![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 4 of 4. This is the beginning of the thread.
Posted by jrbecker on June 11, 2003, at 10:50:12
06/09/2003
Cyberonics Announces Depression Disclosure Timetable
HOUSTON, June 9 /PRNewswire-FirstCall/ -- Cyberonics, Inc. expects to announce the results of its depression pivotal study causality analysis, and release a revised U.S.
PR via NewsEdge Corporation : HOUSTON, June 9 /PRNewswire-FirstCall/ -- Cyberonics, Inc. (Nasdaq: CYBX) expects to announce the results of its depression pivotal study causality analysis, and release a revised U.S. depression regulatory plan and a revised five-year business plan in July 2003. The Company will host a dinner program for investors and analysts, "The Future of VNS Therapy(tm)," on Wednesday, September 24, 2003 at the Plaza Hotel in New York City from 5:00 PM to 10:00 PM during the UBS Warburg Healthcare Conference. A conference call to discuss the depression disclosure timetable and the recent redeployment and realignment of U.S. sales resources will be held at 4:00 PM EDT today."Cyberonics will provide investors with clarity on our five year business plan and the future of VNS Therapy immediately following final determination of depression causality," commented Robert P. Cummins, Cyberonics' Chairman and Chief Executive Officer. "Today on the conference call, we will discuss the depression timetable and Michael Cheney, Senior Vice President Marketing and Sales and Steve Jennings, our new Vice President Sales, both of whom were at our national sales meeting during last week's conference call, will provide investors with an update on the redeployment of our U.S. sales resources into a classic specialty pharmaceutical sales model. We will enter the pre- causality quiet period on June 16, 2003."
The causal relationship between VNS Therapy and the depression pivotal study patients' highly statistically significant and clinically significant one-year outcomes will be determined in July 2003 using a repeated measures linear regression analysis to compare depression improvements over one year in approximately 190 D-02 patients receiving VNS Therapy and treatment as usual with the outcomes of approximately 100 patients in a companion study, D-04, receiving only treatment as usual. In D-04, patients with chronic or recurrent treatment resistant depression who met the critical D-02 inclusion criteria were treated with standard medical management at 13 total study sites including 12 of the 21 D-02 study sites. Cyberonics' revised U.S. depression regulatory plan and a revised five-year corporate business plan will be released at the same time as the causality results.
"The Future of VNS Therapy" dinner program will occur on Wednesday, September 24, 2003 at the Plaza Hotel in New York City from 5:00 PM to 10:00 PM during the UBS Warburg Healthcare Conference. Presentations will be made by Cyberonics management and by epileptologists and psychiatrists involved in the VNS Therapy clinical studies. The VNS dinner program is open to the public and registration is available online at www.cyberonics.com .
Scheduled speakers at the VNS dinner program include:
-- A. John Rush, M.D., Professor and Vice Chairman of Research, Department of Psychiatry, University of Texas Southwestern
-- Mark S. George, M.D., Professor of Psychiatry, Radiology and Neurology; Director, Functional Neuroimaging Division, Psychiatry; Director, Brain Stimulation Laboratory, Medical University of South Carolina
-- Harold A. Sackeim, Ph.D., Professor of Clinical Psychology in Psychiatry & Radiology, Columbia University; Chief, Department of Biological Psychiatry, New York State Psychiatric Institute
-- Lauren B. Marangell, M.D., Associate Professor of Psychiatry; Director, Mood Disorder Center, Baylor College of Medicine
-- James Wheless, M.D., Professor of Neurology and Pediatrics, Department of Neurology; Director, Texas Comprehensive Epilepsy Program, The University of Texas Health Science Center at Houston; Director, Epilepsy Monitoring Unit, Memorial Hermann Children's Hospital
-- Robert P. ("Skip") Cummins, Chairman and Chief Executive Officer, Cyberonics
-- Michael A. Cheney, Senior Vice President Marketing and Sales, Cyberonics
-- W. Steve Jennings, Vice President Sales, Cyberonics
-- Richard L. Rudolph, M.D., Vice President Clinical and Medical Affairs, Cyberonics
-- Pamela B. Westbrook, Vice President Finance, Cyberonics
Conference Call Instructions
Two separate phone lines are necessary to access the conference call and Internet presentation. The audio portion of the conference call may be accessed by dialing 877-451-8943 (if dialing from within the U.S.) or 706-679-3062 (if dialing from outside the U.S.). The conference ID is 1210032; the leader is Pam Westbrook. A replay of the audio portion of the conference call will be available two hours after the completion of the conference call on Monday, June 9, 2003 through Monday, June 23, 2003 by dialing 800-642-1687 (if dialing from within the U.S.) or 706-645-9291 (if dialing outside the U.S.). The replay conference ID access code is 1210032.
You may access the Cyberonics Internet presentation site via the PresentPLUS Gateway address http://www.presentplus.com/conference/gateway.html . To test your system in advance, take the instant system check by clicking on the PresentPLUS Gateway link above, then select Browser Check from the available options. If you encounter difficulty, support solutions will be provided, or you may call PresentPLUS toll-free at 877-549-3137 or email support
presentplus.com with your telephone number for an immediate call back. Once proper compatibility is confirmed, the presentation site can be accessed 10 minutes prior to the scheduled start, beginning at 3:50 PM EDT on Monday, June 9, 2003. Click on the link http://www.presentplus.com/conference/gateway.html , then click on "Attendee Login" from the available options. The event name and password is xcyberonics.
ABOUT VNS AND CYBERONICS
Cyberonics, Inc. was founded in 1987 to design, develop and market medical devices for the long-term treatment of epilepsy and other chronic neurological disorders using a unique therapy, vagus nerve stimulation (VNS). Stimulation is delivered by the VNS Therapy System, an implantable generator similar to a cardiac pacemaker. The VNS Therapy System delivers preprogrammed intermittent mild electrical pulses to the vagus nerve 24 hours a day. The Company's initial market is epilepsy, which is characterized by recurrent seizures. Epilepsy is the second most prevalent neurological disorder. The Cyberonics VNS Therapy System was approved by the FDA on July 16, 1997 for use as an adjunctive therapy in reducing the frequency of seizures in adults and adolescents over 12 years of age with partial onset seizures that are refractory to antiepileptic medications. The VNS Therapy System is also approved for sale as a treatment for epilepsy in all the member countries of the European Union, Canada, Australia and other markets. To date, more than 20,000 epilepsy patients in 24 countries have accumulated over 50,000 patient years of experience using VNS Therapy. VNS Therapy is at various levels of investigational clinical study as a potential treatment for depression, anxiety disorders, Alzheimer's disease, and chronic headache/migraine. The VNS Therapy System is approved for sale in the European Union and in Canada as a treatment for depression in patients with treatment-resistant or treatment intolerant major depressive episodes including unipolar depression and bipolar disorder (manic depression). The Company is headquartered in Houston, Texas and has an office in Brussels, Belgium. For additional information please visit us at www.cyberonics.com .
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended. These statements can be identified by the use of forward-looking terminology, including "may," "believe," "will," "expect," "anticipate," "estimate," "plan," "intend," and "forecast," or other similar words. Such forward-looking statements include statements concerning the timing of the release of the final determination of depression causality and our five year business plan. Statements contained in this press release are based upon information presently available to us and assumptions that we believe to be reasonable. We are not assuming any duty to update this information should those facts change or should we no longer believe the assumptions to be reasonable. Our actual results may differ materially. Important factors that may cause actual results to differ include, but are not limited to: continued market acceptance of VNS Therapy and sales of our product; the development and satisfactory completion of clinical trials and/or market test of VNS Therapy for the treatment of depression, Alzheimer's disease, anxiety, or other indications; adverse changes in coverage or reimbursement amounts by third-parties; intellectual property protection and potential infringement claims; maintaining compliance with government regulations and obtaining necessary government approvals for new applications; product liability claims and potential litigation; reliance on single suppliers and manufacturers for certain components; the accuracy of management's estimates of future expenses and sales; and other risks detailed in from time to time in the Company's filings with the SEC.
SOURCE Cyberonics, Inc.
-0- 06/09/2003
/CONTACT: Pamela Westbrook, Vice President of Finance and CFO of Cyberonics, Inc., +1-281-228-7200, or fax, +1-281-218-9332, or pbw
cyberonics.com ; or Helen Shik, Vice President of Schwartz Communications, +1-781-684-0770 ext. 6587, or fax, +1-781-684-6500, or hshik
schwartz-pr.com , for Cyberonics, Inc./
/Web site: http://www.presentplus.com/conference/gateway.html http://www.cyberonics.com /
(CYBX)
CO: Cyberonics, Inc.; UBS Warburg
ST: Texas, New York
IN: HEA MTC BIO SPM FIN
SU: CCA MAV
JS-CD
-- DAM027 --
0658 06/09/2003 10:13 EDT http://www.prnewswire.com
<< Copyright ©2003 PR Newswire >>
http://www.psychiatry24x7.com/news/detail.jhtml?itemname=p0609044.8rw0
Posted by jrbecker on June 11, 2003, at 11:07:32
In reply to VNS study results to be released soon, posted by jrbecker on June 11, 2003, at 10:50:12
Well, I guess the preliminary results are have already just been released...according to Jim McManamy of McMan's Depression and Bipolar Web, the response rate was 31 percent for actual completers of the 12-month study.
http://www.mcmanweb.com/news.htm> 06/09/2003
>
> Cyberonics Announces Depression Disclosure Timetable
>
> HOUSTON, June 9 /PRNewswire-FirstCall/ -- Cyberonics, Inc. expects to announce the results of its depression pivotal study causality analysis, and release a revised U.S.
>
> PR via NewsEdge Corporation : HOUSTON, June 9 /PRNewswire-FirstCall/ -- Cyberonics, Inc. (Nasdaq: CYBX) expects to announce the results of its depression pivotal study causality analysis, and release a revised U.S. depression regulatory plan and a revised five-year business plan in July 2003. The Company will host a dinner program for investors and analysts, "The Future of VNS Therapy(tm)," on Wednesday, September 24, 2003 at the Plaza Hotel in New York City from 5:00 PM to 10:00 PM during the UBS Warburg Healthcare Conference. A conference call to discuss the depression disclosure timetable and the recent redeployment and realignment of U.S. sales resources will be held at 4:00 PM EDT today.
>
> "Cyberonics will provide investors with clarity on our five year business plan and the future of VNS Therapy immediately following final determination of depression causality," commented Robert P. Cummins, Cyberonics' Chairman and Chief Executive Officer. "Today on the conference call, we will discuss the depression timetable and Michael Cheney, Senior Vice President Marketing and Sales and Steve Jennings, our new Vice President Sales, both of whom were at our national sales meeting during last week's conference call, will provide investors with an update on the redeployment of our U.S. sales resources into a classic specialty pharmaceutical sales model. We will enter the pre- causality quiet period on June 16, 2003."
>
> The causal relationship between VNS Therapy and the depression pivotal study patients' highly statistically significant and clinically significant one-year outcomes will be determined in July 2003 using a repeated measures linear regression analysis to compare depression improvements over one year in approximately 190 D-02 patients receiving VNS Therapy and treatment as usual with the outcomes of approximately 100 patients in a companion study, D-04, receiving only treatment as usual. In D-04, patients with chronic or recurrent treatment resistant depression who met the critical D-02 inclusion criteria were treated with standard medical management at 13 total study sites including 12 of the 21 D-02 study sites. Cyberonics' revised U.S. depression regulatory plan and a revised five-year corporate business plan will be released at the same time as the causality results.
>
> "The Future of VNS Therapy" dinner program will occur on Wednesday, September 24, 2003 at the Plaza Hotel in New York City from 5:00 PM to 10:00 PM during the UBS Warburg Healthcare Conference. Presentations will be made by Cyberonics management and by epileptologists and psychiatrists involved in the VNS Therapy clinical studies. The VNS dinner program is open to the public and registration is available online at www.cyberonics.com .
>
> Scheduled speakers at the VNS dinner program include:
>
> -- A. John Rush, M.D., Professor and Vice Chairman of Research, Department of Psychiatry, University of Texas Southwestern
>
> -- Mark S. George, M.D., Professor of Psychiatry, Radiology and Neurology; Director, Functional Neuroimaging Division, Psychiatry; Director, Brain Stimulation Laboratory, Medical University of South Carolina
>
> -- Harold A. Sackeim, Ph.D., Professor of Clinical Psychology in Psychiatry & Radiology, Columbia University; Chief, Department of Biological Psychiatry, New York State Psychiatric Institute
>
> -- Lauren B. Marangell, M.D., Associate Professor of Psychiatry; Director, Mood Disorder Center, Baylor College of Medicine
>
> -- James Wheless, M.D., Professor of Neurology and Pediatrics, Department of Neurology; Director, Texas Comprehensive Epilepsy Program, The University of Texas Health Science Center at Houston; Director, Epilepsy Monitoring Unit, Memorial Hermann Children's Hospital
>
> -- Robert P. ("Skip") Cummins, Chairman and Chief Executive Officer, Cyberonics
>
> -- Michael A. Cheney, Senior Vice President Marketing and Sales, Cyberonics
>
> -- W. Steve Jennings, Vice President Sales, Cyberonics
>
> -- Richard L. Rudolph, M.D., Vice President Clinical and Medical Affairs, Cyberonics
>
> -- Pamela B. Westbrook, Vice President Finance, Cyberonics
>
> Conference Call Instructions
>
> Two separate phone lines are necessary to access the conference call and Internet presentation. The audio portion of the conference call may be accessed by dialing 877-451-8943 (if dialing from within the U.S.) or 706-679-3062 (if dialing from outside the U.S.). The conference ID is 1210032; the leader is Pam Westbrook. A replay of the audio portion of the conference call will be available two hours after the completion of the conference call on Monday, June 9, 2003 through Monday, June 23, 2003 by dialing 800-642-1687 (if dialing from within the U.S.) or 706-645-9291 (if dialing outside the U.S.). The replay conference ID access code is 1210032.
>
> You may access the Cyberonics Internet presentation site via the PresentPLUS Gateway address http://www.presentplus.com/conference/gateway.html . To test your system in advance, take the instant system check by clicking on the PresentPLUS Gateway link above, then select Browser Check from the available options. If you encounter difficulty, support solutions will be provided, or you may call PresentPLUS toll-free at 877-549-3137 or email support
>
> presentplus.com with your telephone number for an immediate call back. Once proper compatibility is confirmed, the presentation site can be accessed 10 minutes prior to the scheduled start, beginning at 3:50 PM EDT on Monday, June 9, 2003. Click on the link http://www.presentplus.com/conference/gateway.html , then click on "Attendee Login" from the available options. The event name and password is xcyberonics.
>
> ABOUT VNS AND CYBERONICS
>
> Cyberonics, Inc. was founded in 1987 to design, develop and market medical devices for the long-term treatment of epilepsy and other chronic neurological disorders using a unique therapy, vagus nerve stimulation (VNS). Stimulation is delivered by the VNS Therapy System, an implantable generator similar to a cardiac pacemaker. The VNS Therapy System delivers preprogrammed intermittent mild electrical pulses to the vagus nerve 24 hours a day. The Company's initial market is epilepsy, which is characterized by recurrent seizures. Epilepsy is the second most prevalent neurological disorder. The Cyberonics VNS Therapy System was approved by the FDA on July 16, 1997 for use as an adjunctive therapy in reducing the frequency of seizures in adults and adolescents over 12 years of age with partial onset seizures that are refractory to antiepileptic medications. The VNS Therapy System is also approved for sale as a treatment for epilepsy in all the member countries of the European Union, Canada, Australia and other markets. To date, more than 20,000 epilepsy patients in 24 countries have accumulated over 50,000 patient years of experience using VNS Therapy. VNS Therapy is at various levels of investigational clinical study as a potential treatment for depression, anxiety disorders, Alzheimer's disease, and chronic headache/migraine. The VNS Therapy System is approved for sale in the European Union and in Canada as a treatment for depression in patients with treatment-resistant or treatment intolerant major depressive episodes including unipolar depression and bipolar disorder (manic depression). The Company is headquartered in Houston, Texas and has an office in Brussels, Belgium. For additional information please visit us at www.cyberonics.com .
>
> This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended. These statements can be identified by the use of forward-looking terminology, including "may," "believe," "will," "expect," "anticipate," "estimate," "plan," "intend," and "forecast," or other similar words. Such forward-looking statements include statements concerning the timing of the release of the final determination of depression causality and our five year business plan. Statements contained in this press release are based upon information presently available to us and assumptions that we believe to be reasonable. We are not assuming any duty to update this information should those facts change or should we no longer believe the assumptions to be reasonable. Our actual results may differ materially. Important factors that may cause actual results to differ include, but are not limited to: continued market acceptance of VNS Therapy and sales of our product; the development and satisfactory completion of clinical trials and/or market test of VNS Therapy for the treatment of depression, Alzheimer's disease, anxiety, or other indications; adverse changes in coverage or reimbursement amounts by third-parties; intellectual property protection and potential infringement claims; maintaining compliance with government regulations and obtaining necessary government approvals for new applications; product liability claims and potential litigation; reliance on single suppliers and manufacturers for certain components; the accuracy of management's estimates of future expenses and sales; and other risks detailed in from time to time in the Company's filings with the SEC.
>
> SOURCE Cyberonics, Inc.
>
> -0- 06/09/2003
>
> /CONTACT: Pamela Westbrook, Vice President of Finance and CFO of Cyberonics, Inc., +1-281-228-7200, or fax, +1-281-218-9332, or pbw
>
> cyberonics.com ; or Helen Shik, Vice President of Schwartz Communications, +1-781-684-0770 ext. 6587, or fax, +1-781-684-6500, or hshik
>
> schwartz-pr.com , for Cyberonics, Inc./
>
> /Web site: http://www.presentplus.com/conference/gateway.html http://www.cyberonics.com /
>
> (CYBX)
>
> CO: Cyberonics, Inc.; UBS Warburg
>
> ST: Texas, New York
>
> IN: HEA MTC BIO SPM FIN
>
> SU: CCA MAV
>
> JS-CD
>
> -- DAM027 --
>
> 0658 06/09/2003 10:13 EDT http://www.prnewswire.com
>
>
> << Copyright ©2003 PR Newswire >>
>
> http://www.psychiatry24x7.com/news/detail.jhtml?itemname=p0609044.8rw0
>
Posted by Ponder on June 14, 2003, at 1:13:06
In reply to Re: VNS [full] study results to be released soon, posted by jrbecker on June 11, 2003, at 11:07:32
This article contains some interesting stuff on VNS and neuroanatomy, but skip on down to the last three paragraphs for some intriguing and, perhaps, promising info. Neuroimaging technology may allow identification of optimal settings for these stimulators, so even better results may be possible. The increasing, or,at least,lasting efficacy over time looks good, too.
Is Vagus Nerve Stimulation the Next Breakthrough for Treatment-Resistant Depression? Ziad Nahas.
Byline: Ziad Nahas, M.D.
The vagus nerve is classically described as the wandering nerve. It sends signals from the central nervous system to control the peripheral cardiovascular, respiratory and gastrointestinal systems (Foley and DuBois, 1937, as cited in George et al., 2000), but 80% of its fibers are afferent and carry information from the viscera back to the brain. The fibers first enter the midbrain at the nucleus tractus solitaris (NTS) level. From the midbrain, they either loop back out in a reflex arc, connect to the reticular activating system or reach the parabrachial nucleus and its connections to the NTS; raphe nucleus; locus ceruleus; the thalamus; and paralimbic, limbic and cortical regions. It is through this route that vagus nerve stimulation (VNS) modulates brain function. Yoga and deep breathing (primarily regulated by the 10th cranial nerve) are clearly associated with CNS effects. This neuroanatomy may be important in how VNS treats epilepsy and potentially treats depression.
Over the past century, researchers have demonstrated that peripheral modulation of the vagus showed changes in CNS neuronal activity (Chase et al., 1966; MacLean, 1990; Van Bockstaele et al., 1999). The contemporary history of VNS started in 1985, when Zabara (1992) demonstrated the anticonvulsant action of VNS on experimental seizures in dogs during and after the stimulation periods. These lasting beneficial effects meant that residual changes in neurotransmitters or perhaps a certain degree of neuronal plasticity occurred and proved useful in controlling the seizures beyond the immediate stimulation. These observations led to the development of the VNS Therapy System (previously named the Neuro-Cybernetic Prosthesis) and an expanding amount of research, first in different types of seizure disorders (Penry and Dean, 1990), and later in other neuropsychiatric conditions such as depression.
The VNS Therapy pulse generator is a pacemaker-like device implanted in the anterior chest wall. It is linked to leads wrapped around the cervical portion of the left vagus nerve and is easily programmable with an external wand to deliver mild electrical stimulation at a preset intensity, duration, pulse width and duty cycle. The battery life averages eight to 10 years, making VNS an advantageous long-term treatment modality with 100% compliance. The most critical part of the one hour-long implantation procedure is the dissection of the vagus nerve from the carotid artery. The surgical complications are more related to the risks of anesthesia than to rare infections or trauma to the vagus nerve and its branches. Vocal chord paralysis may occur if the recurrent laryngeal nerve is damaged. A few cases of arrhythmias have been reported at the initial onset of the stimulation in the operating room without any long-term consequences. The American Academy of Neurology concluded that VNS for epilepsy is both "effective and safe" and is without significant gastrointestinal or cardiac side effects (Schachter and Saper, 1998), based on studies in both children (Nagarajan et al., 2000) and adults (Schachter and Saper, 1998). The most common side effect has been voice alteration or hoarseness, generally mild and related to the intensity of the output current. The mean overall decline of seizure frequency is approximately 35% compared to baseline at one year and has been shown to increase to 43% after three years of therapy (Morris et al., 1999). Some patients (as many as 10% or more) can be controlled solely with VNS (without anticonvulsant medications), but the majority continues with concomitant, albeit more simplified, pharmacotherapy.
The next chapter of VNS therapy emerged when studies in epilepsy began to offer clinical and later prospective evidence that VNS improved mood independently from seizure control (Elger et al., 2000). This, in addition to the known neuroanatomy of the vagus, the role of anticonvulsants in treating mood disorders (Post, 1990), a positron emission tomography study showing brain activity changes in limbic regions attributed to VNS (Henry et al., 1998) and studies showing that modulating the locus ceruleus neurotransmitters homeostasis played a crucial role in the VNS therapeutic effects (Walker et al., 1999), led to exploring VNS for treating depression.
The first implant for this indication was performed in 1998 by researchers from the Medical University of South Carolina, who led an initial short-term, open-label pilot study of VNS in 30 adult outpatients with treatment-resis-tant, severe, non-psychotic major depressive episodes. This study reported a 30.5% response rate after eight weeks of VNS therapy, with a 50% reduction in baseline on the 28-item Hamilton Rating Scale for Depression (HAM-D-28). In this medication-resistant group, there was a 15.3% complete remission rate (exit HAM-D-28 < 10) (Rush et al., 2000). In a larger (n=60) study of vagus nerve stimulation, a history of treatment resistance and the amount of concurrent antidepressant treatment during the acute VNS trial predicted a poorer VNS outcome (Sackeim et al., 2001). An open, naturalistic follow-up study (Marangell et al., 2002) with an additional nine months of long-term VNS treatment and changes in psychotropic medications showed an improved response rate from 30.5% to 45%. The remission rate significantly increased to 29% at one year. This open-label study provided important evidence that VNS is both feasible and safe. It revealed the antidepressant effect size needed to design larger double-blind pivotal studies. Based on these data, VNS has been approved as a treatment for depression in Europe and Canada, but it has not been approved for this indication by the U.S. Food and Drug Administration.
To overcome the limitations of these open design studies, a multisite, randomized, sham-controlled study was necessary. The logistics imposed by such design were unlike most pharmacological trials. Vagus nerve stimulation can cause voice alterations, which could give away the blind. Research teams were divided into blinded raters and unblinded programmers. At each site visit, subjects had to be seen by the programmer first, who would turn off the device before allowing the blinded rating group to interact with the subjects. These steps applied equally to both active and placebo arms to maximize the integrity of the blind.
A total of 235 subjects with moderate-to-severe refractory depressive episodes were enrolled. They were held constant on their psychotropic medications one month prior to implant and for the duration of the 12-week acute initial phase. After this initial phase, placebo non-responders were crossed over to active stimulation. The initial report did not achieve a statistically significant difference in three-month response with active VNS (15%), compared to the sham group (10%). This may have been in part due to an underpowering of the study and a more severely ill enrolled cohort compared to that which had been originally designed for and expected. In addition, the average intensity of stimulation in this multicenter, double-blind study is less than the stimulation intensity generally seen in epilepsy or in the initial depression study.
As in epilepsy, the predictive factors for positive outcome or guidelines for stimulation parameters have not yet been worked out (Koo et al., 2001), but an effort is underway to maximally increase the intensity of stimulation in non-responders.
Despite the lack of statistical significance demonstrated in the acute period, the therapeutic role of VNS is still unfolding. As in the open study, a gradual and steady response is being noticed. By following the first 36 implanted subjects in an open-label fashion for an additional nine months, during which both pharmacological and parameter dosing changes have been made, a response rate increase of 44% has been observed. Data at one-year follow up for all 235 subjects are not yet available. Clinical observations suggested that some of the responders appear to have stayed in remission longer than with psychotropic medications alone. If this holds true, this will be a great departure from traditional antidepressant treatments (including electroconvulsive therapy).
The mechanisms of action of VNS are still unknown. Human cerebrospinal fluid (CSF) studies in epilepsy patients reveal an increase in 5-HIAA, homovanillic acid (HVA) and g-aminobutyric acid and a decrease in glutamate after three months of treatment (Ben-Menachem et al., 1995). Vagus nerve stimulation causes increases in HVA in depressed subjects, and the increase in CSF norepinephrine may predict a better response to treatment. Patients with high corticotrophin-releasing factor or low 5-HIAA had a poor response to the VNS antidepressant effect (Carpenter et al., 2002). Sleep studies show a normalization of electroencephalograph rhythm patterns (Armitage et al., 2002). Functional brain imaging studies demonstrate that VNS causes immediate and long-term changes in brain regions implicated in neuropsychiatric disorders with vagus innervations. These include the thalamus, cerebellum, orbitofrontal cortex, limbic system, hypothalamus and medulla (Henry et al., 1998; Henry et al., 1999).
At the Medical University of South Carolina, researchers have succeeded in performing blood-oxygen-level function magnetic resonance imaging (BOLD fMRI) studies in depressed patients implanted with VNS generators (Bohning et al., 2001; Lomarev et al., 2002). These results show that VNS activates many anterior para-limbic regions in a dose-dependent fashion that changes over time. It appears that the chronic stimulation dynamically and differentially modulates prefrontal/limbic circuitry. The net effect over 10 weeks of VNS treatment in depressed patients appears to be a gradual deactivation of the limbic regions (Nahas et al., 2002). It is still unclear whether these changes are frequency- or intensity-dependent. Because of the ability to image the immediate effect of VNS on brain activity, the fMRI technique offers a unique opportunity to perform sophisticated parametric studies and is likely to inform us about VNS dosing. Ultimately, VNS/fMRI may also be used to individually determine the best stimulation parameters to help a particular patient (Figure).
Before its widespread use, and given the initial high cost of the implant and surgical procedure, efforts are underway to document whether VNS is both beneficial and cost-effective in the long term for patients with depression. Other VNS open trials are underway in anxiety disorders (posttraumatic stress disorder, panic disorder and obsessive-compulsive disorder), the early stages of Alzheimer's disease, rapid-cycling bipolar disorder and migraine headaches. In a related venue, sub-diaphragmatic bilateral VNS is being tested in morbid obesity as it may modulate satiety signals.
Posted by Lonely on October 28, 2004, at 23:24:08
In reply to VNS study results to be released soon, posted by jrbecker on June 11, 2003, at 10:50:12
Does anyone know where all of this stands now? Also, I'm not quite clear on what VNS is - can anyone provide the "simplified" description? In another post there was something about MRf (or something like that). My husband is going to have spectroscopy (MRIs) to see if he has MS. Is it something like that? Since he's been diagnosed bipolar would it likely show something regarding the BP issue that might be helpful? The drug prescription thing reaches ridiculous heights of taking one after another with many side effects and no real solutions. A psychologist told me about vagal nerve stimulation - is it being used now successfully on a routine basis? Thanks for enlightnening me on all this.
> 06/09/2003
>
> Cyberonics Announces Depression Disclosure Timetable
>
> HOUSTON, June 9 /PRNewswire-FirstCall/ -- Cyberonics, Inc. expects to announce the results of its depression pivotal study causality analysis, and release a revised U.S.
>
> PR via NewsEdge Corporation : HOUSTON, June 9 /PRNewswire-FirstCall/ -- Cyberonics, Inc. (Nasdaq: CYBX) expects to announce the results of its depression pivotal study causality analysis, and release a revised U.S. depression regulatory plan and a revised five-year business plan in July 2003. The Company will host a dinner program for investors and analysts, "The Future of VNS Therapy(tm)," on Wednesday, September 24, 2003 at the Plaza Hotel in New York City from 5:00 PM to 10:00 PM during the UBS Warburg Healthcare Conference. A conference call to discuss the depression disclosure timetable and the recent redeployment and realignment of U.S. sales resources will be held at 4:00 PM EDT today.
>
> "Cyberonics will provide investors with clarity on our five year business plan and the future of VNS Therapy immediately following final determination of depression causality," commented Robert P. Cummins, Cyberonics' Chairman and Chief Executive Officer. "Today on the conference call, we will discuss the depression timetable and Michael Cheney, Senior Vice President Marketing and Sales and Steve Jennings, our new Vice President Sales, both of whom were at our national sales meeting during last week's conference call, will provide investors with an update on the redeployment of our U.S. sales resources into a classic specialty pharmaceutical sales model. We will enter the pre- causality quiet period on June 16, 2003."
>
> The causal relationship between VNS Therapy and the depression pivotal study patients' highly statistically significant and clinically significant one-year outcomes will be determined in July 2003 using a repeated measures linear regression analysis to compare depression improvements over one year in approximately 190 D-02 patients receiving VNS Therapy and treatment as usual with the outcomes of approximately 100 patients in a companion study, D-04, receiving only treatment as usual. In D-04, patients with chronic or recurrent treatment resistant depression who met the critical D-02 inclusion criteria were treated with standard medical management at 13 total study sites including 12 of the 21 D-02 study sites. Cyberonics' revised U.S. depression regulatory plan and a revised five-year corporate business plan will be released at the same time as the causality results.
>
> "The Future of VNS Therapy" dinner program will occur on Wednesday, September 24, 2003 at the Plaza Hotel in New York City from 5:00 PM to 10:00 PM during the UBS Warburg Healthcare Conference. Presentations will be made by Cyberonics management and by epileptologists and psychiatrists involved in the VNS Therapy clinical studies. The VNS dinner program is open to the public and registration is available online at www.cyberonics.com .
>
> Scheduled speakers at the VNS dinner program include:
>
> -- A. John Rush, M.D., Professor and Vice Chairman of Research, Department of Psychiatry, University of Texas Southwestern
>
> -- Mark S. George, M.D., Professor of Psychiatry, Radiology and Neurology; Director, Functional Neuroimaging Division, Psychiatry; Director, Brain Stimulation Laboratory, Medical University of South Carolina
>
> -- Harold A. Sackeim, Ph.D., Professor of Clinical Psychology in Psychiatry & Radiology, Columbia University; Chief, Department of Biological Psychiatry, New York State Psychiatric Institute
>
> -- Lauren B. Marangell, M.D., Associate Professor of Psychiatry; Director, Mood Disorder Center, Baylor College of Medicine
>
> -- James Wheless, M.D., Professor of Neurology and Pediatrics, Department of Neurology; Director, Texas Comprehensive Epilepsy Program, The University of Texas Health Science Center at Houston; Director, Epilepsy Monitoring Unit, Memorial Hermann Children's Hospital
>
> -- Robert P. ("Skip") Cummins, Chairman and Chief Executive Officer, Cyberonics
>
> -- Michael A. Cheney, Senior Vice President Marketing and Sales, Cyberonics
>
> -- W. Steve Jennings, Vice President Sales, Cyberonics
>
> -- Richard L. Rudolph, M.D., Vice President Clinical and Medical Affairs, Cyberonics
>
> -- Pamela B. Westbrook, Vice President Finance, Cyberonics
>
> Conference Call Instructions
>
> Two separate phone lines are necessary to access the conference call and Internet presentation. The audio portion of the conference call may be accessed by dialing 877-451-8943 (if dialing from within the U.S.) or 706-679-3062 (if dialing from outside the U.S.). The conference ID is 1210032; the leader is Pam Westbrook. A replay of the audio portion of the conference call will be available two hours after the completion of the conference call on Monday, June 9, 2003 through Monday, June 23, 2003 by dialing 800-642-1687 (if dialing from within the U.S.) or 706-645-9291 (if dialing outside the U.S.). The replay conference ID access code is 1210032.
>
> You may access the Cyberonics Internet presentation site via the PresentPLUS Gateway address http://www.presentplus.com/conference/gateway.html . To test your system in advance, take the instant system check by clicking on the PresentPLUS Gateway link above, then select Browser Check from the available options. If you encounter difficulty, support solutions will be provided, or you may call PresentPLUS toll-free at 877-549-3137 or email support
>
> presentplus.com with your telephone number for an immediate call back. Once proper compatibility is confirmed, the presentation site can be accessed 10 minutes prior to the scheduled start, beginning at 3:50 PM EDT on Monday, June 9, 2003. Click on the link http://www.presentplus.com/conference/gateway.html , then click on "Attendee Login" from the available options. The event name and password is xcyberonics.
>
> ABOUT VNS AND CYBERONICS
>
> Cyberonics, Inc. was founded in 1987 to design, develop and market medical devices for the long-term treatment of epilepsy and other chronic neurological disorders using a unique therapy, vagus nerve stimulation (VNS). Stimulation is delivered by the VNS Therapy System, an implantable generator similar to a cardiac pacemaker. The VNS Therapy System delivers preprogrammed intermittent mild electrical pulses to the vagus nerve 24 hours a day. The Company's initial market is epilepsy, which is characterized by recurrent seizures. Epilepsy is the second most prevalent neurological disorder. The Cyberonics VNS Therapy System was approved by the FDA on July 16, 1997 for use as an adjunctive therapy in reducing the frequency of seizures in adults and adolescents over 12 years of age with partial onset seizures that are refractory to antiepileptic medications. The VNS Therapy System is also approved for sale as a treatment for epilepsy in all the member countries of the European Union, Canada, Australia and other markets. To date, more than 20,000 epilepsy patients in 24 countries have accumulated over 50,000 patient years of experience using VNS Therapy. VNS Therapy is at various levels of investigational clinical study as a potential treatment for depression, anxiety disorders, Alzheimer's disease, and chronic headache/migraine. The VNS Therapy System is approved for sale in the European Union and in Canada as a treatment for depression in patients with treatment-resistant or treatment intolerant major depressive episodes including unipolar depression and bipolar disorder (manic depression). The Company is headquartered in Houston, Texas and has an office in Brussels, Belgium. For additional information please visit us at www.cyberonics.com .
>
> This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended. These statements can be identified by the use of forward-looking terminology, including "may," "believe," "will," "expect," "anticipate," "estimate," "plan," "intend," and "forecast," or other similar words. Such forward-looking statements include statements concerning the timing of the release of the final determination of depression causality and our five year business plan. Statements contained in this press release are based upon information presently available to us and assumptions that we believe to be reasonable. We are not assuming any duty to update this information should those facts change or should we no longer believe the assumptions to be reasonable. Our actual results may differ materially. Important factors that may cause actual results to differ include, but are not limited to: continued market acceptance of VNS Therapy and sales of our product; the development and satisfactory completion of clinical trials and/or market test of VNS Therapy for the treatment of depression, Alzheimer's disease, anxiety, or other indications; adverse changes in coverage or reimbursement amounts by third-parties; intellectual property protection and potential infringement claims; maintaining compliance with government regulations and obtaining necessary government approvals for new applications; product liability claims and potential litigation; reliance on single suppliers and manufacturers for certain components; the accuracy of management's estimates of future expenses and sales; and other risks detailed in from time to time in the Company's filings with the SEC.
>
> SOURCE Cyberonics, Inc.
>
> -0- 06/09/2003
>
> /CONTACT: Pamela Westbrook, Vice President of Finance and CFO of Cyberonics, Inc., +1-281-228-7200, or fax, +1-281-218-9332, or pbw
>
> cyberonics.com ; or Helen Shik, Vice President of Schwartz Communications, +1-781-684-0770 ext. 6587, or fax, +1-781-684-6500, or hshik
>
> schwartz-pr.com , for Cyberonics, Inc./
>
> /Web site: http://www.presentplus.com/conference/gateway.html http://www.cyberonics.com /
>
> (CYBX)
>
> CO: Cyberonics, Inc.; UBS Warburg
>
> ST: Texas, New York
>
> IN: HEA MTC BIO SPM FIN
>
> SU: CCA MAV
>
> JS-CD
>
> -- DAM027 --
>
> 0658 06/09/2003 10:13 EDT http://www.prnewswire.com
>
>
> << Copyright ©2003 PR Newswire >>
>
> http://www.psychiatry24x7.com/news/detail.jhtml?itemname=p0609044.8rw0
>
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
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