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UnitedHealthcare® Commercial
Medical Policy
VAGUS NERVE STIMULATION
Policy Number: 2017T0101U
Table of Contents
Page
INSTRUCTIONS FOR USE .......................................... 1
BENEFIT CONSIDERATIONS ...................................... 1
COVERAGE RATIONALE ............................................. 1
APPLICABLE CODES ................................................. 2
DESCRIPTION OF SERVICES ...................................... 3
CLINICAL EVIDENCE ................................................. 3
U.S. FOOD AND DRUG ADMINISTRATION .................... 9
CENTERS FOR MEDICARE AND MEDICAID SERVICES .... 9
REFERENCES ........................................................... 9
POLICY HISTORY/REVISION INFORMATION ................ 12
Effective Date: January 1, 2017
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Vagus Nerve Stimulation
INSTRUCTIONS FOR USE
This Medical Policy provides assistance in interpreting UnitedHealthcare benefit plans. When deciding coverage, the
member specific benefit plan document must be referenced. The terms of the member specific benefit plan document
[e.g., Certificate of Coverage (COC), Schedule of Benefits (SOB), and/or Summary Plan Description (SPD)] may differ
greatly from the standard benefit plan upon which this Medical Policy is based. In the event of a conflict, the member
specific benefit plan document supersedes this Medical Policy. All reviewers must first identify member eligibility, any
federal or state regulatory requirements, and the member specific benefit plan coverage prior to use of this Medical
Policy. Other Policies and Coverage Determination Guidelines may apply. UnitedHealthcare reserves the right, in its
sole discretion, to modify its Policies and Guidelines as necessary. This Medical Policy is provided for informational
purposes. It does not constitute medical advice.
UnitedHealthcare may also use tools developed by third parties, such as the MCG™ Care Guidelines, to assist us in
administering health benefits. The MCG™ Care Guidelines are intended to be used in connection with the independent
professional medical judgment of a qualified health care provider and do not constitute the practice of medicine or
medical advice.
BENEFIT CONSIDERATIONS
Before using this policy, please check the member specific benefit plan document and any federal or state mandates,
if applicable.
Essential Health Benefits for Individual and Small Group
For plan years beginning on or after January 1, 2014, the Affordable Care Act of 2010 (ACA) requires fully insured
non-grandfathered individual and small group plans (inside and outside of Exchanges) to provide coverage for ten
categories of Essential Health Benefits (“EHBs”). Large group plans (both self-funded and fully insured), and small
group ASO plans, are not subject to the requirement to offer coverage for EHBs. However, if such plans choose to
provide coverage for benefits which are deemed EHBs, the ACA requires all dollar limits on those benefits to be
removed on all Grandfathered and Non-Grandfathered plans. The determination of which benefits constitute EHBs is
made on a state by state basis. As such, when using this policy, it is important to refer to the member specific benefit
plan document to determine benefit coverage.
COVERAGE RATIONALE
Vagus nerve stimulation (VNS) is proven and medically necessary for treating epilepsy in patients with
ALL of the following:

Medically refractory epileptic seizures with failure of two or more trials of single or combination antiepileptic drug
therapy or intolerable side effects of antiepileptic drug therapy; and

The patient is not a surgical candidate or has failed a surgical intervention; and

No history of left or bilateral cervical vagotomy. The U.S. Food and Drug Administration (FDA) identifies a history
of left or bilateral cervical vagotomy as a contraindication to vagus nerve stimulation.
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It is an expectation that the physician have experience and expertise in the use of vagus nerve stimulation.
Vagus nerve stimulation implants that allow detection and stimulation of increased heart rate (e.g.,
AspireSR™ Model 106) are unproven and not medically necessary for treating epilepsy.
There is limited evidence to determine if vagus nerve stimulation implants that allow detection and stimulation of
increased heart rate are beneficial for improving health outcomes in patients with epilepsy. Larger, long-term studies
are needed to determine if this device is safe and effective.
Vagus nerve stimulation is unproven and not medically necessary for treating ALL other indications,
including but not limited to:

Alzheimer's disease

Anxiety disorder

Autism spectrum disorder

Back and neck pain

Bipolar disorder

Bulimia

Cerebral palsy

Chronic pain syndrome

Cluster headaches

Depression

Fibromyalgia

Heart failure

Migraines

Morbid obesity

Narcolepsy

Obsessive-compulsive disorder

Paralysis agitans

Sleep disorders

Tourette's syndrome
Available studies on the use of vagus nerve stimulation for treating severe, major depression or bipolar disorder
refractory to medical therapy contain methodological flaws such as lack of control group, small sample size, potential
bias, lack of randomization and blinding and lack of statistical power analysis. There is a substantial placebo effect
associated with depression treatments and the lack of data from prospective randomized controlled or comparative
clinical studies considerably limits the conclusions that can be drawn from the available evidence. Furthermore,
preliminary analysis of a randomized controlled trial did not find a statistically significant difference between sham and
active VNS. Definitive patient selection criteria for vagus nerve stimulation (VNS) in patients with treatment-resistant
depression have not yet been established, and significant predictors of response have also not been identified.
Early research has examined the use of vagus nerve stimulation for additional indications. However, because of
limited studies, small sample sizes and weak study designs, there is insufficient data to conclude that vagus nerve
stimulation is safe and/or effective for treating these indications.
APPLICABLE CODES
The following list(s) of procedure and/or diagnosis codes is provided for reference purposes only and may not be all
inclusive. Listing of a code in this policy does not imply that the service described by the code is a covered or noncovered health service. Benefit coverage for health services is determined by the member specific benefit plan
document and applicable laws that may require coverage for a specific service. The inclusion of a code does not imply
any right to reimbursement or guarantee claim payment. Other Policies and Coverage Determination Guidelines may
apply.
CPT Code
61885
Description
Insertion or replacement of cranial neurostimulator pulse generator or receiver,
direct or inductive coupling; with connection to a single electrode array
64553
Percutaneous implantation of neurostimulator electrode array; cranial nerve
64568
Incision for implantation of cranial nerve (e.g., vagus nerve) neurostimulator
electrode array and pulse generator
64570
Removal of cranial nerve (e.g., vagus nerve) neurostimulator electrode array and
pulse generator
CPT® is a registered trademark of the American Medical Association
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HCPCS Code
C1767
Description
Generator, neurostimulator (implantable), nonrechargeable
C1778
Lead, neurostimulator (implantable)
L8679
Implantable neurostimulator, pulse generator, any type
L8680
Implantable neurostimulator electrode, each
L8682
Implantable neurostimulator radiofrequency receiver
L8683
Radiofrequency transmitter (external) for use with implantable neurostimulator
radiofrequency receiver
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
DESCRIPTION OF SERVICES
The vagus nerve, a large nerve in the neck, connects the lower part of the brain to the heart, lungs and intestines.
Vagus nerve stimulation (VNS) uses short bursts of electrical energy directed into the brain via the vagus nerve. The
system, implanted subcutaneously in the upper chest, includes a pulse generator/neurostimulator and electrode that
deliver pulses of current to the left vagus nerve. Following implantation, the generator is programmed to stimulate the
vagus nerve at a rate determined by the patient and physician. These devices generally have two types (modes) of
stimulation: normal (the device stimulates according to preset parameters) and magnet (gives a single, on-demand
stimulation).
The AspireSR Model 106 (Cyberonics now known as LivaNova) is a vagus nerve stimulation generator that has an
additional, optional mode called AutoStim Mode or Automatic Stimulation. This mode monitors and detects tachycardia
heart rates, which may be associated with an impending seizure, and automatically delivers stimulation to the vagus
nerve. The effect of the AutoStim Mode on reducing the number of seizures is being evaluated.
CLINICAL EVIDENCE
Epilepsy
In a Cochrane review, Panebianco et al. (2015) evaluated the current evidence for the efficacy and tolerability of
vagus nerve stimulation when used as an adjunctive treatment for people with drug-resistant partial epilepsy. Five
randomized controlled trials (439 participants) were included in the review. The authors concluded that VNS for partial
seizures appears to be an effective and well tolerated treatment in 439 included participants from five trials. Results of
the overall efficacy analysis show that VNS stimulation using the high stimulation paradigm was significantly better
than low stimulation in reducing frequency of seizures. Results for the outcome "withdrawal of allocated treatment"
suggest that VNS is well tolerated as withdrawals were rare. Adverse effects associated with implantation and
stimulation were primarily hoarseness, cough, dyspnea, pain, paresthesia, nausea and headache, with hoarseness and
dyspnea more likely to occur on high stimulation than low stimulation.
Englot et al. (2015) examined rates and predictors of seizure freedom with VNS. The investigators examined 5554
patients from the VNS therapy Patient Outcome Registry, and also performed a systematic review of the literature
including 2869 patients across 78 studies. Registry data showed a progressive increase over time in seizure freedom
after VNS therapy. Overall, 49% of patients responded to VNS therapy 0 to 4 months after implantation (≥50%
reduction seizure frequency), with 5.1% of patients becoming seizure-free, while 63% of patients were responders at
24 to 48 months, with 8.2% achieving seizure freedom. On multivariate analysis, seizure freedom was predicted by
age of epilepsy onset >12 years, and predominantly generalized seizure type, while overall response to VNS was
predicted by nonlesional epilepsy. Systematic literature review results were consistent with the registry analysis: At 0
to 4 months, 40.0% of patients had responded to VNS, with 2.6% becoming seizure-free, while at last follow-up,
60.1% of individuals were responders, with 8.0% achieving seizure freedom.
Elliott et al. (2011) evaluated the impact of failed intracranial epilepsy surgery (IES) and other surrogate marker of
severe epilepsy on VNS effectiveness. The study included 376 patients (188 females; 265 adults; mean age of 29.4
years at implantation) with treatment resistant epilepsy (TRE) who underwent VNS implantation and had at least 1
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year of follow-up. One hundred ten patients (29.3%) had failed one or more prior craniotomies for TRE and 266
(70.7%) had no history of IES. The mean duration of VNS therapy was 5.1 years. Patients with prior IES were more
commonly male and adult, had a greater number of seizure types, and more commonly had focal or multifocal versus
generalized seizures. There was no significant difference in the mean percentage seizure reduction between patients
with and without a history of IES. There was no correlation between type of failed IES (callosotomy versus resection)
and seizure reduction with VNS therapy. The authors concluded that failed IES did not affect the response to VNS
therapy. Unlike prior reports, patients with callosotomy did not respond better than those who had resective surgery.
Nearly 50% of patients experienced at least 50% reduction in seizure frequency. The authors stated that VNS should
be considered a palliative treatment option for patients with TRE, including patients who failed cranial epilepsy
surgeries.
In the PuLsE trial, Ryvlin et al. (2014) compared outcomes between patients receiving best medical practice (BMP)
alone, and those treated with VNS in addition to BMP (VNS+BMP). In a randomized group of 96 patients, significant
between-group differences in favor of VNS + BMP were observed regarding improvement in health-related quality of
life, seizure frequency, and Clinical Global Impression-Improvement scale (CGI-I) score. More patients in the VNS +
BMP group (43%) reported adverse events (AEs) versus BMP group (21%), a difference reflecting primarily mostly
transient AEs related to VNS implantation or stimulation. According to the authors, this data suggests that VNS as a
treatment adjunct to BMP in patients with pharmacoresistant focal seizures was associated with a significant
improvement in health-related quality of life compared with BMP alone.
In a 2012 clinical guideline for the diagnosis and management of epilepsy, the National Institute for Health and Care
Excellence (NICE) stated that vagus nerve stimulation is indicated for use as an adjunctive therapy in reducing the
frequency of seizures in adults, children, and young people who are refractory to antiepileptic medication but who are
not suitable for resective surgery. This includes adults, children and young people whose epileptic disorder is
dominated by focal seizures (with or without secondary generalization) or generalized seizures (NICE 2012, Updated
February 2016).
AspireSR for Vagus Nerve Stimulation
Boon et al. (2015) investigated the performance of a cardiac-based seizure detection algorithm (CBSDA) that
automatically triggers VNS. Thirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring
unit (EMU). Sixty-six seizures (n=16 patients) were available from the EMU for analysis. In 37 seizures (n=14 patients)
a ≥ 20% heart rate increase was found and 11 (n=5 patients) were associated with ictal tachycardia (iTC). Multiple
CBSDA settings achieved a sensitivity of ≥ 80%. False positives ranged from 0.5 to 7.2/hour. A total of 27/66 seizures
were stimulated within ± 2 min of seizure onset. In 10/17 of these seizures, where triggered VNS overlapped with
ongoing seizure activity, seizure activity stopped during stimulation. Physician-scored seizure severity (NHS3-scale)
showed significant improvement for complex partial seizures (CPS) at EMU discharge and through 12 months. Patientscored seizure severity (total SSQ score) showed significant improvement at 3 and 6 months. Quality of life (QOL)
showed significant improvement at 12 months. The responder rate at 12 months was 29.6% (n=8/27). Safety profiles
were comparable to prior VNS trials. The authors concluded that the investigated CBSDA has a high sensitivity and an
acceptable specificity for triggering VNS. According to the authors, despite the moderate effects on seizure frequency,
combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory
epilepsy patients. The significance of this study is limited by small sample size and short follow-up period. This study
was sponsored by Cyberonics, Inc., the manufacturer of AspireSR.
Fisher et al. (2016) evaluated the performance, safety of the Automatic Stimulation Mode (AutoStim) feature of the
Model 106 Vagus Nerve Stimulation (VNS) Therapy System during a 3-5-day Epilepsy Monitoring Unit (EMU) stay and
long- term clinical outcomes of the device stimulating in all modes. This study was a prospective, unblinded, U.S.
multisite study of the AspireSR in patients with drug-resistant partial onset seizures and history of ictal tachycardia.
VNS Normal and Magnet Modes stimulation were present at all times except during the EMU stay. Outpatient visits at
3, 6, and 12 months tracked seizure frequency, severity, quality of life, and adverse events. Twenty implanted
patients (ages 21-69) experienced 89 seizures in the EMU. A total of 28/38 (73.7%) of complex partial and
secondarily generalized seizures exhibited ≥20% increase in heart rate change. A total of 31/89 (34.8%) of seizures
were treated by Automatic Stimulation on detection; 19/31 (61.3%) seizures ended during the stimulation with a
median time from stimulation onset to seizure end of 35 sec. Mean duty cycle at six-months increased from 11% to
16%. At 12 months, quality of life and seizure severity scores improved, and responder rate was 50%. Common
adverse events were dysphonia (n = 7), convulsion (n = 6), and oropharyngeal pain (n = 3). The authors concluded
that the Model 106 performed as intended in the study population, was well tolerated and associated with clinical
improvement from baseline. The study design did not allow determination of which factors were responsible for
improvements. Study limitations include small sample size (20 patients) and short duration of follow-up (12 months).
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Professional Societies
American Academy of Neurology (AAN)
In a practice parameter update on vagus nerve stimulation for epilepsy, the AAN stated that 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 degree of
improvement in seizure control from VNS remains comparable to that of new antiepileptic drugs (AEDs) but is lower
than that of mesial temporal lobectomy in suitable surgical resection candidates. Because VNS rarely causes complete
seizure remission, and is moderately invasive and expensive, use of VNS is more appropriate in individuals unable to
tolerate or benefit from antiepileptic drugs (AEDs), and for whom a partial reduction in seizure frequency will
significantly improve their quality of life. Sufficient evidence exists to rank VNS for epilepsy as effective and safe,
based on a preponderance of Class I evidence (Fisher, 1999).
In an evidence based guideline update on vagus nerve stimulation for the treatment of epilepsy (Morris et al. 2013),
the AAN makes the following recommendations in addition to those reported in the 1999 assessment:

VNS may be considered as adjunctive treatment for children with partial or generalized epilepsy (level C). VNS
was associated with a greater than 50% reduction in seizure frequency in 55% of 470 children with partial or
generalized epilepsy (14 class III studies) but there was significant heterogeneity in the data.

VNS may be considered in patients with Lennox-Gastaut syndrome (LGS) (level C). VNS was associated with a
greater than 50% seizure reduction in 55% of 113 patients with LGS (4 class III studies).

VNS may be considered progressively effective in patients over multiple years of exposure (level C).

There should be extra vigilance in monitoring for occurrence of site infection in children. There is evidence of an
increase in infection risk at the VNS implantation site in children relative to that in adults.
The AAN defines level C as possibly effective, ineffective or harmful (or possibly useful/predictive or not
useful/predictive) for the given condition in the specified population. Level C rating requires at least one Class II study
or two consistent Class III studies.
International League Against Epilepsy (ILAE)
A taskforce by the ILAE defines drug resistant epilepsy as a failure of adequate trials of two tolerated, appropriately
chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained
seizure freedom (Kwan et al., 2010).
Depression
D01 – D06 Studies Reported to the FDA
Most of the available evidence regarding the safety and efficacy of VNS for depression comes from studies funded by
or performed in collaboration with Cyberonics, Inc. Data from these studies were presented to the U.S. Food and Drug
Administration (FDA) to support the Premarket Approval application. Overall, six studies were performed, designated
D01 to D06. Complete data sets have not been published for all of the studies. In these studies, VNS was performed
using the NeuroCybernetic Prosthesis (NCP®) System, also referred to as the VNS Therapy™ System.
The D01 study was a prospective, open-label, nonrandomized, uncontrolled clinical study. The earliest D01 study
initially enrolled 30 patients and was reported by Rush et al. (2000). Their results suggest that VNS provided
symptom relief in 40% of the patients with major depression and bipolar disorders and that an additional 16% of the
patients had remission of symptoms following VNS. The study limitations include lack of control group, small sample
size, lack of power analysis and ten week follow-up. An additional 30 patients were enrolled and results were reported
by Sackheim et al. (2001). They concluded that mean time from response to treatment was 48.1 days. Based on the
HDRS and MADRS, the results were 30.5%-34% at the 10 week follow-up. Remission was reported in 15.3% of the
patients. Lack of a control or comparator group, small sample size, and short follow-up compromised the quality of
this study.
Marangell et al. (2002) (D01 trial) studied the effectiveness of twelve months of VNS therapy in the 30 patients that
were enrolled in the Rush (2000) study. Twelve of the patients had greater than or equal to 50% improvement on the
HDRS and 15 showed the same level of improvement on the MADRS. Approximately 29% of the patients achieved
remission in this time frame. Limitations of this study included lack of control group, small sample size, and lack of
statistical power analysis.
Nahas et al. (2005) (D01 trial) completed a two year outcome study of 60 patients with VNS for the treatment of
major depressive episodes. The results indicate that remissions rates were 15% at 3 months, 27% after 12 months
and 22% after 2 years. Response rates were 31%, 44% and 42% at 3 month, 12 month and 24 month respectively.
The authors concluded that the VNS treatment may show long term benefit. The lack of a control group, the
concurrent medication therapy and financial relationship with the manufacturer limits the validity of the results.
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In a randomized, sham-controlled clinical trial, Rush et al. (2005a) (D02 trial) reported on vagus nerve stimulation
that involved 235 patients with major depressive disorder or depressed phase bipolar disorder. All patients had a VNS
implanted. After two weeks, the unit was activated in half of the patients. The patients were evaluated ten weeks later.
After ten weeks, 15% of the active treatment and 10% of the sham treatment showed a response. It is noted that
evaluation occurred in 222 patients without explanation of what happened to the balance of the participants. The
authors concluded that VNS did not demonstrate short term efficacy in the treatment of depression. These same
authors completed a twelve month follow up study of 205 of the same patients. (Rush, 2005b)The previously treated
patients received another 9 months of VNS and the participants in the sham group received 12 months of VNS. The
results showed a 27% response rate and a 15.8% remission rate. This study was flawed by the concomitant use of
antidepressants and adjusted treatments of both the VNS and drugs during the study period and the lack of
comparative group. Thirty of the participants required hospitalization for worsened depression. The authors concluded
that VNS was well tolerated but that comparative long term data are needed to determine if the benefits are
attributable to VNS.
Nierenberg et al. (2008) (D02 trial) described the outcome of VNS for bipolar treatment-resistant depression (TRD)
patients participating in the acute and longitudinal pivotal trials and compared their outcome with unipolar TRD
patients in the same trials. Of 235 participants enrolled in the acute study, 25 (11%) were diagnosed with DSM-IV
bipolar I or II disorder. A sham-controlled 12-week trial of VNS preceded 2 years of open treatment. Bipolar and
unipolar subjects were compared on baseline characteristics as well as acute and long-term outcomes. At baseline,
bipolar TRD was as severe as unipolar TRD but with depressive episodes of shorter duration and more failed
antidepressant trials/year. Acute, 1-year, and 2-year outcomes were similar for both groups, even when the definition
of response for bipolar TRD was expanded to include lack of manic symptoms. The study reported that 33% of
patients with unipolar depressive symptoms and 38% of patients with depressive bipolar disease demonstrated a
response at 24 months compared with baseline. According to the investigators, in this hypothesis-generating analysis,
VNS short- and long-term effects on bipolar and unipolar TRD were similar. Because these analyses were post hoc,
these findings should not be interpreted as warranting clinical inference regarding effectiveness of VNS in patients
with bipolar depression.
A case series that included 74 patients with treatment resistant depression found a 34% response rate to VNS at 3
months (end of active treatment period), which increased to 47% at the 12 month follow-up (Schlaepfer, 2008) (D03
trial). There was no comparison group in this study, so response with a different treatment or no treatment is not
known. Also, patients were not blinded, and they had regular clinic visits, both of which could affect responses to a
subjective outcome measure.
George et al. (2005) (D04 trial) completed a one year comparison of 205 patients with VNS and treatment as usual
(ECT plus medications) to 124 patients who received only ECT and antidepressant therapy. The VNS group showed a
27% improvement in the HRSD compared to 13% improvement for the non VNS group This study was flawed by the
lack of randomization, blinding and the non VNS group had at least 10 prior major depressive episodes. All principal
investigators disclosed a financial relationship with the manufacturer.
Other Clinical Trials for Depression
Berry et al. (2013) performed a meta-analysis to compare the response and remission rates in depressed patients
with chronic treatment-resistant depression (TRD) treated with vagus nerve stimulation (VNS) plus treatment as usual
(VNS + TAU) or TAU. The six clinical studies included in the meta‑analysis were two single‑arm studies of VNS + TAU,
a randomized trial of VNS + TAU versus TAU, a single arm study of patients who received TAU, a randomized trial of
VNS + TAU comparing different VNS stimulation intensities, and a nonrandomized registry of patients who received
either VNS + TAU or TAU. Response was based on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the
Clinical Global Impressions scale's Improvement subscale (CGI-I), as these were the two clinician-rated measures
common across all or most studies. Outcomes were compared from baseline up to 96 weeks of treatment with VNS +
TAU (n = 1035) versus TAU (n = 425). MADRS response rate for VNS + TAU at 12, 24, 48, and 96 weeks were 12%,
18%, 28%, and 32% versus 4%, 7%, 12%, and 14% for TAU. The MADRS remission rate for VNS + TAU at 12, 24,
48, and 96 weeks were 3%, 5%, 10%, and 14% versus 1%, 1%, 2%, and 4%, for TAU. Adjunctive VNS Therapy was
associated with a greater likelihood of response and remission compared with TAU. For patients who had responded to
VNS + TAU at 24 weeks, sustained response was more likely at 48 weeks and at 96 weeks. Similar results were
observed for CGI-I response. The authors concluded that for patients with chronic TRD, VNS + TAU has greater
response and remission rates that are more likely to persist than TAU. According to the authors, the primary limitation
of the meta‑analysis involved the individual study designs; namely, that the TAU group data is limited to two trials for
the CGI-I scale and one trial for the MADRS scale; in addition, the nonrandomized study and the randomized, sham‑
controlled study represent the only concurrent head‑to‑head comparisons of VNS + TAU and TAU.
Martin and Martin-Sanchez (2012) conducted a systematic review and meta-analysis of analytical studies to determine
the efficacy of vagus nerve stimulation (VNS) for treatment of depression. Fourteen studies met the selection criteria
and were included in the review. The meta-analysis of efficacy for uncontrolled studies showed a significant reduction
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in scores at the Hamilton Depression Rating Scale endpoint and the percentage of responders was 31.8%. However,
the randomized control trial which covered a sample of 235 patients with depression, reported no statistically
significant differences between the active intervention and placebo groups. To study the cause of this heterogeneity, a
meta-regression was performed. The adjusted coefficient of determination was 0.84, which implies that an 84%
variation in effect size across the studies was explained by baseline severity of depression. The authors stated that
insufficient data are available to conclude whether or not VNS is effective in the treatment of depression. In addition,
it cannot be ruled out that the positive results observed in the uncontrolled studies might have been mainly due to a
placebo effect.
Daban et al. (2008) evaluated the safety and efficacy of vagus nerve stimulation (VNS) in treatment-resistant
depression (TRD) by means of systematic review using the major databases (Medline, Psychological Abstracts,
Current Contents), beginning in January 2000 and ending in September 2007. Ninety-eight references were found,
but only 18 add-on studies (n=1251) met the required quality criteria and were included in the review. Only one
double-blind, randomized study was available and therefore a meta-analysis was not feasible. In a majority of the
preliminary open studies selected for the review, VNS was associated with a significant reduction of the depressive
symptoms (primary outcome: Hamilton Depression Rating Scale, HDRS) in the short and long term. Unfortunately,
the only double-blind study gave rather inconclusive results. Generally, VNS is reported to be a safe and feasible
procedure, despite its invasive nature. The authors concluded that VNS seems to be an interesting new approach to
treating TRD. However, despite the promising results reported mainly in open studies, further clinical trials are needed
to confirm its efficacy in major depression.
In a multicenter, double blind study, Aaronson et al. (2013) compared the safety and effectiveness of different
stimulation levels of adjunctive vagus nerve stimulation (VNS) therapy for the treatment of treatment-resistant
depression (TRD). A total of 331 patients with TRD were randomized to one of three dose groups: Low (0.25 mA
current, 130 μs pulse width), Medium (0.5-1.0 mA, 250 μs), or High (1.25-1.5 mA, 250 μs). A highly treatmentresistant population (>97% had failed to respond to ≥6 previous treatments) was enrolled. Response and adverse
effects were assessed for 22 weeks (end of acute phase), after which output current could be increased, if clinically
warranted. Assessments then continued until week 50 (end of long-term phase). During the acute phase, all groups
showed statistically significant improvement on the primary efficacy endpoint (change in Inventory of Depressive
Symptomatology-Clinician Administered Version [IDS-C]), but not for any between-treatment group comparisons. In
the long-term phase, mean change in IDS-C scores showed continued improvement. Post-hoc analyses demonstrated
a statistically significant correlation between total charge delivered per day and decreasing depressive symptoms; and
analysis of acute phase responders demonstrated significantly greater durability of response at Medium and High
doses than at the Low dose. The authors concluded that TRD patients who received adjunctive VNS showed significant
improvement at study endpoint compared with baseline, and the effect was durable over 1 year. The lack of a
controlled standard treatment comparator group limits the conclusions that can be reached from this study.
In a small, prospective, nonrandomized, controlled study, Sperling et al. (2009) measured improvement in depression
(HDRS28) for 12 months. Changes in the duration of depression-related hospitalization and the number of psychiatric
treatments per year were also evaluated. The study enrolled 9 patients receiving VNS as an adjunct to
pharmacotherapy and psychotherapy and 9 patients, sex-matched and age-matched to the VNS group, who continued
pharmacotherapy and psychotherapy but did not undergo device implantation. VNS significantly improved HDRS28
scores from 23.7 to 10.2 points at 12 months. There was no significant change in the control group. VNS also
significantly decreased the yearly number of days hospitalized from 65 to 44, while the hospitalization rate in the
control group did not change. VNS also reduced the number of psychiatric treatments from 33 to 24 per year. There
was no statistically significant change in this parameter for the control group. The respective values for the control
group were 24.9 and 25.3 treatments per year. While the study results suggest that VNS may improve depression,
the study used only one instrument to assess this outcome and did not include a sham control; therefore, the result
must be interpreted with caution since a placebo effect may have confounded the results. However, the additional
outcomes, duration of hospitalization, and number of psychiatric treatments are indirect measures, suggesting that
VNS may improve depression severity. Nevertheless, the small sample size and lack of blinded assessment are
additional factors compromising the quality of the evidence.
Bajbouj et al. (2010) assessed the efficacy and the safety of VNS in 74 patients with therapy-resistant major
depressive disorder. Psychometric measures were obtained after 3, 12, and 24 months of VNS. Mixed-model
repeated-measures analysis of variance revealed a significant reduction at all the 3 time points in the 28-item
Hamilton Rating Scale for Depression (HRSD28) score, the primary outcome measure. The proportion of patients who
fulfilled the remission criteria remained constant as the duration of VNS treatment increased. Voice alteration, cough,
and pain were the most frequently reported adverse effects. Two patients committed suicide during the study; no
other deaths were reported. No statistically significant differences were seen in the number of concomitant
antidepressant medications. According to the investigators, the results of this 2-year open-label trial suggest a clinical
response and a comparatively benign adverse effect profile among patients with treatment-resistant depression. The
lack of a control group limits the validity of the results of this study.
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A Comparative Effectiveness Review was prepared for the Agency for Healthcare Research and Quality (AHRQ) on
Nonpharmacologic Interventions for Treatment-Resistant Depression in Adults. The report identified only one study
(Rush 2005) comparing VNS to sham, conducted in a Tier 1 major depressive disorder (MDD)/bipolar mix population.
According to the AHRQ report, the majority of measures used by this study found no difference between VNS and
sham on changes in depressive severity or rates of response and remission. Since only a single study was identified
for this comparison, further assessment by key variables was not possible (Gaynes et al. 2011).
In a 2009 guidance document, the National Institute for Health and Care Excellence (NICE) stated that the current
evidence on the safety and efficacy of vagus nerve stimulation (VNS) for treatment resistant depression is inadequate
in quantity and quality. Therefore this procedure should be used only with special arrangements for clinical
governance, consent and audit or research. It should be used only in patients with treatment-resistant depression
(NICE, 2009).
Professional Societies
American Psychiatric Association (APA)
In a clinical practice guideline for the treatment of patients with major depressive disorder, the APA states that
electroconvulsive therapy remains the treatment of best established efficacy against which other stimulation
treatments (e.g., VNS, deep brain stimulation, transcranial magnetic stimulation, other electromagnetic stimulation
therapies) should be compared. The APA states that vagus nerve stimulation (VNS) may be an additional option for
individuals who have not responded to at least four adequate trials of depression treatment, including ECT [III]. For
patients whose depressive episodes have not previously responded to acute or continuation treatment with
medications or a depression focused psychotherapy but who have shown a response to ECT, maintenance ECT may be
considered [III]. Maintenance treatment with VNS is also appropriate for individuals whose symptoms have responded
to this treatment modality [III]. According to the APA, relative to other antidepressive treatments, the role of VNS
remains a subject of debate. However, it could be considered as an option for patients with substantial symptoms that
have not responded to repeated trials of antidepressant treatment. The three APA rating categories represent varying
levels of clinical confidence:

I: Recommended with substantial clinical confidence

II: Recommended with moderate clinical confidence

III: May be recommended on the basis of individual circumstances
(Gelenberg et al. 2010)
Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT)
In 2008-2009, the Canadian Psychiatric Association and the CANMAT partnered to produce evidence-based clinical
guidelines for the treatment of depressive disorders. Among the four forms of neurostimulation for depression
reviewed in the guidelines, electroconvulsive therapy (ECT) had the most extensive evidence, spanning seven decades.
Repetitive transcranial magnetic (rTMS) and vagus nerve stimulation (VNS) have been approved to treat depressed
adults in both Canada and the United States with a much smaller evidence base. Compared to other modalities for the
treatment of major depressive disorder (MDD), the data based is limited by the relatively small numbers of
randomized controlled trials (RCTs) and small sample sizes. The investigators concluded that there is the most
evidence to support ECT as a first-line treatment under specific circumstances and rTMS as a second-line treatment.
Evidence to support VNS is less robust and deep brain stimulation remains an investigational treatment (Kennedy,
2009).
Other Conditions
The use of vagus nerve stimulation has been investigated for other conditions including Alzheimer’s disease (Merrill et
al. 2006), anxiety (George et al. 2008), autism spectrum disorder (Levy et al. 2010), obsessive-compulsive disorder
(George et al. 2008), pain (Napadow et al. 2012; Ness et al. 2000), headaches (Cecchini et al. 2009; Mauskop, 2005;
Hord et al. 2003), obesity (Shikora et al. 2015; Ikramuddin et al. 2014; Sarr et al. 2012), sleep disorders (Marlow,
2001), heart disease/congestive heart failure (Gold et al. 2016: Zannard et al. 2015; Premchand et al. 2016), asthma
(Steyn et al. 2013; Miner et al. 2012), and fibromyalgia (Lange et al. 2011). However, because of limited studies,
small sample sizes and weak study designs, there is insufficient data to conclude that vagus nerve stimulation is safe
and/or effective for treating these indications. Further clinical trials demonstrating the clinical usefulness of vagus
nerve stimulation are necessary before it can be considered proven for these conditions.
Professional Societies
American Society for Metabolic and Bariatric Surgery
A position statement by the American Society for Metabolic and Bariatric Surgery addressing the use vagal blocking
therapy for treating obesity states that the quantity of the data available at this time and the length of follow-up
indicate adequate safety and efficacy in the short term. More prospective studies with longer follow-up are required to
establish the clinically significant efficacy and patient tolerance of this device (Papasavas et al. 2016).
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Additional Search Terms
Neuromodulation, pneumogastric nerve
U.S. FOOD AND DRUG ADMINISTRATION (FDA)
The FDA approved the NeuroCybernetic Prosthesis (NCP)® System (Cyberonics, Inc.) in July 1997 (P970003) for use
as an adjunctive therapy in reducing the frequency of seizures in adults and adolescents over 12 years of age with
medically refractory, partial-onset seizures. Since the original approval, there have been a number of modifications to
the device, the instruments used to implant the electrodes and the stimulator, and the software used to control and
program the stimulator. The NCP System cannot be used in patients after a left or bilateral cervical vagotomy.
Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf/p970003.pdf. (Accessed August 9, 2016)
In August 2001, manufacturers of neurostimulation devices advised against the use of shortwave, microwave or
therapeutic ultrasound diathermy for persons implanted with the devices. Diathermy may potentially cause the
generator or leads to heat up and damage tissue, causing pain and discomfort.
On May 10, 2005, the FDA issued a Public Health Notification regarding MRI-caused injuries in patients with implanted
neurostimulators. Available at:
http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/ucm062125.htm.
(Accessed August 9, 2016)
In July 2005, the VNS Therapy™ System (Cyberonics, Inc.) was approved for marketing by the FDA for the adjunctive
long-term treatment of chronic or recurrent depression for patients 18 years of age or older who are experiencing a
major depressive episode and have not had an adequate response to four or more adequate antidepressant
treatments (PMA Supplement 50). Available at:
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/RecentlyApprovedDevices/ucm078532.htm. (Accessed August 9, 2016)
The AspireSR Model 106 generator received FDA premarket approval in May 2015 (PMA P970003). The AspireSR is
part of Cyberonics’s VNS Therapy System. The AspireSR Model 106 has an additional, optional mode called AutoStim
Mode or Automatic Stimulation. This mode monitors and detects tachycardia heart rates, which may be associated
with an impending seizure, and automatically delivers stimulation to the vagus nerve. This device is from Cyberonics
now known as LivaNova. See the following website for more information:
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm?id=P970003S173. (Accessed July 25, 2016)
On January 14, 2015, the FDA approved the Maestro® VNB system for use in patients 18 years or older who have
been unable to lose weight with a weight-loss program and who have a BMI of at least 40 kg/m2 or greater than 35
kg/m2 with at least 1 other obesity-related condition. As part of the Maestro system approval, the manufacturer must
conduct a five-year postapproval study that will follow at least 100 patients and collect additional safety and
effectiveness data, including weight loss, adverse events, surgical revisions and explants, and changes in obesityrelated conditions. See the following websites for more information:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTopic/pma/pma.cfm?num=P130019

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm430223.htm.
(Accessed August 9, 2016)
To locate marketing clearance information for a specific device or manufacturer, search the Center for Devices and
Radiological Health (CDRH) 510(k) database or the Premarket Approval (PMA) database by product and/or
manufacturer name. Use product code LYJ (stimulator, autonomic nerve, implanted for epilepsy.
CENTERS FOR MEDICARE AND MEDICAID SERVICES (CMS)
Medicare covers vagus nerve stimulation (VNS) when criteria are met. Refer to the National Coverage Determination
(NCD) for Vagus Nerve Stimulation (160.18). Local Coverage Determinations (LCDs) exist, see the LCDs for
Peripheral Nerve and Peripheral Nerve Field Stimulation and Transcranial Magnetic Stimulation (TMS) for the
Treatment of Depression.
(Accessed August 11, 2016)
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electrical charge for treatment-resistant depression: acute and chronic effects. Brain Stimul. 2013 Jul;6(4):631-40.
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Bajbouj M, Merkl A, Schlaepfer TE, et al. Two-year outcome of vagus nerve stimulation in treatment-resistant
depression. J Clin Psychopharmacol. 2010 Jun;30(3):273-81.
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.
Boon P, Vonck K, van Rijckevorsel K, et al. A prospective, multicenter study of cardiac-based seizure detection to
activate vagus nerve stimulation. Seizure. 2015 Nov;32:52-61.
Cecchini AP, Mea E, Tullo V, et al. Vagus nerve stimulation in drug-resistant daily chronic migraine with depression:
preliminary data. Neurol Sci. 2009 May;30 Suppl 1:S101-4.
Daban C, Martinez-Aran A, Cruz N et al. (2008) Safety and efficacy of vagus nerve stimulation in treatment-resistant
depression. A systematic review. Journal of Affective Disorders 110: 1−15.
ECRI Institute. Emerging Technology Evidence Report. Rechargeable Vagal Blocking System (Maestro) for Treating
Obesity. July 2016.
ECRI Institute. Product Brief. AspireSR Generator for the VNS Therapy System (LivaNova, PLC) for Treating Epilepsy.
December 2015.
ECRI Institute. Product Brief. VNS Therapy System (Cyberonics, Inc.) for Treating Refractory Epilepsy. June 2015.
Archived.
Elliott RE, Morsi A, Geller EB, et al. Impact of Failed Intracranial Epilepsy Surgery on the Effectiveness of Subsequent
Vagus Nerve Stimulation. Neurosurgery. 2011 May 6.
Englot DJ, Rolston JD, Wright CW, et al. Rates and Predictors of Seizure Freedom With Vagus Nerve Stimulation for
Intractable Epilepsy. Neurosurgery. 2015 Nov 28.
Fisher RS, Afra P, Macken M, et al. Automatic Vagus Nerve Stimulation Triggered by Ictal Tachycardia: Clinical
Outcomes and Device Performance--The U.S. E-37 Trial. Neuromodulation. 2016 Feb;19(2):188-95.
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;53:666-669.
Gaynes BN, Lux L, Lloyd S, 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)
Evidencebased Practice Center under Contract No. 290-02-0016I.) AHRQ Publication No. 11-EHC056-EF. Rockville, MD:
Agency for Healthcare Research and Quality. September 2011.
Gelenberg AJ, Freeman MP, Markowitz JL, et al.; Work Group on Major Depressive Disorder. Practice Guidelines. Major
Depressive Disorder. Practice Guidelines for the Treatment of Patients with Major Depressive Disorders, 3 rd ed. Am J
Psychiatry. 2010;167(10S).
George MS, Nahas Z, Bohning DE, et al. Vagus nerve stimulation therapy: a research update. Neurology.
2002;59:S56-S61.
George MS, Rush JA, Marangell, LB, et al. A one-year comparison of vagus nerve stimulation with treatment as usual
for treatment resistant depression. Biol Psychiatry. 2005;58:364-373.
George MS, Ward HE Jr, Ninan PT, et al. C. A pilot study of vagus nerve stimulation (VNS) for treatment-resistant
anxiety disorders. Brain Stimul. 2008 Apr;1(2):112-21.
Gold MR, Van Veldhuisen DJ, Hauptman PJ, et al. Vagus Nerve Stimulation for the Treatment of Heart Failure: The
INOVATE-HF Trial. J Am Coll Cardiol. 2016 Jul 12;68(2):149-58.
Hammond EJ, Uthman BM, Reid SA, et al. Electrophysiological studies of cervical vagus nerve stimulation in humans: I.
EEG effects. Epilepsia. 1992;33(6):1013-1020.
Hayes, Inc. Hayes Clinical Research Response. AspireSR Model 106 (Cyberonics) for Vagus Nerve Stimulation.
Lansdale, PA: Hayes, Inc., February 2016.
Hayes, Inc. Hayes Medical Technology Directory Report. Vagus Nerve Stimulation for Depression. Lansdale, PA: Hayes,
Inc., October 2013. Updated August 2015.
Hayes, Inc. Hayes Medical Technology Directory Report. Vagus Nerve Stimulation for Epilepsy. Lansdale, PA: Hayes,
Inc., June 2014. Updated May 2016.
Hord ED, Evans MS, Mueed S, et al. The effect of vagus nerve stimulation on migraines. J Pain. 2003 Nov;4(9):530-4.
Ikramuddin S, Blackstone RP, Brancatisano A, et al. Effect of reversible intermittent intra-abdominal vagal nerve
blockade on morbid obesity: the ReCharge randomized clinical trial. JAMA. 2014 Sep 3;312(9):915-22.
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Kennedy SH, Milev R, Giacobbe P, et al; Canadian Network for Mood and Anxiety Treatments (CANMAT). 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 Oct;117 Suppl 1:S44-53.
Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task
Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010 Jun;51(6):1069-77.
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 Aug 3. doi: 10.1111/j.1526-4637.2011.01203.x.
Levy ML, Levy KM, Hoff D, et al. Vagus nerve stimulation therapy in patients with autism spectrum disorder and
intractable epilepsy: results from the vagus nerve stimulation therapy patient outcome registry. J Neurosurg Pediatr.
2010 Jun;5(6):595-602.
Malow BA, Edwards J, Marzec M, et al. Vagus nerve stimulation reduces daytime sleepiness in epilepsy patients.
Neurology. 2001 Sep 11;57(5):879-84.
Marangell LB, Rush AJ, George MS, et al. Vagus nerve stimulation (VNS) for major depressive episodes: one year
outcomes. Biol Psychiatry. 2002;51(4):280-287.
Martin JL, Martín-Sánchez E. Systematic review and meta-analysis of vagus nerve stimulation in the treatment of
depression: variable results based on study designs. Eur Psychiatry. 2012 Apr;27(3):147-55.
Mauskop A. Vagus nerve stimulation relieves chronic refractory migraine and cluster headaches. Cephalalgia. 2005
Feb;25(2):82-6.
Merrill CA, Jonsson MA, Minthon L, et al. Vagus nerve stimulation in patients with Alzheimer's disease: Additional
follow-up results of a pilot study through 1 year. J Clin Psychiatry. 2006 Aug;67(8):1171-8.
Miner JR, Lewis LM, Mosnaim GS, et al. Feasibility of percutaneous vagus nerve stimulation for the treatment of acute
asthma exacerbations. Acad Emerg Med. 2012 Apr;19(4):421-9. doi: 10.1111/j.1553-2712.2012.01329.x.
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. 2013 Oct 15;81(16):1453-9.
Nahas Z, Marangell LB, Husain MM, et al. Two year outcome of vagus nerve stimulation (VNS) for treatment of major
depressive episodes. J Clin Psychiatry 2005;66:1097-1104.
Napadow V, Edwards RR, Cahalan CM, et al. Evoked pain analgesia in chronic pelvic pain patients using respiratorygated auricular vagal afferent nerve stimulation. Pain Med. 2012 Jun;13(6):777-89.
National Institute for Health and Care Excellence (NICE). Vagus nerve stimulation for treatment-resistant depression.
December 2009.
National Institute for Health and Care Excellence (NICE).CG137. The epilepsies: the diagnosis and management of the
epilepsies in adults and children in primary and secondary care. January 2012. Last updated February 2016.
Ness TJ, Fillingim RB, Randich A, et al. Low intensity vagal nerve stimulation lowers human thermal pain thresholds.
Pain. 2000 May;86(1-2):81-5.
Nierenberg AA, Alpert JE, Gardner-Schuster EE, et al. Vagus nerve stimulation: 2-year outcomes for bipolar versus
unipolar treatment-resistant depression. Biol Psychiatry. 2008 Sep 15;64(6):455-60.
Panebianco M, Rigby A, Weston J, et al. Vagus nerve stimulation for partial seizures. Cochrane Database Syst Rev.
2015 Apr 3;4:CD002896.
Papasavas P, El Chaar M, Kothari SN; American Society for Metabolic and Bariatric Surgery Clinical Issues Committee.
American Society for Metabolic and Bariatric Surgery position statement on vagal blocking therapy for obesity. Surg
Obes Relat Dis. 2016 Mar-Apr;12(3):460-1.
Premchand RK, Sharma K, Mittal S, et al. Extended Follow-Up of Patients With Heart Failure Receiving Autonomic
Regulation Therapy in the ANTHEM-HF Study. J Card Fail. 2016 Aug;22(8):639-42.
Rush AJ, George MS, Sackeim HA, et al. Vagus nerve stimulation (VNS) for treatment-resistant depressions: a
multicenter study. Biol Psychiatry. 2000;47(4):276-286.
Rush JA, Marangell, LB, Sackeim HA, et al. Vagus nerve stimulation for treatment-resistant depression: A randomized
controlled acute phase trial. Biol Psychiatry. 2005a;58:347-354.
Rush JA, Sackeim HA, Marangell, LB, et al. Effects of 12 months of vagus nerve stimulation in treatment-resistant
depression: A naturalistic study. Biol Psychiatry. 2005b;58:355-363.
Ryvlin P, Gilliam FG, Nguyen DK, et al. The long-term effect of vagus nerve stimulation on quality of life in patients
with pharmacoresistant focal epilepsy: The PuLsE (Open Prospective Randomized Long-term Effectiveness) trial.
Epilepsia. 2014 Jun;55(6):893-900.
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Sarr MG, Billington CJ, Brancatisano R, et al.; EMPOWER Study Group. The EMPOWER study: randomized, prospective,
double-blind, multicenter trial of vagal blockade to induce weight loss in morbid obesity. Obes Surg. 2012
Nov;22(11):1771-82.
Schlaepfer TE, Frick C, Zobel A, et al. Vagus nerve stimulation for depression: efficacy and safety in a European study.
Psychol Med. 2008 May;38(5):651-61.
Shikora SA, Wolfe BM, Apovian CM, et al. Sustained Weight Loss with Vagal Nerve Blockade but Not with Sham: 18Month Results of the ReCharge Trial. J Obes. 2015;2015:365604.
Sperling W, Reulbach U, Kornhuber J. Clinical benefits and cost effectiveness of vagus nerve stimulation in a longterm treatment of patients with major depression. Pharmacopsychiatry. 2009;42(3):85-88.
Steyn E, Mohamed Z, Husselman C. Non-invasive vagus nerve stimulation for the treatment of acute asthma
exacerbations-results from an initial case series. Int J Emerg Med. 2013 Mar 19;6(1):7.
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. 2015 Feb 14;36(7):425-33.
POLICY HISTORY/REVISION INFORMATION
Date
03/01/2017




01/01/2017




Action/Description
Updated list of related policies to reflect title change for Community Plan policy
titled Deep Brain and Cortical Stimulation (previously titled Deep Brain
Stimulation)
Reformatted and reorganized policy; transferred content to new template
Updated list of related policies:
o Added reference link to policy titled Implanted Electrical Stimulator for Spinal
Cord
o Removed reference link to the United Behavioral Health New Technology
Evaluation titled Vagus Nerve Stimulation for Major Depressive Disorder
Revised coverage rationale:
o Replaced language indicating “vagus nerve stimulation (VNS) is proven and
medically necessary for treating epilepsy in patients with medically refractory
epileptic seizures” with “vagus nerve stimulation (VNS) is proven and
medically necessary for treating epilepsy in patients with medically refractory
epileptic seizures with failure of two or more trials of single or combination
antiepileptic drug therapy or intolerable side effects of antiepileptic drug
therapy”
o Added language to indicate:

Vagus nerve stimulation implants that allow detection and stimulation of
increased heart rate (e.g., AspireSR™ Model 106) are unproven and not
medically necessary for treating epilepsy

There is limited evidence to determine if vagus nerve stimulation
implants that allow detection and stimulation of increased heart rate are
beneficial for improving health outcomes in patients with epilepsy; larger,
long-term studies are needed to determine if this device is safe and
effective
Updated list of applicable CPT codes; removed 95970, 95974, and 95975
Updated list of applicable HCPCS codes; revised description for L8680
Updated supporting information to reflect the most current description of
services, clinical evidence, FDA and CMS information, and references
Archived previous policy version 2015T0101T
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