Dopaminergic Effects of Adjunctive Aripiprazole on the Brain in Treatment-Resistant Depression
Condition: Major Depressive Disorder
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant
Study type: Interventional

Summary: 
      Aripiprazole has been approved by the FDA for augmenting ineffective/partially effective oral
      antidepressant therapy in patients suffering from major depression. The mechanism by which
      this augmentation is achieved is not known. This study has been designed to test the
      hypothesis that the primary mechanism of action of aripiprazole (ARP) antidepressant
      augmentation is through the dopaminergic pathway. Two positron emission tomography (PET) scan
      procedures and a functional magnetic resonance imaging (fMRI) scan will be used to test this
      hypothesis.
    

Detailed description: 
      This study is designed to help understand the mechanism of action of ARP in major depressive
      disorder (MDD) augmentation. Subjects will undergo exposure to an existing antidepressant
      (Lexapro 10-20mg) for 10 weeks; subjects failing to completely respond to the monotherapy
      antidepressant treatment will receive augmentation with ARP for six weeks. Two placebo phases
      are included in which the subjects will receive one placebo along with the Lexapro for the
      first 6 weeks and a second placebo along with Lexapro for the next two weeks. A baseline
      brain imaging series (MRI and 2 PET/CT scans) will be obtained at week 10, prior to starting
      the aripiprazole, on subjects not responding to Lexapro. A second series of images will be
      obtained at the end of the six weeks of ARP augmentation. The neuroimaging will consist of
      fMRI, a raclopride PET scan, and a fluoro-dopa PET scan.

      Ten normal control subjects will not receive any treatment. They will be age and gender
      matched to study subjects and undergo one set of scans (fMRI,raclopride and FOPA PET scans)
      to use as comparison group for quality control on a non-depressed population and not for data
      analysis.
    

Intervention name(s): Escitalopram; Aripiprazole; Placebo Capsule; Placebo Tablet
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): All subjects will begin on escitalopram and placebo for 8 weeks; Subjects who fail to respond to Escitalopram will continue on Escitalopram and augment with active Aripiprazole.; All subjects will begin on escitalopram and placebo capsule for 8 weeks.; After 8 weeks, subjects will be given a 2 week supply of escitalopram and placebo tablet.
Other intervention name(s): Lexapro; Abilify
Intervention MeSH terms: Aripiprazole; Escitalopram
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: This study is designed to help understand the mechanism of action of aripiprazole in MDD augmentation. Subjects will undergo exposure to en an existing antidepressant (Lexapro 10-20mg) for 10 weeks; subjects failing to completely respond to the monotherapy antidepressant treatment will receive augmentation with aripiprazole for six weeks. We have included two placebo phases to the study in which the subjects received one placebo along with the Lexapro for the first 6 weeks and a second placebo along with Lexapro for the next two weeks (weeks 7 and 8). This double placebo design is to ensure that subjects receiving aripiprazole augmentation have a legitimate response (non-placebo) to the aripiprazole augmentation. Since the N of this study is small and a small % of patients with placebo response could skew the imaging data significantly, the use of a double placebo prior to the start of the true aripiprazole augmentation should reduce or eliminate a placebo response.
Masking: Single (Participant)
Primary purpose: Other
Keywords: Depression; Neuroimaging; Aripiprazole; Mood disorder; PET Scan; fMRI