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): 21.0-70.0,  Depression Male or female subjects, 21 to 70 years of age. 2. Female subjects who are not of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year) or must be using a medically accepted means of contraception. Women using oral contraceptive medication for birth control must also be using a barrier contraceptive. Women of childbearing potential must also have a negative serum Beta-HCG (human chorionic gonadotropin) at pre-study. 3. Subjects must fulfill DSM-IV for Major Depression (296.3) without psychotic features, based on clinical assessment and confirmed by a structured diagnostic interview, the Structured Clinical Interview for DSM-IV TR Axis I Disorders, SCID-P. 4. Subjects have a history of at least one previous episode of depression prior to the current episode. 5. Subjects must have an initial score of greater than or equal to 32 on the Inventory of Depressive Symptoms, Clinician version (IDS-C) at Visit 1 and Visit 2. 6. Subjects must not have greater than a 25% decrease in the IDS-C total scores during washout (between Visits 1 and 2). 7. Each subject must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document. 8. Current major depressive episode of at least 4 weeks duration. 9. Subjects who have not responded to adequate previous trials of at least one antidepressant as determined by the Antidepressant Treatment History Form (ATHF) (score greater than or equal to 3). Additionally, patients who have not completed antidepressants trials of adequate dose and duration due to intolerance to therapy may be induced if they have demonstrated intolerance to greater than or equal to 3 antidepressant medications in the current or a previous episode, and did not meet ATHF for a single adequate treatment trial in the current episode. 3 intolerant trials would count as an adequate failed trial. If this has not been met, the Principal Investigator may allow for a four-week prospective trial of a standard antidepressant (at the patients' and clinicians' discretion) for potential participants who have not responded to at least one adequate trial for the current episode per criteria  Presence of psychotic features or a diagnosis of Schizophrenia or any other psychotic disorder or bipolar disorder as defined in the Diagnostic and Statistical Manual, Version IV (DSM-IV). 11. Subjects with a diagnosis of Obsessive Compulsive Disorder as defined in the DSM-IV. 12. Subjects reporting Borderline or Antisocial Personality disorders. Other Axis II disorders do not qualify one for from the study. 13. Subjects with a history of DSM-IV drug or alcohol dependency or abuse (except for nicotine or caffeine) within the preceding 3 months. 14. Female subjects who are either pregnant or nursing. 15. Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease. 16. Subjects with a history of neutropenia or medication-induced blood dyscrasia. 17. Clinically significant abnormal findings of laboratory parameters, physical examination, EEG, or ECG. 18. Subjects with a lifetime history of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome. 19. Subjects with uncorrected hypothyroidism or hyperthyroidism. 20. Subjects with one or more seizures without a clear and resolved etiology. 21. Treatment with a reversible monoamine oxidase inhibitor (MAOI) within 2 weeks prior to Visit 2. 22. Treatment with fluoxetine within 4 weeks prior to Visit 2. 23. Treatment with clozapine or electroconvulsive therapy (ECT) within 3 months prior to study Visit 2. 24. Judged clinically to be at serious suicidal or homicidal risk. 25. Participation in a clinical trial of another investigational drug within 1 month prior to study entry (visit 1). 26. Patients starting hormonal treatment (e.g., estrogen) in the last 3 months prior to visit 1. 27. Patients undergoing current nonpharmacologic antidepressant treatments, such as light therapy and psychotherapy. 28. Patients will be excluded who have previously failed greater than or equal to 3 lifetime adequate antidepressant trials by ATHF (Sackeim 2001). 29. Patients with any evidence of a seizure disorder as assessed by an EEG with photic stimulation. AND FOR PET SCANS ONLY: WITH MAJOR WILL IN THE OF THIS STUDY. 1. Subjects who are ages 21-70. 2. Subjects with an early age of onset (before age 40). 3. Subjects who either meet melancholic subtype and/or have a first degree relative with bipolar disorder. 4. Negative pregnancy test within 24 hours of positron emission tomography (PET) in women of childbearing potential. 1. Subjects will have been off psychotropic drugs (including zolpidem) for at least 3 weeks (8 weeks for fluoxetine) prior to PET. 2. Subjects with a history of lifetime DSM-IV substance dependence (except for nicotine or caffeine). 3. Subjects with substance abuse within 12 months (except for nicotine or caffeine). 4. Subjects with a current or lifetime history of hypertension or diabetes. 5. Subjects who have reached the annual research radiation exposure limit