Study Comparing Outcomes for Patients With Treatment Resistant Depression Who Receive VNS Therapy at Different Doses

Depression Clinical Trial

Official title:

Randomized Comparison of Outcomes in Patients With Treatment-Resistant Depression Who Receive VNS Therapy Administered at Different Amounts of Electrical Charge

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00305565
• Other study ID #: D-21-US
• Status: Completed
• Phase: Phase 4
• First received: March 20, 2006
• Last updated: December 6, 2013
• Start date: January 2006
• Est. completion date: February 2010

Study information

• Verified date: December 2013
• Source: Cyberonics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This is a postmarket medical device study. The objective of this study is to compare the safety and effectiveness of Vagus Nerve Stimulation (VNS) Therapy administered at different amounts of electrical charge for the treatment of patients with treatment-resistant depression (TRD).

Description:

This is a postmarket medical device study. This study will examine treatment outcomes for patients with TRD who are randomized to VNS Therapy administered at different amounts of electrical charge. The Sponsor, Cyberonics, provides funding for this study. Patients are followed for 54 weeks, 50 of those weeks are following implantation of the VNS Therapy system. No study sites will be permitted to enroll study subjects until Institutional Review Board (IRB) approval has been received. Sites are permitted to be approved by a local or a central IRB.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 331
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient has a diagnosis of chronic or recurrent depression and is currently experiencing a major depressive episode.

• Patient has not had an adequate response to four or more adequate antidepressant treatments from at least two different antidepressant treatment categories.

• Patient has (in the investigator's judgment) sufficient impairment from his/her depression and/or depression treatment that the potential benefits/risks of VNS Therapy are warranted.

• Patient must currently be receiving at least one antidepressant treatment; the patient must be receiving all current antidepressant treatments in a stable regimen.

• If the patient has a current diagnosis of bipolar disorder, the patient must be receiving a mood stabilizer.

• Patient must be 18 years of age or older and of legal age of consent.

• Patient must be able to complete the evaluations specified in the study procedures flow chart.

• Patient must provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization.

Exclusion Criteria:

• Patient has had a bilateral or left cervical vagotomy.

• Patient currently uses, or is expected to use during the study, short-wave diathermy, microwave diathermy, or therapeutic ultrasound diathermy.

• A VNS Therapy System implant would pose an unacceptable surgical or medical risk for the patient.

• Patient is expected to require full body magnetic resonance imaging during the clinical study.

• Patient is acutely suicidal.

• Patient has a history of schizophrenia, schizoaffective disorder, or other psychotic disorder or a current major depressive episode that includes psychotic features (commonly referred to as psychotic depression).

• Patient has a history of rapid cycling bipolar disorder or a current diagnosis of bipolar disorder mixed phase.

• Patient has a history of borderline personality disorder.

• Patient has a history of drug or alcohol dependence within the 12 months prior to the baseline visit or currently takes a narcotic drug five or more days per week.

• Patient is currently enrolled in another investigational study.

• Patient has had a prior VNS Therapy System implant.

Note: Some IRBs may require additional conditions for enrollment.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant

Intervention

Device:
• VNS Therapy
Received output current of 0.25 milliamps (mA)
• VNS Therapy
Received output current of 0.5-1.0 mA
• VNS Therapy
Received output current of 1.0-1.5 mA

Locations

Country	Name	City	State
United States	Dent Neurologic Institute	Amherst	New York
United States	Community Clinical Research, Inc.	Austin	Texas
United States	Pharmasite Research Inc.	Baltimore	Maryland
United States	Sheppard Pratt Hospital	Baltimore	Maryland
United States	Massachusetts General Hospital	Charlestown	Massachusetts
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Evanston Northwestern Hospital	Evanston	Illinois
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Claghorn-Lesem Research Clinic, LTD	Houston	Texas
United States	Northwest Behavioral Research Center	Marietta	Georgia
United States	Center for Anxiety and Depression	Mercer Island	Washington
United States	Eastside Comprehensive Medical Center	New York	New York
United States	New York State Psychiatric Institute	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Butler Hospital	Providence	Rhode Island
United States	Sutter Institute for Medical Research	Sacramento	California
United States	University of Utah	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Brentwood Research Institute	Shreveport	Louisiana
United States	St. Louis University	St. Louis	Missouri
United States	Psychiatric Recovery	St. Paul	Minnesota
United States	SUNY Upstate Medical University	Syracuse	New York
United States	University of Arizona	Tucson	Arizona
United States	Clinical Research Institute	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Cyberonics, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (7)

Aaronson ST, Carpenter LL, Conway CR, Reimherr FW, Lisanby SH, Schwartz TL, Moreno FA, Dunner DL, Lesem MD, Thompson PM, Husain M, Vine CJ, Banov MD, Bernstein LP, Lehman RB, Brannon GE, Keepers GA, O'Reardon JP, Rudolph RL, Bunker M. Vagus nerve stimulat — View Citation

Geddes LA, Baker LE: Principles of Applied Biomedical Instrumentation, third edition. New York; John Wiley & Sons, 1989; 458-461.

George MS, Rush AJ, Marangell LB, Sackeim HA, Brannan SK, Davis SM, Howland R, Kling MA, Moreno F, Rittberg B, Dunner D, Schwartz T, Carpenter L, Burke M, Ninan P, Goodnick P. A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression. Biol Psychiatry. 2005 Sep 1;58(5):364-73. — View Citation

Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS; National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003 Jun 18;289(23):3095-105. — View Citation

Murray CJ, Lopez AD. Evidence-based health policy--lessons from the Global Burden of Disease Study. Science. 1996 Nov 1;274(5288):740-3. — View Citation

Rush AJ, Marangell LB, Sackeim HA, George MS, Brannan SK, Davis SM, Howland R, Kling MA, Rittberg BR, Burke WJ, Rapaport MH, Zajecka J, Nierenberg AA, Husain MM, Ginsberg D, Cooke RG. Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol Psychiatry. 2005 Sep 1;58(5):347-54. — View Citation

Rush AJ, Sackeim HA, Marangell LB, George MS, Brannan SK, Davis SM, Lavori P, Howland R, Kling MA, Rittberg B, Carpenter L, Ninan P, Moreno F, Schwartz T, Conway C, Burke M, Barry JJ. Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study. Biol Psychiatry. 2005 Sep 1;58(5):355-63. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population).	The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.	From Baseline to Study Week 22	No
Secondary	Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population).	The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.; The IDS-C percent of responders at week 22. Response was defined as greater than or equal to 50% improvement from baseline.	From baseline to Study Week 22	No
Secondary	Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population).	The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.; The IDS-C percent of remitters at week 22. Remission was defined as a score of less than or equal to 14 on the IDS-C.	From baseline to Study Week 22	No
Secondary	Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population).	The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.; The IDS-C percent of responders at week 50. Response was defined as greater than or equal to 50% improvement from baseline.	From baseline to Study Week 50	No
Secondary	Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Sustained Responders at Study Week 50 (ITT Population).	The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.; Sustained Response is defined as the percentage of Acute Phase responders (week 22) who were also responders at the end of the Long-term (week 50) phase. An analysis of sustained response was performed using the IDS-C to evaluate the long-term durability of the improvements in depression scores observed with adjunctive VNS Therapy.	From baseline to Study Week 50	No
Secondary	Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population).	The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.; The IDS-C percent of remitters at week 50. Remission was defined as a score of less than or equal to 14 on the IDS-C.	From baseline to Study Week 50	No
Secondary	Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population).	The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes.; The QIDS-C percent of responders at week 22. Response was defined as greater than or equal to 50% improvement from baseline.	From baseline to Study Week 22	No
Secondary	Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population).	The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes.; The QIDS-C percent of remitters at week 22. Remission was defined as a score of less than or equal to 5 on the QIDS-C.	From baseline to Study Week 22	No
Secondary	Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population).	The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes.; The QIDS-C percent of responders at week 50. Response was defined as greater than or equal to 50% improvement from baseline.	From baseline to Study Week 50	No
Secondary	Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population).	The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes.; The QIDS-C percent of remitters at week 50. Remission was defined as a score of less than or equal to 5 on the QIDS-C.	From baseline to Study Week 50	No
Secondary	Montgomery-Asberg Depression Rating Scale (MADRS) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population).	The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes.; The MADRS percent of responders at week 22. Response was defined as greater than or equal to 50% improvement from baseline.	From baseline to Study Week 22	No
Secondary	Montgomery-Asberg Depression Rating Scale (MADRS) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population).	The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes.; The MADRS percent of remitters at week 22. Remission was defined as a score of less than or equal to 9 on the MADRS.	From baseline to Study Week 22	No
Secondary	Montgomery-Asberg Depression Rating Scale (MADRS) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population).	The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes.; The MADRS percent of responders at week 50. Response was defined as greater than or equal to 50% improvement from baseline.	From baseline to Study Week 50	No
Secondary	Montgomery-Asberg Depression Rating Scale (MADRS) Percent Sustained Responders at Study Week 50 (ITT Population).	The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes.; Sustained Response is defined as the percentage of Acute Phase responders (week 22) who were also responders at the end of the Long-term (week 50) phase. An analysis of sustained response was performed using the MADRS to evaluate the long-term durability of the improvements in depression scores observed with adjunctive VNS Therapy.	From Baseline to Study Week 50	No
Secondary	Montgomery-Asberg Depression Rating Scale (MADRS) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population).	The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes.; The MADRS percent of remitters at week 50. Remission was defined as a score of less than or equal to 9 on the MADRS.	From baseline to Study Week 50	No
Secondary	Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 22 of the Acute Phase (ITT Population)	Originally, the Clinical Global Impressions-Improvement (CGI-I) (Guy W 1976)was designed as a 7-item scale used to assess how much the patient's illness had improved or worsened relative to a baseline state at the beginning of the intervention.(1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.); In this study, the CGI-I was categorized into just two groups. A value of 1 (considered a response) was assigned for very much improved (at least 85% improvement) & much improved (at least 60% improvement). A value of 0 (considered non-response) was assigned for: minimally improved (at least 20-25% improvement), no change (between ±15% change), minimally worse (at least 20-55% worse), much worse (at least 60% worse), and very much worse (at least 80% worse). No score was assigned if the investigator did not provide a categorical rating at a particular follow-up visit.	At Study Week 22	No
Secondary	Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 50 of the Long-term Phase (ITT Population).	Originally, the Clinical Global Impressions-Improvement (CGI-I) (Guy W 1976)was designed as a 7-item scale used to assess how much the patient's illness had improved or worsened relative to a baseline state at the beginning of the intervention.(1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.); In this study, the CGI-I was categorized into just two groups. A value of 1 (considered a response) was assigned for very much improved (at least 85% improvement) & much improved (at least 60% improvement). A value of 0 (considered non-response) was assigned for: minimally improved (at least 20-25% improvement), no change (between ±15% change), minimally worse (at least 20-55% worse), much worse (at least 60% worse), and very much worse (at least 80% worse). No score was assigned if the investigator did not provide a categorical rating at a particular follow-up visit.	At Study Week 50	No
Secondary	Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population).	The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.; The IDS-SR percent of responders at week 22. Response was defined as greater than or equal to 50% improvement from baseline.	From baseline to Study Week 22	No
Secondary	Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population).	The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.; The IDS-SR percent of remitters at week 22. Remission was defined as a score of less than or equal to 14 on the IDS-C.	From baseline to Study Week 22	No
Secondary	Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population).	The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.; The IDS-SR percent of responders at week 50. Response was defined as greater than or equal to 50% improvement from baseline.	From baseline to Study Week 50	No
Secondary	Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population).	The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.; The IDS-SR percent of remitters at week 50. Remission was defined as a score of less than or equal to 14 on the IDS-C.	From baseline to Study Week 50	No
Secondary	Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population).	The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.; The IDS-C mean percent change at week 22	From baseline to Study Week 22	No
Secondary	Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population).	The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.; The IDS-C mean change at week 50	From baseline to Study Week 50	No
Secondary	Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population).	The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.; The IDS-C mean percent change at week 50	From baseline to Study Week 50	No
Secondary	Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population).	The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes.; The QIDS-C mean change at week 22	From baseline to Study Week 22	No
Secondary	Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population).	The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes.; The QIDS-C mean percent change at week 22	From baseline to Study Week 22	No
Secondary	Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population).	The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes.; The QIDS-C mean change at week 50	From baseline to Study Week 50	No
Secondary	Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population).	The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes.; The QIDS-C mean percent change at week 50	From baseline to Study Week 50	No
Secondary	Montgomery-Asberg Depression Rating Scale (MADRS) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population).	The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes.; The MADRS mean change at week 22	From baseline to Study Week 22	No
Secondary	Montgomery-Asberg Depression Rating Scale (MADRS) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population).	The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes.; The MADRS mean percent change at week 22	From baseline to Study Week 22	No
Secondary	Montgomery-Asberg Depression Rating Scale (MADRS) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population).	The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes.; The MADRS mean change at week 50	From baseline to Study Week 50	No
Secondary	Montgomery-Asberg Depression Rating Scale (MADRS) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population).	The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes.; The MADRS mean percent change at week 50	From baseline to Study Week 50	No
Secondary	Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population).	The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.; The IDS-SR mean change at week 22	From baseline to Study Week 22	No
Secondary	Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population).	The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.; The IDS-SR mean percent change at week 22	From baseline to Study Week 22	No
Secondary	Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population).	The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.; The IDS-SR mean change at week 50	From baseline to Study Week 50	No
Secondary	Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population).	The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes.; The IDS-SR mean percent change at week 50	From baseline to Study Week 50	No