What is VNS Therapy? Â· VNS (vagus nerve stimulation) Therapy consists of an implanted pacemaker-like device that delivers mild, intermittently pulsed signals to the patientÂ’s left vagus nerve, which then activates various areas of the brain.
Â· Roughly the size of a small pocket-watch and weighing less than one ounce, the device is implanted in the patientÂ’s left chest area. A thin thread-like wire, attached to the generator, runs under the skin to the left vagus nerve in the neck.
Â· The implant procedure typically takes approximately one to two hours.
Â· Although the VNS Therapy surgical procedure does not involve the brain, stimulation of the left vagus nerve has been shown to induce widespread bilateral effects in areas of the brain implicated in seizures and mood disorders and responsible for modulation of key neurotransmitters such as serotonin and norepinephrine.
Â· Using an external dose adjustment system, physicians can adjust the stimulation duration, frequency and intensity.
Indications for VNS Therapy
VNS (vagus nerve stimulation) Therapy is FDA approved as an adjunctive, long-term treatment for chronic or recurrent depression for patients 18 year 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 was previously approved in the U.S. in 1997 as an adjunctive therapy for reducing the frequency of seizures in adults and adolescents over 12 years of age with partial-onset seizures which are refractory to antiepileptic medications.
VNS Therapy is currently approved for sale as a treatment for epilepsy in all the member countries of the European Union, Canada, Australia and other markets. VNS Therapy System is also approved for sale in the European Union (March 2001) and in Canada (April 2001) as a treatment for depression in patients with treatment-resistant or treatment intolerant major depressive episodes including unipolar depression and bipolar disorder (manic depression).
VNS Therapy will soon be available in many major cities. It will be available first in cities where the clinical studies were conducted including Dallas, Houston, Charleston, San Francisco, Chicago, and New York among others.
VNS Therapy is at various levels of investigational clinical studies as a potential treatment for anxiety disorders, AlzheimerÂ’s disease, bulimia and chronic headache/migraine.
VNS Therapy Clinical Studies in Depression
In 2003 and 2004, clinical studies were concluded in the United Sates to support the approval of VNS Therapy for the adjunctive long-term treatment of chronic and recurrent depression. Results from these studies were incorporated into a PMA-Supplement application submitted to the FDA for approval on October 27, 2003. An amendment to this submission was made in September 2004 with additional long-term data.
For many patients, VNS Therapy offers significant improvements in physical, mental and emotional well-being, vitality and social interaction.1
Clinical study results indicate VNS Therapy has the potential to provide relief to those with longstanding depression which has not responded to other antidepressant therapies.2 Study results also show that patients who use VNS Therapy may continue to show clinical improvement in both their depression symptoms and quality of life over time.3
Results from clinical trials indicate that VNS Therapy is not associated with sexual dysfunction or memory impairment. Animal studies also reveal no evidence of impaired fertility or harm to the fetus due to VNS Therapy. Sleep disturbance and weight gain (commonly reported with other antidepressant treatments) have been reported by less than two percent of patients receiving VNS Therapy.
Because VNS Therapy is not a drug, it produces no drug interactions with concurrent antidepressant medications.
VNS Therapy Experience in Epilepsy
To date, more than 30,000 patients worldwide have accumulated over 79,000 patient years of experience using VNS Therapy.
The implant procedure does not involve the brain and is a short outpatient procedure. There is a very low incidence rate of minor complications.
VNS Therapy has been proven to effectively decrease seizures.4 Many physicians and patients report that the quality of life is improved by the reduction in frequency and severity of seizures.5
VNS Therapy provides seizure reduction and quality-of-life benefits that improve over time. 6
Common Side Effects with VNS Therapy
The common side effects associated with VNS Therapy include hoarseness, sore throat, shortness of breath and coughing.7
Side effects typically occur only during stimulation and typically diminish over time.8
Frequent Ask Questions
Is VNS Therapy for depression currently available to treat people with depression? Yes, the FDA has now approved VNS Therapy as an adjunctive (add-on), long-term treatment for 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 is also approved for use in Europe and Canada for depression in patients with treatment-resistant or treatment intolerant major depressive episodes including unipolar depression and bipolar disorder (manic depression). Why was VNS Therapy studied for patients with chronic or recurrent treatment-resistant depression? VNS Therapy received FDA approval in 1997 for the treatment of adults and adolescents over 12 years of age with partial onset seizures that are refractory to antiepileptic medications. To date, more than 30,000 patients have been treated with VNS Therapy. The suggested link between VNS Therapy and potential antidepressant efficacy lies primarily in the fact that many of the patients with epilepsy who were treated with VNS Therapy reported improved mood. Subsequent clinical studies demonstrated that patients with epilepsy experienced significantly improved mood when treated with VNS Therapy, and these mood improvements occurred irrespective of seizure control. Additionally, some anticonvulsant medications have been shown to have antidepressant or mood stabilizing efficacy. Although the VNS Therapy surgical procedure does not involve the brain, stimulation of the left vagus nerve has been shown to induce widespread bilateral effects in areas of the brain implicated in seizures and mood disorders and responsible for modulation of key neurotransmitters such as serotonin and norepinephrine. VNS Therapy offers a unique safety profile. To date, more than 30,000 patients with epilepsy worldwide have accumulated over 79,000 patient years of experience using VNS Therapy as an approved anticonvulsant treatment. VNS Therapy also provides assured patient adherence. VNS Therapy is very well tolerated and there are no drug interactions with VNS Therapy and concurrent antidepressant medication.
What studies have been conducted to determine VNS TherapyÂ’s efficacy in treating depression?
CyberonicsÂ’ VNS Therapy depression study program began with the first pilot study implant in July 1998. The depression study program includes the following studies: a 60- patient acute and long-term pilot study (D-01); a 235-patient double blind, randomized, placebo controlled 8-week fixed dose acute pivotal study with an open label long-term extension (D-02); a 127-patient long-term observational study of patients with chronic or recurrent treatment-resistant depression treated only with treatment as usual (D-04); neuroimaging, neurochemical and sleep mechanism of action studies; and several healthcare utilization and cost effectiveness studies. The patients in these studies were experiencing chronic or recurrent treatment-resistant depression. In the D-02 and D-04 studies, the average lifetime illness exceeded 25 years and the average duration of the current depressive episode exceeded 48 months. In January 2002, Cyberonics announced that the difference in the D-02 treatment and placebo group in the 24-item Hamilton Rating Scale (HAM-D) response rates at the end of the eight-week fixed dose acute study was clinically meaningful, but not statistically significant. In September 2002, Cyberonics submitted a revised, prospective long-term pivotal study analysis plan to the FDA. That plan was designed to determine the statistical and clinical significance of the long-term improvements from baseline in all D-02 study patients treated over a one-year period with adjunctive VNS Therapy and treatment as usual. Additionally, the study would compare D-02 outcomes with the outcomes of the D- 04 patients who were treated only with treatment as usual.
What do the studies demonstrate about VNS Therapy for depression?
Clinical study results demonstrate that VNS Therapy is effective in treating chronic or recurrent treatment-resistant depression, and that patients with depression who respond to treatment with VNS Therapy are likely to maintain their improvement.19 In the 12-month follow-up of D-02 patients, 30 percent of patients with chronic or recurrent depression responded to VNS Therapy compared to 13 percent of D-04 patients receiving medication only, but no VNS Therapy. Seventeen percent of patients treated with VNS Therapy achieved remission,20 compared to seven percent of patients receiving medication only, but no VNS Therapy.21 Patients with depression who achieve remission no longer meet the criteria for major depression. Overall, it has been shown that VNS Therapy may improve the quality of life of patients who have been treated for depression.22 When should VNS Therapy for treatment-resistant depression be considered? VNS Therapy for treatment-resistant depression has been indicated as an adjunctive long- term treatment for patients 18 years or older with chronic or recurrent depression who are experiencing a major depressive episode and have not had an adequate response to four or more adequate antidepressant treatments.
How does VNS Therapy work?
VNS Therapy is delivered via a small pacemaker-like device that is implanted just under the skin during a short, outpatient procedure that does not involve the brain. The device is implanted in the left chest area. A thin flexible wire connects the device to the left vagus nerve in the neck. Once activated by the physician, the device sends precisely timed and measured mild pulses to the left vagus nerve. The stimulation dose is adjusted via an external telemetric wand and special software to stimulate the vagus nerve at regular intervals, 24 hours a day. Using this dose adjustment system, physicians can adjust the timing and amount of the stimulation the patient receives. There is an extensive body of data demonstrating the association between vagus nerve stimulation and brain activation. Brain imaging studies have demonstrated that VNS Therapy modulates blood flow and/or metabolism in many areas of the brain that are affected in mood disorders.
What are the side effects of VNS Therapy?
Side effects associated with VNS Therapy are mild to moderate, typically stimulation related and typically decrease over time. The most commonly reported side effects during the depression clinical studies were hoarseness, paresthesia (an abnormal sensation such as tingling), dysphagia (difficulty swallowing) and dyspnea (shortness of breath).23
How much will VNS Therapy cost?
The cost of VNS Therapy for the treatment of epilepsy is approximately $20,000 to $25,000 initially. Hospital charges vary, so the cost can differ. In epilepsy, most third party payors reimburse for the procedure, as well as Medicare and Medicaid in most states. It is anticipated that the experience in depression may be similar over time. The dose settings impact how long the battery will last. For example, the battery may last 3 years at a higher setting, compared with 8 years at a lower setting.
Where will VNS Therapy be available?
VNS Therapy will soon be available in most major cities. It will be available first in cities where the clinical studies were conducted including Dallas, Houston, Charleston, San Francisco, Chicago and New York among others. How can patients learn more information about VNS Therapy for treating depression?
Knowledgement Cyberonics Inc. provide most of the information for this article. For more information about VNS Therapy, patients can call 1-877-NOW-4-VNS or visit www.VNSTherapy.com.
To learn more about health issues or supplements, visit zhion.com. To learn about depression, visit depression. To read corporate fact sheet about Cyberonic Inc., visit Cyberonic.
REFERENCES 1 Marangell L., Rush AJ, George M, et al. Â“Vagus Nerve Stimulation (VNS) for Major Depressive Episodes: One Year Outcomes.Â” Biological Psychiatry; 2002. (51)4:284, 285Â–86.
2 Rush AJ, George M, Sackeim HA, Marangell L, et al. Â“Vagus Nerve Stimulation (VNS) for Treatment-Resistant Depressions: A Multicenter Study.Â” Biological Psychiatry; 2000. (47);4:276-286.
3 Marangell L., Rush AJ, George M, et al. Â“Vagus Nerve Stimulation (VNS) for Major Depressive Episodes: One Year Outcomes.Â” Biological Psychiatry; 2002. (51)4:284, 285Â–86.
4 Kaakaji W, Geller EB, Bingaman WE. Â“Vagal Nerve Stimulation for the Treatment of Refractory Seizures: A Preliminary Experience.Â” Poster #1360 Presented at the 1999 American Association of Neurological Surgeons Meeting.
5 Tatum WO, Johnson KD, Goff S, et al. Â“Vagus nerve stimuation and drug reduction.Â” Neurology; 2001. (56)4:562.
6 Morris G, Mueller W. Â“Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy.Â” Neurology; 1999. (53)7:1733Â–34.
8 Â“PatientÂ’s Manual for Vagus Nerve Stimulation with the NeuroCybernetic Prosthesis (NCPÂ®) System,Â” Produced by Cyberonics, October 2000.
19 Marangell L, Rush JA, George MS, et al. Â“Vagus Nerve Stimulation (VNS) for Major Depressive Episodes: One Year Outcomes,Â” Biological Psychiatry, 2002; 51 (4) 280 - 287
20 Rush AJ, George M, Sackeim HA, Marangell L, et al. Â“A One-Year Longitudinal Study of VNS Therapy in Patients with Treatment-Resistant Depression,Â” Presented at the 42nd American College of Neuropsychopharmacology Annual Meeting
21 Cyberonics Depression PMA Supplement (PMA-S) to the U.S. Food and Drug Administration (FDA). Produced by Cyberonics, October 2003.
22Sackheim HA, Rush JA, George MS, et al. Â“Vagus Nerve Stimulation for Treatment- Resistant Depression: Efficacy, Side Effects and Predictors of Outcome,Â” Journal of Neuropsychopharmacology. 2001; (25):5:713-728.
23 Marangell L, Rush JA, George MS, et al. Â“Vagus Nerve Stimulation (VNS) for Major Depressive Episodes: One Year Outcomes,Â” Biological Psychiatry, 2002; 51 (4) 280 Â– 287.