Glutamatergic and GABAergic Mediators of Antidepressant Response in Major Depression
Condition: MDD; Citalopram; Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major
Intervention: citalopram
Intervention description: citalopram 20-40 mg daily
Intervention MeSH terms: Citalopram
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Intervention model description: Open-label administration of citalopram to participants with major depressive disorder. MRI scans performed at baseline and days 3, 7, and 42. An age- and gender-matched group of healthy volunteers did not receive citalopram and received on MRI scan to perform between-group baseline analyses.
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      Primarily, this study seeks to evaluate whether citalopram treatment is associated with an
      increase in the Glutamine (Gln)/Glutamate (Glu) ratio in the anterior cingulate cortex (ACC)
      from baseline to day 3 of treatment. Additionally, this study would like to examine whether
      citalopram treatment is associated with an increase in the Gln/Glu ratio in the ACC from
      baseline to day 7 of treatment. In order to more fully examine baseline neurochemical and
      functional abnormalities in participants with MDD, we also seek to scan a group of age- and
      sex-matched non-depressed comparison individuals in order to perform between-group analyses
      of baseline neuroimaging measures.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female age ≥ 18 and ≤ 65

          2. Meets DSM-IV criteria for MDD

          3. Current score of ≥ 18 on the 21-item Hamilton Depression Rating Scale (HAM-D).

        Exclusion Criteria:

          1. Unwillingness or inability to provide written informed consent.

          2. Current suicidal ideation

          3. Active psychotic symptoms

          4. Lifetime history of bipolar disorder, schizophrenia, or OCD

          5. Failed treatment with an adequate trial of ≥ 2 antidepressants during the current
             major depressive episode ("failure" will be defined as ≤ 50% subjective improvement,
             and an "adequate trial" will be defined as at least 4 weeks of treatment using at
             least the minimum dose of the antidepressant recommended by the manufacturer in
             product labeling)

          6. DSM-IV diagnosis of alcohol or substance dependence, with the exception of nicotine
             dependence, within three months prior to screening

          7. Any history of treatment with electroconvulsive therapy

          8. Positive urine toxicology screen for any drug of abuse or excluded medication at
             screening. Opiate pain medication being taken for a medical condition is exempt from
             needing a negative opiate screen.

          9. Clinically significant medical or neurologic disease, as judged by the principal
             investigator, which would increase the risk to the participant or interfere with
             interpretation of results

         10. Female participants with a positive urine pregnancy test at screening

        12. Pregnancy. Females of childbearing potential must be using an effective contraceptive
        method (e.g., abstinence, prescription oral contraceptives, contraceptive injections,
        double-barrier method, male partner sterilization).

        13. Any screening laboratory abnormality deemed clinically significant by the investigator
        14. A QTc interval on screening ECG of ≥ 450 msec. 15. Use of any excluded medications (see
        Section 6.7 below) that cannot be discontinued during the screening phase 16. Previous
        failure to respond to treatment with citalopram that would, in the judgment of the
        investigator, constitute an adequate trial in MDD 17. Treatment with any investigational
        medications within 30 days prior to screening 18. Any contraindications to having an MRI
        scan, including cardiac pacemakers, metal vascular clips or stents, artificial heart
        valves, certain kinds of prostheses, brain stimulator devices, implanted drug pumps, ear
        implants, eye implants or known metal fragments in eyes, exposure to shrapnel or metal
        filings (wounded in military combat, sheetmetal workers, welders, and others), transdermal
        drug delivery systems, and certain tattoos with metallic ink 19. Left-handedness