Functional and Neurochemical Correlates of Treatment Response in Major Depressive Disorder

Terminated

• Conditions: Treatment-Resistant Depression

• Registration Number: NCT01598324
• Lead Sponsor: Mclean Hospital

Brief Summary

This is an ancillary study to a clinical trial that is being conducted at Massachusetts General Hospital. Investigators at MGH are conducting a clinical trial to test the efficacy of ziprasidone together with escitalopram for treatment-resistant depression (NCT00633399). This observational study will involve magnetic resonance scans to examine brain chemistry (neurotransmitter levels), brain activity, and functional connections between brain regions before and after participating in the trial. The neurotransmitters of interest are glutamate, glutamine, and GABA. Comparisons will be made between individuals who receive ziprasidone and individuals who receive an inactive placebo. Differences between participants who respond to standard antidepressants and those who require additional medication will also be examined. All participants will have a baseline magnetic resonance scan before starting medication. The second scan will be after 8 weeks of escitalopram treatment for those who respond or following 8 weeks of escitalopram plus ziaprasidone or placebo (16 weeks after starting) for those who do not respond to escitalopram alone. Participants will complete standard rating scales for depression at each visit.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-05-09
• Study First Submitted QC: 2012-05-12
• Study First Posted: 2012-05-15
• Study Start: 2012-07
• Primary Completion: 2013-04
• Status Verified: 2013-08
• Last Update Submitted: 2013-08-10
• Last Update Posted: 2013-08-13

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

• Aged 18-65
• Meets DSM-IV criteria for major depressive disorder
• Meets eligibility criteria for clinical trial of ziprasidone augmentation of escitalopram
• Capable of providing informed consent

Exclusion Criteria

• Meets exclusion criteria for augmentation clinical trial protocol
• Pregnancy or unwillingness to avoid pregnancy during trial
• Current or past psychosis or bipolar disorder
• Substance abuse or dependence in the past six months
• Clinically significant suicidality
• Unstable cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease or uncontrolled seizures
• Use of a concomitant medication that acts on glutamate or GABA neurotransmission
• Contraindication to magnetic resonance imaging (metal implant or device, occupational metal exposure, significant claustrophobia)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Glutamate level in antidepressant non-responders	8 weeks after starting combination therapy phase	Glutamate levels are measured by magnetic resonance spectroscopy 8 weeks after starting treatment with ziprasidone or placebo in addition to escitalopram.

Secondary Outcome Measures

Name	Time	Method
Glutamine level in treatment-responders following six weeks of antidepressant and non-responders following six weeks of adjunctive treatment.	8 weeks or 16 weeks
Glutamine level in treatment-responders following six weeks of antidepressant and non-responders following six weeks of adjunctive treatment	8 weeks
GABA level in treatment-responders following six weeks of antidepressant and non-responders following six weeks of adjunctive treatment	8 weeks
Glutamine level in antidepressant non-responders	8 weeks	Glutamine levels are measured by magnetic resonance spectroscopy 6 weeks after starting treatment with ziprasidone or placebo together with escitalopram.
GABA level in antidepressant non-responders	8 weeks	GABA levels are measured by magnetic resonance spectroscopy 6 weeks after starting treatment with ziprasidone or placebo together with escitalopram.
Functional connectivity in default mode network measured by functional magnetic resonance imaging (fMRI) in treatment-resistant individuals receiving adjunctive treatment	8 weeks after starting combination therapy phase	Functional connectivity will be measured by performing fMRI in the resting state.
Functional connectivity in default mode network measured by functional magnetic resonance imaging (fMRI) in treatment-resistant individuals receiving adjunctive treatment and treatment-responders receiving an antidepressant	8 weeks

Trial Locations

Locations (1)

McLean Hospital - McLean Imaging Center; 🇺🇸 Belmont, Massachusetts, United States