Quetiapine Prolong, Escitalopram and Hypothalamic-pituitary-adrenocortical (HPA) Axis Activity in Depressed Patients

Inclusion criteria

For inclusion in the study patients must fulfil all of the following criteria:

• Inpatients (the admission to hospital occurs independently from study participation)
• Provision of written informed consent
• A diagnosis of major depression by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV) (unipolar depression: 296.2, 296.3)
• Female and male patients aged 18 to 65 years
• Female patients of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) pregnancy test at enrolment and e willing to use a reliable method of birth control (i.e. barrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive, intrauterine device, or tubal litigation) during the study.
• Able to understand and comply with the requirements of the study as judged by the investigator.
• A sum score of at least 18 on the 21-item version of the Hamilton Depression Rating Scale (21-HAMD)

Exclusion criteria

Any of the following is regarded as a criterion for exclusion from the study:

• 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 and/or escitalopram, 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 3A4 inducers in the 14 days preceding enrolment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids
• Use of monoamine oxidase inhibitors (MAOIs) or other serotonergic drugs (e.g. triptans) in the 14 days preceding enrolment
• Use of oral anticoagulants in the 14 days preceding enrolment
• History of bleeding disorders.
• Use of drugs which are mainly metabolized by cytochrome P450 2D6 having a low therapeutic index (e.g. flecainide, propafenone, metoprolol) in the 14 days preceding enrolment
• Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation
• Substance or alcohol dependence at enrolment (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. congestive heart failure, angina pectoris, hypertension) as judged by the investigator
• Involvement in the planning and conduct of the study
• Previous enrolment or randomisation of treatment in the present study.
• Participation in another drug trial within 4 weeks prior enrolment 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 enrolment 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 randomisation. 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 Note: If a diabetic patient meets one of these criteria, the patient is to be excluded even if the treating physician believes that the patient is stable and can participate in the study.
• An absolute neutrophil count (ANC) of 1.5 x 109 per liter
• Abnormal laboratory parameters of clinical relevance before enrolment
• Abnormal blood pressure, abnormal electrocardiogram, and/or abnormal electroencephalogram with clinical relevance before enrolment
• Psychotropic drugs within 3 days before and throughout the study with the exception of zopiclon (up to 7.5 mg per day) in case of sleep difficulties and lorazepam (up to 2 mg per day) in case of inner tension and anxiety