Clinical Policy Title: Vagus nerve stimulation

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1 Clinical Policy Title: Vagus nerve stimulation Clinical Policy Number: Effective Date: September 1, 2013 Initial Review Date: May 15, 2013 Most Recent Review Date: April 10, 2018 Next Review Date: April 2019 Policy contains: Seizure. Medically refractory seizures. Vagus nerve. Related policies: CP# CP# Laser thermal ablation for epileptic seizures Phrenic (diaphragmatic) nerve stimulation ABOUT THIS POLICY: Prestige Health Choice has developed clinical policies to assist with making coverage determinations. Prestige Health Choice s clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peer-reviewed professional literature. These clinical policies, along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state- or plan-specific definition of medically necessary, and the specific facts of the particular situation are considered by Prestige Health Choice when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. Prestige Health Choice s clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the treatment decisions for their patients. Prestige Health Choice s clinical policies are reflective of evidencebased medicine at the time of review. As medical science evolves, Prestige Health Choice will update its clinical policies as necessary. Prestige Health Choice s clinical policies are not guarantees of payment. Coverage policy Prestige Health Choice considers the use of vagus nerve stimulation (VNS) to be clinically proven and, therefore, medically necessary when the following criteria are met (Boon, 2018; Englot, 2011; Food and Drug Administration [FDA], 2017; Hayes, 2015): Patient criteria include all of the following: The individual is age 4 years or older. The individual is diagnosed with severe generalized epilepsy with atonic or tonic-clonic seizures. The individual experiences partial onset seizures that are refractory to anti-epileptic (AED) medication therapy, including individuals who are allergic to or suffer debilitating side effects of AEDs. Any one of the following is true: The individual has declined intracranial surgery. The individual has failed other surgical intervention. The individual is not a candidate for surgical resection. 1

2 Limitations: Coverage determinations are subject to benefit limitations and exclusions as delineated by the state Medicaid authority. The Florida Medicaid website may be accessed at All other uses of vagus nerve stimulation are not medically necessary. In addition: Individuals with a progressive disorder, such as malignant brain neoplasm or a progressive metabolic or degenerative disorder, should not receive vagus nerve stimulation. The U.S. Food and Drug Administration (FDA) states: o A NeuroCybernetic Prosthesis (NCP) vagus nerve stimulation system is contraindicated for individuals with a history of left or bilateral cervical vagotomy. o The VNS Therapy System (Cyberonics, Inc., Houston, Texas) device is approved for individuals of age 4 years and older. It cannot be used after a bilateral or left cervical vagotomy. o Individuals with an implanted vagus nerve stimulation device should not have any type of diathermy (shortwave, microwave, or therapeutic ultrasound), regardless of whether the device is switched on or off. Diathermy can cause energy to be concentrated into or reflected by the device, leading to heating and tissue damage, or can damage the device. Diagnostic ultrasound is not contraindicated. Transmitter adjustments usually occur in an outpatient setting. Alternative covered services: Pharmacotherapy with anticonvulsant medications. Desensitization of nerve receptors. Background The vagus nerve is a paired cranial nerve that originates in the brainstem and ends in the abdominal region. It carries both somatic and visceral afferent and efferent signals. The majority of its fibers are visceral afferents with widespread distribution. VNS works on the basis that the vagal visceral afferents provide a diffuse central nervous system projection. The activation of the diffuse pathways affects neural excitability. Although the exact mechanism of vagus nerve stimulation on neuronal excitability is not fully defined, it is known to activate well-defined reflexes and evoke potentials from the cerebellum, cerebral cortex, hippocampus, and thalamus. Vagus nerve stimulation has been used with success for individuals with epilepsy. A vagus nerve stimulation system is composed of an electrode array, an implantable generator, and an external programming device. The programming device is used to make adjustments and changes to the stimulation settings, which are transmitted to the implanted generator. The vagus nerve stimulation generator must be surgically implanted in the upper-left area of the chest, or under the left arm. The left 2

3 vagus nerve is selected due to its limited cardiac effects. A thin, platinum-based wire is affixed to the vagus nerve and attached to the electrode array. The flexible electrodes are threaded under the skin and connected to the vagus nerve stimulation generator. After implantation is completed, the external programmer is coded with instructions to stimulate the vagus nerve at a rate determined by the individual and the physician (Heck, 2002). The programming may be done for specific frequencies and is designed to reduce the volume of the recipient s seizure activity. Revisions to the vagus nerve stimulation system, such as replacing the battery-powered generator, usually occur every one to five years. The FDA has approved several vagus nerve stimulation systems. None is approved for children younger than 12 years of age. The implantation of a vagus nerve stimulation device in children younger than 12 years of age is considered an off-label use. The National Institute for Health and Clinical Excellence (NICE) guidelines support the use of vagus nerve stimulation for refractory epilepsy in children when all of the following criteria are met (NICE, 2004): The vagus nerve stimulation implantation procedure is performed by a specialized pediatric epilepsy team. The vagus nerve stimulation implantation procedure is directed by developmentally appropriate pre- and post-device implantation. There is quality-of-life (QOL) monitoring after vagus nerve stimulation implantation. Epilepsy is diagnosed by the occurrence and type of recurrent, unprovoked seizure activity, and electroencephalography (EEG) readings. Seizures occur when there are errant electrical discharges within the brain. They manifest with different physical symptoms relating to the area of brain where the errant electrical activity is located. Seizures are classified and subtyped by EEG. They are classified as general onset, complex partial, or simple partial, and are distinguished by level of consciousness. Partial seizures affect only one hemisphere of the brain. Generalized seizures have errant electrical activity in large areas, and may affect both sides of the brain. Even with the advent of new medications and surgical techniques for the treatment of epilepsy, 20 percent to 50 percent of individuals with epilepsy have breakthrough seizures or experience adverse effects of anti-seizure medications. Current peer-reviewed medical literature and accepted evidence support the efficacy of vagus nerve stimulation as a useful palliative alternative to reduce the frequency of seizures for individuals who have severe generalized epilepsy with atonic or tonic-clonic seizures. Peer-reviewed literature also supports the use of vagus nerve stimulation as an effective treatment for medically refractory partial-onset seizures, as well as in individuals who have failed surgery, are not candidates for surgery, and are not able to benefit from AEDs. Some of the benefits of using vagus nerve stimulation may include a reduction in seizure frequency, improved recovery periods after seizures, and a lessening of seizure clusters. Although vagus nerve stimulation may reduce the frequency and magnitude of seizure activity, individuals still need to remain on an anti-seizure medicinal regimen. In addition, individuals need to be apprised of the possible adverse effects of vagus nerve stimulation therapy, including cough, headache, neck and incisional pain, and voice alterations (Schlaepfer, 2008). A meta-analysis of vagus nerve stimulation identified 74 clinical trials with 3,321 individuals with intractable 3

4 epilepsy (Englot, 2011a). Participants of studies showed an average 36 percent to 45 percent reduction in seizure frequency at three to 12 months after implantation, and a 51 percent reduction after more than one year of using the therapy. Post-traumatic epilepsy and tuberous sclerosis were positive predictors of a favorable outcome. Complete seizure abatement occurred in rare instances, and at least 25 percent of individuals did not respond to the vagus nerve stimulation systems. An additional study by Englot (2011b) suggests that children ages years and individuals with generalized epilepsy benefited significantly from vagus nerve stimulation in contrast to their exclusion from the initial approval of the device. Children younger than 12 years of age had responses similar to older counterparts with no increase in complications. Klinkenberg (2012) found similar results in 41 children with intractable epilepsy. However, the small size of the population samples limits the applicability of these conclusions to clinical practice. In July 2005, the FDA approved a vagus nerve stimulation therapy system called NCP System (Cybertronics Inc., Houston, Texas) for use as an adjunctive treatment in individuals age 18 and older with chronic or recurrent depression who have experienced a major depressive episode and have not adequately responded to four or more antidepressant treatments. Vagus nerve stimulation has been studied as a treatment for depression. Early available studies for vagus nerve stimulation use in depression were subsidized by the leading manufacturer of the device and were significantly flawed, particularly with regard to the lack of randomized controlled trials (RCTs) and statistical analysis. Several systematic reviews have examined the effectiveness of vagus nerve stimulation for use in treatment-resistant depression (TRD) (Mark, 2006; Daban, 2008; Gaynes, 2011; Martin, 2012; Mitchell, 2013). However, only one double-blind, randomized study was identified with inconclusive results. There have been no studies to date that have demonstrated improved health outcomes with the use of vagus nerve stimulation when compared to other treatment modalities for TRD. A systematic review by Martin (2012) identified a study with 235 participants that revealed no statistical differences between the control and the placebo groups, citing insufficient data were available to confirm that vagus nerve stimulation was or was not effective in the treatment of depression. Though FDA approved, current peer-reviewed published literature does not at this time support the use of vagus nerve stimulation devices for the treatment of depression. Clinical trials for the use of vagus nerve stimulation for treatment-resistant depression do not demonstrate the effectiveness of vagus nerve stimulation therapy on health outcomes in an investigational setting. Data from studies lacking a control group are of limited value (Bajbouj, 2010). The American Psychiatric Association (APA) practice guideline for the treatment of major depressive disorders states that electroconvulsive therapy remains the best established efficacy above other stimulation therapies (Gelenberg, 2010). In addition, there are no Class I evidence statements from any professional health care societies for the use of vagus nerve stimulation in acute or chronic depression, and there is insufficient evidence to recommend the use of vagus nerve stimulation for other neuropsychiatric disorders. (Fisher, 1999; Kennedy, 2009; NICE, 2009; Bauer, 2013). Searches Prestige Health Choice searched PubMed and the databases of: 4

5 UK National Health Services Centre for Reviews and Dissemination. Agency for Healthcare Research and Quality s National Guideline Clearinghouse and other evidence-based practice centers. The Centers for Medicare & Medicaid Services (CMS). We conducted searches on March 2, Search terms were: "vagus nerve stimulation" [MeSH]. We included: Systematic reviews, which pool results from multiple studies to achieve larger sample sizes and greater precision of effect estimation than in smaller primary studies. Systematic reviews use predetermined transparent methods to minimize bias, effectively treating the review as a scientific endeavor, and are thus rated highest in evidence-grading hierarchies. Guidelines based on systematic reviews. Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not simple cost studies), reporting both costs and outcomes sometimes referred to as efficiency studies, which also rank near the top of evidence hierarchies. Findings There is evidence that vagus nerve stimulation can reduce seizure frequency, with 14 percent to 79 percent of patients experiencing at least a 50 percent mean reduction; however, a portion of this treatment benefit can be attributed to a placebo response (Hayes, 2015). The treatment benefit is maintained for up to 13 years. Adults and children age >12 years seem to benefit equally from the treatment. Most studies to date have included patients with a broad range of epilepsy syndromes associated with intractable partial seizures classified as simple, complex, or secondarily generalized. Some evidence was available specifically investigating vagus nerve stimulation for generalized seizures and other epileptic syndromes. While the results from these studies suggest that vagus nerve stimulation therapy may also be effective for these types of seizures, the quality of the evidence was poor, and none of the studies was sufficiently powered to estimate the treatment benefit and to draw conclusions regarding seizure type and responsiveness to vagus nerve stimulation. The results of these initial studies will need to be confirmed in RCTs before any definitive conclusions can be drawn. Data from nonrandomized controlled trials suggest that vagus nerve stimulation may effectively treat epilepsy in other patient populations, including those with brain tumors and post-traumatic epilepsy. However, the quality of these studies is poor and additional data from RCTs are necessary to determine whether vagus nerve stimulation is better than alternative treatments for these populations. Several nonrandomized controlled studies have compared the effectiveness of vagus nerve stimulation with other interventions, including intracranial surgery. Evidence suggests that vagus nerve stimulation may be more effective in some cases, although the quality of the studies was poor and additional data from RCTs are needed. 5

6 A number of studies have evaluated the effect of vagus nerve stimulation on QOL, mood, and cognition in patients with epileptic syndromes. The results showed that vagus nerve stimulation may improve these outcomes in some patients, but the specific number and type of improvements were inconsistent among studies. While vagus nerve stimulation improved QOL in several studies, in others, especially in studies with very small sample size, improvements were not significant or were noted in only one or two domains; however, insufficient power to detect a significant effect makes interpretation of these results difficult. Safety data for vagus nerve stimulation are available for up to 11 years. The most common complications associated with vagus nerve stimulation therapy were voice alterations, hoarseness, cough, pain, dyspnea, infection, paresthesia, headache, and pharyngitis. These problems were generally mild, occurred only during stimulation, and decreased over time or could be resolved by changing device parameters. In some cases, the NCP had to be repositioned or removed, due to infection or device malfunction, but in most cases the device was successfully exchanged or reimplanted. A study that compared the incidence of definite/probable seizure with the expected baseline rate for epilepsy revealed no increased risk of mortality that could be attributed to the use of vagus nerve stimulation devices. Preliminary evidence suggests that patients with generalized and other types of seizures may experience similar complications and are not at a higher risk for negative side effects than patients with partial seizures. There is currently insufficient evidence to suggest that effectiveness may vary by patient characteristics. Characteristics that may predict vagus nerve stimulation success include the age at epilepsy onset, the age at vagus nerve stimulation implantation, the duration of epilepsy before vagus nerve stimulation implantation, predominant seizure types, and whether a patient has had previous intracranial surgery. Preliminary data from studies of poor quality suggest that young children (age 12 years) and older adults (age >50 years) are likely to benefit at least as much from vagus nerve stimulation as other populations. Furthermore, there is evidence that shorter durations of epilepsy before implantation predict better success. Evidence is conflicting with regard to age at epilepsy onset. Some evidence suggests that a history of previous intracranial surgery does not predict success of vagus nerve stimulation treatment. Concrete predictors of a treatment response have not been established, and additional research is required to substantiate these preliminary findings. Based on a review of abstracts of published literature (Hayes, 2016), there is insufficient evidence to inform evidence-based decisions regarding the AspireSR Model 106 by Cyberonics. In small clinical studies, the device appears to perform as expected by delivering an electrical stimulation in response to the detected increase in heart rate, which may herald a pending seizure. Duration and frequency of seizures were decreased in patients who received automatically delivered stimulation. The AutoStim mode eliminates the need for patient and caregiver interaction with the device, unlike the magnet mode of previous iterations. Larger studies with long-term clinical outcomes are needed to determine the reliability, safety, and consistency of this novel device. There is insufficient evidence to conclude that vagus nerve stimulation improves depression, QOL, and function in patients with major depressive disorder (MDD) and bipolar disorder. The best level of evidence (Hayes, 2015) was derived from one 12-week, double-blind, randomized controlled study. There was a 6

7 statistically significant difference in only one secondary outcome measure. The results of a study comparing vagus nerve stimulation plus standard treatment with standard treatment alone were also conflicting. While the primary data analysis suggested that vagus nerve stimulation plus standard treatment was superior to standard treatment alone, there was significant heterogeneity among patients, and if the analysis were adjusted to account for these differences, significance was lost. The results from the longterm uncontrolled studies suggest that patients who respond to the treatment at three or 12 months are likely to maintain the response for up to 24 months. However, long-term studies lowered the threshold for the definition of responders; therefore, actual long-term response rates might be lower. Furthermore, a large, randomized, dose-finding study failed to demonstrate a dose response relationship for vagus nerve stimulation therapy. Vagus nerve stimulation is associated with severe complications and therefore the riskbenefit ratio does not favor the use of vagus nerve stimulation therapy for TRD. A low-quality body of evidence from three clinical reports (n=28 to 294) assessed the net health benefit of the Maestro Rechargeable System for controlling obesity. One fair-quality double-blind RCT (n=294) compared active and sham treatment with the Maestro device for 9 hours daily (Hayes, 2016). A second fair-quality double-blind RCT (n=239) compared active and sham treatment with the Maestro device for 12 hours daily. A prospective case series of very poor quality (n=28) involved treatment of obese patients with type 2 diabetes with the Maestro device for 12 to 15 (mean, 14) hours daily. The overall quality of the evidence was assessed taking into consideration the quality of individual studies; the precision, directness, and consistency of data; and the applicability of the data to general practice. Overall, the body of evidence is insufficient to draw conclusions about the efficacy of the Maestro device in that two RCTs failed to reach pre-specified co-primary weight loss endpoints. Comparison and synthesis of results are limited because the studies used slightly different treatment protocols; used different definitions for primary outcome measures; and because one used an inert sham device whereas the other reported delivery of a very low level of electrical charge via the sham implant to the vagus nerve. The investigators reported that this may have confounded the study results. Importantly, neither RCT had sufficient follow-up length to determine the long-term durability of device-induced weight loss or the safety of prolonged device use. Policy updates: A systematic review (Cimpianu, 2017) examined invasive and noninvasive vagus nerve stimulation as treatment for treatment-refractory depression, dementia, schizophrenia, somatoform disorder, and other psychiatric disorders and found the efficacy of vagus nerve stimulation in affective disorders to be promising, but noted there is a need for more controlled and naturalistic studies in this regard. In other conditions like schizophrenia, Alzheimer's disease, obsessive-compulsive disorder (OCD), Parkinson s disease (PD), post-traumatic stress disorder (PTSD), and fibromyalgia, there were either no effects or preliminary data on efficacy was inconclusive with regard to the efficacy of vagus nerve stimulation. In 2018, the policy was updated as follows. Six peer-reviewed publications and an FDA Summary of Safety and Effectiveness Data document were added to the reference list. Four of the peer-reviewed publications and the Summary of Safety and Effectiveness Data were added to the summary of clinical evidence. The 7

8 reference for one guideline was updated. The FDA released a Summary of Safety and Effectiveness Data expanding the indicated ages to include ages 4 11, for use of the VNS Therapy System as an adjunctive therapy in reducing the frequency of seizures in those with partial onset seizures that are refractory to antiepileptic medications (FDA, 2017). The coverage policy has been revised to reflect this expansion. In two systematic reviews, vagus nerve stimulation was found to be effective for epilepsy among adults (Boon, 2018) and in Dravet syndrome, a rare pediatric condition marked by epileptic activity among other symptoms (Dibué-Adjei, 2017). A third meta-analysis found that vagus nerve stimulation in children with epilepsy is less effective among those with intellectual disabilities (Sourbron, 2017). Two previous studies have found vagus nerve stimulation to be cost-effective in pediatric patients (Helmers, 2012; Majoie, 2001). A Cochrane review found a lack of studies comparing approaches to epilepsy treatment including vagus nerve stimulation, intracranial stimulation, best medical practice, or surgery (Sprengers, 2017). Vagus nerve stimulation was found to be associated with higher rates of sleep apnea in meta-analysis, suggesting the need to take measures of sleeping behaviors at presentation and during follow-up (Romero-Osorio, 2018). Summary of clinical evidence: Citation Boon (2018) Neurostimulation for drug-resistant epilepsy Romero-Osorio (2018) Changes in sleep patterns after vagus nerve stimulation, deep brain stimulation or epilepsy surgery Cimpianu (2017) Vagus nerve stimulation in psychiatry: A systematic review of the available evidence Dibué-Adjei (2017) Content, Methods, Recommendations This systematic review found moderate-quality evidence for the efficacy of vagus nerve stimulation in adults with drug-resistant partial epilepsies. This systematic review of 36 studies found that vagus nerve stimulation causes sleep apnea, dependent of the stimulation variables. However, modifying these settings can revert the condition. Measures of sleep parameters should be included during the initial evaluation and follow-up of those considered for invasive procedures for epilepsy control, especially with vagus nerve stimulation due to the risk of sleep apnea. High-quality, comparative studies of various types of nerve stimulation are needed. Systematic review of vagus nerve stimulation as treatment for treatment-refractory depression, dementia, schizophrenia, somatoform disorder, and other psychiatric disorders. Found the efficacy of vagus nerve stimulation in affective disorders to be promising, but noted there is a need for more controlled and naturalistic studies. For schizophrenia, Alzheimer's disease, OCD, PD, PTSD, and fibromyalgia, either no effects or preliminary data on efficacy was inconclusive with regard to the efficacy of vagus nerve stimulation. Efficacy of adjunctive vagus nerve Dravet syndrome is a rare pediatric disease marked by severe epileptic encephalopathy with intractable seizures, recurrent status epilepticus and cognitive decline. This meta-analysis 8

9 Citation stimulation in patients with Dravet syndrome: A metaanalysis of 68 patients FDA (2017) Summary of safety and effectiveness data (SSED). VNS Therapy System. Sourbron (2017) Vagus nerve stimulation in children: A focus on intellectual disability Sprengers (2017) Deep brain and cortical stimulation for epilepsy Hayes (2016) AspireSR Model 106 (Cyberonics) for vagus nerve stimulation Hayes (2016) Content, Methods, Recommendations included 13 studies comprising 68 patients. Over half (52.9%) of patients experienced more than 50% reduction of seizures. The average seizure reduction was 50.8%, but this could only be assessed in 28 patients. Several studies (seven of 13 studies) reported additional treatment benefits; however, these could not be assessed systematically due to limitations in the data. Among those with Dravet syndrome, vagus nerve stimulation appears to reduce seizure frequency. The authors suggest that controlled trials of VNS in this rare condition using patient-centric outcome measures are indicated. This supplement expands the indication. This meta-analysis examined the findings of seven studies that analyzed vagus nerve stimulation for children with epilepsy, among children with and without intellectual disabilities. This analysis found that vagus nerve stimulation was less effective at treating pediatric epilepsy among children with intellectual disabilities than it was among those without intellectual disabilities (Mantel-Haenszel meta-analysis; p = 0.028, odds ratio 0.18, 95%, confidence interval 95% 0.039, 0.84). Improvement in QOL was demonstrated in numerous studies. The most frequent adverse events reported were transient and well tolerated. No side effects were reported on cognition and behavior. The authors state that the results suggest that vagus nerve stimulation should be considered early on in the treatment of this subgroup. Numerous sources of bias include a preponderance of retrospective studies, differences in follow-up, lack of control arms, heterogeneous series, and a limited number of participants. No trials comparing intracranial stimulation to best medical practice, surgery, or vagus nerve stimulation have been published. Insufficient evidence exists regarding the AspireSR Model 106 vagus nerve stimulation by Cyberonics. In small clinical studies, the device appears to perform as expected in patients who received automatically delivered stimulation. Larger outcome studies are needed. Maestro Rechargeable System (EnteroMedics Inc.) for vagal blocking for Insufficient evidence exists regarding the Maestro Rechargeable System for controlling obesity: o One fair-quality double-blind RCT (n=294) compared active and sham treatment with the Maestro device for 9 hours daily. o A second fair-quality double-blind RCT (n=239) compared active and sham treatment 9

10 Citation obesity control Hayes (2016) Vagus nerve stimulation for depression Hayes (2015) Content, Methods, Recommendations with the Maestro device for 12 hours daily. o A very-poor-quality prospective case series (n=28) involved treatment of obese patients with type 2 diabetes with the Maestro device for 12 to 15 (mean, 14) hours daily. There have been no studies to date that have demonstrated improved health outcomes with the use of vagus nerve stimulation when compared to other treatment modalities for depression. A systematic review with 235 participants revealed no statistical differences between the control and the placebo groups, citing insufficient data to confirm that vagus nerve stimulation was or was not effective in the treatment of depression. The APA practice guideline for the treatment of major depressive disorders states that electroconvulsive therapy remains the best established efficacy above other stimulation therapies. Vagus nerve stimulation for epilepsy Vagus nerve stimulation can reduce seizure frequency, with 14 percent to 79 percent of patients experiencing at least a 50 percent mean reduction. A portion of this treatment benefit can be attributed to a placebo response. The treatment benefit is maintained for up to 13 years. Indicated for intractable partial seizures classified as simple, complex, or secondarily generalized. References Professional society guidelines/other: Fisher R, Handforth A. Reassessment: VNS for epilepsy: a report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (AAN). Neurology. 1999; 53: Reaffirmed October 17, Gelenberg AJ, Freeman MP, Markowitz JC, et al. American Psychiatric Association (APA). Practice guideline for the treatment of patients with major depressive disorder. Third edition. October 2010; reaffirmed October Accessed March 14, Hayes Inc., Hayes Health Clinical Research Response. AspireSR Model 106 (Cyberonics) for Vagus Nerve Stimulation. Lansdale, Pa. Hayes Inc.; February Hayes Inc., Hayes Health Medical Technology Report. Vagus Nerve Stimulation for Epilepsy. Lansdale, Pa. Hayes Inc.; May Hayes Inc., Hayes Health Technology Brief. Maestro Rechargeable System (EnteroMedics Inc.) for Vagal Blocking for Obesity Control. Lansdale, Pa. Hayes Inc.; February

11 Hayes Inc., Hayes Health Technology Brief. Vagus Nerve Stimulation for Depression. Lansdale, Pa. Hayes Inc.; August Institute for Clinical Systems Improvement. Adult Depression in Primary Care. Updated March more/catalog_guidelines_and_more/catalog_guidelines/catalog_behavio ral_health_guidelines/depression/. Accessed March 2, Kennedy SH, Milev R, Giacobbe P, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults: IV. Neurostimulation therapies. J Affect Disord. 2009; 117:S44-S53. National Institute for Health and Clinical Excellence (NICE). IPG050 Vagus nerve stimulation for refractory epilepsy in children guidance. NICE website. Accessed March 2, National Institute for Health and Clinical Excellence (NICE). Vagus nerve stimulation for treatment-resistant depression. December Accessed March 2, National Institute of Neurological Disorders and Stroke (NINDS). National Institutes of Health. NINDS epilepsy information page. NINDS website. Updated April 3, Disorders/Epilepsy-Information-Page. Accessed March 14, U.S. Food and Drug Administration (FDA). New Device Approval VNS Therapy System. P970003/S050. Updated June 23, Accessed March 2, Peer-reviewed references: Amar, A., Apuzzo, M., Liu C. Vagus nerve stimulation therapy after failed cranial surgery for intractable epilepsy: results from the vagus nerve stimulation therapy patient outcome registry. Neurosurgery. 2008; 62 Suppl 2: Bajbouj M, Merkl A, Schlaepfer TE, et al. Two-year outcome of vagus nerve stimulation in treatmentresistant depression. J Clin Psychopharmacol. 2010; 30(3): Bauer M, Pfennig A, Severus E, Whybrow PC, Angst J, Moller HJ. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders. World J Biol Psychiatry. 2013; 14(5): Boon P, De Cock E, Mertens A, Trinka E. Neurostimulation for drug-resistant epilepsy: a systematic review of clinical evidence for efficacy, safety, contraindications and predictors for response. Curr Opin Neurol. 2018;31(2):

12 Cimpianu CL, Strube W, Falkai P, Palm U, Hasan A. Vagus nerve stimulation in psychiatry: a systematic review of the available evidence. J Neural Transm (Vienna). 2017;124(1): Daban C, Martinez-Aran A, Cruz N, Vieta E. Safety and efficacy of vagus nerve stimulation in treatmentresistant depression. A systematic review. J Affect Disord. 2008; 110(1-2):1-15. Dibué-Adjei M, Fischer I, Steiger HJ, Kamp MA. Efficacy of adjunctive vagus nerve stimulation in patients with Dravet syndrome: A meta-analysis of 68 patients. Seizure. 2017;50: Englot DJ, Chang EF, Auguste KI. Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response. J Neurosurg. 2011; 115(6): (a) Englot DJ, Chang EF, Auguste KI. Efficacy of vagus nerve stimulation for epilepsy by patient age, epilepsy duration, and seizure type. Neurosurg Clin N Am. 2011; 22(4):443-8, v. (b) Gaynes BN, Lux L, Lloyd S, Hansen RA, Gartlehner G, Thieda P, et al. Nonpharmacologic Interventions for Treatment-Resistant Depression in Adults. Comparative Effectiveness Review No. 33. (Prepared by RTI International-University of North Carolina (RTI-UNC) Evidence based Practice Center under Contract No I.) AHRQ Publication No. 11-EHC056-EF. Rockville, MD: Agency for Healthcare Research and Quality. April 2016 Update. Accessed March 2, George MS, Aston-Jones G. Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tdcs). Neuropsychopharmacology. 2010; 35(1): Gurbani S, Chayasirisobhon S, Cahan L, et al. Neuromodulation Therapy with Vagus Nerve Stimulation for Intractable Epilepsy: A 2-Year Efficacy Analysis Study in Patients under 12 Years of Age. Epilepsy Res Treat. 2016: Heck C, Helmers S, DeGiorgio. VNS therapy, epilepsy, and device parameters: scientific parameters and recommendations for use. Neurology. 2002; 59(6):1-12. Helmers SL, Duh MS, Guerin A, et al. Clinical and economic impact of vagus nerve stimulation therapy in patients with drug-resistant epilepsy. Epilepsy & behavior: E&B. 2011;22(2): Klinkenberg S, van den Bosch CN, Majoie HJ, et al. Behavioural and cognitive effects during vagus nerve stimulation in children with intractable epilepsy a randomized controlled trial. Eur J Paediatr Neurol. 2013; 17(1): Kostov H, Larsson PG, Roste GK. Is vagus nerve stimulation a treatment option for patients with drugresistant idiopathic generalized epilepsy? Acta Neurol Scand Suppl. 2007; 187:

13 Majoie HJ, Berfelo MW, Aldenkamp AP, Evers SM, Kessels AG, Renier WO. Vagus nerve stimulation in children with therapy-resistant epilepsy diagnosed as Lennox-Gastaut syndrome: clinical results, neuropsychological effects, and cost-effectiveness. Journal of clinical neurophysiology. 2001;18(5): Mark D. Vagus nerve stimulation for treatment-resistant depression. Chicago, IL, USA: Blue Cross and Blue Shield Association, Technology Evaluation Center. TEC Assessment Program; 21(7) Martin JL, Martin-Sanchez E. Systematic review and meta-analysis of vagus nerve stimulation in the treatment of depression: variable results based on study designs. Eur Psychiatry. 2012; 27(3): Montavont A, Demarquay G, Ryvlin P, et al. Long-term efficiency of vagus nerve stimulation (VNS) in nonsurgical refractory epilepsies in adolescents and adults [article in French]. Rev Neurol (Paris). 2007; 163(12): Osoegawa C, Gomes JS, Grigolon RB, et al. Non-invasive brain stimulation for negative symptoms in schizophrenia: An updated systematic review and meta-analysis. Schizophr Res Romero-Osorio O, Gil-Tamayo S, Narino D, Rosselli D. Changes in sleep patterns after vagus nerve stimulation, deep brain stimulation or epilepsy surgery: Systematic review of the literature. Seizure. 2018;56:4-8. Rush AJ, Marangell LB, Sackeim HA, et al. Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol Psychiatry. 2005; 58(5): Schlaepfer TE, Frick C, Zobel A, et al. Vagus nerve stimulation for depression: efficacy and safety in a European study. Psychol Med 2008; 38: Sourbron J, Klinkenberg S, Kessels A, Schelhaas HJ, Lagae L, Majoie M. Vagus Nerve Stimulation in children: A focus on intellectual disability. Eur J Paediatr Neurol. 2017;21(3): Sperling W, Reulbach U, Kornhuber J. Clinical benefits and cost effectiveness of vagus nerve stimulation in a long-term treatment of patients with major depression. Pharmacopsychiatry. 2009; 42(3): Sprengers M, Vonck K, Carrette E, Marson AG, Boon P. Deep brain and cortical stimulation for epilepsy. Cochrane Database Syst Rev. 2017;7:Cd Tecoma ES, Iragui VJ. Vagus nerve stimulation use and effect in epilepsy: what have we learned? Epilepsy Behavior. 2006; 8(1); You SJ, Kang HC, Kim HD, et al. Vagus nerve stimulation in intractable childhood epilepsy: a Korean multicenter experience. J Korean Med Sci. 2007; 22(3):

14 CMS National Coverage Determinations (NCDs): Vagus Nerve Stimulation (VNS). CMS Medicare Coverage Database website. p=title&keywordlookup=title&keywordsearchtype=and&keywordsearchtype=and&bc=gaaaacaaaaa A&. Accessed March 2, Electrical Nerve Stimulators. CMS Medicare Coverage Database website. yword=nerve&keywordlookup=title&keywordsearchtype=and&list_type=ncd&bc=gaaaacaaaaaaaa% 3d%3d&. Accessed March 2, Assessing Patient's Suitability for Electrical Nerve Stimulation Therapy. CMS Medicare Coverage Database website. Word=nerve&KeyWordLookUp=Title&KeyWordSearchType=And&list_type=ncd&bc=gAAAACAAAAAAAA%3 d%3d&. Accessed March 2, Local Coverage Determinations (LCDs): No LCDs identified as of the writing of this policy. Commonly submitted codes Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is not an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and bill accordingly. CPT Code Description Comments Insertion or replacement of cranial neurostimulator pulse generator or receiver, direct or inductive coupling; with connection to a single electrode array Insertion or replacement of cranial neurostimulator pulse generator or receiver, direct or inductive coupling; with connection to two or more electrode arrays Revision or removal of cranial neurostimulator pulse generator or receiver Percutaneous implantation of neurostimulator electrode array; cranial nerve Incision for implantation of cranial nerve (e.g., vagus nerve) neurostimulator electrode array and pulse generator Revision or replacement of cranial nerve (e.g., vagus nerve) neurostimulator electrode array, including connection to existing pulse generator Removal of cranial nerve (e.g., vagus nerve neurostimulator electrode array and pulse generator Revision or removal of peripheral neurostimulator electrode array. 14

15 CPT Code Description Comments Electronic analysis of implanted neurostimulator pulse generator system (e.g., rate, pulse amplitude, pulse duration, configuration of wave form, battery status, electrode selectability, output modulation, cycling, impedance and patient compliance measurements); simple or complex brain, spinal cord, or peripheral (i.e., cranial nerve, peripheral nerve, sacral nerve, neuromuscular) neurostimulator pulse generator/transmitter, without reprogramming Complex cranial nerve neurostimulator pulse generator/transmitter, with intraoperative or subsequent programming, with or without nerve interface testing, first hour Complex cranial nerve neurostimulator pulse generator/transmitter, with intraoperative or subsequent programming, each additional 30 minutes after first hour (list separately in addition to code for primary procedure). ICD-10 Code Description Comments G Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, intractable, with status epilepticus. G Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, intractable, without status epilepticus. G Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, intractable, with status epilepticus. G Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, intractable, without status epilepticus. G Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, intractable, with status epilepticus. G Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, intractable, without status epilepticus. G Generalized idiopathic epilepsy and epileptic syndromes, intractable, with status epilepticus. G Generalized idiopathic epilepsy and epileptic syndromes, intractable, without status epilepticus. G Other generalized epilepsy and epileptic syndromes, intractable, with status epilepticus. G Other generalized epilepsy and epileptic syndromes, intractable, without status epilepticus. G Other epilepsy, intractable, with status epilepticus. G Other epilepsy, intractable, without status epilepticus. G Lennox-Gastaut syndrome, not intractable, with status epilepticus. G Lennox-Gastaut syndrome, intractable, with status epilepticus. G Lennox-Gastaut syndrome, intractable, without status epilepticus. G Epileptic spasms, intractable, with status epilepticus. G Epileptic spasms, intractable, without status epilepticus. G Epilepsy, unspecified, intractable, with status epilepticus. G Epilepsy, unspecified, intractable, without status epilepticus. G40.A11 Absence epileptic syndrome, intractable, with status epilepticus. G40.A19 Absence epileptic syndrome, intractable, without status epilepticus. G40.B11 Juvenile myoclonic epilepsy, intractable, with status epilepticus. G40.B19 Juvenile myoclonic epilepsy, intractable, without status epilepticus. R56.9 Unspecified convulsions. 15

16 HCPCS Level II Code N/A Description No applicable codes Comments 16