Primary Outcome Measures:
- Use of PET and fMRI to demonstrate the differential pattern of dopaminergic activity, dopamine receptor binding in the putamen and caudate and correlation these findings to MADRS in MDD subjects treated with escitalopram and aripiprazole. [ Time Frame: PET, fMRI and MADRS testing done at start of adjuctive aripiprazole and after 6 weeks of combined therapy ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Correlation of D2binding before and after adjunctive aripiprazole with emergence of extrapyramidal symptoms and akathisia. [ Time Frame: PET scans and EPS assessment conducted at start of aripiprazole and after 6 weeks of combination therapy. ] [ Designated as safety issue: No ]
Drug: escitalopram and adjunctive aripiprazole and placebo
escitalopram 20 mg per day plus placebo for 10 weeks followed by escitalopram 20mg and aripiprazole 10 mg for 6 weeks
This is an eighteen week study including a two week taper off period. Forty five subjects will be started on 10mg escitalopram then titered to 20mg plus placebo. After 10 weeks of treatment, those subjects who do not respond to the escitalopram, as defined by a 50% reduction in their MADRS score, will be started on adjunctive aripiprazole at 2mg, titered to 10mg. Subjects will remain on the both the escitalopram and aripiprazole for 6 weeks. At week 10 prior to starting the adjunctive aripiprazole and week 16 (end of treatment) the subjects will receive the PET and MRI scans. The neuroimaging will consist of fMRI, a raclopride PET scan, and a fluoro-dopa PET scan.
Ten normal control subjects will undergo one set of scans (fMRI,raclopride and FOPA PET scans) to use as comparison group.