Vortioxetine, 5, 10, and 20 mg, Relapse Prevention Study in Adults With Major Depressive Disorder (MDD)

Inclusion Criteria:

1. In the opinion of the investigator, the participant is capable of understanding andcomplying with protocol requirements.
2. The participant or, when applicable, the participant's legally acceptablerepresentative signs and dates a written, informed consent form and any requiredprivacy authorization prior to the initiation of any study procedures.
3. Suffers from recurrent major depressive disorder (MDD) as the primary diagnosisaccording to Diagnostic & Statistical Manual of Mental Disorders, 4th Edition - TextRevision (DSM-IV-TR) criteria (classification code 296.3x), and the current episode isconfirmed by the Mini International Neuropsychiatric Interview (MINI).
4. Reported duration of the current episode is ≥8 weeks and ≤18months.
5. Had at least 2 other major depressive episodes (MDEs) before the current episode.
6. Has a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥26 at theScreening and Baseline I visits.
7. Is a man or woman aged 18 to 75 years, inclusive.
8. A female participant of childbearing potential who is sexually active with anonsterilized male partner agrees to routinely use adequate contraception from signingof the informed consent throughout the duration of the study and for 30 days after thelast dose.

Exclusion Criteria:

1. Has received any investigational compound within 30 days prior to screening or 5half-lives prior to screening, whichever is longer.
2. Has previously or is currently participating in this study.
3. Has participated in 2 or more clinical studies in the year prior to screening, or hasparticipated in a clinical trial for a psychiatric condition that is exclusionary perthis protocol.
4. Is an immediate family member, study site employee, or is in a dependent relationshipwith a study site employee who is involved in conduct of this study (eg, spouse,parent, child, sibling) or may consent under duress.
5. Has one or more of the following:
6. Any current psychiatric disorder which is the primary focus of treatment otherthan MDD as defined in the DSM-IV-TR, and assessed by the MINI.
7. Current or history of: manic or hypomanic episode, schizophrenia or any otherpsychotic disorder, including schizoaffective disorder, major depression withpsychotic features, bipolar depression with psychotic features, obsessivecompulsive disorder (OCD), mental retardation, organic mental disorders, ormental disorders due to a general medical condition as defined in the DSM-IV-TR.
8. Current diagnosis or history of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV-TR that has not been infull and sustained remission for at least 3 months from the day of screening (Participant must also have negative urine drug screen at Screening and BaselineI.)
9. Presence or history of a clinically significant neurological disorder (includingepilepsy) as determined by the investigator.
10. Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiplesclerosis, Huntington disease, etc).
11. Any Axis II disorder as defined by DSM-IV-TR that might compromise the study.
12. The current depressive symptoms of the participant are considered by the investigatorto have been resistant to 2 adequate antidepressant treatments of at least 6 weeksduration each.
13. Has a history of lack of response to previous adequate treatment with vortioxetine forany MDD episode with adequate treatment considered to be known dose of vortioxetine inthe approved recommended dose range for at least 6 weeks duration.
14. Has received electroconvulsive therapy, vagal nerve stimulation, or repetitivetranscranial magnetic stimulation within 6 months prior to Screening.
15. Has started receiving formal cognitive or behavioral therapy, systematic psychotherapywithin 30 days from screening or plans to initiate such therapy during the study (supportive therapy, marital therapy and bereavement counseling are allowed).
16. Has a significant risk of suicide according to the investigator's clinical judgment orhas a score ≥5 on item 10 (suicidal thoughts) of the MADRS or has made a suicideattempt in the previous 6 months.
17. Is required to take excluded medications or it is anticipated that the participantwill require treatment with at least 1 of the disallowed concomitant medicationsduring the study.
18. Has a clinically significant unstable illness, for example hepatic impairment or renalinsufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine,neurological, rheumatologic, immunologic, hematological, infectious, dermatologicaldisorder or metabolic disturbance. Note: For the purposes of this protocol fibromyalgia, obstructive sleep apnea, chronicpain diagnosis, and morbid obesity (BMI of > 40) are considered unstable due to thepotential impact on assessment of the primary endpoint.
19. Has a known history of or currently has increased intraocular pressure or is at riskof acute narrow-angle glaucoma.
20. Has 1 or more laboratory value outside the normal range, based on the blood or urinesamples taken at the Screening Visit, that are considered by the investigator to beclinically significant; or the participant has any of the following values at theScreening Visit:
21. A serum creatinine value >1.5 times the upper limits of normal (ULN).
22. A serum total bilirubin value >1.5 xULN.
23. A serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value >2 xULN.
24. Has glycosylated hemoglobin (HbA1C) ≥7% at screening and no prior diagnosis ofdiabetes and/or treatment for diabetes. NOTE: Participants with known stable diabetesare not excluded.
25. Has a thyroid stimulating hormone (TSH) value outside the normal range at theScreening Visit that is deemed clinically significant by the investigator. NOTE: FreeT4 will be checked if TSH is out of range. If free T4 is abnormal the participant willbe excluded.
26. Has clinically significant abnormal vital signs as determined by the investigator.
27. Has an abnormal electrocardiogram (ECG) as determined by the central reader andconfirmed as clinically significant by the investigator.
28. Is positive for Hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV)antibodies, or has a history of human immunodeficiency virus (HIV) infection.
29. Has a disease or takes medication that, in the opinion of the investigator, couldinterfere with the assessments of safety, tolerability or efficacy.
30. The participant, in the opinion of the investigator, is unlikely to comply with theclinical study protocol or is unsuitable for any reason.
31. Has a history of hypersensitivity or allergies to vortioxetine.
32. If female, the participant is pregnant or lactating or intending to become pregnantbefore, during, or within 1 month after participating in this study; or intending todonate ova during such time period.
33. The participant is considered to be treatment resistant, eg, the participant has notresponded to adequate monotherapy treatments of at least 6 weeks' duration, or hasonly responded to combination or augmentation therapy.