough and voice alterations.
Some of the benefits of using VNS may include less-severe or shorter seizures, a reduction in seizure frequency, improved recovery periods after seizures, and a lessening of seizure clusters. Individuals undergoing VNS must be aware that seizure control improves over time, and that although VNS may reduce the frequency and magnitude of seizure activity, the need remains for ongoing, concurrent, anti-seizure medical regimen.
Vagus nerve stimulation (VNS) is delivered via a pacemaker-like device called a pulse generator that is surgically implanted in the left upper chest underneath the skin. The pulse generator is connected to the vagus nerve via a bipolar electrical lead and delivers electrical impulses to the nerve at preprogrammed durations, frequencies and currents. The impulses are further transmitted to centers in the brain to achieve the therapeutic effects.
The stimulator is generally activated two to four weeks after implantation, although in some cases it may be activated in the operating room at the time of implantation. The physician programs the stimulator with a small hand-held computer, programming software, and a programming wand. The strength and duration of the electrical impulses are programmed. The amount of stimulation varies by case, but is usually initiated at a low level and slowly increased to a suitable level for the individual. The device runs continuously and is programmed to turn on and shut off for specific periods of time (for example, 30 seconds on, and 5 minutes off).
Patients are provided with a handheld magnet to control the stimulator at home (which must be activated by the physician to magnet mode). When the magnet is placed over the pulse generator site and then moved away, extra stimulation is delivered, regardless of the treatment schedule. Holding the magnet over the pulse generator will turn the stimulation off. Removing it will resume the stimulation cycle. This can be done by the patient, family members, friends or caregivers.
The evidence for vagus nerve stimulation (VNS) in individuals who have seizures refractory to medical treatment includes randomized controlled trials (RTCs) and multiple observational studies. The RCTs reported a significant reduction in seizure frequency for patients with partial-onset seizures. The uncontrolled studies have consistently reported large reductions for broader range of seizure types in both adults and children. The evidence is sufficient to determine that the technology results in meaningful improvement in net health outcomes. Therefore, implantable VNS may be considered medically necessary for patients with medically refractory seizures and for whom surgery is not recommended or for whom surgery has failed.
Treatment Resistant Depression
The evidence based on current published peer-reviewed literature for vagus nerve stimulation (VNS) in individuals who have treatment resistant depression is insufficient. The clinical trials for the use of VNS in treatment resistant depression do not demonstrate the effectiveness of VNS therapy on health outcomes. Also, it is not clear if VNS is as effective as alternative treatment modalities for patients with treatment resistant depression. Further studies are needed. Therefore, vagus nerve stimulation (VNS) is considered investigational for the treatment of treatment resistant depression.
Vagus Nerve Stimulation as a Treatment of Other Conditions
Vagus nerve stimulation (VNS) therapy has been investigated for use in other conditions, including but not limited to headaches, obesity, essential tremor, heart failure, fibromyalgia, tinnitus, and traumatic brain injury, the published peer reviewed evidence is limited and not sufficient to permit conclusions on efficacy. VNS is considered investigational including but not limited to these indications.
Vagus nerve stimulation therapy is being studied in individuals with chronic heart failure. A multicenter, randomized clinical trial The INOVATE-HF trial to evaluate the efficacy of implantable vagus nerve stimulation (device CardioFit) versus optimal medical therapy among patients with stable heart failure. The INOVATE-HF trial failed to show that vagus nerve stimulation improved clinical outcomes versus optimal medical therapy. This trial was terminated early due to futility for the primary outcome. The primary outcome, death or heart failure hospitalization occurred in 30.3% of the vagus nerve stimulation group versus 25.8% of the control group. Secondary outcome quality of life, NYHA class, and 6 minute walking distance were favorably affected by vagus nerve stimulation. Interpretation: Among individuals with stable heart failure, vagus nerve stimulation did not reduce the rate of death or hospitalization for heart failure. Reverse modeling also did not improve with vagus nerve stimulation. However, quality of life, NYHA class, and 6-minute walking distance were favorably affected by vagus nerve stimulation. This study information was posted April 2016. The use of vagus nerve stimulation for the treatment of heart failure warrants further study.
Vagus nerve stimulation (VNS) has been investigated for use in fibromyalgia. Lange et al in 2011 conducted a single arm Phase I/II trial of 14 individuals with fibromyalgia. Side effects and tolerability were similar to those found in disorders currently treated with VNS. Preliminary outcome measures suggested that VNS maybe a useful adjunct treatment for fibromyalgia patients resistant to conventional therapeutic management, but further research is required to better understand its actual role in the treatment of fibromyalgia.
Based on peer reviewed medical literature vagus nerve stimulation has been studied in the treatment of essential tremor resulting in no improvement in upper extremity tremors. Based on the reported studies VNS is not likely to have any clinically meaningful effect on essential tremor treatment.
Vagus nerve stimulation (VNS) has been studied in the treatment of obesity and it has been suggested that VNS might affect food cravings of individuals. However, limitations in studies include small sample size, lack of randomization and heterogeneity of groups that prevented conclusions about impact of VNS on eating behavior. Study findings need to be validated in large, well designed controlled studies to evaluate the impact of VNS on eating behavior and obesity.
The clinical efficacy of vagus nerve stimulation for the treatment of tinnitus has been studied in a case series involving 10 individuals that suggests that VNS may be associated with clinical improvements in individuals with tinnitus. The findings of this study need to be validated in large, well designed controlled studies to evaluate the impact of VNS on tinnitus.
Traumatic Brain Injury
Vagus nerve stimulation (VNS) is being investigated to augment recovery from traumatic brain injury. It is proposed that early stimulation of the vagus nerve accelerates the rate and extent of behavioral and cognitive recovery after fluid percussion brain injury in rats. Shi et. al. (2013) received FDA approval to conduct a pilot prospective randomized trial to demonstrate objective improvement in clinical outcome by placement of VNS in individuals who are recovering from severe traumatic brain injury. If this study demonstrates that VNS can be safely and positively impact outcome, then a larger randomized prospective crossover trial will be proposed.
Nonimplantable Vagus Nerve Stimulation (Transcutaneous Vagus Nerve Stimulation (t-VNS))
The transcutaneous VNS (t-VNS®) system uses a non-invasive approach that combines a stimulation unit and ear electrode to stimulate the auricular branch of the vagus nerve (which supplies the skin over the concha of the ear) for the treatment of pharmacoresistant epilepsy. Individuals self-administer electric stimulation for several hours per day. Currently, the device does not have FDA approval.
Transcutaneous VNS has been investigated for a number of conditions. Some evidence for the efficacy of t-VNS for epilepsy comes from 1 small RCT, which reported lower seizure rates for active t-VNS-treated patients compared with sham controls; however, the high dropout rates in this study limit conclusions that may be drawn. One small RCT which compared t-VNS wish sham stimulation for the treatment of depression demonstrated some improvements in depression scores with t-VNS; however, the lack of comparisons between groups limits conclusions that may be drawn. Additional RCT evidence is needed to permit conclusions about whether t-VNS is associated with improved outcomes for epilepsy, depression, or other conditions.
The body of evidence for the use of transcutaneous VNS (t-VNS) consists of small RCTs with methodologic limitations and case series. The evidence is insufficient to allow conclusions on the efficacy of t-VNS, and there are no transcutaneous stimulation devices that have U.S. Food and Drug Administration approval; therefore, transcutaneous VNS is considered investigational.
Treatment of Chronic Headaches
Per the American Headache Society regarding stimulators for the treatment of headache states that stimulation of the vagal nerve has been described as a means to treat both migraine and cluster headache in patients who have not responded to conventional treatment. A hand held device was developed to make this more convenient and less dangerous than implanted stimulators. The device is considered a noninvasive vagal nerve stimulator (nVNS). The advantage of this type of intervention is that it does not involve surgery. The device is held by the patient to the neck on the same side as the pain, and a low level electrical stimulation is discharged. This can be used preventively or at onset of pain. In the few patients who have tried it for migraine and cluster headaches, about half have responded. However, it is important to state that no scientific studies with placebo have been published on the nVNS as of early 2014, and so the evidence of its safety and effectiveness cannot be established. Also, nVNS does not have Food and Drug Administration (FDA) approval for use in the United States at this time.
Vagus Nerve Blocking Therapy
Vagal nerve blocking therapy for obesity consists of an implantable device that delivers electrical stimulation to branches of the vagus nerve on the anterior abdominal wall. The intent is to cause intermittent blocking of signals to the intra-abdominal vagus nerve to disrupt hunger sensations and induce feelings of satiety.
Obesity is a major cause of premature death and is linked to serious illnesses including heart disease, type 2 diabetes, sleep apnea, osteoarthritis, and certain types of cancer. Lifestyle interventions, especially changes to diet and exercise are the first line treatment of obesity. These interventions can be enhanced by participating in a structured weight loss program and/or by psychological interventions. There are also prescription weight loss medications available which have limited evidence of efficacy and there are adverse effects associated with their use. Weight loss (bariatric) surgery is another potential option for patients who have failed conservative treatments.
Vagal nerve blocking therapy is being investigated as another potential option for obese patients. The vagus nerve consists of 2 long cranial nerves that extend from the brain to the viscera. The vagus nerve winds through the abdomen and has branches that come into contact with the heart, lung, stomach, and other body parts. The vagus nerves plays a major role in autonomic and sympathetic nervous system functioning, including regulation of heartbeat and breathing. It is also involved in regulation of the digestive system, although its exact role in controlling appetite and feelings of satiety is unknown. Vagal nerve blocking therapy involves intermittent blocking of signals to the intra-abdominal vagus nerve, with the intent of disrupting hunger sensations and inducing feelings of satiety.
In January 2015, the U.S. Food and Drug Administration (FDA) approved a medical device specifically designed to provide vagal nerve blocking therapy for regulation of weight in obese patients. This device, the Maestro Rechargeable system, includes neuroblocking pulse generator that is implanted subcutaneously on the thoracic sidewall and flexible leads approximately 47 cm in length that are placed on the abdominal anterior and posterior vagal nerve trunks. External components include mobile charge, a transmit coil, a programmable microprocessor, and customized software. The system delivers high-frequency pulses of electrical current to vagal nerve trunks; therapy parameters and the treatment schedule can be customized by a clinician. Like other surgical interventions, there is potential adverse effects. In addition, there may be other unintended consequences of disrupting signals to a particular portion of the vagus nerve.
The evidence for vagal nerve blocking therapy in individuals who have obesity includes 2 sham controlled randomized trials (EMPOWER and ReCharge). Based on the EMPOWER study, VBLOC therapy to treat morbid obesity was safe, but weight loss was not greater in treated compared to controls; clinically important weight loss, however, was related to hours of the device use. Post study analysis suggested that the system electrical safety checks (low charge delivered via the system for electrical impedance, safety, and diagnostic checks) may have contributed to weight loss in the control group. Based on the ReCharge study the objective was to evaluate the effectiveness and safety of intermittent, reversible vagal blockade therapy for obesity treatment. The coprimary efficacy objectives were to determine whether the vagal nerve block was superior in mean percentage excess weight loss to sham by a 10-point margin with at least 55% of patients in the vagal block group achieving a 20% loss and 45% achieving a 25% loss. The primary safety objective was to determine whether the rate of serious adverse events related to device, procedure or therapy in the vagal block group was less than 15%. Among the patients with morbid obesity, the use of vagal nerve block therapy compared with a sham control device did not meet either of the prespecified coprimary efficacy objectives, although weight loss in the vagal block group was statistically greater than in the sham device group. The treatment was well tolerated, having met the primary safety objective. Additional studies are needed to compare effectiveness of vagal nerve block with other obesity treatments and to assess long-term durability of weight loss and safety. The evidence is insufficient to determine the effects of this technology on health outcomes.
Practice Guidelines and Position Statements
American Academy of Neurology (AAN)
In 1999, the American Academy of Neurology (AAN) released a consensus statement on the use of VNS in adults that stated, “VNS is indicated for adults and adolescents over 12 years of age with medically intractable partial seizures who are not candidates for potentially curative surfical resections, such as lesionectomies or mesial temporal lobectomies.
In 2013, the American Academy of Neurology (AAN) issued an evidence based guideline update: vagus nerve stimulation for the treatment of epilepsy, that stated:
American Psychiatric Association (APA):
The American Psychiatric Association guidelines on treatment of major depressive disorder in adults, updated in November 2010, includes the following statement on the use of VNS: “Vagus nerve stimulation (VNS) may be an additional option for individuals who have not responded to at least four adequate trials of antidepressant treatment, include ECT (electroconvulsive therapy), with a level of evidence III (May be recommended on the basis of individual circumstances).”
European Headache Federation
In 2013, the European Headache Federation issued a consensus statement on neuromodulation treatments for chronic headaches, which makes the following statement about the use of VNS: “Due to the lack of evidence, VNS should only be employed in chronic headache suffers using a randomized placebo controlled trial design.”
American Headache Society
In 2014, the American Headache Society issued information regarding stimulators for the treatment of headache and stated the following regarding vagal nerve stimulation (VNS): “Stimulation of the vagal nerve has been described as a means to treat both migraine and cluster headache in patients who have not responded to conventional treatment. A hand held device was developed to make this far more convenient and less dangerous than implanted stimulators. The device is called a noninvasive vagal nerve stimulator (nVNS). The device is held by the patient to the neck on the same side as the pain, and a low level electrical stimulation is discharged. This can be used preventatively or at onset of pain. However, it is important to state that no scientific studies with placebo have been published on the nVNS as of early 2014, and the evidence for its safety and effectiveness is merely the reports of the less than 50 patients who have used it and reported its effects. nVNS does not have FDA approval for use in the United States at this time.”
The FDA approved vagus nerve stimulator (VNS) therapy as adjunctive treatment for adults and children 12 years of age and older whose partial onset seizures are refractory to antiepileptic drugs.
To date, the FDA has not granted 501(k) clearance or PMA to any non-implantable t-VNA device for any indication for use in the United States. Cerbomed GmbH (Erlangen, Germany) has developed a t-VNS® System with NEMOS® that received European clearance (CE mark) in 2011 for treatment of drug-resistant epilepsy.
Another noninvasive VNS device called the gammaCore® (ElectroCore, LLC, Basking Ridge, NJ) is currently being investigated for the treatment of cluster/migraine headaches, severe gastroparesis, and other conditions. The gammaCore is currently unavailable for commercial distribution in the United States and has not received FDA 510(k) clearance or PMA for any indication.
January 14, 2015 Maestro Rechargeable System (EnteroMedics, St. Paul, MN) was approved by the U.S. Food and Drug Administration (FDA) through the premarket approval process for use in adults aged 18 years and older who have a body mass index (BMI) of 40 to 45 kg/m2 or a BMI of 35 to 39.9 kg/m2 with 1 or more obesity related conditions such as high blood pressure or high cholesterol and have failed at least 1 supervised weight management program within the past 5 years. Implantable components are incompatible with magnetic resonance imaging. Additional contraindications to use of the device include conditions such as cirrhosis of the liver, portal hypertension and clinically significant hiatal hernia, and the presence of a previously implanted medical device. FDA product code: PIM.
Implantable vagus nerve stimulation (VNS) may be considered medically necessary when both of the following criteria is met:
Note: Medically refractory seizures are defined as seizures that occur in spite of therapeutic levels of antiepileptic drugs or seizures that cannot be treated with therapeutic levels of antiepileptic drugs because of intolerable adverse effects of these drugs.
Replacement and Revisions
Replacement or revisions of an implantable vagus nerve stimulator and/or leads is considered medically necessary in an individual that meets the above criteria.
Vagus Nerve Stimulation (VNS) is considered investigational as treatment of all other conditions, including but not limited to the following:
Based on peer reviewed literature the use of vagus nerve stimulation has been examined for additional indications. However, there are limited studies and there is insufficient evidence to conclude that vagus nerve stimulation is safe and/or effective for treating these indications and therefore, is considered investigational.
Non-Implantable Vagus Nerve Stimulation
Non-implantable vagus nerve stimulation (transcutaneous vagus nerve stimulation (t-VNS)) devices are considered investigational for all indications.
The body of evidence for the use of non-implantable vagus nerve stimulation (transcutaneous vagus nerve stimulation (t-VNS)) consists of small RCTs with methodologic limitations and case series. The evidence is insufficient to allow conclusions on the efficacy of non-implantable vagus nerve stimulation, and there are no non-implantable vagus nerve stimulation (transcutaneous vagus nerve stimulation devices) that have U.S. Food and Drug Administration (FDA) approval; therefore, non-implantable vagus nerve stimulation (transcutaneous VNS) is considered investigational.
Vagal Nerve Block Therapy
Intra-abdominal vagal nerve blocking therapy is considered investigational for all indications, including but not limited to the treatment of obesity.
Based on the peer reviewed medical literature the safety and/or effectiveness cannot be established for intra-abdominal vagal nerve blocking therapy. Additional studies are needed to compare effectiveness of vagal nerve blocking therapy with other obesity treatments and to assess long-term durability of weight loss and safety. The evidence is insufficient to determine the effects of this technology on health outcomes and therefore, is considered investigational.
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