Quetiapine in Melancholic Depression

Inclusion criteria * Provision of written informed consent * A diagnosis of major depression with melancholic features by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV) * Females and males aged 18-65 years * Female patients of childbearing potential must be using a reliable method of contraception and have a negative urine human chorionic gonadotropin (HCG) test at enrollment * Able to understand and comply with the requirements of the study * Subjects will have a Hamilton Depression Rating Scale, 28-item version (HDRS-28) score of at least 20 at the baseline visit. Exclusion criteria * Pregnancy or lactation * Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others * Known intolerance or lack of response to quetiapine fumarate, as judged by the investigator * Use of any of the following cytochrome P450 3a4 inhibitors in the 14 days preceding enrolment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir * Use of any of the following cytochrome P450 inducers in the 14 days preceding enrolment including, but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, and St. John's Wort. * Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation Women using oral contraceptives or other medications that directly affect estrogen or progesterone system in the body. * Subjects taking corticosteroids or other medications that directly influence HPA axis function * Subjects with certain lifestyle habits (i.e. working night shift) that could affect the function of the HPA axis * History of substance dependence in the past year or meets criteria for a substance abuse disorder in the past three months. * Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment * Unstable or inadequately treated medical illness (e.g. diabetes, angina pectoris, hypertension) as judged by the investigator * Participation in another drug trial within 4 weeks prior to enrollment into this study * An absolute neutrophil count (ANC) of 1.5 x 109 per liter * Patients who have initiated a new psychotherapy or behavioral therapy from a mental health professional in the past 3 months * A lifetime DSM-IV history of a psychotic disorder, a bipolar disorder, or dementia. * History of psychosurgery * Axis II disorder * History of seizures, excluding febrile seizures in childhood. * Clinically relevant abnormal laboratory results. * Patients who have received monoamine oxidase inhibitors, tricyclics, SSRIs, antipsychotics, or lithium within two weeks prior to randomization, or fluoxetine within four weeks prior to randomization. * Electroconvulsive therapy (ECT) within three months of start of study * History of mental retardation. * History of major neurological illness, including any history of significant head trauma. * Contraindications to magnetic resonance imaging, including claustrophobia and/or the presence of ferrous material that might make an MRI scan hazardous. * Patients will be excluded from the study if they indicate at screening that they know someone who has previously participated in the study.