Inclusion Criteria:

• Provision of written informed consent
• A diagnosis of Major Depressive Episode by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV)
• Females or Males aged 21 - 60 years
• Female subjects of childbearing potential must be using a reliable method of contraception and have a negative serum human chorionic gonadotropin (HCG) test at enrollment
• Able to understand and comply with the requirements of the study
• 17-item Hamilton Depression Rating Scale (HDRS) score > 15
• Hamilton Anxiety Scale (HAM-A) score > 15
• Satisfy criteria to undergo an MRI scan based on MRI screening questionnaire

• Able to be managed as outpatients for initial assessment and during treatment as ascertained by the following:

  • Symptoms not worsening by more than 10 points on the HDRS during the course of the study.
  • No danger to self or others.

Exclusion Criteria:

• Pregnancy or lactation
• Meeting DSM-IV criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, atypical psychosis, mental retardation, or organic mental (including organic mood) disorder
• Subjects 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, St. John's Wort, and glucocorticoids
• Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation
• Substance or alcohol dependence at enrollment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria
• Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within four weeks prior to enrollment
• Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment
• Unstable or inadequately treated medical illness (angina pectoris, hypertension) as judged by the investigator
• Involvement in the planning and conduct of the study
• Previous enrollment or randomization of treatment in the present study.
• Participation in another drug trial within four weeks prior enrollment into this study or longer in accordance with local requirements
• A subject with Diabetes Mellitus; people who develop hyperglycemia will be removed from the study
• An absolute neutrophil count (ANC) of 1.5 x 109 per liter
• Use of psychotropics in the past two weeks. If on fluoxetine in the past, then should not have been on this medication for four weeks.
• History of lack of response to Quetiapine extended release.
• Acutely suicidal or homicidal or requiring inpatient treatment.
• Metallic implants.