Patient description: A 46-year-old Asian woman with MDD complains of persistent feelings of sadness and loss of interest in daily activities. She states that her mood is still depressed most of the days. She complains of loss of energy and feelings of worthlessness nearly every day. She is on anti-depressants for the past 6 months, but the symptoms are still present. She does not drink alcohol or smoke. She used to exercise every day for at least 30 min., but she doesn't have enough energy to do so for the past 3 weeks. She also has some digestive issues recently. She is married and has 4 children. She is menopausal. Her husband was diagnosed with colon cancer a year ago and is undergoing chemotherapy. Her past medical history is unremarkable. Her family history is negative for any psychologic problems. Her HAM-D score is 20.

Clinical trial eligibility criteria: eligible ages (years): 18.0-64.0,  Depressive Disorder, Major Subjects must have the ability to comprehend the Informed Consent Form Male or female outpatients, aged 18-64, inclusive A primary diagnosis of major depressive disorder, single episode or recurrent Subjects must, in the investigator's opinion and based on the subject's history, have met depression for at least 8 weeks prior to the Screening Visit Subjects with symptom severity considered to be at least moderate to severe by the investigator Women of childbearing potential are only eligible IF they commit to consistent and correct use of an acceptable method of birth control that must be documentation at each visit  Subjects whose mood-related symptoms are better accounted for by a diagnosis other than depression; subjects diagnosed with Alzheimer's Disease or other form of dementia; subjects diagnosed with a current/recent eating disorder such as anorexia nervosa or bulimia; subjects with a diagnosed history of schizophrenia, schizoaffective disorder, or Bipolar Disorder Subjects with any history of a significant abnormality of the neurological system (including dementia and other cognitive disorders or significant head injury) or any history of seizures (convulsions) Subjects have a positive urine test at screening for illegal drug use and/or who have a history of substance abuse or dependence (alcohol or drugs) within the past 12 months Subjects who are currently receiving regularly scheduled psychotherapy (individual or group), plan to start psychotherapy during the trial or have received regularly scheduled psychotherapy during the 12 week period prior to the Screening Visit Subjects who have a history of failing to respond to adequate treatment with an antidepressant, i..e, failure to improve following administration of at least two other antidepressants, each given for at least 4 weeks Subjects who, in the investigator's judgement, pose a homicidal or serious suicidal risk, have made a suicide attempt within the 6 months preceding screening or who have ever been homicidal Subjects who have received the following treatments for depression in the past: electroconvulsive therapy (ECT), vagal stimulation, or transcranial magnetic stimulation (TMS) within the 6 months prior to the Screening Visit Subjects with an unstable medical disorder; or with a disorder that otherwise would likely interfere with the activity of the study medication (orvepitant) Subjects have any screening laboratory abnormality that in the investigator's judgement is considered to be clinically significant Subjects with an abnormal thyroid test at the Screening Visit. Subjects maintained on thyroid medication must have normal thyroid levels for a period of at least six months prior to the Screening Visit