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Vagus Nerve Stimulation

Policy Number: MP-260

Latest Review Date: February 2022

Category:  Surgery                                                                 

POLICY:

Vagus Nerve Stimulation (VNS) may be considered medically necessary as a treatment of medically refractory seizures.

Vagus Nerve Stimulation (VNS) is considered investigational as a treatment of all other conditions including but not limited to:  essential tremor, headaches, depression, obesity, Alzheimer’s disease, chronic heart failure, upper-limb impairment due to stroke, fibromyalgia, tinnitus and traumatic brain injury.

Transcutaneous non-implantable vagus nerve stimulation is considered not medically necessary and investigational for all indications.

POLICY GUIDELINES:

Medically refractory seizures are defined as seizures that occur despite therapeutic levels of antiepileptic drugs or seizures that cannot be treated with therapeutic levels of antiepileptic drugs because of intolerable adverse events of these drugs.

Vagus nerve stimulation has been evaluated for the treatment of obesity. This indication is addressed in Medical Policy# 598- Vagus Nerve Blocking Therapy for Treatment of Obesity.

DESCRIPTION OF PROCEDURE OR SERVICE:

Stimulation of the vagus nerve can be performed by means of a pulsed electrical stimulator implanted within the carotid artery sheath. This technique has been proposed as a treatment for refractory seizures, depression, and other disorders. There are also devices available that are implanted at different areas of the vagus nerve. This policy also addresses devices that stimulate the vagus nerve transcutaneously.

Vagus Nerve Stimulation

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 generalized seizures, and it has been investigated for a range of other conditions.

While the mechanisms for the antiepileptic effects of vagal nerve stimulation are not fully understood, the basic premise of VNS in the treatment of epilepsy is that vagal visceral afferents have a diffuse central nervous system projection, and activation of these pathways has a widespread effect on neuronal excitability. Electrical stimulus 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. There are also vagal efferent pathways that innervate the heart, vocal cords, and other laryngeal and pharyngeal muscles, and provide parasympathetic innervation to the gastrointestinal tract that may also be stimulated by VNS.

The type of VNS device addressed in this policy consists of an implantable, programmable electronic pulse generator that delivers stimulation to the left vagus nerve at the carotid sheath. The pulse generator is connected to the vagus nerve via a bipolar electrical lead. Surgery for implantation of a vagal nerve stimulator involves implantation of the pulse generator in the infraclavicular region and wrapping two spiral electrodes around the left vagus nerve within the carotid sheath. The programmable stimulator may be programmed in advance to stimulate at regular times or on demand by patients or family by placing a magnet against the subclavicular implant site.

Other types of vagus nerve stimulators that are placed in contact with the trunks of the vagus nerve at the gastroesophageal junction are not addressed in this policy.

KEY POINTS:

The most recent update covered the period through January 3, 2022.

Summary of Evidence

Implantable Vagus Nerve Stimulation

For individuals who have seizures refractory to medical treatment who receive vagus nerve stimulation (VNS), the evidence includes randomized controlled trials (RCTs) and multiple observational studies. Relevant outcomes are symptoms, change in disease status, and functional outcomes. The RCTs have reported a significant reduction in seizure frequency for patients with partial-onset seizures. The uncontrolled studies have consistently reported large reductions for a broader range of seizure types in both adults and children. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have treatment-resistant depression who receive VNS, the evidence includes 2 RCTs evaluating the efficacy of implanted VNS for treatment-resistant depression compared to sham, 1 RCT comparing therapeutic to low-dose implanted VNS, nonrandomized comparative studies, and case series. Relevant outcomes are symptoms, change in disease status, and functional outcomes. The sham-controlled RCTs only reported short-term results and found no significant improvement in the primary outcome. The low-dose VNS controlled trial reported no statistically significant differences between the dose groups for change in depression symptom score from baseline. Other available studies are limited by small sample sizes, potential selection and confounding biases, and lack of a control group in the case series. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have chronic heart failure who receive VNS, the evidence includes a systematic review including 4 RCTs and case series. Relevant outcomes are symptoms, change in disease status, and functional outcomes. Meta-analyses of the RCTs evaluating chronic heart failure found significant improvements in New York Heart Association functional class, quality of life, 6-minute walk-test, and N-terminal-pro brain natriuretic peptide levels in patients treated with VNS compared to control. An analysis of the ANTHEM-HF uncontrolled trial evaluated longer-term outcomes of VNS use in chronic heart failure. They found that left ventricular (LV) ejection fraction improved by 18.7%, 19.3%, and 34.4% at 12, 24, and 36 months, respectively, with high-intensity VNS. Individuals with low-intensity VNS only had significant improvement in LV ejection fraction at 24 months (12.3%). Although this data is promising, a lack of a no-VNS comparator group precludes drawing conclusions based on findings from the uncontrolled studies. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have upper-limb impairment due to stroke who receive VNS, the evidence includes 3 pilot RCTs. Relevant outcomes are symptoms, change in disease status, and functional outcomes. Two RCTs compared VNS plus rehabilitation to rehabilitation alone; 1 failed to show significant improvements for the VNS group on response and function outcomes, but the other, which had a larger patient population, found a significant difference in response and function outcomes. The other RCT compared VNS to sham and found that although VNS significantly improved response rate, there were 3 serious adverse events related to surgery. Longer-term follow-up studies are needed to evaluate long-term efficacy and safety. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have essential tremor, headache, fibromyalgia, autism, or tinnitus who receive VNS, the evidence includes case series. Relevant outcomes are symptoms, change in disease status, and functional outcomes. Case series are insufficient to make conclusions regarding efficacy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Transcutaneous Vagus Nerve Stimulation

For individuals with cluster headaches who receive transcutaneous VNS to prevent cluster headaches, the evidence includes one RCT. Relevant outcomes are symptoms, change in disease status, quality of life and functional outcomes. One RCT for prevention of cluster headache showed a reduction in headache frequency but did not include a sham treatment group. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with cluster headache who receive noninvasive transcutaneous VNS (nVNS) to treat acute cluster headache, the evidence includes RCTs. Relevant outcomes are symptoms, change in disease status, quality of life and functional outcomes. (ACT1) and (ACT2) RCTs compared nVNS to sham for treatment of acute cluster headache in patients including both chronic and episodic cluster headache. In ACT1, there was no statistically significant difference in the overall population in the proportion of patients with pain score of 0 or 1 at 15 minutes into the first attack and no difference in the proportion of patients who were pain-free at 15 minutes in 50% or more of the attacks. In the episodic cluster headache subgroup (n=85) both outcomes were statistically significant favoring nVNS although the interaction p-value was not reported. In ACT2, the proportion of attacks with pain intensity score of 0 or 1 at 30 minutes was higher for nVNS in the overall population (43% vs. 28%, p=0.05) while the proportion of attacks that were pain-free at 15 minutes was similar in the 2 treatment groups in the overall population (14% vs. 12%). However, a statistically significantly higher proportion of attacks in the episodic subgroup (n=27) were pain-free at 15 minutes in the nNVS group compared to sham (48% vs. 6%, p<0.01). These studies suggest that people with episodic and chronic cluster headaches may respond differently to acute treatment with nVNS. Studies designed to focus on episodic cluster headache are needed. The measurements of quality of life and functional outcomes have not been reported. Treatment periods ranged from only 2 weeks to 1 month with extended open-label follow-up of up to 3 months. There are few adverse events of nVNS and they are mild and transient. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with migraine headache who receive nVNS to treat acute migraine headache, the evidence includes 1 RCT. Relevant outcomes are symptoms, change in disease status, quality of life and functional outcomes. One RCT has evaluated nNVS for acute treatment of migraine with nVNS in 248 patients with episodic migraine with/without aura. There was not a statistically significant difference in the primary outcome of the proportion of participants who were pain-free without using rescue medication at 120 minutes (30% vs. 20%; p = 0.07). However, the nVNS group had a higher proportion of patients with decrease in pain from moderate or severe to mild or no pain at 120 minutes (41% vs. 28%; p=0.03) and a higher proportion of patients who were pain-free at 120 for 50% or more of their attacks (32% vs. 18%; p=0.02). There are few adverse events of nVNS and they are mild and transient. The measurements of quality of life and functional outcomes were not reported and the double-blind treatment period was 4 weeks with an additional four weeks of open-label treatment. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with chronic migraine headache who receive nVNS to prevent migraine headache, the evidence includes two RCTs. The relevant outcomes are symptoms, change in disease status, quality of life and functional outcomes. The (EVENT) RCT was a feasibility study of prevention of migraine that was not powered to detect differences in efficacy outcomes. It does not demonstrate the efficacy of nVNS for prevention of migraine. The (PREMIUM) RCT was a phase 3, multicenter, sham-controlled RCT including 341 randomized participants with a 12-week double-blind treatment period. The results of PREMIUM demonstrated that nVNS was not statistically significantly superior to sham. with respect to the outcomes of reduction of at least 50% in migraine days from baseline to the last 4 weeks, reduction in number of migraine days from baseline to the last 4 weeks or acute medication days. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have other neurologic, psychiatric, or metabolic disorders (eg, epilepsy, depression, schizophrenia, noncluster headache, impaired glucose tolerance) who receive transcutaneous VNS, the evidence includes RCTs and case series for some of the conditions. Relevant outcomes are symptoms, change in disease status, and functional outcomes. The RCTs are all small and have various methodologic problems. None showed definitive efficacy of transcutaneous VNS in improving patient outcomes. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Practice Guidelines and Position Statements

American Academy of Neurology

In 1999, the American Academy of Neurology released a consensus statement on the use of vagus nerve stimulation (VNS) in adults, which 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. The guidelines were updated in 2013 and reaffirmed in 2019, stating: “VNS may be considered for seizures in children, for LGS [Lennox-Gastaut syndrome]-associated seizures, and for improving mood in adults with epilepsy (Level C). VNS may be considered to have improved efficacy over time (Level C).

American Psychiatric Association

Updated in 2010, the American Psychiatric Association guidelines on the treatment of major depressive disorder in adults, 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, including ECT [Electroconvulsive therapy],” with a level of evidence III (May be recommended on the basis of individual circumstances).

National Institute for Health and Care Excellence

The National Institute for Health and Care Excellence issued guidance on use of transcutaneous  stimulation of the cervical branch of the vagus nerve for cluster headache and migraine in 2016 (IPG552).  The guidance states: “Current evidence on the safety of transcutaneous stimulation of the cervical branch of the vagus nerve for cluster headache and migraine raises no major concerns. The evidence on efficacy is limited in quantity and quality.” The guidance also comments that further research is needed to clarify whether the procedure is used for treatment or prevention, for cluster headache or migraine, appropriate patient selection, and treatment regimen and suggests that outcome measures should include changes in the number and severity of cluster headache or migraine episodes, medication use, quality of life in the short and long term, side effects, acceptability, and device durability.

NICE also published a Medtech innovation briefing in 2018 on nVNS for cluster headache (MIB162). The briefing states that the 'intended place in therapy would be as well as standard care, most likely where standard treatments for cluster headache are ineffective, not tolerated or contraindicated' and that key uncertainties around the evidence are that 'people with episodic and chronic cluster headaches respond differently to treatment with gammaCore. The optimal use of gammaCore in the different populations in unclear. The NICE published a Medical technologies guidance [MTG46] on gammaCore for cluster headache in December 2019. The recommendations state that evidence supports using gammaCore to treat cluster headache and that gammaCore is not effective in everyone with cluster headache.

In 2020, the NICE published an Interventional Procedure Overview on implanted vagus nerve stimulation for treatment-resistant depression (IPG679). The guidance states: "Evidence on the safety of implanted vagus nerve stimulation for treatment-resistant depression raises no major safety concerns, but there are frequent, well-recognized side effects. Evidence on its efficacy is limited in quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research." The guidance further states that "NICE encourages further research into implanted vagus nerve stimulation for treatment-resistant depression, in the form of randomized controlled trials with a placebo or sham stimulation arm. Studies should report details of patient selection. Outcomes should include validated depression rating scales, patient-reported quality of life, time to onset of effect and duration of effect, and any changes in concurrent treatment."

U.S. Preventive Services Task Force Recommendations

Not applicable.

KEY WORDS:

Vagus nerve stimulation (VNS), partial-onset seizures, depression, headaches, essential tremor, Alzheimer’s disease, VNS (t-VNS®), VNS (gammaCore®) Non-implantable Vagus Nerve stimulation, Maestro® System, transcutaneous vagus nerve stimulation, AspireSR®, NeuroCybernetic Prosthesis (NCP®), Sapphire D, GammaCore Sapphire CV, nVNS

APPROVED BY GOVERNING BODIES:

In 1997, the NeuroCybernetic Prosthesis (NCP®) System, a vagus nerve stimulation (VNS) device, was approved by the U.S. Food and Drug Administration (FDA) through the premarket approval (PMA) process. The device was approved for use in conjunction with drugs or surgery “as an adjunctive treatment of adults and adolescents over 12 years of age with medically refractory partial onset seizures.” There have been subsequent expanded approvals.

In May 2015, a related VNS therapy, AspireSR® (LivaNova), received supplemental premarketing approval from FDA, although the device was recalled in August 2017. The AspireSR® device detects high heart rates associated with seizures and responds with stimulation. Adjunctive use of the AspireSR® for the treatment of epileptic seizures was indicated for patients over 4 years of age who suffer from partial-onset seizures that do not respond to antiepileptic medication.

On May 30, 2017, the gammaCore-S (electroCore® LLC), a noninvasive vagus nerve stimulation device, was cleared for marketing through the 510(K) process (K171306) for the acute treatment of adults with episodic cluster headaches. When the device is applied to the side of the neck by the patient, a mild electrical stimulation of the vagus nerve is carried to the central nervous system. Each stimulation using gammaCore-S lasts 2 minutes. The patient controls the stimulation strength.

Cerbomed has developed a transcutaneous VNS (t-VNS®) 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 electric stimulation for several hours a day; no surgical procedure is required. The device received the CE mark in Europe in 2011, but has not been FDA approved for use in the United States. Electrocore has developed a noninvasive VNS (gammaCore®) that is currently being investigated for headache; the device does not have FDA approval.

Table 1 includes updates on FDA approval and clearance for VNS devices. This table also includes the updates pertinent to this evidence review.

Table 1. FDA-Approved or -Cleared Vagus Nerve Stimulators

Device Name

Manufacturer

Approved/Cleared

PMA/510(k)

Product Code(s)

Indications

 

NeuroCybernetic Prosthesis (NCP®)

LIvaNov(Cyberonics)

1997

P970003

 

Indicated or adjunctive treatment of adults and adolescents >12 y of age with medically refractory partial-onset seizures

 

 

 

2005

P970003/S50

 

Expanded indication for adjunctive long-term treatment of chronic or recurrent depression for patients ≥18 y of age experiencing a major depressive episode and have not had an adequate response to ≥4 adequate antidepressant treatments

 

 

 

2017

P970003/S207

 

Expanded indicated use as adjunctive therapy for seizures in patients ≥4 y of age with partial-onset seizures that are refractory to antiepileptic medications

 

GammaCore®

ElectroCore

2017/2018

DEN150048/K171306/K173442

PKR, QAK

Indicated for acute treatment of pain associated with episodic cluster and migraine headache in adults using noninvasive VNS on the side of the neck

 

GammaCore-2®,GammaCore-Sapphire®

ElectroCore

2017/2018

K172270/K180538/K182369

PKR

Indicated for:

Adjunctive use for the preventive treatment of cluster headache in adult patients.

The acute treatment of pain associated with episodic cluster headache in adult patients.

The acute treatment of pain associated with migraine headache in adult patients. 

 

GammaCore Sapphire CV

electroCore, Inc.

EUA

N/A

N/A

Indicated  for:

Adult patients with known or suspected COVID-19 who are experiencing exacerbation of asthma-related dyspnea and reduced airflow, and for whom approved drug therapies are not tolerated or provide insufficient symptom relief as assessed by their healthcare provider, using non-invasive VNS on either side of the patient’s neck during the COVID-19 pandemic.

 

FDA: Food and Drug Administration; PMA: premarket approval; VNS: vagus nerve stimulation.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP contracts: FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.  Special benefit consideration may apply.  Refer to member’s benefit plan.

CURRENT CODING: 

CPT Codes:    

61885

Insertion or replacement of cranial neurostimulator pulse generator or receiver, direct or inductive coupling; with connection to a single electrode array

61886

Insertion or replacement of cranial neurostimulator pulse generator or receiver, direct or inductive coupling; with connection to two or more electrode arrays  

64553

Percutaneous implantation of neurostimulator electrodes array; cranial nerve

64568

Open implantation of cranial nerve (eg, vagus nerve) neurostimulator electrode array and pulse generator

64569

Revision or replacement of cranial nerve (e.g., Vagus nerve) neurostimulator electrode array.  Including connection to pulse generator

64570

Removal of cranial nerve (e.g., vagus nerve) Neurostimulator electrode array and pulse generator

95976

Electronic analysis of implanted neurostimulator pulse generator/transmitter (e.g., contact group[s], interleaving, amplitude, pulse width, frequency [Hz], on/off cycling, burst, magnet mode, dose lockout, patient selectable parameters, responsive neurostimulation, detection algorithms, closed loop parameters, and passive parameters) by physician or other qualified health care professional; with simple cranial nerve neurostimulator pulse generator/transmitter programming by physician or other qualified health care professional (Effective 01/01/2019)

95977

Electronic analysis of implanted neurostimulator pulse generator/transmitter (eg, contact group[s], interleaving, amplitude, pulse width, frequency [Hz], on/off cycling, burst, magnet mode, dose lockout, patient selectable parameters, responsive neurostimulation, detection algorithms, closed loop parameters, and passive parameters) by physician or other qualified health care professional; with complex cranial nerve neurostimulator pulse generator/transmitter programming by physician or other qualified health care professional (Effective 01/01/2019)

HCPCS:

K1020

Non-invasive vagus nerve stimulator (Effective 4/01/21)

L8680

Implantable neurostimulator electrode (with any number of contact points), each

L8681

Patient programmer (external) for use with implantable programmable neurostimulator pulse generator, replacement only

L8682

Implantable neurostimulator radiofrequency receiver

L8683

Radiofrequency transmitter (external) for use with implantable neurostimulator radiofrequency receiver

L8684

Radiofrequency transmitter (external) for use with implantable sacral root neurostimulator receiver for bowel and bladder management, replacement

L8685

Implantable neurostimulator pulse generator, single array, rechargeable, includes extension

L8686

Implantable neurostimulator pulse generator, single array, non-rechargeable, includes extension

L8687

Implantable neurostimulator pulse generator, dual array, rechargeable, includes extension

L8688

Implantable neurostimulator pulse generator, dual array, non-rechargeable, includes extension

L8689

External recharging system for battery (internal) for use with implantable neurostimulator, replacement only

PREVIOUS CODING:

95974

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); complex cranial nerve neurostimulator pulse generator/transmitter, with intraoperative or subsequent programming, with or without nerve interface testing, first hour (Deleted 12/31/18)

95975

; with intraoperative or subsequent programming each additional 30 minutes after the first hour (list separately in addition to code for primary procedure) hour (Deleted 12/31/18)

REFERENCES:

  1. Aaronson ST, Carpenter LL, Conway CR et al. Vagus nerve stimulation therapy randomized to different amounts of electrical charge for treatment-resistant depression: acute and chronic effects. Brain Stimul 2013; 6(4):631-40.

  2. Aaronson ST, Sears P, Ruvuna F, et al. A 5-Year Observational Study of Patients With Treatment-Resistant Depression Treated WithVagus Nerve Stimulation or Treatment as Usual: Comparison of Response, Remission, and Suicidality. Am J Psychiatry. Jul 01 2017; 174(7): 640-648.

  3. Aihua L, Lu S, Liping L, et al. A controlled trial of transcutaneous vagus nerve stimulation for the treatment of pharmacoresistant epilepsy. Epilepsy Behav. Oct 2014; 39:105-110.

  4. Amar AP, Heck CN, Levy ML, et al. An institutional experience with cervical vagus nerve trunk stimulation for medically refractory epilepsy: rationale, technique, and outcome. Neurosurgery. Dec 1998; 43(6):1265-1276; discussion 1276-1280.

  5. Amar AP, et al.  Vagus nerve stimulation for control of intractable seizures in childhood, Pediatric Neurosurgery, April 2001; 34(4): 218-223.

  6. Amar AP, et al.  Vagus nerve stimulation therapy after failed cranial surgery for intractable epilepsy:  Results from the vagus nerve stimulation therapy patient outcome registry, Neurosurgery, November 2004; 55(5): 1086-1093.

  7. Amar AP, et al.  Vagus nerve stimulation therapy for patients with persistent seizures after epilepsy, Stereotactic and Functional Neurosurgery, January 2003; 80(1-4): 9-13.

  8. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 2010; Third. Available online at: psychiatryonline.org/pdfaccess.ashx?ResourceID=243261&PDFSource=6. Last accessed February 20, 2014.

  9. Ardesch JJ, Buschman HP, Wagener-Schimmel LJ, et al. Vagus nerve stimulation for medically refractory epilepsy: a long-term follow-up study. Seizure. Oct 2007; 16(7):579-585.

  10. Arya R, Greiner HM, Lewis A et al. Predictors of Response to Vagus Nerve Stimulation in Childhood-Onset Medically Refractory Epilepsy. J Child Neurol 2013

  11. Bajbouj M, Merkl A, Schlaepfer TE et al. Two-year outcome of vagus nerve stimulation in treatment-resistant depression. J Clin Psychopharmacol 2010; 30(3):273-81.

  12. Bauer S, Baier H, Baumgartner C, et al. Transcutaneous Vagus Nerve Stimulation (tVNS) for Treatment of Drug-Resistant Epilepsy: A Randomized, Double-Blind Clinical Trial (cMPsE02). Brain Stimul. May-Jun 2016; 9(3): 356-363.

  13. Berry SM, Broglio K, Bunker M et al. A patient-level meta-analysis of studies evaluating vagus nerve stimulation therapy for treatment-resistant depression. Med Devices (Auckl) 2013; 6:17-35.

  14. Ben-Menachem E, Hellstrom K, Waldton C, et al. Evaluation of refractory epilepsy treated with vagus nerve stimulation for up to 5 years. Neurology. Apr 12 1999; 52(6):1265-1267.

  15. Ben-Menachem E, Manon-Espaillat R, Ristanovic R, et al. Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures. First International Vagus Nerve Stimulation Study Group. Epilepsia. May-Jun 1994; 35(3):616-626.

  16. Blue Cross Blue Shield Association. Vagus nerve stimulation for treatment-resistant depression. Technology Evaluation Center Assessment Program, August 2005, Vol. 20, No. 8.

  17. Blue Cross Blue Shield Association.  Vagus nerve stimulation for treatment-resistant depression.  Technology Evaluation Center Assessment Program, August 2006, Vol. 21, No. 7.

  18. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Chronic vagus nerve stimulation for treatment of seizures. TEC Assessments 1998; Volume 13 Tab 9.

  19. Bodenlos JS, Kose S, Borckardt JJ, et al. Vagus nerve stimulation acutely alters food craving in adults with depression. Appetite 2007; 48(2):145-53.

  20. Bottomley JM, LeReun C, Diamantopoulos A, et al. Vagus nerve stimulation (VNS) therapy in patients with treatment resistant depression: A systematic review and meta-analysis. Compr Psychiatry. Dec 12 2019; 98: 152156.

  21. Centers for Medicare & Medicaid Services. NCD for Vagus Nerve Stimulation for Treatment of Seizures. Medicare Coverage Database, July 2007. www.cms.hhs.gov.

  22. Chavel SM, Westerveld M, Spencer S. Long-term outcome of vagus nerve stimulation for refractory partial epilepsy. Epilepsy Behav. Jun 2003; 4(3):302-309.

  23. Conway CR, Olin B, Aaronson ST, et al. A prospective, multi-center randomized, controlled, blinded trial of vagus nerve stimulation for difficult to treat depression: A novel design for a novel treatment. Contemp Clin Trials. Aug 2020; 95: 106066.

  24. Corcoran CD, Thomas P, Phillips J, et al. Vagus nerve stimulation in chronic treatment-resistant depression: preliminary findings of an open-label study. Br J Psychiatry 2006; 189:282-3. www.clinicaltrials.gov/.

  25. Corcoran Ciaran D, Thomas P, et al. Vagus nerve stimulation in chronic treatment-resistant depression: Preliminary findings of an open-label study. British Journal of Psychiatry 2006; 189: 282-283.

  26. Cristancho P, Cristancho MA, Baltuch GH et al. Effectiveness and safety of vagus nerve stimulation for severe treatment-resistant major depression in clinical practice after FDA approval: outcomes at 1 year. J Clin Psychiatry 2011; 72(10):1376-82.

  27. Critchley HD, Lewis PA, Orth M, et al. Vagus nerve stimulation for treatment-resistant depression: Behavioral and neural effects on encoding negative material. Psychosom Med, January 2007; 69(1): 17-22. (Abstract)

  28. Cukiert A, Cukiert CM, Burattini JA et al. A prospective long-term study on the outcome after vagus nerve stimulation at maximally tolerated current intensity in a cohort of children with refractory secondary generalized epilepsy. Neuromodulation 2013; 16(6):551-6.

  29. Daban C, Martinez-Aran A, Cruz N, et al.  Safety and efficacy of vagus nerve stimulation in treatment-resistant depression. A systematic review. J Affect Disord 2008; 110(1-2).

  30. Dawson J, Liu CY, Francisco GE, et al. Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial. Lancet. Apr 24 2021; 397(10284): 1545-1553.

  31. Dawson J, Pierce D, Dixit A, et al. Safety, feasibility, and efficacy of vagus nerve stimulation paired with upper- limb rehabilitation after ischemic stroke. Stroke. Jan 2016; 47(1):143-150.

  32. de Coo IF, Marin JC, Silberstein SD, et al. Differential efficacy of non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A meta-analysis. Cephalalgia, 2019 Jun 28; 39(8).

  33. De Ferrari GM, Crijns HJ, Borggrefe M, et al. Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure. EUR Heart J 2010 Nov 12. [Epub ahead of print] Available online at: eurheartj.oxfordjournals.org/content/ehj/32/7/847/full.pdf

  34. De Ferrari GM, Crijns HJ, Borggrefe M, et al. Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure. Eur Heart J. Apr 2011; 32(7):847-855. 

  35. DeGiorgio C, Heck C, Bunch S, et al. Vagus nerve stimulation for epilepsy: Randomized comparison of three stimulation paradigms. Neurology 2005; 65: 317-319.

  36. DeGiorgio CM, et al. Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures, Epilepsia, September 2000; 41(9): 1195-1200.

  37. De Ridder D, Vanneste S, Engineer ND et al. Safety and Efficacy of Vagus Nerve Stimulation Paired With Tones for the Treatment of Tinnitus: A Case Series. Neuromodulation 2013.

  38. Diener HC, Goadsby PJ, Ashina M, et al. Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine: The multicentre, double-blind, randomised, sham-controlled PREMIUM trial.. Cephalalgia, 2019 Sep 17; 39(12).

  39. Dougherty DD and Rauch SL. Somatic therapies for treatment-resistant depression: New neurotherapeutic interventions. Psychiatr Clin N Am 2007; 30: 31-37.

  40. Elger G, et al.  Vagus nerve stimulation is associated with mood improvements in epilepsy patients, Epilepsy Research, December 2000; 42(2-3): 203-210.

  41. Engineer CT, Hays SA, Kilgard MP. Vagus nerve stimulation as a potential adjuvant to behavioral therapy for autism and other neurodevelopmental disorders. J Neurodev Disord. 2017; 9:20.

  42. 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):1248-55.

  43. Englot DJ, Rolston JD, Wright CW, et al. Rates and predictors of seizure freedom with vagus nerve stimulation for intractable epilepsy. Neurosurgery. Sep 2016; 79(3):345-353.

  44. Fisher RS, Handforth A. Reassessment: vagus nerve stimulation for epilepsy: a report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 1999; 53(4):666-9.

  45. Fitzgerald PB and Daskalakis ZJ.  The use of repetitive transcranial magnetic stimulation and vagal nerve stimulation in the treatment of depression.  Curr Opin Psychiatry 2008; 21(1):25-9.

  46. Food and Drug Administration. Class 2 Device Recall Model 106 AspireSR Generators (P970003S173). 2017; https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRES/res.cfm?id=157567. Accessed January 25, 2018.

  47. Food and Drug Administration. Premarket Application Approval NeuroCybernetic. 2017; https://www.accessdata.fda.gov/cdrh_docs/pdf/p970003s207b.pdf. Accessed September 18, 2017.

  48. Food and Drug Administration. Premarket Approval Application gammaCore. 2017; https: //www.accessdata.fda.gov/cdrh_docs/pdf17/K171306.pdf. Accessed September 18, 2017.

  49. Food and Drug Administration. Summary of Safety and Effectiveness Data: VNS TherapyTM System. 2005; https://www.accessdata.fda.gov/cdrh_docs/pdf/p970003s050b.pdf. Accessed February 10, 2020.

  50. Food and Drug Administration. Letter of Authorization: gammaCore Sapphire CV. https://www.fda.gov/media/139967/download#:~:text=Healthcare%20Facilities%20and%20Healthcare%20Providers&text=M.,CV%20must%20make%20electroCore%2C%20Inc. Accessed April 15, 2021.

  51. Frost M, Gates J, Helmers SL, et al. Vagus nerve stimulation in children with refractory seizures associated with Lennox-Gastaut syndrome. Epilepsia. Sep 2001; 42(9):1148-1152.

  52. Garcia-Navarrete E, Torres CV, Gallego I et al. Long-term results of vagal nerve stimulation for adults with medication-resistant epilepsy who have been on unchanged antiepileptic medication. Seizure 2013; 22(1):9-13.

  53. Gaul C, Diener HC, Silver N, et al. Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): A randomised controlled study. Cephalalgia. May 2016; 36(6):534-546.

  54. Gaul, CC, Magis, DD, Liebler, EE, Straube, AA. Effects of non-invasive vagus nerve stimulation on attack frequency over time and expanded response rates in patients with chronic cluster headache: a post hoc analysis of the randomised, controlled PREVA study. NA.

  55. Gaynes BN, Asher G, Gartlehner G, Hoffman V, Green J, Boland E, Lux L, Weber RP, Randolph C, Bann C, Coker-Schwimmer E,Viswanathan M, Lohr KN. Definition of Treatment-Resistant Depression in the Medicare Population [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2018 Feb 9.

  56. George MS, et al.  A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression, Biological Psychiatry 2005; 58: 364-373.

  57. George MS, et al. Vagus nerve stimulation for the treatment of depression and other neuropsychiatric disorders.  Expert Rev Neurother 2007; 7(1): 63-74. (Abstract)

  58. Goadsby PJ, de Coo IF, Silver N, et al. Non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A randomized, double-blind, sham-controlled ACT2 study. Cephalalgia. Jan 1 2017:333102417744362.

  59. Goadsby PJ, Grosberg BM, Mauskop A, et al. Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study. Cephalalgia. Oct 2014; 34(12):986-993.

  60. Grazzi, LL, Egeo, GG, Calhoun, AA, McClure, CC, Liebler, EE, Barbanti, PP. Non-invasive Vagus Nerve Stimulation (nVNS) as mini-prophylaxis for menstrual/menstrually related migraine: an open-label study. NA. 

  61. Grazzi, LL, Tassorelli, CC, de Tommaso, MM, Pierangeli, GG, Martelletti, PP, Rainero, II, Geppetti, PP, Ambrosini, AA, Sarchielli, PP, Liebler, EE, Barbanti, PP, Tassorelli, CC, Bitetto, VV, De Icco, RR, Martinelli, DD, Sances, GG, Bianchi, MM, Grazzi, LL, Padovan, AA, de Tommaso, MM, Ricci, KK, Vecchio, EE, Cortelli, PP, Cevoli, SS, Pierangeli, GG, Terlizzi, RR, Martelletti, PP, Negro, AA, Chiariello, GG, Rainero, II, De Martino, PP, Gai, AA, Govone, FF, Masuzzo, FF, Rubino, EE, Torrieri, MM, Vacca, AA, Geppetti, PP, Chiarugi, AA, De Cesaris, FF, Puma, SS, Lupi, CC, Marone, II, Ambrosini, AA, Perrotta, AA, Sarchielli, PP, Bernetti, LL, Corbelli, II, Romoli, MM, Simoni, SS, Verzina, AA, Barbanti, PP, Aurilia, CC, Egeo, GG, Fofi, LL, Liebler, EE, Andersson, AA, Spitzer, LL, Marin, JJ, McClure, CC, Thackeray, LL, Baldi, MM, Di Maro, DD. Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: a post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial. J Headache Pain. 2019 Jan 7; 20(1):1. 

  62. Handforth A, DeGiorgio CM, Schachter SC, et al. Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology. Jul 1998; 51(1):48-55.

  63. Handforth A, et al.  Vagus nerve stimulation for essential tremor:  A pilot efficacy and safety trial, Neurology, November 2003; 61(10): 1401-1405.

  64. Hasan A, Wolff-Menzler C, Pfeiffer S, et al. Transcutaneous noninvasive vagus nerve stimulation (tVNS) in the treatment of schizophrenia: a bicentric randomized controlled pilot study. Eur Arch Psychiatry Clin Neurosci. Oct 2015; 265(7):589-600.

  65. He W, Jing X, Wang X et al. Transcutaneous auricular vagus nerve stimulation as a complementary therapy for pediatric epilepsy: a pilot trial. Epilepsy Behav 2013; 28(3):343-6.

  66. Healy S, Lang J, Te Water Naude J et al. Vagal nerve stimulation in children under 12 years old with medically intractable epilepsy. Childs Nerv. Syst. 2013; 29(11):2095-9.

  67. Hein E, Nowak M, Kiess O, et al. Auricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study. J Neural Transm. May 2013; 120(5):821-827.

  68. Hornig GW, et al.  Left vagus nerve stimulation in children with refractory epilepsy:  An update, Southern Medical Journal, May 1997; 90(5): 484-488.

  69. Hosain S, et al.  Vagus nerve stimulation treatment for Lennox-Gastaut syndrome, Journal of Child Neurology, August 2000; 15(8): 509-512.

  70. Hsieh T, Chen M, McAfee A, et al.  Sleep-related breathing disorder in children with vagal nerve stimulators.  Pediatr Neurol 2008; 38(2):99-103.

  71. Huang F, Dong J, Kong J, et al. Effect of transcutaneous auricular vagus nerve stimulation on impaired glucose tolerance: a pilot randomized study. BMC Complement Altern Med. 2014; 14:203.

  72. Huf RL, Mamelak A, Kneedy-Cayem K. Vagus nerve stimulation therapy: 2-year prospective open-label study of 40 subjects with refractory epilepsy and low IQ who are living in long-term care facilities. Epilepsy Behav. May 2005; 6(3):417-423.

  73. International Headache Society. International Classification of Headache Disorders. 2018; https://www.ichd-3.org. Accessed January 8, 2019.

  74. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.

  75. Jacobson:  Psychiatric Secrets, 2nd edition, Copyright © 2001 Hanley and Belfus.

  76. Kang HC, Hwang YS, Kim DS, et al. Vagus nerve stimulation in pediatric intractable epilepsy: a Korean bicentric study. Acta Neurochir Suppl. 2006; 99:93-96.

  77. Kimberley TJ, Pierce D, Prudente CN, et al. Vagus Nerve Stimulation Paired With Upper Limb Rehabilitation After Chronic Stroke. Stroke, 2018 Oct 26; 49(11). 

  78. Kinfe, TT, Pintea, BB, Muhammad, SS, Zaremba, SS, Roeske, SS, Simon, BB, Vatter, HH. Cervical non-invasive vagus nerve stimulation (nVNS) for preventive and acute treatment of episodic and chronic migraine and migraine-associated sleep disturbance: a prospective observational cohort study. NA.

  79. Kirse DJ, et al.  Vagus nerve stimulator implantation in children, Archives of Otolaryngology-Head and Neck Surgery, November 2002; 128(11): 1263-1268.

  80. Klinkenberg S, Aalbers MW, Vles JS, et al. Vagus nerve stimulation in children with intractable epilepsy: a randomized controlled trial. Dev Med Child Neurol. Sep 2012; 54(9):855-861.

  81. Klinkenberg S, van den Bosch CN, Majoie HJ et al. Behavioral and cognitive effects during vagus nerve stimulation in children with intractable epilepsy - a randomized controlled trial. Eur J Paediatr Neurol 2013; 17(1):82-90.

  82. Kosel M, et al.  Beyond the treatment of epilepsy:  New applications of vagus nerve stimulation in psychiatry, CNS Spectrum, July 2003; 8(7): 515-521.

  83. Kostov H, Larsson PG and Roste GK.  Is vagus nerve stimulation a treatment option for patients with drug-resistant idiopathic generalized epilepsy? Acta Neurol Scand Suppl 2007; 187:55-8.

  84. Kostov H, Larsson PG, et al.  Is vagus nerve stimulation a treatment option for patients with drug-resistant idiopathic generalized epilepsy?  Acta Neurologica Scandinavica Supplementum, January 2007; 187: 55-58. (Abstract)

  85. Kreuzer PM, Landgrebe M, Resch M, et al. Feasibility, safety and efficacy of transcutaneous vagus nerve stimulation in chronic tinnitus: an open pilot study. Brain Stimul. Sep-Oct 2014; 7(5):740-747.

  86. Kutlu N, Ozden AV, Alptekin HK, et al. The Impact of Auricular Vagus Nerve Stimulation on Pain and Life Quality in Patients with Fibromyalgia Syndrome. Biomed Res Int. 2020; 2020: 8656218.

  87. Labar D, et al.  Vagus nerve stimulation for medication-resistant generalized epilepsy.  E04 VNS Study Group. Neurology, April 1999; 52(7): 1510-1512.

  88. Lange G, Janal MN, Maniker A et al. Safety and efficacy of vagus nerve stimulation in fibromyalgia: a phase I/II proof of concept trial. Pain Med 2011; 12(9):1406-13.

  89. Liu AY, Rajji TK, Blumberger DM, et al. Brain stimulation in the treatment of late-life severe mental illness other than unipolar nonpsychotic depression. Am J Geriatr Psychiatry. Mar 2014; 22(3):216-240.

  90. Majoie HJ, Berfelo MW, Aldenkamp AP, et al. Vagus nerve stimulation in children with therapy-resistant epilepsy diagnosed as Lennox-Gastaut syndrome: clinical results, neuropsychological effects, and cost-effectiveness. J Clin Neurophysiol. Sep 2001; 18(5):419-428.

  91. Majoie HJ, Berfelo MW, Aldenkamp AP, et al. Vagus nerve stimulation in patients with catastrophic childhood epilepsy, a 2-year follow-up study. Seizure. Jan 2005; 14(1):10-18.

  92. Marangell LB, et al. Vagus nerve stimulation (VNS) for major depressive episodes:  One year outcomes, Biological Psychiatry, February 2002; 51(4): 280-287.

  93. Marangell LB, Suppes T, Zboyan HA et al. A 1-year pilot study of vagus nerve stimulation in treatment-resistant rapid-cycling bipolar disorder. J Clin Psychiatry 2008; 69(2):183-9.

  94. Martelletti P, Jensen RH, Antal A, et al. Neuromodulation of chronic headaches: position statement from the European Headache Federation. J Headache Pain. Oct 21 2013; 14(1):86.

  95. Martelletti, PP, Barbanti, PP, Grazzi, LL, Pierangeli, GG, Rainero, II, Geppetti, PP, Ambrosini, AA, Sarchielli, PP, Tassorelli, CC, Liebler, EE, de Tommaso, MM, Tassorelli, CC, Bitetto, VV, De Icco, RR, Martinelli, DD, Sances, GG, Bianchi, MM, Grazzi, LL, Padovan, AA, de Tommaso, MM, Ricci, KK, Vecchio, EE, Cortelli, PP, Cevoli, SS, Pierangeli, GG, Terlizzi, RR, Martelletti, PP, Negro, AA, Chiariello, GG, Rainero, II, De Martino, PP, Gai, AA, Govone, FF, Masuzzo, FF, Rubino, EE, Torrieri, MM, Vacca, AA, Geppetti, PP, Chiarugi, AA, De Cesaris, FF, Puma, SS, Lupi, CC, Marone, II, Ambrosini, AA, Perrotta, AA, Sarchielli, PP, Bernetti, LL, Corbelli, II, Romoli, MM, Simoni, SS, Verzina, AA, Barbanti, PP, Aurilia, CC, Egeo, GG, Fofi, LL, Liebler, EE, Andersson, AA, Spitzer, LL, Marin, JJ, McClure, CC, Thackeray, LL, Baldi, MM, Di Maro, DD. Consistent effects of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: additional findings from the randomized, sham-controlled, double-blind PRESTO trial. J Headache Pain. 2018 Dec 18; 19(1):120. 

  96. 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):147-55.

  97. Mauskop A.  Vagus nerve stimulation relieves chronic refractory migraine and cluster headaches. Cephalgia, February 2005; 25(2): 82-86.

  98. McAllister-Williams RH, Sousa S, Kumar A, et al. The effects of vagus nerve stimulation on the course and outcomes of patient’s with bipolar disorder in a treatment-resistant depressive episode: a 5-year prospective registry. Int J Bipolar Disord. May 02 2020; 8(1): 13.

  99. Michael JE, Wegener K, Barnes DW. Vagus nerve stimulation for intractable seizures: one year follow-up. J Neurosci Nurs. Dec 1993; 25(6):362-366.

  100. Montavont A, Demarquay G, Ryvlin P, et al. Long-term efficiency of vagus nerve stimulation (VNS) in non-surgical refractory epilepsies in adolescents and adults [article in French]. Rev Neurol (Paris) 2007; 163(12):1169-77.

  101. Morris GL, et al. Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. Neurology, November 1999, Vol. 53, No. 8.

  102. Morris GL, 3rd, Gloss D, Buchhalter J, et al. Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. Oct 15 2013; 81(16):1453-1459. 

  103. Murphy JV, et al. Vagal nerve stimulation in refractory epilepsy: The first 100 patients receiving vagal nerve stimulation at a pediatric epilepsy center. Archives of Pediatrics and Adolescent Medicine, June 2003; 157(6): 560-564.

  104. Murphy JV. Left vagal nerve stimulation in children with medically refractory epilepsy: The Pediatric VNS Study Group. Journal of Pediatrics, May 1999; 134(5): 563-566.

  105. Nahas Z, et al. Two-year outcome of vagus nerve stimulation (VNS) for treatment of major-depressive episodes. Journal of Clinical Psychiatry, September 2005; 66(9): 1097-1104.

  106. National Institute for Health and Care Excellence. Transcutaneous stimulation of the cervical branch of the vagus nerve for cluster headache and migraine (IPG552). 2016; https://www.nice.org.uk/guidance/ipg552. Accessed February 5, 2020.

  107. National Institute for Health and Care Excellence. GammaCore for cluster headache (MIB162). 2018. https://www.nice.org.uk/advice/mib162. Accessed February 10, 2020.

  108. National Institute for Health and Care Excellence. Medical technologies guidance [MTG46]: gammaCore for cluster headache. December 2019. https://www.nice.org.uk/guidance/MTG46. Accessed January 2, 2020.

  109. National Institute for Health and Care Excellence. Implanted vagus nerve stimulation for treatment-resistant depression - Interventional Procedures Guidance (IPG679). 2020; https://www.nice.org.uk/guidance/ipg679/chapter/1-Recommendations. Accessed January 4, 2021.

  110. Nearing BD, Libbus I, Carlson GM, et al. Chronic vagus nerve stimulation is associated with multi-year improvement in intrinsic heart rate recovery and left ventricular ejection fraction in ANTHEM-HF. Clin Auton Res. Jun 2021; 31(3): 453-462.

  111. O’Keane V, et al. Changes in hypothalamic-pituitary-adrenal axis measures after vagus nerve stimulation therapy in chronic depression. Biological Psychiatry, July 2005.

  112. Orosz I, McCormick D, Zamponi N, et al. Vagus nerve stimulation for drug-resistant epilepsy: a European long-term study up to 24 months in 347 children. Epilepsia. Oct 2014; 55(10):1576-1584.

  113. Panebianco M, Rigby A, Weston J, et al. Vagus nerve stimulation for partial seizures. Cochrane Database Syst Rev. Apr 03 2015; (4):Cd002896.

  114. Parker AP, Polkey CE, Binnie CD, et al. Vagal nerve stimulation in epileptic encephalopathies. Pediatrics. Apr 1999; 103(4 Pt 1):778-782.

  115. Patwardhan RV, et al. Efficacy of vagal nerve stimulation in children with medically refractory epilepsy. Neurosurgery, December 2000; 47(6): 1353-1357.

  116. Premchand RK, Sharma K, Mittal S, et al. autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure: results of the ANTHEM-HF trial. J Card Fail. Nov 2014; 20(11):808-816.

  117. Renfroe JB, et al.  Earlier use of adjunctive vagus nerve stimulation therapy for refractory epilepsy, Neurology, September 2002; 59(6 Suppl 4): S26-30.

  118. Rong P, Liu A, Zhang J, et al. Transcutaneous vagus nerve stimulation for refractory epilepsy: a randomized controlled trial. Clin Sci (Lond). Apr 01 2014.

  119. Rush AJ, et al. Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: A naturalistic study. Biological Psychiatry 2005; 58: 355-363.

  120. Rush AJ, et al. Vagus nerve stimulation (VNS) for treatment-resistant depressions: A multicenter study. Biological Psychiatry, February 2000; 47(4): 276-286.

  121. Rush AJ, et al. Vagus nerve stimulation for treatment-resistant depression: A randomized, controlled acute phase trial. Biological Psychiatry, September 2005; 58(5): 347-354.

  122. Ryvlin P, Gilliam FG, Nguyen DK, et al. The long-term effect of vagus nerve stimulation on quality of life in patients with pharmaco-resistant focal epilepsy: the PuLsE (Open Prospective Randomized Long-term Effectiveness) trial. Epilepsia. Jun 2014; 55(6):893-900.

  123. Sackeim HA, Brannan SK, Rush JA, et al. Durability of antidepressant response to vagus nerve stimulation (VNSTM). Int J Neuropsychopharmacol, February 2007; 1-10. (Abstract)

  124. Sackeim HA, et al. Vagus nerve stimulation (VNS) for treatment-resistant depression:  Efficacy, side effects, and predictors of outcome. Neuropsychopharmacology, November 2001; 25(5): 713-728.

  125. Saneto RP, Sotero de Menezes MA, Ojemann JG, et al. Vagus nerve stimulation for intractable seizures in children. Pediatric Neurology 2006, Vol. 35, No. 5, pp. 323-326.

  126. Sant'Anna LB, Couceiro SLM, Ferreira EA, et al. Vagal Neuromodulation in Chronic Heart Failure With Reduced Ejection Fraction: A Systematic Review and Meta-Analysis. Front Cardiovasc Med. 2021; 8: 766676.

  127. Scherrmann J, et al. Vagus nerve stimulation: Clinical experience in a large patient series. Journal of Clinical Neurophysiology, September 2001; 18(5): 408-414.

  128. Shi C, Flanagan SR, Samadani U. Vagus nerve stimulation to augment recovery from severe traumatic brain injury impeding consciousness: a prospective pilot clinical trial. Neurol Res 2013; 35(3):263-76.

  129. Shiozawa P, Silva ME, Carvalho TC, et al. Transcutaneous vagus and trigeminal nerve stimulation for neuropsychiatric disorders: a systematic review. Arq Neuropsiquiatr. Jul 2014; 72(7):542-547.

  130. Silberstein, SS, Calhoun, AA, Lipton, RR, Grosberg, BB, Cady, RR, Dorlas, SS, Simmons, KK, Mullin, CC, Liebler, EE, Goadsby, PP, Saper, JJ, Calhoun, AA, Cady, RR, Dexter, JJ, Silberstein, SS, Young, WW, Marmura, MM, Nahas-Geiger, SS, Da Silva, AA, Saper, JJ, Weintraub, JJ, Prestegaard, AA, Sinka, EE, Grosberg, BB, Vollbracht, SS, Issa, SS, Lipton, RR, Mullin, KK, Pavlovic, JJ, Robbins, MM, Goadsby, PP, Gelfand, AA, Eller, MM. Chronic migraine headache prevention with noninvasive vagus nerve stimulation: The EVENT study. NA. 

  131. Silberstein SD, Mechtler LL, Kudrow DB, et al. Non-invasive vagus nerve stimulation for the Acute Treatment of Cluster Headache: findings from the randomized, double-blind, sham-controlled ACT1 Study. Headache. Sep 2016; 56(8):1317-1332.

  132. Shuchman Miriam. Approving the vagus-nerve stimulator for depression. NEJM, April 2007; 356: 16.

  133. Sjogren MJ, et al. Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer’s disease: A pilot study. Journal of Clinical Psychiatry, November 2002: 63(11): 972-980.

  134. Stefan H, Kreiselmeyer G, Kerling F et al. Transcutaneous vagus nerve stimulation (t-VNS) in pharmacoresistant epilepsies: a proof of concept trial. Epilepsia 2012; 53(7):e115-8.

  135. Tassorelli, CC, Grazzi, LL, de Tommaso, MM, Pierangeli, GG, Martelletti, PP, Rainero, II, Dorlas, SS, Geppetti, PP, Ambrosini, AA, Sarchielli, PP, Liebler, EE, Barbanti, PP, Tassorelli, CC, Bitetto, VV, De Icco, RR, Martinelli, DD, Sances, GG, Bianchi, MM, Grazzi, LL, Padovan, AA, de Tommaso, MM, Ricci, KK, Vecchio, EE, Cortelli, PP, Cevoli, SS, Pierangeli, GG, Terlizzi, RR, Martelletti, PP, Negro, AA, Chiariello, GG, Rainero, II, De Martino, PP, Gai, AA, Govone, FF, Masuzzo, FF, Rubino, EE, Torrieri, MM, Vacca, AA, Geppetti, PP, Chiarugi, AA, De Cesaris, FF, Puma, SS, Lupi, CC, Marone, II, Ambrosini, AA, Perrotta, AA, Sarchielli, PP, Bernetti, LL, Corbelli, II, Romoli, MM, Simoni, SS, Verzina, AA, Barbanti, PP, Aurilia, CC, Egeo, GG, Fofi, LL, Liebler, EE, Andersson, AA, Spitzer, LL, Marin, JJ, McClure, CC, Thackerey, LL, Baldi, MM, Di Maro, DD. Noninvasive vagus nerve stimulation as acute therapy for migraine: The randomized PRESTO study. NA. 

  136. Tecoma ES and Iragui VJ. Vagus nerve stimulation use and effect in epilepsy: What have we learned? Epilepsy Behav 2006; 8(1); 127-36.

  137. Terra VC, Furlanetti LL, Nunes AA, et al. Vagus nerve stimulation in pediatric patients: Is it really worthwhile? Epilepsy Behav. Feb 2014; 31:329-333.

  138. Tfelt-Hansen, PP, Pascual, JJ, Ramadan, NN, Dahlf, CC, D'Amico, DD, Diener, HH, Hansen, JJ, Lanteri-Minet, MM, Loder, EE, McCrory, DD, Plancade, SS, Schwedt, TT. Guidelines for controlled trials of drugs in migraine: third edition. A guide for investigators. NA. 

  139. Tisi G, Franzini A, Messina G, et al. Vagus nerve stimulation therapy in treatment-resistant depression: a series report. Psychiatry Clin Neurosci. Aug 2014; 68(8):606-611.

  140. Trimboli, MM, Al-Kaisy, AA, Andreou, AA, Murphy, MM, Lambru, GG. Non-invasive vagus nerve stimulation for the management of refractory primary chronic headaches: A real-world experience. NA. 

  141. 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):442-5.

  142. You SJ, Kang HC, Ko TS, et al. Comparison of corpus callosotomy and vagus nerve stimulation in children with Lennox-Gastaut syndrome. Brain Dev 2008; 30(3):195-9.

  143. Tso AR, Marin J, Goadsby PJ. Noninvasive vagus nerve stimulation for treatment of indomethacin-sensitive headaches. JAMA Neurol. Oct 1 2017; 74(10):1266-1267.

  144. Yu C, Ramgopal S, Libenson M, et al. Outcomes of vagal nerve stimulation in a pediatric population: A single center experience. Seizure. Feb 2014; 23(2):105-111.

  145. Vonck K, Boon P, D'Have M, et al. Long-term results of vagus nerve stimulation in refractory epilepsy. Seizure. Sep 1999; 8(6):328-334.

  146. Vonck K, Thadani V, Gilbert K, et al. Vagus nerve stimulation for refractory epilepsy: a transatlantic experience. J Clin Neurophysiol. Jul-Aug 2004; 21(4):283-289.

  147. Wu D, Ma J, Zhang L, et al. Effect and Safety of Transcutaneous Auricular Vagus Nerve Stimulation on Recovery of Upper Limb Motor Function in Subacute Ischemic Stroke Patients: A Randomized Pilot Study. Neural Plast. 2020; 2020: 8841752.  

  148. Wu K, Wang Z, Zhang Y, et al. Transcutaneous vagus nerve stimulation for the treatment of drug-resistant epilepsy: a meta-analysis and systematic review. ANZ J Surg. Apr 2020; 90(4): 467-471.

  149. Zannad F, De Ferrari GM, Tuinenburg AE, et al. Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the neural cardiac therapy for heart failure (NECTAR-HF) randomized controlled trial. Eur Heart J. Aug 31 2014.

  150. Zannad F, De Ferrari GM, Tuinenburg AE, et al. Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the Neural Cardiac Therapy for Heart Failure (NECTAR-HF) randomized controlled trial. Eur Heart J. Feb 14 2015; 36(7):425-433. 

POLICY HISTORY:

Medical Policy Group, March 2006 (3)

Medical Policy Administration Committee, March 2006

Available for comment March 14-April 27, 2006

Medical Policy Group, September 2006 (1)

Medical Policy Group, October 2007 (1)

Medical Policy Group, March 2009 (4)

Medical Policy Group, March 2010 (3)

Medical Policy Administration Committee, April 2010

Available for comment April 8-May 23, 2010

Medical Policy Group, December 2010 – code updates

Medical Policy Group, March 2011 (3): Description, Policy, Key Points, References updated

Medical Policy Group, December 2011 (3): 2012 Code Updates – verbiage change to codes 64553. 95974 & 95975

Medical Policy Group, March 2012 (3): 2012 Update – Key Points & References

Medical Policy Panel, March 2013

Medical Policy Group, April 2013 (3): 2013 Updates to Key Points; no change in policy statement

Medical Policy Panel March 2014

Medical Policy Group March 2014 (4):  Updated Description, updated policy section by adding that VNS for tinnitus and traumatic brain injury also added non-implantable vagus nerve stimulation devices are investigational.  Reworked Key Points Updated Key Words and References.

Available for comment May 2 through July 5, 2014

Medical Policy Group, May 2014 (5):  2014 Coding Update:  Deleted code L8680 effective July 1, 2014.

Medical Policy Group, June 2014 (5): Quarterly 2014 Coding Update:  Code L8680 did not delete; Removed delete date and moved code up under active codes.

Medical Policy Panel, March 2015

Medical Policy Group, March 2015 (6):  Updates to Description, Key Points, Key Words, Codes and References; no change to policy statement.

Medical Policy Panel, February 2016

Medical Policy Group, February 2016 (6):  Updates to Description, Key Points, Approved by Governing Bodies and References; no changes to policy statement.

Medical Policy Panel, October 2017

Medical Policy Group, October 2017 (6): Updates to Description, Key Points, Governing Bodies, Practice Guidelines and References. Added “upper-limb impairment due to stroke” to policy statement.

Medical Policy Panel March 2018

Medical Policy Group, April 2018 (6) Updates to Description, Key Points, Key Words, Governing Bodies and References.

Medical Policy Group, December 2018:  2019 Annual Coding Update.  Added CPT codes 95976 and 95977 to the Current coding section. Moved CPT codes from Current coding section to previous coding. Created previous coding section to include codes 95974 and 95975.

Medical Policy Panel, February 2019

Medical Policy group, March 2019 (3): 2019 Updates to Description, Key Points, Practice Guidelines and Position Statements, and References. No changes to policy statement or intent.

Medical Policy Panel, February 2020

Medical Policy Group, March 2020 (3): 2020 Updates to Key Points, Practice Guidelines and Position Statements, and References. No changes to policy statement or intent.

Medical Policy Group, March 2021: Quarterly Coding Update.  Added new code K1020 to Current Coding. Added Key Word Sapphire D.

Medical Policy Panel, February 2021

Medical Policy Group, March 2021 (3): 2021 Updates to Key Points, Practice Guidelines and Position Statements, and References. Added Policy Guidelines section. Policy statement updated to remove “not medically necessary,” no other changes to policy statement or intent.

Medical Policy Group, April 2021 (3): Additional 2021 Update to add new Noninvasive Vagus Nerve Stimulator. Added GammaCore CV and nVNS to Key Words. Updated Approved by Governing Bodies due to the emergency use authorization by the FDA for use in an acute setting or at home during Covid-19 pandemic. Added one reference. No changes to policy statement or intent.

Medical Policy Group, December 2021: 2022 Annual Coding Update.  Revised CPT code 64568 changes: “Open” added to descriptor and “incision for” removed.

Medical Policy Panel, February 2022

Medical Policy Group, February 2022 (3): 2022 Updates to Key Points, Practice Guidelines and Position Statements, Approved by Governing Bodies, and References. No changes to policy statement or intent.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.