CompletedNCT00953745Updated Apr 19, 2018Results posted

Dopaminergic Effects of Adjunctive Aripiprazole on the Brain in Treatment-Resistant Depression

An interventional study of Escitalopram and Aripiprazole in Major Depressive Disorder, sponsored by Washington University School of Medicine. Completed at 1 site in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-04-19.

Sponsored by Washington University School of Medicine · Not applicable, Interventional, and Other

Phase: Not applicable
Study type: Interventional
Enrollment: 43
Allocation: Non-randomized
Ages: 18 Years to 55 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Major Depressive Disorder

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Keywords

Depression
Neuroimaging
Aripiprazole
Mood disorder
PET Scan
fMRI

In context

Depression

8,057 studies on the registry are indexed under Depression; 1,641 are open to participants now.

This study's enrollment of 43 is below the median of 84 across 6,720 interventional studies indexed under Depression.

Browse Depression studies →

Lead sponsor

Washington University School of Medicine is the lead sponsor of 1,765 studies on the registry; 271 are open to participants now.

Of its 324 completed or terminated interventional studies of FDA-regulated products, 212 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 55 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

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

Study design

Phase: Not applicable
Primary purpose: Other
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: Single (Participant)
Enrollment: 43 participants (actual)

Study arms

Active comparator
Depressed 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.
Drug: Escitalopram · Drug: Aripiprazole · Drug: Placebo Capsule · Drug: Placebo Tablet
No intervention
Control Participants
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.

Interventions

DrugEscitalopram
All subjects will begin on escitalopram and placebo for 8 weeks
Also known as: Lexapro
DrugAripiprazole
Subjects who fail to respond to Escitalopram will continue on Escitalopram and augment with active Aripiprazole.
Also known as: Abilify
DrugPlacebo Capsule
All subjects will begin on escitalopram and placebo capsule for 8 weeks.
DrugPlacebo Tablet
After 8 weeks, subjects will be given a 2 week supply of escitalopram and placebo tablet.

What researchers measure

Primary outcomes

Fluorodopa Uptake Values in Brain Images of Aripiprazole Augmentation Responders
A ratio of the image derived radioactivity concentration and the whole body concentration of the injected radioactivity specifically in a cluster within the right medial caudate (see data below).
Time frame: Week 10 and Week 16 (6 weeks of combined therapy)

Secondary outcomes

Depression Symptom Change on The Montgomery-Åsberg Depression Rating (MADRS) Scale Between ARP Responders and Non-responders.
Montgomery-Åsberg Depression Rating (MADRS) Scale scores compared between the 6 week Aripiprazole augmentation groups (responds vs. non-responders). Total range of the MADRS is 0 to 60, with a score of greater than 34 indicating severe depression, 20-34 indicating moderate depression, 7-19 mild depression, and 0-6 normal or absent of symptoms.
Time frame: Week 10 and Week 16 (6 weeks of combined therapy)

Results

Posted Apr 19, 2018

Participant flow

Phase 1: 8 Weeks Escitalopram + Placebo

Participant flow — Phase 1: 8 Weeks Escitalopram + Placebo
Milestone	Depressed Participants	Control Participants
Started	37	6
Completed	24	6
Not completed	13	0
Withdrew: Pregnancy	1	0
Withdrew: Withdrawal by subject	2	0
Withdrew: Lost to follow-up	3	0
Withdrew: Adverse event	1	0
Withdrew: Screen failures	6	0

Phase 2: 2 Weeks Escitalopram + Placebo

Participant flow — Phase 2: 2 Weeks Escitalopram + Placebo
Milestone	Depressed Participants	Control Participants
Started	18	0
Completed	17	0
Not completed	1	0
Withdrew: Pregnancy	1	0

ARP Phase: 6 Weeks Escitalopram + ARP

Participant flow — ARP Phase: 6 Weeks Escitalopram + ARP
Milestone	Depressed Participants	Control Participants
Started	17	0
Completed	17	0
Not completed	0	0

Outcome measures

PrimaryFluorodopa Uptake Values in Brain Images of Aripiprazole Augmentation Responders

A ratio of the image derived radioactivity concentration and the whole body concentration of the injected radioactivity specifically in a cluster within the right medial caudate (see data below).

Time frame:: Week 10 and Week 16 (6 weeks of combined therapy)
Reported as:: Mean · FDOPA ratio in the right medial caudate

Fluorodopa Uptake Values in Brain Images of Aripiprazole Augmentation Responders
FDOPA ratio in the right medial caudate	ARP Responders	ARP Non-Responders
Week 10	1.297 ± 0.176	1.363 ± 0.180
Week 16	1.333 ± 0.175	1.350 ± 0.252

Statistical analysis

ARP Responders · t-test, 1 sided · p = 0.029 (paired t-test thresholded at cluster level significance of p=0.001; family-wise error multiple comparisons corrected)

SecondaryDepression Symptom Change on The Montgomery-Åsberg Depression Rating (MADRS) Scale Between ARP Responders and Non-responders.

Montgomery-Åsberg Depression Rating (MADRS) Scale scores compared between the 6 week Aripiprazole augmentation groups (responds vs. non-responders). Total range of the MADRS is 0 to 60, with a score of greater than 34 indicating severe depression, 20-34 indicating moderate depression, 7-19 mild depression, and 0-6 normal or absent of symptoms.

Time frame:: Week 10 and Week 16 (6 weeks of combined therapy)
Reported as:: Mean · score on the MADRS scale

Depression Symptom Change on The Montgomery-Åsberg Depression Rating (MADRS) Scale Between ARP Responders and Non-responders.
score on the MADRS scale	ARP Responders	ARP Non-Responders
Week 10	27.9 ± 5.6	31.7 ± 12.7
Week 16	6.5 ± 3.0	25.3 ± 5.5

Statistical analysis

ARP Responders · t-test, 2 sided · p = <0.001
ARP Non-Responders · t-test, 2 sided · p = 0.366

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Depressed Participants	—	2/37 (5.4%)	24/37 (64.9%)
Control Participants	—	0/6 (0%)	0/6 (0%)

Most frequent serious events

Most frequent serious events
Event	Depressed Participants	Control Participants
Birth of a baby (deception by subject)Pregnancy, puerperium and perinatal conditions	1/27	0/6
PregnancyPregnancy, puerperium and perinatal conditions	1/27	0/6

Most frequent other events

Showing 10 of 12

Most frequent other events
Event	Depressed Participants	Control Participants
Increased fatigueNervous system disorders	11/37	0/6
NauseaGastrointestinal disorders	7/37	0/6
HeadacheNervous system disorders	5/37	0/6
AkathisiaNervous system disorders	4/37	0/6
RestlessnessNervous system disorders	4/37	0/6
Vivid dreamingNervous system disorders	4/37	0/6
Decreased libidoNervous system disorders	3/37	0/6
DizzinessEar and labyrinth disorders	3/37	0/6
InsomniaNervous system disorders	2/37	0/6
Increased sweatingNervous system disorders	2/37	0/6

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Depressed Participants	Control Participants	Total
Mean	41.69 (19 to 54)	45.67 (31 to 54)	42.27 (19 to 54)

Sex: Female, Male
Sex: Female, Male(Participants)	Depressed Participants	Control Participants	Total
Female	27	5	32
Male	10	1	11

Region of Enrollment
Region of Enrollment(participants)	Depressed Participants	Control Participants	Total
United States	37	6	43

Study locations

1 site

Washington University in St. Louis, School of Medicine
Saint Louis, Missouri 63110, United States

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 19, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00953745
Lead sponsor: Washington University School of Medicine
Collaborators: Bristol-Myers Squibb
Responsible party: Sponsor
First posted: Aug 6, 2009
Start date: May 2009
Primary completion: Jun 2012
Completion: Dec 2012
Results posted: Apr 19, 2018
Last update: Apr 19, 2018

Study contacts

Charles R Conway, MD

principal investigator · Washington University School of Medicine

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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