Dopaminergic Effects of Adjunctive Aripiprazole on the Brain in Treatment-Resistant Depression
Major Depressive Disorder
About this trial
This is an interventional other trial for Major Depressive Disorder focused on measuring Depression, Neuroimaging, Aripiprazole, Mood disorder, PET Scan, fMRI
Eligibility Criteria
Treatment Group
Inclusion Criteria:
- Subjects with known history of MDD verified using the Mini International Neuropsychiatric Interview and a Hamilton Depression Rating Scale 17-item score of at least 18
- Subjects must have failed to respond to one previous adequate dose-duration trial of antidepressant therapy
- Must complete the MRI screening tool and demonstrate ability to receive an MRI
- For entry into the ARP augmentation phase the subject must be a non-responder to the escitalopram phase as demonstrated by a MADRS score at week 10, that is not reduced by greater than 50% from baseline.
Exclusion Criteria:
- Subjects cannot be smokers
- No significant history of anxiety disorder
- Cannot be pregnant or lactating and sexually active women of childbearing potential must use a medically accepted means of contraception
- The following DSM-IV diagnoses are excluded: Organic mental disorder; substance abuse/dependence, including alcohol, active within the last year; schizophrenia, paranoid or delusional disorders; other psychotic disorders; panic disorder; generalized anxiety disorder; obsessive-compulsive disorder, or post-traumatic stress disorder; bipolar disorder; bulimia nervosa; anorexia nervosa
- Subjects with serious suicidal risks
- Subjects who have taken any antidepressant medication other than escitalopram within 5 half lives, of the most recent antidepressant taken
- Subjects involved in any other form of treatment for depression
- Subjects who have demonstrated any previous inadequate antidepressant response to electroconvulsive therapy (ECT)
- Subjects who have received ECT for the current depression episode
- Subjects who have been hospitalized within 4 weeks of the study
- Subjects who have received treatment with a monoaminoxidase inhibitor within 2 weeks of enrollment
- Subjects with a known allergy, hypersensitivity, or previous unresponsiveness to aripiprazole or known intolerance to any study medications
- Subjects with a history of participation in any investigational medication trial in the past month
- A positive drug screen or substance use disorder in the past 12 months
- History of any thyroid pathology
- History of serotonin syndrome or neuroleptic malignant syndrome
- History of seizure disorder
- Subjects who have participated in a trial using PET scans in the past 12 months and in any trial in the past 30 days.
Control Group
Inclusion Criteria:
- Ages 18-55 matched to a study subject
- Must be a healthy subject with no significant medical history
- Must complete the MRI screening tool and demonstrate ability to receive an MRI
Exclusion Criteria:
- Cannot be a smoker
- Cannot be pregnant or lactating and sexually active women of childbearing potential must use a medically accepted means of contraception
- Any DSM-IV or II diagnosis as assessed by the MINI
- Subjects with a positive drug screen or substance use disorder in the past 12 months
Sites / Locations
- Washington University in St. Louis, School of Medicine
Arms of the Study
Arm 1
Arm 2
Active Comparator
No Intervention
Depressed Participants
Control Participants
Subjects with treatment-resistant depression (TRD) will be administered the Hamilton Depression Rating Scale (HAM-D 17) for entry and will receive escitalopram combined with an adjunctive placebo capsule for 8 weeks. Subjects who fail to respond will continue to receive escitalopram and additionally change to receive a placebo tablet resembling the active augmentation agent Aripiprazole (ARP) for 2 weeks. Subjects who fail to respond to escitalopram after the 2 phase placebo treatment will enter the ARP augmentation phase of the study and will receive escitalopram augmentation with ARP. Subjects will have 3 neuroimaging scans: F-DOPA PET, raclopride PET, and functional MRI conducted after 10 weeks of treatment and repeated after 6 weeks of ARP treatment.
Non-depressed, age- and sex-matched subjects without a DSM-IV Axis I diagnosis will serve as controls. They will not receive antidepressant, ARP, or any drug augmentation and will be used as quality control to compare the pre-ARP and post-ARP treatment brain images.