Neuroimaging Of Treatment Effects in Treatment-Resistant Depression
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Purpose
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 antidepressant augmentation through the dopaminergic pathway. Two positron emission tomography (PET) scan procedures and a functional magnetic resonance imaging (MRI) scan will be used to test this hypothesis.
| Condition | Intervention |
|---|---|
|
Major Depressive Disorder |
Drug: escitalopram and adjunctive aripiprazole and placebo |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Dopaminergic Effects of Adjunctive Aripiprazole on the Brain in Treatment-Resistant Depression: A Raclopride/F-DOPA Positron Emission Tomography and Functional MRI Study. |
- 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 ]
- 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 ]
| Estimated Enrollment: | 55 |
| Study Start Date: | May 2009 |
| Estimated Study Completion Date: | February 2012 |
| Estimated Primary Completion Date: | February 2012 (Final data collection date for primary outcome measure) |
-
Drug: escitalopram and adjunctive aripiprazole and placebo
- escitalopram
- Lexapro
- aripiprazole
- Abilify
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.
Eligibility| Ages Eligible for Study: | 18 Years to 55 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Major Depressive following DSM-IV criteria
- At least one failed adequate dose trial of an antidepressant
- Medication free or antidepressant wash-out of at least two weeks or 5 half-lives whichever is longer
- Lexapro allowed
Exclusion Criteria:
- Smokers
- Suicidality
- History of anxiety disorder
- Pregnant or lactating women or sexually active women of child bearing potential who are not using medically accepted means of contraception
- Organic mental disorders
- Substance abuse/dependence
- Schizophrenia and psychotic disorders
- Panic disorder, generalized anxiety disorder, bulimia nervosa and anorexia nervosa
- Other current forms of treatment for depression
- Demonstrated previous inadequate antidepressant response to ECT
- ECT for the current episode of depression
- Hospitalized within four weeks of the study
- MAO-I treatment within two weeks of enrollment.
- Known allergy, hypersensitivity or previous unresponsiveness to aripiprazole or known intolerance to any study medication
- Positive drug screen
- History of any thyroid pathology
- History of serotonin syndrome or neuroleptic malignant syndrome
- History of seizure disorder
- Participation in a trial using PET scans in the past twelve months
Contacts and Locations| Contact: Martha E Cornell, BSN | 314-362-0038 | cornellm@wustl.edu |
| United States, Missouri | |
| Washington University in St. Louis, School of Medicine | Recruiting |
| St. Louis, Missouri, United States, 63110 | |
| Contact: Martha E Cornell, BSN 314-362-0038 | |
| Principal Investigator: Charles R Conway, MD | |
| Principal Investigator: | Charles R Conway, MD | Washington University in St. Louis, School of Medicine |
More Information
No publications provided
| Responsible Party: | Charles R. Conway, MD, Washington University in St. Louis |
| ClinicalTrials.gov Identifier: | NCT00953745 History of Changes |
| Other Study ID Numbers: | 2009-0419 |
| Study First Received: | August 4, 2009 |
| Last Updated: | August 8, 2011 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Washington University School of Medicine:
|
Depression Neuroimaging Aripiprazole |
Mood disorder PET Scan fMRI |
Additional relevant MeSH terms:
|
Depression Depressive Disorder Depressive Disorder, Major Behavioral Symptoms Mood Disorders Mental Disorders Dexetimide Citalopram Aripiprazole Antiparkinson Agents Anti-Dyskinesia Agents Central Nervous System Agents Therapeutic Uses Pharmacologic Actions Parasympatholytics |
Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Muscarinic Antagonists Cholinergic Antagonists Cholinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Antidepressive Agents, Second-Generation Antidepressive Agents Psychotropic Drugs Serotonin Uptake Inhibitors Neurotransmitter Uptake Inhibitors Serotonin Agents Antipsychotic Agents |
ClinicalTrials.gov processed this record on May 19, 2013