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

NCT00953108 | Completed Phase 3

• 1 other identifier: QUE/09
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depression

Outcome Measures

Primary Outcomes (1)

• serial dexamethasone/CRH tests

  week 0, 1, and 5

Study Arms (2)

quetiapine

EXPERIMENTAL

Drug: quetiapine

escitalopram

ACTIVE COMPARATOR

Drug: escitalopram

Interventions

quetiapine DRUG

300 mg per day

quetiapine

escitalopram DRUG

escitalopram 10 mg per day

escitalopram

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead

Study Sites (1)

Department of Psychiatry, Ludwig-Maximilian-University

Munich, Bavaria, 80336, Germany

Location

Related Publications (1)

• Sarubin N, Nothdurfter C, Schmotz C, Wimmer AM, Trummer J, Lieb M, Uhr M, Baghai TC, Wetter TC, Buhner M, Rupprecht R, Schule C. Impact on cortisol and antidepressant efficacy of quetiapine and escitalopram in depression. Psychoneuroendocrinology. 2014 Jan;39:141-151. doi: 10.1016/j.psyneuen.2013.10.008. Epub 2013 Oct 23.

  PMID: 24275013 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Quetiapine Fumarate; Escitalopram

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Propylamines; Amines; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: August 5, 2009
• First Posted: August 6, 2009
• Study Start: September 1, 2009
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: February 12, 2013

Record last verified: 2013-02

Locations

DE (1)