Functional and Neurochemical Correlates of Treatment Response in Major Depressive Disorder

Overview

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.

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: April 2013

Arms, Groups and Cohorts

  • escitalopram responders no augmentation
    • Participants who show a clinical response following 8 weeks on an SSRI will have a final magnetic resonance scan at the end of 8 weeks and will complete the study at that time.
  • Ziprasidone augmentation
    • Participants who do not respond to escitalopram and are randomized to ziprasidone augmentation will have a final magnetic resonance scan following 8 weeks on ziprasidone.
  • Placebo augmentation
    • Participants who do not respond to escitalopram and are randomized to placebo augmentation will have a final magnetic resonance scan following 8 weeks on placebo.

Clinical Trial Outcome Measures

Primary Measures

  • Glutamate level in antidepressant non-responders
    • Time Frame: 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 Measures

  • Glutamine level in treatment-responders following six weeks of antidepressant and non-responders following six weeks of adjunctive treatment.
    • Time Frame: 8 weeks or 16 weeks
  • Glutamine level in treatment-responders following six weeks of antidepressant and non-responders following six weeks of adjunctive treatment
    • Time Frame: 8 weeks
  • GABA level in treatment-responders following six weeks of antidepressant and non-responders following six weeks of adjunctive treatment
    • Time Frame: 8 weeks
  • Glutamine level in antidepressant non-responders
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 8 weeks

Participating in This Clinical Trial

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)

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Mclean Hospital
  • Collaborator
    • Pfizer
  • Provider of Information About this Clinical Study
    • Principal Investigator: Tara Lauriat, Principal Investigator – Mclean Hospital

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.