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,  Major Depressive Disorder Alcohol Abuse Alcohol Dependence DSM-IV diagnostic for MDD (diagnosis based on Structured Clinical Interview for DSM-IV, Patient Edition; SCID I/P) 2. Written informed consent 3. Men and women aged 18-64 years 4. Current diagnosis of alcohol abuse/dependence as per SCID I/P  Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician. These patients will be immediately referred to appropriate clinical treatment. 2. Pregnant women or women of childbearing potential who are not using a medically accepted means of contraception (defined as oral contraceptive pill or implant, condom, diaphragm, spermicide, IUD, s/p tubal ligation, partner with vasectomy). 3. Known history of serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease. 4. History of seizure disorder, brain injury, any history of known neurological disease (multiple sclerosis, degenerative disease such as ALS, Parkinson disease and any movement disorders, etc.). 5. Clinical or lab evidence of untreated hypothyroidism. 6. History or current diagnosis of the following DSM-IV psychiatric illness: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, patients with mood congruent or mood incongruent psychotic features, patients with substance use disorders (excluding alcohol and nicotine) active within the last 12 months. 7. Current use of other psychotropic drugs, including current use of benzodiazepines, hypnotics, anticonvulsants. Concomitant use of antihistamine drugs will be allowed. Patients will need to be off all antidepressants for at least two weeks by the time of the baseline visit, and four weeks for fluoxetine, and off benzodiazepines and other psychotropics for at least one week. The decision about whether to taper existing medications should be made by the individual and their primary treater based on clinical care and will not be made for purposes of study enrollment. allowed. 8. Patients who have failed to respond during the course of their current major depressive episode to at least two adequate antidepressant trials. An adequate antidepressant trial is defined as six weeks or more of treatment with escitalopram > 20mg/day or its antidepressant equivalent: (fluoxetine 40mg/day, sertraline > 100 mg/day, paroxetine > 40 mg/day, fluvoxamine > 100 mg/day, citalopram > 40 mg/day, escitalopram > 20 mg/day, venlafaxine > 150 mg/day, and duloxetine > 60 mg/day). 9. Any depression-focused or substance-abuse focused psychotherapy (family or marital counseling would be allowed). 10. Patients who have taken an investigational psychotropic drug within the past year. 11. Need for medical or inpatient detoxification from alcohol. This determination will be made by the screening clinician, based on clinical judgement as in the multicenter STAR*D study (PHRC #2000-P-001955 in accordance with methods used in the multi-center STAR-D study