Intervention: Quetiapine
Trial phase: Phase 4
ATC code: N05AH04
SMILES: OCCOCCN1CCN(C2=Nc3ccccc3Sc3ccccc32)CC1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 12
Group description: Patients assigned to receive Quetiapine

•Quetiapine XR 100 mg/h.s. will be the starting dose and increased by 100 mg q h.s. q day to a target dose of 300 mg/h.s. by day three and continued on 300 mg/h.s. through week three. Between weeks four and eight, there will be flexible dosing up to 800 mg/h.s. or reductions in doses to no lower than 200 mg/h.s. Incremental increases or decreases in dose will be no more than 100 mg/h.s. over a minimum of one week, unless a patient is unable to tolerate the current dose. Patients unable to tolerate at least 200 mg/h.s. will be discontinued from the study.
Eligibility criteria:
Inclusion Criteria:

Written informed consent
Diagnosis of Major Depressive Disorder with Psychotic Features by the DSM-IV
Females and Males between the ages of 18-85 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 enrolment
Able to understand and comply with the requirements of the study
Initial HAM-D-17 score of > 16, both at the screen visit and at the baseline visit.
Participants must have an initial BPRS score of > 25 and at least one of the following: > 5 for item 1, > 5 for item 5, > 5 for item 8, > 4 for item 9, > 1 for item 10, > 1 for item 11; these BPRS criteria msut be met both at the screen visit and at the baseline visit.
Participants must have an initial CGI score of > 2, both at the screen visit and at the baseline visit.

Exclusion Criteria:

Pregnancy or lactation
Any DSM-IV Axis I disorder not defined in the inclusion criteria
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 enrollment 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 randomization
Substance or alcohol dependence within the past three months (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 4 weeks prior to enrolment
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
Involvement in the planning and conduct of the study
Previous enrolment or randomization of treatment in the present study.
Participation in another drug trial within 4 weeks prior enrollment into this study or longer in accordance with local requirements

A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:

Unstable DM defined as enrollment glycosylated hemoglobin (HbA1c) > 8.5%.
Admitted to hospital for treatment of DM or DM related illness in past 12 weeks.
Not under physician care for DM.
Physician responsible for patient's DM care has not indicated that patient's DM is controlled.
Physician responsible for patient's DM care has not approved patient's participation in the study
Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to randomization. For thiazolidinediones (glitazones) this period should not be less than 8 Weeks.
Taking insulin whose daily dose on one occasion in the past 4 weeks has been more than 10% above or below their mean dose in the preceding 4 weeks
An absolute neutrophil count (ANC) of 1.5 x 10^9 per liter
Patients with a history seizure disorder; unstable physical disorders (cardiovascular, hepatic, renal, respiratory, endocrine, neurologic, or hematologic); or any physical disorder judged to significantly affect central nervous system function.
Patients who are currently treated with antidepressants other than the selective serotonin reuptake inhibitors, with mood stabilizing or antipsychotic drugs other than quetiapine.
Patients with known arrhythmias or arrhythmias noted on screening EKG.
Outpatients with a CGI score of 7.