Download Implantable Electrical Nerve Stimulators

MEDICAL POLICY
POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
Original Issue Date (Created):
7/1/2002
Most Recent Review Date (Revised):
3/29/2016
Effective Date:
11/15/2016
POLICY
RATIONALE
DISCLAIMER
POLICY HISTORY
PRODUCT VARIATIONS
DEFINITIONS
CODING INFORMATION
DESCRIPTION/BACKGROUND
BENEFIT VARIATIONS
REFERENCES
I. POLICY
Vagus Nerve Stimulator
The vagus nerve stimulator may be considered medically necessary as a treatment of medically
refractory seizures. Medically refractory seizures are defined as seizures that occur in spite of
therapeutic levels of antiepileptic drugs or seizures that cannot be treated with therapeutic levels
of antiepileptic drugs because of intolerable adverse effects of these drugs.
The use of a vagus nerve stimulator is considered investigational for treatment of other
conditions including but not limited to heart failure, fibromyalgia, depression, essential tremor,
headaches, obesity, tinnitus, and traumatic brain injury, as there is insufficient evidence to
support a conclusion concerning the health outcomes or benefits associated with this procedure.
Peripheral Nerve Stimulator
Implantation of a peripheral nerve stimulator may be considered medically necessary to
alleviate chronic intractable pain.
Autonomic (phrenic) Nerve Stimulator
Implantation of an autonomic (phrenic) nerve stimulator may be considered medically
necessary for the treatment of patients with partial or complete respiratory insufficiency.
Implantation of an autonomic nerve stimulator other than phrenic nerve is considered
investigational, as there is insufficient evidence to support a conclusion concerning the health
outcomes or benefits associated with this procedure.
Implantation of an autonomic (phrenic) nerve stimulator for conditions other than partial or
complete respiratory insufficiency is considered investigational, as there is insufficient evidence
to support a conclusion concerning the health outcomes or benefits associated with this
procedure.
Page 1
MEDICAL POLICY
POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
Cross-references:
MP-1.042 Deep Brain Stimulation
MP-6.020 Electrical Stimulation Modalities
MP-1.141 Peripheral Subcutaneous Field Stimulation (PSFS)
MP-1.069 Spinal Cord Stimulation
II. PRODUCT VARIATIONS
TOP
This policy is applicable to all programs and products administered by Capital BlueCross unless
otherwise indicated below.
FEP PPO*
* Refer to FEP Medical Policy Manual MP-7.01.20, Vagus Nerve Stimulation. The FEP Medical
Policy Manual can be found at: www.fepblue.org
* The FEP program dictates that all drugs, devices or biological products approved by the U.S.
Food and Drug Administration (FDA) may not be considered investigational. Therefore, FDAapproved drugs, devices or biological products may be assessed on the basis of medical
necessity.
III. DESCRIPTION/BACKGROUND
TOP
Vagus Nerve Stimulation (VNS)
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 therapeutic effects of VNS are not fully understood, the basic
premise of VNS in the treatment of various conditions 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.
Page 2
MEDICAL POLICY
POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
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 2 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 are also available. The Maestro® System (EnteroMedics,
St. Paul, MN) consists of a subcutaneously-implanted pulse generator and electrodes that are
placed in contact with the trunks of the vagus nerve at the gastroesophageal junction. These types
of stimulators differ in the location of the pulse generator and electrodes and the stimulation
programming settings, and are not addressed in this policy.
Potential Indications for VNS
VNS was originally approved for the treatment of medically refractory epilepsy. Significant
advances have occurred in surgical treatment for epilepsy and in medical treatment of epilepsy
with newly developed and approved medications. Despite these advances, however, 25% to 50%
of patients with epilepsy experience breakthrough seizures or suffer from debilitating adverse
effects of antiepileptic drugs. VNS has been used as an alternative to or adjunct to epilepsy
surgery or medications as a therapy for refractory seizures.
Based on observations that patients treated with VNS experienced improvements in mood, VNS
has been evaluated for the treatment of refractory depression. VNS has been investigated for
multiple other conditions which may be affected by either the afferent or efferent stimulation of
the vagus nerve, including headaches, tremor, obesity, heart failure, fibromyalgia, tinnitus, and
traumatic brain injury.
Regulatory Status
In 1997, FDA approved a VNS device called the NeuroCybernetic Prosthesis (NCP®) system
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.”
Since 1997, it has been reported that recipients of a vagus nerve stimulator have experienced
improvements in mood. Therefore, there has been research interest in VNS as a treatment for
refractory depression. On July 15, 2005, Cyberonics received PMA supplement approval by
FDA for the VNS Therapy™ System “for the adjunctive long-term treatment of chronic or
recurrent depression for patients 18 years of age or older who are experiencing a major
depressive episode and have not had an adequate response to four or more adequate
antidepressant treatments.”
VNS therapy has also been investigated for use in other conditions such as headaches, obesity,
and essential tremors. FDA product code: LYJ.
Page 3
MEDICAL POLICY
POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
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.
Peripheral Nerve Stimulator
Peripheral nerve stimulation involves the implantation of electrodes around a selected peripheral
nerve and is used to treat chronic intractable pain. Electrodes are placed around a selected
peripheral nerve. The stimulating electrode is connected by an insulated lead to a receiver unit
that is inserted subcutaneously at a depth not greater than half an inch. Sciatic and ulnar nerves
are common sites for implantation. Stimulation of the nerve is created by a generator that is
connected to an antenna that is attached to the skin surface over the receiver unit.
Autonomic (phrenic) Nerve Stimulator
The phrenic nerve stimulator provides electrical stimulation of the patient's phrenic nerve to
contract the diaphragm rhythmically and produce breathing in patients who have hypoventilation
(a state in which an abnormally low amount of air enters the lungs). The device has been used
successfully to treat hypoventilation caused by a variety of conditions, including respiratory
paralysis resulting from lesions of the brain stem and cervical spinal cord and chronic pulmonary
disease with ventilatory insufficiency. The phrenic nerve stimulator is intended to be an
alternative to management of patients with respiratory insufficiency who are dependent upon the
usual therapy of intermittent or permanent use of a mechanical ventilator as well as maintenance
of a permanent tracheotomy stoma.
However, an implanted phrenic nerve stimulator can be effective only if the patient has an intact
phrenic nerve and diaphragm. Moreover, nerve injury may occur during the surgical procedure
and if sufficient injury is incurred, the device will not prove useful to the patient. Consequently,
it is possible for such a device to be indicated for a patient but, due to injury sustained during
implant, fail to assist the patient, resulting in a return to the use of mechanical ventilation.
IV. RATIONALE
TOP
Vagus Nerve Stimulator
Page 4
MEDICAL POLICY
POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
Treatment of Seizures
Vagus Nerve Stimulation for Adult Partial-Onset Seizures
The policy regarding treatment of seizures has expanded the indications over time but was
originally based, in part, on a 1998 TEC Assessment1 that offered the following conclusions.



Published evidence from 2 large, well-designed multicenter randomized trials involving
over 300 patients demonstrates that the use of vagus nerve stimulation (VNS) as an
adjunct to optimal use of antiepileptic drugs in the treatment of medically refractory
patients with at least 6 partial-onset seizures/month reduces seizure frequency by
approximately 25% after 3 months of treatment. In patients who achieve an initial
reduction in seizure frequency, the beneficial treatment effect appears to be maintained
and may increase with time.
Adverse effects are mild and consist primarily of hoarseness or voice change during “on”
periods of stimulation.
There is limited information about the use of VNS in patients with other types of seizure
disorders.
Based on this TEC Assessment, earlier versions of this policy supported the use of VNS for
partial-onset seizures for patients older than 12 years of age. A randomized controlled trial
(RCT) published in 2014 reported long-term quality of life outcomes for 112 patients with
pharmacoresistant focal seizures, which supported the beneficial effects of VNS for this group.2
VNS for Adult Generalized Seizures
Tecoma and Iragui observed in a 2006 review that, since approval of VNS for partial seizures, a
number of case series including patients with generalized seizures have been published. These
series report seizure reduction rates similar to or greater than those reported in partial epilepsy
and note that “this body of evidence suggests that VNS has broad antiepileptic efficacy.”3 The
authors suggest that these results may be particularly important because resective epilepsy
surgery is generally not feasible in these patients.
Other reports published since the Tecoma and Iragui review are consistent with the authors’
observations. In a French study of 50 consecutive refractory adolescents and adults who were not
eligible for surgery and 11 of whom had generalized epilepsy, 58% were classified as responders
at 3 year follow-up.4 Generalized epilepsy was predictive of a better outcome than partial
epilepsy seizures. Seizure reduction of 61% was also reported in a case series of 12 patients with
drug-resistant idiopathic generalized epilepsy.5 Garcia-Navarrete et al evaluated outcomes after
18 months of follow-up for a prospectively followed cohort of 42 patients with medicationresistant epilepsy who underwent VNS implantation.6 Subjects’ seizure types were
heterogeneous, but 52% had generalized epilepsy. Pharmacotherapy was unchanged during the
course of the study. Twenty-seven subjects (63%) were described as “responders,” defined as
having a 50% or greater reduction in seizure frequency compared with the year before VNS
implantation. The reduction in seizure frequency was not statistically significantly different
between subjects with generalized and focal epilepsy.
Page 5
MEDICAL POLICY
POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
VNS for Childhood Seizures
Since publication of the 1998 TEC assessment, there has been interest in expanding the use of
VNS to younger patients. Several studies have now reported results that support the safety and
efficacy of the device in children with refractory seizures.7 For example, 60 pediatric patients
were treated as part of the double-blind clinical trials conducted to support the U.S. Food and
Drug Administration (FDA) application.8 At 18 months, the median reduction in seizure
frequency was 50%, similar to the results achieved in adults. Adverse events were also similar to
those recently reported in adults,9 and none resulted in termination of stimulation. Hornig et al
reported on a case series of 19 pediatric patients, with observation periods ranging up to 30
months.10 Overall, 50% of patients had a 50% reduction in seizure frequency. Patwardhan et al
reported that among 38 patients aged 11 months to 16 years with medically refractory seizures,
both generalized and partial-onset, 29% had a greater than 90% reduction in seizure frequency
after VNS implantation, while 39% had 50% to 90% reduction.11 Healy et al reported that among
16 patients younger than 12 years who underwent VNS implantation at a single center, 9 (56%)
experienced a reduction in their seizure frequency of 50% or more.12 Results from an add-on
study to an RCT designed to compare high-output with low-output VNS stimulation among 41
children with medically refractory epilepsy suggest that VNS does not have adverse effects on
cognitive or psychosocial outcomes.13 Other studies of pediatric patients that included patients
with generalized and partial-onset seizures have supported the use of VNS in reducing seizure
frequency. These have included a series of 41 children treated with VNS, randomized to a highor low-dose stimulation protocol,14 a retrospective case-control study with 36 VNS patients
compared with 72 age- and sex-matched controls with refractory epilepsy not treated with
VNS,15 a retrospective cohort study including 252 pediatric patients with a variety of seizure
types treated with VNS,16 and a retrospective cohort study of 347 children with a variety of
seizure types followed for up to 2 years postimplantation.17
Similar to adult studies, pediatric studies suggest that VNS improves seizure frequency in
generalized epilepsy syndromes. In a multicenter study of 28 children with refractory seizures,
You et al reported that 15 children (53.6%) showed a greater than 50% reduction in seizure
frequency and 9 (32%) had a greater than 75% reduction, and there were no significant
differences when groups were compared by seizure type or etiology.18 Tecoma and Iragui cite a
multicenter retrospective analysis of 50 children with Lennox Gastaut syndrome (LGS) treated
with VNS.3 Median seizure reduction at 6 months was 88% for tonic seizures and 81% for
atypical absence. You et al compared VNS and total corpus callosotomy for LGS.19 Of the 14
patients who underwent a corpus callosotomy, 9 (64%) had a greater than 50% reduction in
seizure frequency and 5 (36%) had a greater than 75% reduction. Of the 10 patients who
underwent VNS implantation, 7 (70%) had a greater than 50% reduction in seizure frequency
and 2 (20%) had a greater than 75% reduction. For 24 children with LGS or LGS-like syndrome
who underwent VNS implantation, Cukiert et al reported that at least a 50% seizure frequency
decrease was seen for 35 different seizure types.20
The major limitations of VNS are the following issues: stimulation generally does not
completely eliminate seizures, and it is not possible to predict which patients will optimally
Page 6
MEDICAL POLICY
POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
respond. One meta-analysis that included 74 retrospective and prospective studies assessing VNS
efficacy in seizures found that predictors of efficacy included generalized epilepsy or mixed
seizure types (compared with partial-onset seizures) and age younger than 18 years.21 In 2013,
Arya et al reported results of a single-center retrospective chart review that included 43 pediatric
patients who underwent VNS implantation over a 5-year period; the authors found that absence
of magnetic resonance imaging lesion predicted a good outcome.22 These studies support the use
of VNS in children, in patients with generalized epilepsy, and in those who are not candidates for
surgery (ie, no identified structural brain abnormality).
Section Summary
The evidence on the efficacy of VNS for treatment of refractory seizures consists of 2 RCTs and
numerous uncontrolled studies. The RCTs both 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
large reduction in seizures includes substantial numbers of patients who achieve a greater than
50% reduction in seizure frequency.
Treatment of Refractory Depression
Interest in the application of VNS for treatment of refractory depression is related to reports of
improvement in depressed mood among epileptic patients undergoing VNS.23 TEC Assessments
written in 2005 and updated in 2006 concluded that evidence was insufficient to permit
conclusions of the effect of VNS therapy on health outcomes.24,25 The available evidence for
these TEC Assessments included study groups assembled by the manufacturer of the device
(Cyberonics) and have since been reported on in various publications.26,27 Analyses from these
study groups were presented for FDA review and consisted of a case series of 60 patients
receiving VNS (Study D-01), a short-term (ie, 3-month) sham-controlled RCT of 221 patients
(Study D-02), and an observational study comparing 205 patients on VNS therapy with 124
patients receiving ongoing treatment for depression (Study D-04).28 Patients who responded to
sham treatment in the short-term RCT (10%) were excluded from the long-term observational
study.
The primary outcome evaluated was the relief of depression symptoms that can usually be
assessed by any one of many different depression symptom rating scales. A 50% reduction from
baseline score is considered to be a reasonable measure of treatment response. An improvement
in depression symptoms may allow reduction of pharmacologic therapy for depression, with a
reduction in adverse effects related to that form of treatment. In the studies evaluating VNS
therapy, the 4 most common instruments used were the Hamilton Rating Scale for Depression,
Clinical Global Impression, Montgomery and Asberg Depression Rating Scale, and the
Inventory of Depressive Symptomatology (IDS).
Several case series studies published before the randomized trial showed rates of improvement,
as measured by a 50% improvement in depression score of 31% at 10 weeks to greater than 40%
Page 7
MEDICAL POLICY
POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
at 1 to 2 years, but there are some losses to follow-up.29-31 Natural history, placebo effects, and
patient and provider expectations make it difficult to infer efficacy from case series data.
The randomized study (D-02) that compared VNS therapy with a sham control (implanted but
inactivated VNS) showed a nonstatistically significant result for the principal outcome.27,28
Fifteen percent of VNS subjects responded versus 10% of control subjects (p=0.31). The
Inventory for Depressive Symptomatology Systems Review (IDS-SR) score was considered a
secondary outcome and showed a difference in outcome that was statistically significant in favor
of VNS (17.4% vs 7.5%, respectively, p=0.04).
The observational study that compared patients participating in the RCT and a separately
recruited control group (D-04 vs D-02, respectively) evaluated VNS therapy out to 1 year and
showed a statistically significant difference in the rate of change of depression score.26,28
However, issues such as unmeasured differences between patients, nonconcurrent controls,
differences in sites of care between VNS therapy patients and controls, and differences on
concomitant therapy changes raise concern about this observational study. Analyses performed
on subsets of patients cared for in the same sites, and censoring observations after treatment
changes, generally showed diminished differences in apparent treatment effectiveness of VNS
and almost no statistically significant differences.28 Patient selection for the randomized trial and
the observational comparison trial may be of concern. VNS is intended for treatment-refractory
depression, but the entry criteria of failure of 2 drugs and a 6-week trial of therapy may not be a
strict enough definition of treatment resistance. Treatment-refractory depression should be
defined by thorough psychiatric evaluation and comprehensive management. It is important to
note that patients with clinically significant suicide risk were excluded from all VNS studies.
Given these concerns about the quality of the observational data, these results did not provide
strong evidence for the effectiveness of VNS therapy.
In addition to the results of the TEC Assessment, several systematic reviews and meta-analyses
have addressed the role of VNS in treatment resistant depression. A systematic review of the
literature for VNS of treatment-resistant depression identified the randomized trial previously
described among the 18 studies that met the study’s inclusion criteria.32 VNS was found to be
associated with a reduction in depressive symptoms in the open studies. However, results from
the only double-blind trial were considered to be inconclusive.27,28 Daban et al concluded that
further clinical trials are needed to confirm efficacy of VNS in treatment-resistant depression.
In a meta-analysis that included 14 studies, Martin and Martin-Sanchez reported that among the
uncontrolled studies in their analysis, 31.8% of subjects responded to VNS treatment.33
However, results from a meta-regression to predict each study’s effect size suggested that 84%
of the observed variation across studies was explained by baseline depression severity. Berry et
al reported results from a meta-analysis of 6 industry-sponsored studies of safety and efficacy for
VNS in treatment-resistant depression, which included the D-01, D-02, Bajbouj et al (D-03), D04, and Aaronson et al (D-21) study results.34 In addition, the meta-analysis used data from a
registry of patients with treatment-resistant depression (335 patients receiving VNS and
treatment as usual and 301 patients receiving treatment as usual) that were unpublished at the
Page 8
MEDICAL POLICY
POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
time of the meta-analysis publication (ClinicalTrials.gov identifier: NCT00320372). The authors
report that adjunctive VNS was associated with a greater likelihood of treatment response (odds
ratio, 3.19; 95% confidence interval [CI], 2.12 to 4.66). However, the meta-analysis did not have
systematic study selection criteria, limiting the conclusions that can be drawn from it.
In 2014, Liu et al conducted a systematic review of brain stimulation treatments, including deep
brain stimulation, electroconvulsive therapy, transcranial magnetic stimulation, and VNS, for
mental illnesses other than nonpsychotic unipolar depression in adults 65 years or older.35 The
authors identified 2 small studies which evaluated the effect of VNS on cognition in patients
with Alzheimer disease, 1 with 10 subjects and 1 with 17 subjects, which were mixed in
demonstrating clinical improvements.
In 2013, Aaronson et al reported results from an active-controlled trial in which 331 patients with
a history of chronic or recurrent bipolar disorder or major depressive disorder, with a current
diagnosis of a major depressive episode, were randomized to 1 of 3 VNS current doses (high,
medium, low).36 Patients had a history of failure to respond to at least 4 adequate dose/duration
of antidepressant treatment trials from at least 2 different treatment categories. After 22 weeks,
the current dose could be adjusted in any of the groups. At follow-up visits at weeks 10, 14, 18,
and 22 after enrollment, there was no statistically significant difference between the dose groups
for the study’s primary outcome, change in IDS score from baseline. However, the mean IDS
score improved significantly for each of the groups from baseline to the 22-week follow-up. At
50 weeks of follow-up, there were no significant differences between the treatment dose groups
for any of the depression scores used. Most patients completed the study; however, there was a
high rate of reported adverse events, including voice alteration in 72.2%, dyspnea in 32.3%, and
pain in 31.7%. Interpretation of the IDS improvement over time is limited by the lack of a no
treatment control group. Approximately 20% of the patients included had a history of bipolar
disorder; as such, the results may not be representative of most patients with treatment resistant
unipolar depression.
Other case series do not substantially strengthen the evidence supporting VNS. A case series
study by Bajbouj et al that followed patients for 2 years showed that 53.1% (26/49) patients met
criteria for a treatment response and 38.9% (19/49) met criteria for remission.37 A small study of
9 patients with rapid-cycling bipolar disorder showed improvements in several depression rating
scales over 40 weeks of observation.38 Another case series by Cristancho et al that followed
patients for 1 year showed that 4 of 15 responded and 1 of 15 remitted according to the principal
response criteria.39 In a 2014 case series which included 27 patients with treatment resistant
depression, 5 patients demonstrated complete remission after 1 year and 6 patients were
considered responders.40
Adverse effects of VNS therapy included voice alteration, headache, neck pain, and cough,
which are known from prior experience with VNS therapy for seizures. Regarding specific
concerns for depressed patients such as mania, hypomania, suicide, and worsening depression,
there does not appear to be a greater risk of these events during VNS therapy.28
Page 9
MEDICAL POLICY
POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
Section Summary
There is 1 RCT evaluating the efficacy of VNS for resistant depression. This study reported only
short-term results and found no significant improvement for the primary outcome with VNS.
Other available studies, which include nonrandomized comparative studies and case series, are
limited by relatively small sizes and the potential for bias in selection; the case series are further
limited by the lack of a control group .Given the limitations of this literature, combined with the
lack of substantial new clinical trials, the scientific evidence is considered to be insufficient to
permit conclusions concerning the effect of this technology on major depression.
Other Conditions
Treatment of Essential Tremor
Handforth et al studied VNS in 9 patients with essential tremor.41 Four weeks after implantation
of the VNS device, tremor assessment using a masked videotape of patients was performed.
Raters found no improvement in upper-extremity tremors. Therefore, the authors of the study
concluded that VNS is not likely to have any clinically meaningful effect in essential tremor
treatment.
Treatment of Headaches
Drawing on the analgesic effects noted with VNS in the treatment of depression, Mauskop
evaluated VNS in 5 patients with severe, refractory chronic cluster and migraine headaches.42
Mauskop reported excellent results in 1 patient who was able to return to work and significant
improvement in 2 patients. Other than nausea developed by 1 patient, VNS was well-tolerated.
Cecchini et al evaluated VNS in 4 patients suffering from daily headache and chronic migraine.43
However, these studies are too small to draw conclusions on the effects of VNS for the treatment
of headache, and further study is needed.
Treatment of Obesity
Unintended weight loss has been observed in participants in studies of VNS, prompting interest
in use of the technology to prevent or treat obesity. Bodenlos et al investigated whether VNS
might affect food cravings in patients with chronic, treatment-resistant depression.44 They
recruited 33 participants and divided them into 3 groups; 11 subjects receiving VNS for
depression, 11 patients with depression but not receiving VNS, and 11 healthy controls. Most
participants (42%) had a body mass index (BMI) in the normal range. Participants viewed food
images on a computer in random order and then a second time in the same order and were asked
after each viewing how much they would like to eat each food if it were available and how well
they would be able to resist tasting each one. VNS devices were turned on for one viewing and
off for the other. The depression VNS group had greater differences in food cravings between
viewings in the sweet food category than the other 2 groups. No significant differences between
groups were found for foods in proteins and vegetables/fruits categories. A significant proportion
of the variability in VNS-related changes in cravings for sweet foods was attributed to clinical
VNS device settings, depression scores, and BMI. A number of limitations in the study prevent
drawing conclusions about the impact of VNS on eating behavior including small study size,
Page 10
MEDICAL POLICY
POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
selection and lack of randomization, heterogeneity of groups with respect to depression, BMI,
and age. Comorbidities including anxiety and medical conditions and drugs that might influence
food intake and cravings were not considered. Large, well-designed and executed controlled
studies are needed to evaluate the impact of VNS on eating behavior and obesity.
Treatment of Chronic Heart Failure
In 2014, Zannand et al reported results from the NECTAR-HF trial, a randomized, shamcontrolled trial, with outcomes from VNS in patients with severe left ventricular (LV)
dysfunction, despite optimal medical therapy.45 Ninety-six patients were implanted with VNS
and randomized in a 2:1 manner to VNS ON or VNS OFF for 6 months. Programming of the
generator was performed by a physician unblinded to treatment assignment, while all other
investigators and site study staff involved in end point data collection were blinded to
randomization. Sixty-three patients were randomized to the intervention, of whom 59 had paired
pre-post data available, while 32 were randomized to control, of whom 28 had paired data
available. The analysis was a modified intention-to-treat. For the primary end point of change in
left ventricular end systolic diameter (LVESD) from baseline to 6 months, there were no
significant differences between groups (p=0.60 between-group difference in LVESD change).
Other secondary efficacy end points related to LV remodeling parameters, LV function, and
circulating biomarkers of heart failure, did not differ between groups, with the exception of 36Item Short-Form Health Survey Physical Component score, which showed greater improvement
in the VNS ON group than in the control group (from 36.3 to 41.2 in the VNS ON group vs from
37.7 to 38.4 in the control group; p=0.02). Subject blinding was found to be imperfect, which
may have biased the subjective outcome data reporting.
In the ANTHEM-HF study, 60 patients with heart failure with reduced ejection fraction were
implanted with VNS, randomly assigned to right- or left-sided implantation (n=29 and 31,
respectively), and followed for 6 months.46 Overall, from baseline to 6-month follow-up, LV
ejection fraction improved by 4.5% (95% CI, 2.4 to 6.6), left ventricular end systolic volume
(LVESV) improved by -4.1 mL (95% CI, -9.0 to 0.8), LVESD improved by -1.7 mm (95% CI, 2.8 to -0.7), heart rate variability improved by 17 ms (95% CI, 6.5 to 28), and 6-minute walk
distance improved by 56 m (95% CI, 37 to 75). A case series phase 2 trial of VNS therapy for
chronic heart failure was published previously, which reported improvements in New York Heart
Association class quality of life, 6-minute walk test, and LV ejection fraction.47
Treatment of Fibromyalgia
Lange et al conducted a phase 1/2 trial of VNS of 14 patients with fibromyalgia.48 At 3 months, 5
patients had attained efficacy criteria based on a composite measure of improvement of
fibromyalgia symptoms. At 11 months, 8 patients met efficacy criteria. This single-arm trial does
not provide sufficient evidence for efficacy of VNS for this indication.
Treatment of Tinnitus
A 10-patient case series by De Ridder et al suggested that VNS may be associated with clinical
improvements in patients with tinnitus.49
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POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
Treatment of Traumatic Brain Injury
Shi et al have FDA approval to conduct a small pilot study to evaluate VNS in the treatment of
traumatic brain injury.50
Nonimplantable VNSs
Transcutaneous VNS for Epilepsy
Aihua et al reported results from a series of 60 patients with pharmacoresistant epilepsy treated
with a transcutaneous VNS (t-VNS) device, who were randomly assigned to receive stimulation
over the earlobe (control group) or the Ramsay-Hunt zone, which includes the external auditory
canal and the conchal cavity and is considered to be the somatic sensory territory of the vagus
nerve.51 Thirty patients were randomized to each group; 4 subjects from the treatment group
were excluded from analysis due to loss to follow-up (n=3) or adverse effects (n=1), while 9
subjects from the control group were excluded from analysis due to loss to follow-up (n=2) or
increase or lack of decrease in seizures or other reasons (n=7). In the treatment group, compared
with baseline, the median monthly seizure frequency was significantly reduced after 6 months
(5.5 vs 6.0; p<0.001) and 12 months (4.0 vs 6.0; p<0.001) of t-VNS therapy. At 12-month
follow-up, t-VNS group subjects had a significantly lower median monthly seizure frequency
compared with the control group (4.0 vs 8.0; p<0.001).
Two small case series were identified that used a transcutaneous stimulator (t-VNS device) for
treatment of medication refractory seizures. In a small case series of 10 patients with treatment
resistant epilepsy, Stefan et al reported that 3 patients withdrew from the study, while 5 of 7
patients reported a reduction in seizure frequency.52 In another small case series, He et al
reported that among 14 pediatric patients with intractable epilepsy who were treated with
bilateral t-VNS stimulation, of the 13 patients who completed follow-up, mean reduction in selfreported seizure frequency was 31.8% after 8 weeks, 54.1% from week 9 to 16, and 54.2% from
week 17 to 24.53
Transcutaneous VNS for Psychiatric Disorders
Hein et al reported results of 2 pilot RCTs of a t-VNS device for the treatment of depression, one
which included 22 subjects and one with 15 subjects.54 In the first study, 11 subjects each were
randomized to active or sham t-VNS. At 2 weeks follow-up, Beck Depression Inventory (BDI)
self-rating scores in the active-stimulation group decreased from 27.0 to 14.0 (p< 0.000), while
the sham-stimulated patients did not show significant reductions in the BDI (31.0–25.8 points).
In the second study, 7 patients were randomized to active t-VNS and 8 patients were randomized
to sham t-VNS. In this study, BDI self-rating scores in the active stimulation group decreased
from 29.4 to 17.4 (p<0.05) after 2 weeks, while the sham-stimulated patients did not show
significant change in BDI (28.6 to 25.4). The authors do not report direct comparisons in BDI
change between the sham- and active-stimulation groups.
Shiozawa et al conducted a systematic review of studies evaluating the evidence related to
transcutaneous trigeminal or VNS for psychiatric disorders.55 In the article text, the authors state
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POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
that they reviewed studies, 4 of which addressed t-VNS for psychiatric disorders and included a
total of 84 subjects. Of those 4, 3 of the studies evaluated physiologic parameters in healthy
patients, and 1 evaluated pharmacoresistant epilepsy (Stefan et al, previously described52). The
authors also include a fifth study in 1 data table, although not in their text or reference list (Hein
et al, previously described54) Overall, the studies included were limited by small size and poor
generalizability.
Transcutaneous VNS for Other Disorders
Goadsby et al reported results from an open-label pilot study of t-VNS for the treatment of
migraine with or without aura.56 Eighty migraine attacks were self-treated by 27 patients, of an
initial sample of 30 patients (2 patients treated no migraine attacks with the device, 1 patient
treated only an aura). Of 54 moderate or severe attacks treated, 12 subjects (22%) were pain-free
at 2 hours posttreatment. Thirteen subjects reported adverse events, which were all considered
mild or moderate.
Kreuzer et al reported a single-armed pilot study of t-VNS with 2 different devices for the
treatment of tinnitus.57 Forty-eight subjects were included in the study’s primary intention-totreat analysis. For the study’s primary outcome of change in mean Tinnitus Questionnaire (TQ)
score from baseline to 6-month follow-up, for the 24 subjects in the first phase of the study, who
had used an earlier generation t-VNS device (Cerbomed), the TQ total score decreased by 3.7
points (p=0.036). Nine subjects (37.5%) were considered responders. For the 24 subjects in the
second phase of the study, who had used a later-generation t-VNS device (Cerbomed), the mean
TQ score decreased by 2.8 points (p=0.014). Eleven subjects were considered responders
(45.8%). In a per-protocol analysis, which included 28 subjects who received treatment, there
was no significant improvement in TQ scores. The authors conclude that t-VNS treatment did
not result in significant improvement in tinnitus.
Huang et al reported results of a pilot RCT of a t-VNS device that provides stimulation to the
auricle for the treatment of impaired glucose tolerance.58 The study included 70 patients with
impaired glucose tolerance who were randomized to active or sham t-VNS, along with 30
controls who received no t-VNS treatment. After 12 weeks of treatment, patients who received
active t-VNS were reported to have significantly lower 2-hour glucose tolerance test results than
those who received sham t-VNS (7.5 vs 8 mmol/L; p=0.004).
Section Summary
Transcutaneous VNS has been investigated for a number of conditions. Some evidence for the
efficacy of t-VNS for epilepsy comes 1 small RCT, which reported lower seizure rates for active
t-VNS-treated patients compared with sham controls; however, the high dropout rates in this
study limit conclusions that may be drawn. One small RCT which compared t-VNS with sham
stimulation for the treatment of depression demonstrated some improvements in depression
scores with t-VNS; however, the lack of comparisons between groups limits conclusions that
may be drawn. Additional RCT evidence is needed to permit conclusions about whether t-VNS
is associated with improved outcomes for epilepsy, depression, or other conditions.
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IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
Ongoing and Unpublished Clinical Trials
A search of ClinicalTrials.gov in January 2015 identified the following comparative studies of
VNS that are currently enrolling patients (see Table 1).
Table 1: Ongoing Comparative Studies of VNS
Trial Name
Noninvasive Neurostimulation of the Vagus Nerve
for the Treatment of Cluster Headache
A Randomized Multicenter Study for the Acute Relief
of Episodic and Chronic Headache
Pilot Study: Anti-inflammatory Effect of Perioperative
Stimulation of the Vagus Nerve
Controlled Randomized Vagus Nerve Stimulation
(VNS) Therapy Versus Resection (CoRaVNStiR)
Increase Of Vagal Tone in CHF (INOVATE-HF)
Trials No.
NCT01792817
Planned
Enrollment
150
Estimated Study
Completion Date
Jun 2014
NCT01958125
108
Mar 2014
NCT01572155
24
Sep 2014
NCT02089243
40
NCT01303718
650
Jul 2016
(follow-up through Jul 2017)
Jun 2015
Summary of Evidence
For patients with refractory seizures, evidence from randomized controlled trials (RCTs) and
multiple observational studies supports a reduction in seizure frequency following vagus nerve
stimulation (VNS). A TEC Assessment concluded that the evidence is sufficient to permit
conclusions on the efficacy of this technique for treatment of refractory seizures. Therefore, VNS
may be considered medically necessary for patients with refractory seizures.
For patients with depression, there is some evidence supporting improvements in depressive
symptoms after VNS. However, there are a number of limitations of these data, including
uncertain clinical significance, lack of evidence on durability, and lack of comparison with
alternative treatments. As a result, it is not clear if VNS is as effective as alternatives for specific
populations of patients with depression, and VNS is considered investigational for this
indication.
For other conditions, including but not limited to headaches, obesity, essential tremor, heart
failure, fibromyalgia, tinnitus, and traumatic brain injury, the evidence is limited and not
sufficient to permit conclusions on efficacy. VNS is considered investigational for these
indications.
The body of evidence for the use of transcutaneous VNS (t-VNS) consists of small RCTs with
methodologic limitations and case series. The evidence is insufficient to allow conclusions on the
efficacy of t-VNS, and there are no transcutaneous stimulation devices that have U.S. Food and
Drug Administration approval; therefore, transcutaneous VNS is considered investigational.
Practice Guidelines and Position Statements
American Academy of Neurology
In 1999, the American Academy of Neurology (AAN) released a consensus statement on the use
of VNS in adults that stated, “VNS is indicated for adults and adolescents over 12 years of age
with medically intractable partial seizures who are not candidates for potentially curative surgical
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MEDICAL POLICY
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IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
resections, such as lesionectomies or mesial temporal lobectomies.”59 AAN released an update to
these guidelines in 2013 that stated, “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).”60
American Psychiatric Association
The American Psychiatric Association guidelines on the treatment of major depressive disorder
in adults, updated in November 2010, includes the following statement on the use of VNS:
“Vagus nerve stimulation (VNS) may be an additional option for individuals who have not
responded to at least four adequate trials of antidepressant treatment, including ECT
[electroconvulsive therapy],” with a level of evidence III (May be recommended on the basis of
individual circumstances).61
European Headache Federation
In 2013, the European Headache Federation issued a consensus statement on neuromodulation
treatments for chronic headaches, which makes the following statement about the use of VNS:
“Due to the lack of evidence, VNS should only be employed in chronic headache sufferers using
a randomized, placebo controlled trial design.”62
U.S. Preventive Services Task Force Recommendations
Not applicable.
Medicare National Coverage
Medicare has a national coverage determination for VNS. Medicare coverage policy notes that
“Clinical evidence has shown that vagus nerve stimulation is safe and effective treatment for
patients with medically refractory partial onset seizures, for whom surgery is not recommended
or for whom surgery has failed. Vagus nerve stimulation is not covered for patients with other
types of seizure disorders that are medically refractory and for whom surgery is not
recommended or for whom surgery has failed.” Effective for services performed on or after May
4, 2007, VNS is not reasonable and necessary for resistant depression.63
V. DEFINITIONS
TOP
EPILEPSY is a group of neurologic disorders characterized by recurrent episodes of
convulsive seizures, sensory disturbances, abnormal behavior, loss of consciousness, or all
of these. Common to all types of epilepsy is an uncontrolled electrical discharge from the
nerve cells of the cerebral cortex.
PARTIAL ONSET SEIZURES refers to seizures that have a discrete focal onset. There are
three subtypes of partial onset seizures:
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IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034

Simple partial seizures: these do not involve alteration of consciousness but may
have observable motor components or may solely be a subjective sensory or
emotional phenomenon.

Complex partial seizures: these are partial-onset seizures that involve an alteration of
consciousness.

Complex partial seizures, secondarily generalized: These are partial-onset seizures
that progress to involve both sides of the brain and result in a complete loss of
consciousness.
PHRENIC NERVE is a nerve that arises mainly from the fourth cervical nerve and is
primarily the motor nerve of the diaphragm but also sends sensory fibers to the
pericardium.
VAGUS NERVE refers to either one of the longest pair of cranial nerves mainly responsible
for parasympathetic control over the heart and many other internal organs, including
thoracic and abdominal viscera.
VISCERAL AFFERENT FIBERS are the nerve fibers of the visceral nervous system that
receive stimuli, carry impulses toward the central nervous system, and share the sensory
ganglia of the cerebrospinal nerves with the somatic sensory fibers.
VI. BENEFIT VARIATIONS
TOP
The existence of this medical policy does not mean that this service is a covered benefit
under the member’s contract. Benefit determinations should be based in all cases on the
applicable contract language. Medical policies do not constitute a description of benefits. A
member’s individual or group customer benefits govern which services are covered, which
are excluded, and which are subject to benefit limits and which require preauthorization.
Members and providers should consult the member’s benefit information or contact Capital
for benefit information.
VII. DISCLAIMER
TOP
Capital’s medical policies are developed to assist in administering a member’s benefits, do not constitute
medical advice and are subject to change. Treating providers are solely responsible for medical advice and
treatment of members. Members should discuss any medical policy related to their coverage or condition
with their provider and consult their benefit information to determine if the service is covered. If there is a
discrepancy between this medical policy and a member’s benefit information, the benefit information will
govern. Capital considers the information contained in this medical policy to be proprietary and it may only
be disseminated as permitted by law.
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MEDICAL POLICY
POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
VIII. CODING INFORMATION
TOP
Note: This list of codes may not be all-inclusive, and codes are subject to change at any
time. The identification of a code in this section does not denote coverage as
coverage is determined by the terms of member benefit information. In addition, not
all covered services are eligible for separate reimbursement.
Covered when medically necessary:
CPT
Codes ®
63650
63655
64568
64569
64570
64575
64585
64590
Current Procedural Terminology (CPT) copyrighted by American Medical Association. All Rights Reserved.
HCPCS Code
C1767
C1778
C1816
C1820
C1883
C1897
L8679
L8680
L8681
L8682
L8683
L8685
L8686
L8687
L8688
L8689
L8695
Description
Generator, neurostimulator (implantable), non-rechargeable
Lead, neurostimulator (implantable)
Receiver and/or transmitter, neurostimulator (implantable)
Generator, neurostimulator (implantable), with rechargeable battery and charging
system
Adaptor/extension, pacing lead or neurostimulator lead (implantable)
Lead, neurostimulator test kit (implantable)
Implantable neurostimulator, pulse generator, any type
Implantable neurostimulator electrode (with any number of contact points), each
Pt program for implant neurostim
Implantable neurostimulator radiofrequency receiver
Radiofrequency transmitter (external) for use with implantable neurostimulator
radiofrequency receiver
Implantable neurostimulator pulse generator, single array, rechargeable, includes
extension
Implantable neurostimulator pulse generator, single array, non-rechargeable, includes
extension
Implantable neurostimulator pulse generator, dual array, rechargeable, includes
extension
Implantable neurostimulator pulse generator, dual array, non-rechargeable, includes
extension
External recharging system for battery (internal) for use with implantable
neurostimulator, replacement only
External recharging system for battery (external) for use with implantable
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MEDICAL POLICY
POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
HCPCS Code
L8696
Description
neurostimulator, replacement only
Antenna (external) for use with implantable diaphragmatic/phrenic nerve stimulation
device, replacement, each
*If applicable, please see Medicare LCD or NCD for additional covered diagnoses.
ICD-10-CM
Diagnosis Code*
Description
G89.0
Central pain syndrome
G40.001
Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes
with seizures of localized onset, not intractable, with status epilepticus
G40.009
Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes
with seizures of localized onset, not intractable, without status epilepticus
G40.011
Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes
with seizures of localized onset, intractable, with status epilepticus
G40.019
Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes
with seizures of localized onset, intractable, without status epilepticus
G40.111
Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes
with simple partial seizures, intractable, with status epilepticus
G40.119
Localization-related (focal)(partial) symptomatic epilepsy and epileptic syndromes
with simple partial seizures, intractable, without status epilepticus
G40.211
Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes
with complex partial seizures, intractable, with status epilepticus
G40.219
Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes
with complex partial seizures, intractable, without status epilepticus
G40.311
Generalized idiopathic epilepsy and epileptic syndromes, intractable, with status
epilepticus
G40.319
Generalized idiopathic epilepsy and epileptic syndromes, intractable, without status
epilepticus
G40.511
Special epileptic syndromes, intractable, with status epilepticus
G40.519
Special epileptic syndromes, intractable, without status epilepticus
G40.811
Other epilepsy, intractable, with status epilepticus
G40.819
Other epilepsy, intractable, without status epilepticus
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MEDICAL POLICY
POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
ICD-10-CM
Diagnosis Code*
Description
G40.89
Other seizures
G40.911
Epilepsy, unspecified, intractable, with status epilepticus
G40.919
Epilepsy, unspecified, intractable, without status epilepticus
G40.A01
Absence epileptic syndrome, not intractable, with status epilepticus
G40.A09
Absence epileptic syndrome, not intractable, without status epilepticus
G40.A11
Absence epileptic syndrome, intractable, with status epilepticus
G40.A19
Absence epileptic syndrome, intractable, without status epilepticus
G40.B11
Lennox-Gastaut syndrome, not intractable, with status epilepticus
G40.B12
Lennox-Gastaut syndrome, not intractable, without status epilepticus
G89.21
Chronic pain due to trauma
G89.22
Chronic post-thoracotomy pain
G89.28
Other chronic postprocedural pain
G89.3
Neoplasm related pain (acute) (chronic)
G89.4
Chronic pain syndrome
J80
Acute respiratory distress syndrome
J95.1
Acute pulmonary insufficiency following thoracic surgery
J95.2
Acute pulmonary insufficiency following nonthoracic surgery
J95.3
Chronic pulmonary insufficiency following surgery
J95.82
Postprocedural respiratory failure
J96.0
Acute respiratory failure
J96.1
Chronic respiratory failure
J96.2
Acute and chronic respiratory failure
J96.9
Respiratory failure, unspecified
*If applicable, please see Medicare LCD or NCD for additional covered diagnoses.
IX. REFERENCES
TOP
Vagus Nerve Stimulation
1. 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.
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AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
2. 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. Jun 2014;55(6):893-900.
PMID 24754318
3. Tecoma ES, Iragui VJ. Vagus nerve stimulation use and effect in epilepsy: what have we
learned? Epilepsy Behav. Feb 2006;8(1):127-136. PMID 16376157
4. 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):1169-1177.
5. Kostov H, Larsson PG, Roste GK. Is vagus nerve stimulation a treatment option for patients
with drug-resistant idiopathic generalized epilepsy? Acta Neurol Scand Suppl. 2007;187:5558. PMID 17419830
6. 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. Jan 2013;22(1):9-13. PMID 23041031
7. Amar AP, Levy ML, McComb JG, et al. Vagus nerve stimulation for control of intractable
seizures in childhood. Pediatr Neurosurg. 2001;34(4):218-223.
8. Murphy JV. Left vagal nerve stimulation in children with medically refractory epilepsy. The
Pediatric VNS Study Group. J Pediatr. May 1999;134(5):563-566. PMID 10228290
9. Morris GL, 3rd, Mueller WM. Long-term treatment with vagus nerve stimulation in patients
with refractory epilepsy. The Vagus Nerve Stimulation Study Group E01-E05. Neurology.
Nov 10 1999;53(8):1731-1735. PMID 10563620
10. Hornig G, Murphy JV, Schallert G, et al. Left vagus nerve stimulation in children with
refractory epilepsy: an update. South Med J. 1997;90(5):484-488.
11. Patwardhan RV, Stong B, Bebin EM, et al. Efficacy of vagal nerve stimulation in children
with medically refractory epilepsy. Neurosurgery. 2000;47(6):1353-1358.
12. 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. Nov 2013;29(11):2095-2099.
PMID 23681311
13. Klinkenberg S, van den Bosch CN, Majoie HJ, et al. Behavioural and cognitive effects during
vagus nerve stimulation in children with intractable epilepsy - a randomized controlled trial.
Eur J Paediatr Neurol. Jan 2013;17(1):82-90. PMID 22878130
14. 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. PMID 22540141
15. 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. PMID 24210463
16. 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. PMID 24309238
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IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
17. 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. PMID 25231724
18. 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):442-445.
19. 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):195-199.
20. 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. Nov 2013;16(6):551-556.
PMID 23738578
21. 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):1248-1255. PMID 21838505
22. Arya R, Greiner HM, Lewis A, et al. Predictors of Response to Vagus Nerve Stimulation in
Childhood-Onset Medically Refractory Epilepsy. J Child Neurol. Dec 5 2013. PMID
24309242
23. Elger H, Hoppe C, Falkai P, et al. Vagus nerve stimulation is associated with mood
improvements in epilepsy patients. Epilepsy Res. 2000;42(3-Feb):203-210.
24. Blue Cross and Blue Shield Assocation Technology Evaluation Center (TEC). Vagus nerve
stimulation for treatment-resistant depression. TEC Assessments. 2006;Volume 21, Tab 7.
25. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Vagus nerve
stimulation for treatment-resistant depression. TEC Assessments. 2005;Volume 21, Tab 7.
26. George MS, Rush AJ, Marangell LB, et al. A one-year comparison of vagus nerve stimulation
with treatment as usual for treatment-resistant depression. Biol Psychiatry. 2005;58(5):364373.
27. Rush AJ, Marangell LB, Sackeim HA, et al. Vagus nerve stimulation for treatment-resistant
depression: a randomized, controlled acute phase trial. Biol Psychiatry. 2005;58(5):347354.
28. U.S. Food and Drug Administration Center for Devices and Radiological Health. Summary
of Safety and Effectiveness Data for the Vagus Nerve Stimulation (VNS) Therapy System.
http://www.fda.gov/ohrms/dockets/ac/04/briefing/4047b1_02_Summary%20of%20Safety%20
and%20Effectiveness.pdf. Accessed January 28, 2016.
29. 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.
30. Rush AJ, George MS, Sackheim HA, et al. Vagus nerve stimulation (VNS) for treatmentresistant depression: a multicenter study. Biol Psychiatry. 2000;47(4):276-286.
31. Sackeim HA, Rush AJ, George MS, et al. Vagus nerve stimulation (VNS) for treatmentresistant depression; efficacy, side effects and predictors of outcome.
Neuropsychopharmacology. 2001;25(5):713-728.
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IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
32. 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. Sep 2008;110(1-2):115. PMID 18374988
33. 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. Apr 2012;27(3):147-155. PMID 22137776
34. 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. PMID 23482508
35. 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. PMID 23891366
36. 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. Jul 2013;6(4):631-640. PMID 23122916
37. 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):273-281.
38. 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):183-189.
39. 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):1376-1382.
40. 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. PMID
25215365
41. Handforth A, Ondo WG, Tatter S, et al. Vagus nerve stimulation for essential tremor: a pilot
efficacy and safety trial. Neurology. 2003;61(10):1401-1405.
42. Mauskop A. Vagus nerve stimulation relieves chronic refractory migraine and cluster
headaches. Cephalalgia. 2005;25(2):82-86.
43. Cecchini AP, Mea E, Tullo V, et al. Vagus nerve stimulation in drug-resistant daily chronic
migraine with depression: preliminary data. Neurol Sci. 2009;30(suppl 1):S101-104.
44. Bodenlos JS, Kose S, Borckardt JJ, et al. Vagus nerve stimulation acutely alters food craving
in adults with depression. Appetite. 2007;48(2):145-153.
45. 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. PMID 25176942
46. 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. PMID 25187002
47. 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. 2011;32(7):847-855.
Page 22
MEDICAL POLICY
POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
Available online at http://eurheartj.oxfordjournals.org/content/ehj/32/7/847.full.pdf.
Accessed January 27, 2016.
48. 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):1406-1413.
49. 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. Nov 20 2013. PMID 24255953
50. 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.
Apr 2013;35(3):263-276. PMID 23485054
51. 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.
PMID 25240121
52. Stefan H, Kreiselmeyer G, Kerling F, et al. Transcutaneous vagus nerve stimulation (t-VNS)
in pharmacoresistant epilepsies: a proof of concept trial. Epilepsia. Jul 2012;53(7):e115118. PMID 22554199
53. 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. Sep
2013;28(3):343-346. PMID 23820114
54. 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. PMID 23117749
55. 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. PMID 25054988
56. 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. PMID
24607501
57. 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. PMID 24996510
58. 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. PMID 24968966
59. 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. Sep 11 1999;53(4):666-669. PMID 10489023
60. 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. PMID
23986299
Page 23
MEDICAL POLICY
POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
61. American Psychiatric Association. Practice Guideline for the Treatment of Patients with
Major Depressive Disorder. 2010;
Third:http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.
pdf. Accessed January 27, 2016.
62. 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. PMID 24144382
63. Centers for Medicare and Medicaid Services. National Coverage Determination (NCD) for
VAGUS Nerve Stimulation (VNS) (160.18). http://www.cms.gov/medicare-coveragedatabase/details/ncddetails.aspx?NCDId=230&ncdver=2&CoverageSelection=National&KeyWord=vagus&Key
WordLookUp=Title&KeyWordSearchType=And&where=%252520index&nca_id=%252520
195&bc=gAAAABAAAAAAAA%3d%3d&. Accessed January 27, 2016.
Autonomic (phrenic) nerve Stimulator
Marion, D. Pacing the diaphragm: Patient selection, evaluation, implantation and
complications. In: UptoDate Online Journal [serial online}. Waltham, MA: UpToDate;
updated December 2. 2014.. [Website] : www.uptodate.com . Accessed February 2, 2014.
Peripheral Nerve Stimulation
Huntoon MA, Burgher AH. Ultrasound-Guided Permanent Implantation of Peripheral Nerve
Stimulation (PNS) System for Neuropathic Pain of the Extremities: Original Cases and
Outcomes. Pain Med. 2009 Nov; 10(8):1369-1377.
Other Sources:
Centers for Medicare and Medicaid Services (CMS) National Coverage Determination
(NCD) 160.18, Vagus Nerve Stimulation for the Treatment of Seizures. Effective
07/23/07 [Website]: http://www.cms.gov/medicare-coverage-database/details/ncddetails.aspx?NCDId=230&ncdver=2&DocID=160.18&bc=gAAAABAAAAAA&
Accessed February 9, 2015.
Centers for Medicare and Medicaid Services (CMS) National Coverage Determination
(NCD) 160.19, Phrenic Nerve Stimulator. [Website]: http://www.cms.gov/medicarecoverage-database/details/ncddetails.aspx?NCDId=244&ncdver=1&DocID=160.19&bc=gAAAABAAAAAA&.
Accessed February 9, 2015.
Centers for Medicare and Medicaid Services (CMS) National Coverage Determination
(NCD) 160.7, Electric Nerve Stimulators. Effective 08/07/95. [Website]:
http://www.cms.gov/medicare-coverage-database/details/ncdPage 24
MEDICAL POLICY
POLICY TITLE
IMPLANTABLE ELECTRICAL NERVE STIMULATORS (VAGUS,
AUTONOMIC NERVE AND PERIPHERAL NERVE STIMULATORS)
POLICY NUMBER
MP-1.034
details.aspx?NCDId=240&ncdver=1&DocID=160.7&bc=gAAAABAAAAAA&
Accessed February 9, 2015
X. POLICY HISTORY
MP 1.034
TOP
CAC 7/27/04
CAC 10/26/04
CAC 10/25/05
CAC 10/31/06
CAC 9/25/07
CAC 7/29/08
CAC 1/27/09
CAC 1/26/10 Consensus
CAC 4/26/11 Consensus
CAC 8/28/12 Minor revision. Two new investigational indications were added
for vagus nerve stimulation to include treatment of heart failure and
fibromyalgia.
Codes reviewed 8/13/12 klr
01/3/13- 2013 New codes added-skb
CAC 7/30/2013 Consensus
12/20/2013- New 2014 Code updates made.
01/2015-New 2015 codes added to policy.
CAC 3/25/14 Consensus review. References updated. No changes to the policy
statements. FEP variation revised to refer to the FEP medical policy manual.
CAC 3/24/15 Consensus review. Tinnitus, and traumatic brain injury added to
list of “all other” investigational indications. Rationale added. References
updated. Codes reviewed.
CAC 3/29/16 Consensus review. Peripheral subcutaneous field stimulation
codes removed from this policy - refer to MP - 1.141 Peripheral Subcutaneous
Field Stimulation (PSFS). Rationale and references updated. Coding updated.
Admin Change 11/15/16 – Variation Reformatting 10/21/16
TOP
Health care benefit programs issued or administered by Capital BlueCross and/or its subsidiaries,
Capital Advantage Insurance Company®, Capital Advantage Assurance Company® and Keystone Health
Plan® Central. Independent licensees of the BlueCross BlueShield Association. Communications issued
by Capital BlueCross in its capacity as administrator of programs and provider relations for all
companies.
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