Surgery Section - Vagus Nerve Stimulation

IMPORTANT REMINDER

This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status.

Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control.

The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care.

Description

Seizures have been defined as paroxysmal disorders of the central nervous system characterized by abnormal cerebral neuronal discharge, with or without a loss of consciousness. Seizures have been further sub classified into those with a generalized onset, beginning throughout the brain, and those with a partial onset, having a discrete focal onset. There are three principal subtypes of partial-onset seizures:

• 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.

In the past ten years there have been significant advances in surgical treatment for epilepsy and in medical treatment of epilepsy with newly developed and approved medications. Despite these advances, however, 25-50% of patients with epilepsy experience breakthrough seizures or suffer from debilitating adverse effects of antiepileptic drugs. Vagal nerve stimulation (VNS) has been 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.

While the mechanisms for the antiepileptic effects of vagal nerve stimulation are not fully understood, the basic premise of VNS in the treatment of epilepsy is that vagal visceral afferents have a diffuse central nervous system projection, and activation of these pathways has a widespread effect upon neuronal excitability. Surgery for implantation of a vagus nerve stimulator involves wrapping 2 spiral electrodes around the left vagus nerve within the carotid sheath. The electrodes are connected to an infraclavicular generator pack. The programmable stimulator may be programmed in advance to stimulate at regular times or upon demand by patients or family by placing a magnet against the subclavicular implant site. In 1997 the FDA approved a vagus nerve stimulator device called the NeuroCybernetic Prosthesis (NCP®) system.  The device was approved for use in conjunction with drugs or surgery “as an adjunctive treatment of adults and adolescents under 12 years of age with medically intractable 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 vagus nerve stimulation as a treatment of refractory depression, anxiety disorders, and bulimia.  On July 15, 2005, the FDA granted PMA approval for the VNS Therapy System (Cyberonics, Inc.) “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.”

Most recently, VNS has been investigated as a treatment of headaches, essential tremors, bulimia, anorexia nervosa, anxiety, intractable hiccups, and to improve cognition in patients with mild to moderate Alzheimer's disease. The standard for treating the cognitive effects of Alzheimer's disease is the drug class of cholinesterase inhibitors. About 40% of Alzheimer's patients treated with cholinesterase inhibitors experience improvement.

Policy/Criteria

Scientific Background

This policy is based in part on a 1998 TEC assessment (2) and studies published since the assessment.

The TEC assessment offered the following conclusions:

1. Published evidence from two large, well-designed multicenter trials involving over 300 patients demonstrates that the use of vagal nerve stimulation 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 effects appear to be maintained or increased over time.
2. Adverse effects are mild and consist primarily of hoarseness of voice change during "on" periods of stimulation.
3. The 1998 TEC assessment also concluded that there is limited information about the use of vagal nerve stimulation patients with other types of seizure disorders.

A 2000 updated literature search revealed several published studies addressing the use of vagus nerve stimulation in patients with medically refractory generalized tonic-clonic seizures. (3-6) Morris et al documented long term treatment effects in 24 patients with generalized seizures. This was one phase of the Vagus Nerve Stimulation Study Group. The difference in outcomes between the patients with partial-onset seizures and those with generalized tonic-clonic seizures and Lennox-Gastaut syndrome is not statistically significant. Vagus nerve stimulation may result in a reduction of tonic and tonic-clonic seizures. The data base from the Vagus Nerve Stimulation Trial indicates that over 50% of individuals will experience a greater than 50% reduction in seizures and that approximately 30% will experience a greater than 75% reduction in seizures. The improvement in quality of life for these patients is significant.

An updated MEDLINE database search was conducted. 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, and these report seizure reduction rates similar or greater than those reported in partial epilepsy and that “this body of evidence suggests that VNS has broad antiepileptic efficacy.” (27) The authors suggest that these results may be particularly important since resective epilepsy surgery is generally not feasible in these patients. More recent reports are consistent with their observations. In a French study of 50 consecutive refractory adolescents and adults who were not eligible for surgery and of who 11 had generalized epilepsy, 58% were classified as responders at 3 years follow-up. (28) Generalized epilepsy was predictive of a better outcome than partial epilepsy seizures. The authors conclude that VNS is a useful palliative procedure in severe generalized epilepsies with atonic or tonic-clonic seizures resulting in frequent falls and entails less risk than callosotomy. In a multicenter study of 28 children with refractory seizures You et al reported that15 children (53.6%) showed a >50% reduction in seizure frequency and 9 (32%) had a >75% reduction, and there were no significant differences when groups were compared by seizure type or etiology. (29) Tecoma cites a multicenter retrospective analysis of 50 children with Lennox-Gestaut syndrome (LGS) treated with VNS. (27) Median seizure reduction at 6 months was 88% for tonic seizures and 81% for atypical absences. You et al compared VNS and total corpus callosotomy for LGS. (30) 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. Seizure reduction of 61% was also reported in a case series of 12 patients with drug-resistant idiopathic generalized epilepsy. (31) Based on these data one can conclude that VNS is an effective treatment for refractory seizures other than partial epilepsy. Therefore the policy statement has been revised to state that VNS may be considered medically necessary for patients whose seizures are refractory to medical treatment, or who have failed or are not candidates for resective epilepsy surgery.

Vagal Nerve Stimulation in Children

The original FDA approval limited the use of vagal nerve stimulation to those over the age of 12. Since that time, there has been interest in expanding the use of vagal nerve stimulation to younger patients. Several studies have now reported results that support the safety 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 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 reported in adults (3), and none resulted in termination of stimulation. Hornig and colleagues reported on a case series of 19 pediatric patients, with observation periods ranging up to 30 months. (9) Overall, 50% of patients had a 50% reduction in seizure frequency. Patwardhan and colleagues reported that among 38 patients aged 11 months to 16 years, 29% had a greater than 90% reduction in seizure frequency, while 39% had 50% to 90% reduction. (10) The major limitations of vagal nerve stimulation are the facts that stimulation generally does not completely eliminate seizures and it is not possible to predict which patients will optimally respond. Therefore, some authors suggest that vagal nerve stimulation may be most appropriately used in patients with refractory seizures who are not candidates for surgery (i.e., bilateral or unresectable foci or no identified structural abnormality).

A January 2004 search of the published medical literature based on MEDLINE revealed additional studies that support the safety and effectiveness of the device for adults and children with partial onset seizures refractory to medical therapy. (11,12)

A case series found that 8 of 9 children who had vagal nerve stimulators exhibited sleep-related breathing disorder with polysomnographic assessment. (32) In one child, severe obstructive sleep apnea (apneahypopnea index of 37) was observed when the stimulator was turned on, but resolved completely when the stimulator was turned off. Further study of this potential complication is warranted.

Vagal Nerve Stimulation as a 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. (13) However, studies examining VNS for the treatment of depression are limited, and all published and unpublished data concerning clinical outcomes of VNS therapy for the indication of treatment-resistant depression come from company-sponsored clinical studies. The June 2005 TEC Assessment, Vagus Nerve Stimulation for Treatment-Resistant Depression, concluded that evidence was insufficient to permit conclusions of the effect of VNS therapy on health outcomes. (14) The available evidence for the TEC Assessment included study groups assembled by the manufacturer of the device (Cyberonics), and reported on in various publications. 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 (i.e., 3-month) randomized sham-controlled clinical trial of 221 patients (Study D-02), and an observational study comparing 205 patients on VNS therapy compared to 124 patients receiving ongoing treatment for depression (Study D-04). (15) Patients who responded to sham treatment in the short-term randomized, controlled trial (approximately 10%) were excluded from the long-term observational study.

The primary outcome evaluated in the TEC Assessment 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 side 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).

The case series data show rates of improvement, as measured by a 50% improvement in depression score of 31% at 10 weeks to greater than 40% at 1 to 2 years, but there are some losses to follow-up. (15-18) Natural history, placebo effects, and patient and provider expectations make it difficult to infer efficacy from case series data.

The randomized study (D-02), which compared VNS therapy to a sham control (implanted but inactivated VNS), showed a non-statistically significant result for the principal outcome. (16) Fifteen percent of VNS subjects responded, versus 10% of control subjects (p=0.31). The IDS-SR was considered a secondary outcome, and showed a difference in outcome that was statistically significant in favor of VNS (17.4% versus 7.5%, p=0.04).

The observational study comparing patients participating in the randomized clinical trial and a separately recruited control group (D-04 vs. D-02) evaluated VNS therapy out to 1 year and showed a statistically significant difference in the rate of change of depression score. (15) 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. Given these concerns about the quality of the observational data, these results did not provide strong evidence for the effectiveness of VNS therapy.

In 2006, the TEC Assessment for use of VNS for treatment-resistant depression was updated and information from the Executive Summary is included in the paragraphs below. (22) That assessment reviewed the available evidence to determine if VNS therapy is effective for treatment-resistant depression. Articles reviewed were case series, randomized trials, or observational studies evaluating clinical outcomes of VNS therapy. In the prior TEC Assessment (14), results were available only from documents posted to the FDA Web site. Subsequently, the same studies have been published in peer-reviewed journals, almost unchanged from the FDA documents. New publications analyze the same data in various ways examining duration of benefit.

The relevant clinical evidence evaluating VNS consists of a case series of 60 patients receiving VNS, a short-term (i.e., 3-month) randomized, sham-controlled clinical trial (RCT) of 222 patients, and an observational study comparing 205 of the RCT patients on VNS therapy to 124 patients receiving usual treatment for depression. Patients who responded to sham treatment in the short-term randomized, controlled trial (approximately 10%) were excluded from the long-term observational study.

Patient selection was a concern for all studies. 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.

The case series data show rates of improvement, as measured by a 50% improvement in depression score of 31% at 10 weeks to greater than 40% at 1 to 2 years, but there are some losses to follow-up.  Natural history, placebo effects, and patient and provider expectations make it difficult to infer efficacy from case series data.

The randomized study that compared VNS therapy to a sham control (implanted but inactivated VNS) did not show a statistically significant result for the principal outcome at 3 months. (23) Fifteen percent of VNS subjects responded, versus 10% of control subjects (p=0.25). There was a statistically significant result for a secondary outcome.

An observational study comparing patients participating in the randomized clinical trial and a separately recruited control group evaluated VNS therapy out to 1 year. (24) This observational study showed a statistically significant difference in the rate of change of depression score. However, issues such as unmeasured differences between patients and 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. Given these concerns about the quality of the observational data, these results are insufficient to support the effectiveness of VNS therapy.

Additional reanalysis of these same data to evaluate persistence of response show that among those who achieve a response at 3 or 12 months, 60%–75% of such patients are judged to remain a responder after 1 year. In the context of relatively low overall response rates, these data do not provide evidence of efficacy.

Review of the literature through May 19, 2008 did not locate any new studies which would alter the conclusions or policy statements for use of VNS for treatment-resistant depression.

A systematic review of the literature for VNS of treatment-resistant depression identified one randomized trial (reference 23, reviewed above) out of 18 studies that met the study’s inclusion criteria. (33) VNS was found to be associated with a reduction in depressive symptoms in the open studies. For example, a preliminary report from an ongoing European multicenter open-label efficacy and safety study of VNS for treatment-resistant depression described one responder (out of 11) at 3 months, 2 responders at 6 months, and 6 responders (55%) at one year; 3 patients (27%) were considered to be in remission. (25) However, results from the only double-blind trial were considered to be inconclusive. (23) Daban concluded that further clinical trials are needed to confirm efficacy of VNS in treatment –resistant depression. Ongoing studies include an industry-sponsored dose-comparison study of VNS and a registry for patients with treatment-resistant depression. (26) In a recent review, Fitzgerald and Daskalakis state that “given the invasive nature of vagal nerve stimulation and potential side effects, further research is urgently required”. (34) Given the limitations of prior literature as described in the 2006 TEC Assessment, combined with the lack of substantial new literature, the scientific evidence is considered to be insufficient to permit conclusions concerning the effect of this technology on major depression. Therefore; the policy statement relevant to depression remains unchanged.

Miscellaneous Applications of VNS

VNS therapy is being investigated for a variety of disorders including bulimia, anxiety disorders, Alzheimer’s disease, migraine headaches, and obesity.  Evidence is preliminary and as yet insufficient to reach conclusions concerning the effectiveness of vagus nerve stimulation for these conditions.

A pilot study on the use of VNS to improve the cognitive functioning in patients with mild to moderate Alzheimer's disease has been published. (19) Sjögren and colleagues implanted ten Alzheimer's disease patients and observed a median improvement of 2.5 points of cognitive functioning on the Alzheimer's Disease Assessment Scale after six months of stimulation therapy in the seven responders. Three of the responders were on concurrent cholinesterase inhibitor therapy. The reported outcomes, while promising, are preliminary. Further study is needed in the way of randomized, controlled clinical trials with sufficient numbers of patients and longer-term outcomes before conclusions concerning the effectiveness and safety of VNS in Alzheimer's disease patients can be reached.

Handforth and colleagues studied VNS in nine patients with essential tremor. (20) Four weeks after implantation of the VNS device, tremor assessment using a masked videotape of patients was performed. Evaluators found no improvement in upper extremity tremor. Therefore, the authors of the study concluded that VNS is not likely to have any clinically meaningful effect in essential tremor treatment.

Drawing on the analgesic effects noted with VNS in the treatment of depression, Mauskop evaluated VNS in five patients with severe refractory chronic cluster and migraine headaches. (21) Mauskop reported excellent results in one patient who was able to return to work and significant improvement in two patients. Other than nausea developed by one patient, VNS was well tolerated. However, this study is too small to draw conclusions on the effects of VNS for the treatment of headache, and further study is needed.

Unintended weight loss has been observed in participants in studies of vagus nerve stimulation 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. (35) 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 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, 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. No new published studies of other applications of VNS were identified. A phase II pilot study of VNS for treatment of fibromyalgia is ongoing.

An updated literature search through  May 19, 2008 based on the MEDLINE database did not return any new published clinical trial data on VNS therapy for essential tremor, Alzheimer’s disease, cluster or migraine headaches, bulimia, anorexia nervosa, chronic refractory hiccups, or anxiety disorders.  Therefore, VNS therapy for these diagnoses is unchanged.

Safety

Adverse effects of VNS therapy include 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.

References

1. BlueCross BlueShield Association Medical Policy Reference Manual, Policy No. 7.01.20
2. 1998 TEC Assessment: Chronic vagus nerve stimulation for the treatment of seizures.
3. Morris et al. Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. Neurology 1999;53(8):1727-35
4. DeGiorgio et al. Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures. Epilepsia 2000;41(9):1195-200
5. Hosain et al. Vagus nerve stimulation treatment for Lennox-Gestaut syndrome. J Child Neurol 2000;15(8):509-12
6. Labar et al. Vagus nerve stimulation for medication-resistant generalized epilepsy. Neurology 1999;52(7):1510-1512
7. Amar AP, Levy ML, McComb JG, Apuzzo MLJ. Vagus nerve stimulation for control of intractable seizures in childhood. Pediatr Neurosurg 2001;34:218-23
8. Murphy JV. Left vagal nerve stimulation in children with medically refractory epilepsy. J Pediatr 1999;134:563-67
9. Hornig G, Murphy JV, Schallert G, Tilton C. Left vagus nerve stimulation in children with refractory epilepsy. South Med J 1997;90: 484-88
10. Patwardhan RV, Strong B, Bebin EM et al. Efficacy of vagal nerve stimulation in children with medically refractory epilepsy. Neurosurgery 2000;47(6):1353-8
11. Kirse DJ, Werle AH, Murphy JV et al. Vagus nerve stimulator implantation in children. Arch Otolaryngol Head Neck Surg 2002;128(11):1263-30
12. Renfroe JB, Wheless JW. Earlier use of adjunctive vagus nerve stimulation therapy for refractory epilepsy. Neurology 2002;59(6 suppl 4):S26-30
13. Elger H, Noppe C, Falkai P et al. Vagus nerve stimulation in association with mood improvements in epilepsy patients. Epilepsy Res 2000;42:203-10
14. TEC Assessment: Vagus Nerve Stimulation for Treatment-Resistant Depression, 2006; Vol.20, Tab 8 http://blueweb.bcbs.com/global_assets/special_content/tec_assessments/vol20/20_08.pdf (Verified 11/25/08)
15. 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 (PDF). (Verified 5/30/08)
16. Rush AJ, George MS, Sackheim HA et al. Vagus nerve stimulation for treatment resistant depression: a multicenter study. Biol Psychiatr 2000;47:273-75
17. Sackheim HA, Rush AJ, George MS et al. Vagus nerve stimulation (VNS) for treatment resistant depression: efficacy, side effects and predictors of outcomes. Neuropsychopharmacology 2001;25(5):713-28
18. Marangell LB, Rush AJ, George MS et al. Vagus nerve stimulation (VNS) for major depressive episodes:  one-year outcomes. Biol Psychiatry 2002;51(4):280-7
    
19. Sjögren MJ, Hellstrom PT, Jonsson MA, et al. Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer's disease: a pilot study. J Clin Psychiatry 2002;63(11):972-80
20. Handforth A, Ondo WG, Tatter S et al. Vagus nerve stimulation for essential tremor: a pilot efficacy and safety trial. Neurology 2003;61(10):1401-5
21. Mauskop A. Vagus nerve stimulation relieves chronic refractory migraine and cluster headaches. Cephalgia 2005;25(2):82-6
22. TEC Assessment: 2006; http://www.bcbs.com/blueresources/tec/vols/#21 (Verified 05/30/08)
23. Rush AJ, Marangell LB, Sackheim HA et al. Vagus nerve stimulation for treatment-resistant depression: A randomized, controlled acute phase trial. Biol Psychiatry 2005;58:347-54
24. 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;58:364-73
25. Corcoran CD, Thomas P, Phillips J et al. Vagus nerve stimulation in chronic treatment-resistant depression: preliminary findings of an open-label study. Br J Psychiatry 2006; 189:282-3
26. www.clinicaltrials.gov
27. Tecoma ES, Iragui VJ. Vagus nerve stimulation use and effect in epilepsy: what have we learned? Epilepsy Behav 2006;8(1);127-36
28. Montavont A, Demarquay G, Ryvlin P et al. Long-term efficiency of vagus nerve stimulation (VNS) in non-surgical refractory epilepsies in adolescents and adults [article in French] . Rev Neurol (Paris) 2007; 163(12):1169-77
29. You SJ, Kang HC, Kim HD et al. Vagus nerve stimulation in intractable childhood epilepsy: a Korean multicenter experience. J Korean Med Sci 2007; 22(3):442-5
30. You SJ, Kang HC, Ko TS et al. Comparison of corpus callosotomy and vagus nerve stimulation in children with Lennox-Gastaut syndrome. Brain Dev 2008; 30(3):195-9
31. 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; 187:55-8
32. Hsieh T, Chen M, McAfee A et al. Sleep-related breathing disorder in children with vagal nerve stimulators. Pediatr Neurol 2008; 38(2):99-103
33. Daban C, Martinez-Aran A, Cruz N et al. Safety and efficacy of vagus nerve stimulation in treatmentresistantdepression. A systematic review. J Affect Disord 2008; 110(1-2)
34. Fitzgerald PB, Daskalakis ZJ. The use of repetitive transcranial magnetic stimulation and vagal nerve stimulation in the treatment of depression. Curr Opin Psychiatry 2008; 21(1):25-9
35. Bodenlos JS, Kose S, Borckardt JJ et al. Vagus nerve stimulation acutely alters food craving in adults with depression. Appetite 2007; 48(2):145-53

Cross References

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