Treatment Outcome in Major Depressive Disorder

Summary

Major Depressive Disorder (MDD) is one of the most severe and frequently occurring brain disorders worldwide. It has been linked to serotonergic dysfunction, sexual dysfunction, vulnerability to stress and neuro-inflammation. However, at the same time the etiological understanding is limited. Most antidepressants act on the serotonin (5- HT) system, yet between 30-50 % of patients with MDD does not respond successfully to 5-HT acting drugs. Recent experimental models from our group suggest that cerebral 5-HT levels in vivo can be indexed through molecular brain imaging of the 5-HT 4 receptor (5-HT4R) with a novel Positron Emission Tomography (PET) ligand (11C-SB207145). Also, our human studies have confirmed that cerebral synaptic 5-HT is inversely related to 5-HT4R binding and this technique thus can be used to investigate the role of 5-HT tone in the brain in MDD with differential responses to standard antidepressant treatment. By using multimodal neuroimaging technology, we aim to determine the status of the 5-HT system prior to and after either successful or failed neuropharmacological intervention in a non-randomized longitudinal open clinical trial. 100 untreated patients with moderate to severe MDD will be included. Data collection from various neurobiological domains (i.e, 5-HT4R PET imaging, Magnetic Resonance Imaging (MRI), functional MRI (fMRI), electroencephalogram (EEG), psychometrics, neuropsychological tests, and peripheral biomarkers) will be conducted before, during and after 12 weeks of antidepressant treatment. The objective is to identify predictors of pharmacological antidepressant treatment response in depressed individuals before and after 8 weeks of antidepressant treatment.

Conditions

• Major Depressive Disorder

Interventions

DRUG

Escitalopram

Patients will be treated with an antidepressant drug (escitalopram) at flexible standard doses for 12 weeks. If no response after 4 weeks; shift to duloxetine arm.

DRUG

Duloxetine

Patients who at 4 weeks of escitalopram have not responded will be shifted to duloxetine at flexible standard dosages.

Sponsors & Collaborators

• Center for Integrated Molecular Brain Imaging, Copenhagen, Denmak

  collaborator OTHER

• Psychiatric Centre Copenhagen

  collaborator UNKNOWN

• Central Visitation, Region Hovedstaden

  collaborator UNKNOWN

• Rigshospitalet, Denmark

  lead OTHER

Principal Investigators

• Gitte M Knudsen, MD,Prof. · Neurobiology Research Unit

Study Design

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-08-31

Primary Completion

2019-07-31

Completion

2019-07-31

Countries

• Denmark

Study Locations