Major Depressive Disorder
Conditions
Keywords
Depression, Treatment, Imaging
Brief summary
While there are many effective options for treating a major depressive episode, there are no clinical markers that predict the likelihood of remission with an initial trial of either an antidepressant medication or psychotherapy. More critically, there are also no reliable predictors that might anticipate failure to such standard treatments either alone or in combination. This project will characterize imaging-based brain subtypes that distinguish groups of depressed patients who later remit or not to SSRI pharmacotherapy or cognitive behavior therapy (CBT), respectively. To define these subtypes, a prospectively-treated cohort of 100 patients will be randomized to receive either escitalopram (s-CIT) or CBT for the first 12 weeks, with non-remitters to either first treatment crossed over to receive an additional 12 weeks of treatment with combined treatment. Non-remitters to both treatments will thus define a relatively treatment resistant third subgroup. Resting-state 18F-fluoro-deoxyglucose (FDG) positron emission tomography (PET) scans will be acquired prior to initiating antidepressant therapy, with pre-treatment scan patterns associated with three possible outcomes (CBT remission, s-CIT remission, and non-remission to both) assessed using multivariate analytic methods. A second PET scan, acquired early in the treatment course, will be used to assess the likelihood of response to the specific treatment first assigned. The proposed studies are a first step towards defining brain-based biomarkers predictive of differential treatment outcome in major depression; most critically, patterns distinguishing patients at risk for treatment resistance. Identification of such biomarkers has additional implications for future testing of novel therapies in patients with distinct brain signatures, including development of evidence-based treatment algorithms for individual patients.
Detailed description
SPECIFIC AIMS Aim 1. To define baseline regional glucose metabolic patterns (measured using FDG PET) associated with differential clinical remission to each of two well-established, randomly delivered first-line antidepressant treatments-the SSRI escitalopram (s-CIT) or cognitive behavioral therapy (CBT) with cross-over treatment for non-remitters (sequential course of treatment model). Aim 2. To define metabolic change patterns, occurring early in the course of both s-CIT and CBT, associated with successful and unsuccessful clinical remission to each intervention.
Interventions
DRUGescitalopram
Participants will receive treatment with escitalopram for 12 weeks.
BEHAVIORALCognitive Behavioral Therapy (CBT)
CBT will include 16 1 hour sessions provided over 12 weeks.
Sponsors
National Institute of Mental Health (NIMH)
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patients between the ages of 18 and 60. (no subjects with first episode over age 50. This is an attempt to exclude patients with 'vascular depression' who have a potentially different pathophysiology and treatment response compared to idiopathic MDD. * DSM-IV criteria for unipolar Major Depressive Disorder. * HAM-D (24 item) score \>/= 18 at Screening, \>/= 15 at Baseline. * Co-morbid conditions (other than those listed under
Exclusion criteria
below) will be accepted as long as MDD is the primary diagnosis (based on predominance and sequential development of symptoms). * Acceptable method of birth control (oral contraceptives, Depo-Provera, Norplant, condoms with spermicide. A vasectomy is acceptable in the framework of a stable monogamous relationship. Sexually inactive women must agree to contraception if they become sexually active during the study. * Educational level, degree of understanding and reliability so that participation is feasible. * Informed consent to participate and comply in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Remission Defined as Hamilton Depression Rating Scale-17 Score of Less Than or Equal to 7 at 12 Weeks | Measured at week 12 | \# of study participants with Hamilton Depression-17-item score less than or equal to 7. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Defined as 50% Change in Hamilton Depression Rating Scale-17 Score at 12 Weeks | Measured at week 12. | Number of participants with a 50% change from Baseline on the Hamilton Depression Rating Scale-17-item score |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Escitalopram escitalopram : Participants will receive treatment with escitalopram for 12 weeks. | 42 |
| Cognitive Behavioral Therapy Cognitive Behavioral Therapy (CBT) : CBT will include 16 1 hour sessions provided over 12 weeks. | 40 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Cognitive Behavioral Therapy | Escitalopram | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants | 42 Participants | 82 Participants |
| Age, Continuous | 42.2 years STANDARD_DEVIATION 9.5 | 41.2 years STANDARD_DEVIATION 6.8 | 41.68 years STANDARD_DEVIATION 8.22 |
| Region of Enrollment United States | 40 participants | 42 participants | 82 participants |
| Sex: Female, Male Female | 22 Participants | 26 Participants | 48 Participants |
| Sex: Female, Male Male | 18 Participants | 16 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 42 | 21 / 40 |
| serious Total, serious adverse events | 0 / 42 | 0 / 40 |
Outcome results
Primary
Remission Defined as Hamilton Depression Rating Scale-17 Score of Less Than or Equal to 7 at 12 Weeks
\# of study participants with Hamilton Depression-17-item score less than or equal to 7.
Time frame: Measured at week 12
Population: completed study participants in 12-week-trial
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Escitalopram | Remission Defined as Hamilton Depression Rating Scale-17 Score of Less Than or Equal to 7 at 12 Weeks | 12 participants |
| Cognitive Behavioral Therapy | Remission Defined as Hamilton Depression Rating Scale-17 Score of Less Than or Equal to 7 at 12 Weeks | 12 participants |
Secondary
Response Defined as 50% Change in Hamilton Depression Rating Scale-17 Score at 12 Weeks
Number of participants with a 50% change from Baseline on the Hamilton Depression Rating Scale-17-item score
Time frame: Measured at week 12.
Population: completers
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Escitalopram | Response Defined as 50% Change in Hamilton Depression Rating Scale-17 Score at 12 Weeks | 18 participants |
| Cognitive Behavioral Therapy | Response Defined as 50% Change in Hamilton Depression Rating Scale-17 Score at 12 Weeks | 18 participants |