Please select the eligibility criteria that correspond to the clinical trial below.
Title: Impact of Quetiapine Prolong and Escitalopram on the Hypothalamic-pituitary-adrenocortical (HPA)-Axis Activity in Depressed Patients
Brief Summary: In former studies of the investigators research group the investigators could also demonstrate acute inhibitory effects of the antidepressant mirtazapine on ACTH and cortisol release in normal controls (Schüle et al. 2002), most likely mediated via antagonism at central 5-HT2- and H1-receptors. In contrast to mirtazapine, serotonin or norepinephrine reuptake inhibiting antidepressants acutely stimulate ACTH and cortisol secretion (Schüle 2007). The investigators also performed a study in depressed patients who were treated either with mirtazapine or with reboxetine using serial dexamethasone/CRH tests (week 0, 1, and 5) as a parameter for HPA axis activity. Mirtazapine, but not the norepinephrine reuptake inhibitor reboxetine was able to significantly reduce HPA axis activity already within one week (Schüle et al. 2006). Mirtazapine is known to have an earlier onset of antidepressant action than do SSRIs such as sertraline (Behnke et al. 2003) or antidepressants with dual mechanism of action such as venlafaxine (Benkert et al. 2006), possibly due to its rapid inhibition of HPA axis activity in unipolar depressed patients.

Since mirtazapine and quetiapine have similar effects on the HPA system in healthy male volunteers (i.e. inhibition of ACTH and cortisol secretion), a rapid attenuation of HPA axis activity is also expected during quetiapine XR treatment in depressed patients.

Therefore, in the present study the investigators goal is to investigate whether quetiapine fumarate XR at a dosage of 300 mg per day has an impact on HPA axis activity in unipolar depressed patients, as measured by serial dexamethasone/CRH tests (week 0, 1, and 5) and salivary cortisol profiles and whether putative effects of quetiapine XR on the HPA system are related to its antidepressant efficacy.


Options:
A: Inclusion Criteria:

* Metastatic small-cell lung cancer
* Metastatic high-grade neuroendocrine carcinoma of any organ system (high-grade defined by Ki-67 ≥ 20% and/or ≥ 20 mitoses/10 (HPF).
* Received at least one line of prior chemotherapy treatment for metastatic disease.
* Daily chemotherapy must be completed ≥ 2 weeks prior to registration
* Weekly chemotherapy must be completed ≥ 2 weeks prior to registration
* Chemotherapy every 2 weeks must be completed ≥ 3 weeks prior to registration
* Chemotherapy every 3 weeks must be completed ≥ 4 weeks prior to registration
* ECOG Performance Status 0 to 2
* Measurable disease by RECIST 1.1 criteria
* Age at least 18 years
* Estimated life expectancy at least 3 months
* Absolute neutrophil count ≥ 1,500/ mm³
* Platelets ≥ 100,000/mm³
* Hemoglobin ≥ 9 g/dL
* Total bilirubin ≤ 1.5 mg/dL, OR ≤ 2 X ULN if tumor involves the liver
* AST(SGOT)
* ALT(SGPT) ≤ 3 X ULN
* Creatinine ≤ 1.5 X ULN
* Creatinine clearance ≥ 45 mL/min/1.73m²) for patients with creatinine levels above institutional normal
* QT interval corrected using Fridericia's method (QTcF) \< 450 msec (males) or \< 470 msec (females)
* PR \< 240 msec
* QRS \< 100 msec
* Brain metastases must be asymptomatic and have been adequately treated with radiation finishing at least 1 week prior to initiation of study treatment.
* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Clinically-significant ventricular arrhythmia including cardiac arrest
* Myocardial infarction from coronary artery disease within 3 months of study enrollment
* Implantable pacemaker or implantable cardioverter defibrillator
* NYHA Class III or greater congestive heart failure
* Other clinically-significant cardiac disorders
* Family history of long QT syndrome.
* Concomitant or expected treatment with strong inhibitors of cytochrome p450 CYP2D6, specifically including Bupropion; Fluoxetine; or Paroxetine (must be discontinued at least 2 weeks or 5-half lives prior to the initiation of desipramine, whichever is shortest, except fluoxetine which requires at least a 5-week washout period).
* Use of medications known to increase risk of torsades de pointes, including Amiodarone; Arsenic trioxide; Astemizole; Azithromycin; Bepridil; Chloroquine; Chlorpromazine; Cisapride; Citalopram; Clarithromycin; Disopyramide; Dofetilide; Domperidone; Droperidol; Erythromycin; Flecainide; Halofantrine; Haloperidol; Ibutilide; Levomethadyl; Mesoridazine; Methadone; Moxifloxacin; Pentamidine; Pimozide; Probucol; Procainamide; Quinidine; Sotalol; Sparfloxacin; Terfenadine; Thioridazine; Vandetanib
* Other anti-depressant or anti-psychotic medications including selective serotonin re-uptake inhibitors (SSRIs); other tricyclic, monoamine oxidase inhibitors (MAOIs); serotonin-norepinephrine reuptake inhibitors (SNRIs, typical or atypical anti-psychotic)
* Metoclopramide (Reglan) because of increased risk of extrapyrimidal symptoms and neuroleptic malignant syndrome
* Symptomatic orthostatic hypotension despite adequate volume resuscitation.
* Medical history of narrow angle glaucoma
* Bipolar disorder, ongoing or active within the last 5 years
* Suicidal ideation, ongoing or active within the last 5 years
* Suicide attempt, ongoing or active within the last 5 years
* Pregnancy
* Breastfeeding
* Receiving any other investigational agents
* Any other serious or unstable concomitant systemic disorder that in the opinion of the investigator is incompatible with the clinical study
B: Inclusion Criteria:

1. Male or female, aged \>18 years.
2. Current DSM IV diagnosis of Major Depressive Disorder.
3. Under palliative care.
4. Confirmed diagnosis of cancer.
5. Not on any antidepressants

Exclusion Criteria:

1. Clinical significant abnormal laboratory values.
2. Clinically significant abnormal ECG.
3. Documented history of other psychiatric diagnosis (schizophrenia, bipolar disorder, organic brain disorder, dementia etc.)
C: Inclusion criteria:

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

1. Inpatients (the admission to hospital occurs independently from study participation)
2. Provision of written informed consent
3. A diagnosis of major depression by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV) (unipolar depression: 296.2, 296.3)
4. Female and male patients aged 18 to 65 years
5. 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.
6. Able to understand and comply with the requirements of the study as judged by the investigator.
7. 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:

1. Pregnancy or lactation
2. Any DSM-IV Axis I disorder not defined in the inclusion criteria
3. Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others
4. Known intolerance or lack of response to quetiapine fumarate and/or escitalopram, as judged by the investigator
5. 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
6. 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
7. Use of monoamine oxidase inhibitors (MAOIs) or other serotonergic drugs (e.g. triptans) in the 14 days preceding enrolment
8. Use of oral anticoagulants in the 14 days preceding enrolment
9. History of bleeding disorders.
10. 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
11. Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation
12. Substance or alcohol dependence at enrolment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria
13. Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrolment
14. Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment
15. Unstable or inadequately treated medical illness (e.g. congestive heart failure, angina pectoris, hypertension) as judged by the investigator
16. Involvement in the planning and conduct of the study
17. Previous enrolment or randomisation of treatment in the present study.
18. Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements
19. 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.
20. An absolute neutrophil count (ANC) of 1.5 x 109 per liter
21. Abnormal laboratory parameters of clinical relevance before enrolment
22. Abnormal blood pressure, abnormal electrocardiogram, and/or abnormal electroencephalogram with clinical relevance before enrolment
23. 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
D: Inclusion Criteria:

* Histologic documentation of prostate cancer, any stage Life expectancy of \> nine months
* Prior or current androgen deprivation for treatment or control of prostate cancer to include:
* Bilateral Orchiectomy
* LHRH agonist (with or without antiandrogen therapy) ie: leuprolide (Lupron), goserelin (Zoladex), bicalutamide (Casodex), flutamide (Eulexin), or similar agents
* Chemotherapy
* Radiation (Patients may undergo concurrent radiation therapy to the prostate, prostate + seminal vesicles, and/or pelvis). Seed implants are allowed
* Participant report of hot flash frequency of an average of four or more per day, as defined by sweating, flushing, sensation of warmth, night sweats (Average of 28 per week)
* Hot flashes must be moderate or severe (See appendix A for hot flash definitions)
* Grade 2 (Moderate flashes) are warmer, produce obvious perspiration, and last 2 to 3 minutes
* Grade 3 (Severe flashes) causes profuse perspiration, generate intense heat, last longer and interfere with ongoing activity
* Age \>21
* No allergies to soy or dairy products
* No current use of SSRIs, SNRI's, MAOIs, or Linezolide
* No uncontrolled hypertension (160/90) or greater than Class I American Heart Association functional capacity
* No history of mania, hypomania, bipolar disorder, or anorexia nervosa
* No history of seizures
* No history of hepatic dysfunction)
* Must have a telephone
* Signed protocol-specific Informed Consent
* Participants consuming soy foods or soy based supplements must continue on a stable regimen during study participation
* Patients should maintain same treatment and medications for prostate cancer throughout entire study.
* No change in treatment for 2 weeks prior to registration.
* Current use of medications and herbal supplements for hot flashes are allowed if on a stable regimen throughout the entire study. (Does not include anti-depressants)

Exclusion Criteria:

* Anticipated changes in prostate cancer treatment plan (i.e., hormonal manipulation, changes in chemotherapy)
* Concurrent antidepressant therapy
* History of intolerance to venlafaxine
* Recent (within 14 days) use of venlafaxine (Effexor XRTM), monoamine oxidase inhibitor, SSRI (selective serotonin reuptake inhibitor), or SNRI (selective norepinephrine reuptake inhibitor)
* History of seizure disorder

Answer: C