The primary objective of this study is to assess short, mid and long-term clinical outcomes in patients with difficult to treat depression (such as patients with treatment resistant depression) treated with Vagus Nerve Stimulation (VNS) Therapy as adjunctive therapy.
Be at least 18 years of age.
Have a documented primary diagnosis of chronic (>2 years) or recurrent (2 or more prior episodes) major depressive episode that has not adequately responded to an adequate number of antidepressant treatments, as per local medical standards. This diagnosis must be confirmed using the MINI.
Provide written Ethics Committee (EC) or Institutional Review Board (IRB) approved informed consent and Health Insurance Portability and Accountability Act (HIPAA, US only) authorization (as applicable according to local requirements).
Currently is receiving at least one antidepressant treatment (i.e., antidepressant drug, maintenance electroconvulsive therapy, or formal psychotherapy including supportive psychotherapy) or mood stabilizing treatment for bipolar patients (such as lithium, anticonvulsants, or atypical antipsychotics).
None
The population under study comprises a real-world patient population with difficult to treat depression: patients diagnosed with unipolar or bipolar disorder with chronic or recurrent depression who fail to achieve an adequate response to standard psychiatric management. The diagnosis of depression and comorbid disorders will be determined based on the Mini International Neuropsychiatric Interview (MINI).
Cohort
Prospective
Vagal Nerve Simulation (VNS) Therapy
DeviceA VNS Therapy System used for vagus nerve stimulation and consisting of an implantable VNS Therapy generator, lead, and external programming system.
The primary endpoint of this study is response defined as reduction in Montgomery Åsberg Depression Rating Scale (MADRS) total score of at least 50% from baseline to 12 months post implant.
MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Each item yields a score of 0 to 6. The overall score ranges from 0 to 60. Higher MADRS score indicates more severe depression. A 'Responder' is a subject that achieved ≥ 50% reduction from baseline in MADRS total score at the M12 assessment. A 'Non-Responder' is any patient who did not achieve ≥ 50% reduction from baseline in MADRS score at the M12 assessment. No formal hypothesis testing is presented; all the proposed statistical tests are descriptive in nature. The Primary endpoint analysis as defined above will be done only on patients that are enrolled while in a major depressive episode (MDE); the cut off point for current MDE at time of implant will be a MADRS score of 20. For the patients with a MADRS score below 20 at time of enrollment, only the continuous change in MADRS can be described (as the MADRS can only worsen or stay the same).
Duration of response
computed as the difference between the first recorded date post baseline that response is achieved (MADRS reduction from baseline ≥ 50%) and the first date at which MADRS again increased to a level of \<40% from baseline.
Change in MADRS
Change in MADRS over time
Cumulative response
Cumulative percentage of first-time MADRS responders (MADRS reduction from baseline ≥ 50%) at any post-baseline visit.
Cumulative remission
Cumulative percentage of subjects in remission (MADRS ≤9) at any post-baseline visit.
