Treatment Outcome in Major Depressive Disorder

• Status: Completed
• Trial end date: 2019-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rigshospitalet, Denmark
• Collaborators: Center for Integrated Molecular Brain Imaging; Center for Integrated Molecular Brain Imaging, Copenhagen, Denmak; Central Visitation, Region Hovedstaden; Psychiatric Centre Copenhagen
• Treatments: Citalopram; Dexetimide; Duloxetine Hydrochloride; Serotonin; Serotonin Uptake Inhibitors

Criteria

Inclusion Criteria:

• Moderate to severe depression

• Age 18-65 years

• No previous antidepressant treatment the last 2 months

• Informed and signed consent

Exclusion Criteria:

• More than one previous attempt with antidepressant drugs

• Duration of current depression more than 2 years

• Current or previous psychiatric severe co-morbidity

• Acute suicidal ideation

• Psychotic

• Previous non-response to Selective Serotonin Reuptake Inhibitor (SSRI)

• Contraindication for SSRI treatment

• More suitable with treatment of alternative anti-depressive drug.

• Severe somatic co-morbidity

• Somatic medicine that can influence the trial

• Contraindications for MR-scanning

• Previous exposure to radioactivity > 10 milli sievert (mSv) within the last year

• Alcohol or drug abuse

• Previous severe head trauma

• Pregnancy

• Breast-feeding

• Insufficient Danish skills