Medical Policy: 07.01.60
Original Effective Date: November 2000
Reviewed: September 2017
Revised: September 2017
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.
While the mechanisms for the therapeutic effects VNS are not fully understood, the basic premise of VNS in the treatment of various conditions is that 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. Electrical stimulation is applied to axons of the vagus nerve, which have their cell bodies in the nodose and junctional ganglia and synapse on the nucleus of the solitary tract in the brainstem. From the solitary tract nucleus, vagal afferent pathways project to multiple areas of the brain. 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 an implantable, programmable electronic pulse generator that delivers stimulation to the left vagus nerve at the carotid sheath. Surgery for implantation of a vagus nerve stimulator involves implantation of the pulse generator in the infraclavicular region and wrapping 2 spiral electrodes around the left vagus nerve within the carotid sheath. The programmable stimulator may be programmed in advance to stimulate at regular intervals or on demand by patients or family by placing a magnet against the subclavicular implant site.
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.
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.
The evidence for vagus nerve stimulation (VNS) in individuals who have treatment resistant depression includes 1 randomized controlled trial (RCT) and other nonrandomized comparative studies and case series. The RCT reported only short-term results and found no significant improvement for the primary outcome. Other available studies are limited by small sample sizes, potential selection bias, and lack of a control group in the case series. Further studies are needed. The evidence is insufficient to determine the effects of the technology on net health outcomes. Therefore, vagus nerve stimulation (VNS) is considered investigational for the treatment of treatment resistant depression.
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.
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.
Vagus nerve stimulation has been proposed in a number of other indications, including but not limited to, treatment resistant depression, bipolar disorders, heart failure, fibromyalgia, essential tremor, headaches, obesity, tinnitus and traumatic brain injury. The peer reviewed medical literature regarding the use of vagus nerve stimulation for these other indications is limited and therefore conclusions about the safety and efficacy cannot be made at this time. Further studies are needed. Vagus nerve stimulation devices are not FDA approved for treatment of these indications.
Transcutaneous vagus nerve stimulation (tVNS) is being investigated as a noninvasive alternative to surgery for implantable vagus nerve stimulation and is being investigated for a number of indications including but not limited to headaches, psychiatric disorders (depression, schizophrenia), epilepsy and impaired glucose tolerance.
A non-implantable transcutaneous vagus nerve stimulation (tVNS) hand held battery powered stimulation unit and ear electrode combines to purportedly stimulate the auricular branch of the vagus nerve through the skin over the concha of the outer ear to deliver treatment. Stimulation treatment is administered by the individual for several hours per day.
On April 14, 2017, the U.S. Food and Drug Administration (FDA) approved gammaCore Non-invasive Vagus Nerve Stimulator ( ElectroCore LLC, Basking Ridge, New Jersey) intended to provide non-invasive vagus nerve stimulation (nVNS) on the side of the neck. The gammaCore device is indicated for the acute treatment of pain associated with episodic cluster headache in adult patients. The portability of the stimulation device allows patients to self-administer treatment for up to 4 attacks or 8 treatments totaling 24 stimulations a day. GammaCore can be used in combination with medication if needed.
The FDA approval was based on subgroup analyses from two clinical trials for the Acute Treatment of Cluster Headache (ACT1 and ACT2). Both trials were prospective, double-blind, placebo controlled, randomized controlled trials (RCTs) evaluating the use of gammaCore® (non-invasive VNS [nVNS]) versus sham treatment. One hundred fifty individuals with acute cluster headaches were randomized into the ACT1 study; 133 of whom were included in the intention to treat population (nVNS = 60; sham = 73). The response rate was not significantly different for the total population (nVNS 26.7%; sham 15.1%; P = 0.1). A predetermined subgroup analysis between subjects with episodic cluster headaches (eCH) and chronic cluster headaches (cCH) demonstrated statistically significant higher response rates among individuals with eCH in the nVNS arm versus the sham arm (nVNS 34.2%; sham 10.6%; P = 0.008), but a statistically significant difference was not realized in the cCH subgroup (nVNS 13.65%; sham 23.1%; P = 0.48). Sustained response rates were also significantly higher with nVNS for the eCH cohort (P = 0.008) and total population (P = 0.04). Importantly, the study was not powered to demonstrate independent statistical significance for the subgroup analyses, nor were the P values adjusted for multiple comparisons. The authors concluded that nVNS represents a novel and promising option for eCH.
An abstract for the ACT2 study was presented at the American Academy of Neurology 2017 Annual Meeting. ACT2 evaluated the use of gammaCore® (non-invasive VNS) for the acute treatment of pain associated with episodic or chronic cluster headache. Ninety two individuals were randomized into the ACT2 study (nVNS = 48; sham = 44). The response rate was not significantly different for the total population (nVNS 14%; sham 12%; P = NR). A statistically significant higher response rate among individuals with eCH in the nVNS arm (n=14) versus the sham arm (n=13) (nVNS 48%; sham 6%; P = 0.01), but a statistically significant difference was not realized in the cCH subgroup (nVNS n=34; sham n=31). Despite FDA approval, current published peer-reviewed literature does not support the use of non-invasive VNS for cluster headaches.
The evidence for transcutaneous vagal nerve stimulation (tVNS) in individuals who have epilepsy, depression, schizophrenia, headache (episodic cluster headaches), or impaired glucose tolerance includes small randomized trials, case series and systematic review. Studies are all small and have various methodologic problems. None show definitive efficacy of transcutaneous vagal nerve stimulation (tVNS) in improving outcomes among patients. Current studies are limited by lack of a comparator and small sample sizes. Further studies are needed to determine the safety and efficacy. The evidence is insufficient to determine the effects of this technology on net health outcomes.
More than one-third (36.5%) of U.S. adults have obesity which is defined as a body max index (BMI) 30.0 or higher (based on the U.S. Centers for Disease Control and Prevention).
Obesity is a major cause of premature death and is linked to serious illnesses including heart disease, type 2 diabetes, stroke, 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.
Vagus nerve blocking therapy is being investigated as another potential treatment 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. Vagus 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 vagus nerve trunks; therapy parameters and the treatment schedule can be customized by a clinician. Like other surgical interventions, there is the potential for 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.
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 surgical 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:
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: “electroconvulsive therapy (ECT) remains the treatment of best established efficacy against which other stimulation treatments (e.g. vagus nerve stimulation (VNS), deep brain stimulation, transcranial magnetic stimulation, other electromagnetic stimulation therapies) should be compared. Vagus nerve stimulation (VNS) may be an additional option for individuals who have not responded to at least four adequate trials of antidepressant treatment, including ECT, with a level of evidence III (May be recommended on the basis of individual circumstances).”
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.”
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.”
In 2016, the American Society for Metabolic and Bariatric Surgery published a position statement that included the following conclusions and recommendations on vagus nerve blocking therapy for the treatment of obesity:
In 1997, the NeuroCybernetic Prosthesis (NCP) system (Cyberonics), a vagus nerve stimulation (VNS) device was approved by the U.S. Food and Drug Administration (FDA) through the premarket approval (PMA) process for use in conjunction with drugs or surgery, as adjunctive treatment for adults and children 12 years of age and older with medically refractory partial onset seizures.
July 2005, Cyberonics received PMA supplement approval by FDA for the VNS therapy system for the adjunctive long-term treatment of chronic or recurrent depression for patients 18 years of age or older who are experiencing a major depressive episode and have not had an adequate response to four or more adequate antidepressant treatments.
Cerbomed has developed a transcutaneous vagal nerve stimulator (tVNS) system that uses a combined stimulation unit and ear electrode to stimulate the auricular branch of the vagus nerve, which supplies the skin over the concha of the ear. Patients self- administer electrical stimulation for several hours a day; no surgical procedure is required. The device received European clearance (CE mark) in 2011, but has not been FDA approved for use in the United States.
January 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.
April 2017, the U.S. Food and Drug Administration (FDA) approved gammaCore Non-invasive Vagus Nerve Stimulator ( ElectroCore LLC, Basking Ridge, New Jersey) intended to provide non-invasive vagus nerve stimulation (nVNS) on the side of the neck. The gammaCore device is indicated for the acute treatment of pain associated with episodic cluster headache in adult patients.
Implantable vagus nerve stimulation (VNS) may be considered medically necessary when both of the following criteria are 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 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 transcutaneous vagus nerve stimulation (tVNS) devices are considered investigational for all indications.
The evidence for transcutaneous vagal nerve stimulation (tVNS) in individuals who have epilepsy, depression, schizophrenia, headache (episodic cluster headaches), or impaired glucose tolerance includes small randomized trials, case series and systematic review. Studies are all small and have various methodologic problems. None show definitive efficacy of transcutaneous vagal nerve stimulation (tVNS) in improving outcomes among patients. Current studies are limited by lack of a comparator and small sample sizes. Further studies are needed. The evidence is insufficient to determine the effects of this technology on net health outcomes.
Intra-abdominal vagus 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 vagus 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 net health outcomes and therefore, is considered investigational.
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