December 10, 2003

News Release: Cyberonics'Depression PMA-S Accepted for Filing By FDA

Cyberonics, Inc. (Nasdaq: CYBX) today announced that it has been formally notified in a conference call with FDA that FDA has deemed the depression PMA-S application suitable for filing. The official filing date for regulatory timeline purposes is October 27, 2003. FDA has begun their in-depth review of Cyberonics'depression PMA-Supplement.

'We are pleased with FDA's timely filing of our depression submission,' commented Robert P. ('Skip') Cummins, Cyberonics'Chairman and Chief Executive Officer. 'FDA's in-depth review of our 87-volume, 460 patient PMA-Supplement has now formally begun. We are looking forward to facilitating FDA's timely interactive review of the consistent, compelling, statistically and clinically significant data supporting the safety and effectiveness of VNS 'as an adjunctive long-term treatment of chronic or recurrent depression for patients who are experiencing a major depressive episode that has not had an adequate response to two or more antidepressant treatments. 'We are making no changes to our depression regulatory timeline guidance and remain confident that we will receive FDA's final decision regarding approvability by October 2004.'

HISTORY OF VNS THERAPY DEPRESSION STUDIES

Cyberonics'comprehensive 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 a 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 suffering from 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.

Highly statistically and clinically significant acute and long-term response and remission rates were observed in the D-01 pilot study. The first implant in the D-02 pivotal study occurred in August 2000. In January 2002, Cyberonics announced that although clinically meaningful, the difference in the D-02 treatment and placebo group HRSD-24 response rates at the end of the eight-week fixed dose acute study was not statistically significant. In September 2002, after determining the likely contributors to the lack of statistical significance, Cyberonics submitted a revised, prospective long- term pivotal study analysis plan to FDA. That plan is 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 VNS Therapy and treatment as usual and to determine the causal relationship between those outcomes and VNS Therapy by comparing those D-02 outcomes with the outcomes of the D-04 patients treated only with treatment as usual.

In January 2003, Cyberonics announced that the one-year data from its D-02 depression pivotal study, analyzed pursuant to the D-02 analysis plan submitted to the FDA in September 2002, showed statistically and clinically significant improvements compared to baseline. Statistical significance was determined using a repeated measures linear regression technique to analyze improvements from pre-treatment baseline in the 24-item Hamilton Rating Scale (HRSD-24) during one year of VNS Therapy. The HRSD-24 improvements observed over the first year were highly significant with a p-value < 0.001. The secondary measures of statistical significance showed similarly positive results. Clinical significance was determined by analyzing the percent of patients who showed a sustained HRSD-24 response between nine and 12 months of treatment with VNS Therapy. In the absence of published literature that defines a long-term success criterion, Cyberonics'psychiatric clinical advisors suggested that a sustained response rate of approximately 30% would be significant. Approximately 30% of the patients from the original acute treatment group and 25% of all patients in the analysis showed a sustained response between months nine and 12.

In July 2003, Cyberonics announced that the preliminary one-year results from its D-02 VNS Therapy(TM) depression pivotal study and D-04 companion study of chronic and recurrent treatment resistant depression, analyzed pursuant to the D-02 analysis plan submitted to the U.S. Food and Drug Administration (FDA) in September 2002, showed a highly statistically significant causal relationship (p-value < 0.001) between VNS Therapy and the depression improvements from baseline observed in the D-02 VNS Therapy study. The causal relationship between VNS Therapy and the D-02 patients'one-year outcomes was determined using a repeated measures linear regression analysis to compare depression improvements as measured by the Inventory of Depressive Symptomatology-Self Report (IDS-SR) over one year in 205 D-02 patients receiving VNS Therapy and treatment as usual with the IDS-SR outcomes of 124 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. Statistically and clinically significant differences in the physician and patient reported D-02 and D-04 patients'one-year response and remission rates were also observed. One-year response rates, defined as at least a 50% improvement in depression symptoms as measured by the IDS-SR and HRSD-24 (24 item clinician rated Hamilton Rating Scale for Depression) were 21% and 30%, respectively in D-02 and 12% and 13%, respectively in D-04. One-year remission rates, defined as the percentage of patients free of depressive symptoms after one year of treatment, were 16% and 17%, respectively in D-02 and 5% and 7%, respectively in D-04.

In October 2003 Cyberonics submitted an 87-volume PMA-Supplement (PMA-S) to the U.S. Food and Drug Administration (FDA) seeking approval to market the VNS Therapy System in the United States as 'as an adjunctive long-term treatment of chronic or recurrent depression for patients who are experiencing a major depressive episode that has not had an adequate response to two or more antidepressant treatments.'That PMA-S included acute and one-year data and analyses on 335 patients treated with VNS plus treatment as usual and 125 patients treated only with treatment as usual. FDA accepted the depression PMA-S for filing on December 9, 2003. The official filing date for regulatory timeline purposes is October 27, 2003. Cyberonics expects to receive FDA's decision regarding approvability of the depression PMA-S by October 2004.

ABOUT VNS THERAPY 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 Economic Area, Canada, Australia and other markets. To date, more than 22,000 epilepsy patients in 24 countries have accumulated over 56,000 patient years of experience using VNS Therapy. The VNS Therapy System is approved for sale in the European Economic Area 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). 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. An 87-volume, 460 patient PMA-Supplement (PMA-S) requesting approval to market the VNS Therapy System in the United States as an adjunctive long-term treatment of chronic or recurrent depression for patients who are experiencing a major depressive episode that has not had an adequate response to two or more antidepressant treatments was submitted to FDA and accepted for filing by FDA effective October 27, 2003. The Company is headquartered in Houston, Texas and has an office in Brussels, Belgium. For additional information please visit us at www.cyberonics.com .

FORWARD LOOKING STATEMENTS

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 and process of U.S. regulatory approval of VNS Therapy for depression and the timing of a final FDA decision regarding approvability. 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; our ability to hire, train and retain personnel; the accuracy of management's estimates of future events, sales, expenses and earnings; and other risks detailed in from time to time in the Company's filings with the SEC.

SOURCE Cyberonics, Inc.

Pamela Westbrook, Vice President of Finance and CFO ofCyberonics, Inc., +1-281-228-7200, or fax, +1-281-218-9332, This email address is being protected from spambots. You need JavaScript enabled to view it. ; or Helen Shik, Vice President of Schwartz Communications,+1-781-684-0770, ext. 6587, or fax, +1-781-684-6500, This email address is being protected from spambots. You need JavaScript enabled to view it. , for Cyberonics, Inc.

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