Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder (MDD), Cognitive Behavioral Therapy (CBT), Escitalopram, Quantitative EEG (QEEG)
Brief summary
The purpose of this research study is to find out if a test can predict whether someone with depression will get better with treatment. We also want to find out whether there are changes in the brains of depressed patients having different types of treatment (drug therapy vs. talk therapy). We hope that a test called QEEG (Quantitative Electroencephalogram) can tell us if a treatment is going to work, even before the person starts to feel better. Hypothesis 1: Response to treatment will correlate with changes in QEEG metrics. Hypothesis 2: QEEG parameters, different from those that predict response to pharmacotherapy, will be associated with response to CBT.
Detailed description
To our knowledge, QEEG has not been studied in the prediction of response to CBT, an important and widely used non-pharmacologic approach to treating depression. Establishing QEEG technology as a predictor of response to CBT could help to guide treatment selection for individual patients. It is probable that certain patient populations are more likely to respond to either psychotherapeutic or psychopharmacological interventions, while others may benefit from a combination of treatment modalities. This study will provide preliminary information about the utility of QEEG as a predictor of response in psychotherapy and will furnish the knowledge base of QEEG changes related to clinical variables, providing pilot data for a study in a larger sample. We have hypothesized that clinical response will correlate with changes in QEEG metrics from beginning to two weeks after treatment, and that QEEG parameters, different from those that predict response to pharmacotherapy, will be associated with response to CBT.
Interventions
BEHAVIORALCognitive Behavioral Therapy (CBT)
The CBT group will receive weekly 50-minute individual sessions over the course of 12 weeks conducted by experienced therapists who are trained in manual based CBT.
DRUGEscitalopram
The medication group will receive open label treatment of escitalopram, 10-20 mg/day, flexible dose, for 12 weeks, and will be seen every two weeks by a study physician.
Sponsors
National Alliance for Research on Schizophrenia and Depression
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects will be adults, ages 18 to 75 years. * Written informed consent * MDD, current according to the fourth version of the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) * 17-item Hamilton Depression Rating Scale (HAM-D-17) score of \> 14 at baseline. * Subjects who are not currently taking any antidepressant or other psychotropic medications and who have been free of these medications for 4 weeks prior to screening visit.
Exclusion criteria
* Women who are pregnant, lactating, or planning a pregnancy during the study. * Women of child bearing potential who are not using a medically accepted means of contraception (to include oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine device, tubal ligation, or a partner with vasectomy). * Any uncontrolled psychiatric disorder. * Current use of psychotropic medications. * Psychotic features in the current episode or a history of psychotic features. * Alcohol or substance abuse or dependence within the past three months. * History of head trauma or seizure disorder. * History of intolerance of the study medication. * Failure to respond to escitalopram up to 20 mg for at least 6 weeks. * Failure to respond to 2 or more adequate antidepressant trials (6 weeks or longer on a therapeutic dose, equivalent to fluoxetine 40mg) in the current episode. * Currently enrolled in other depression-focused psychotherapy and unwilling to cease treatment. * Subjects who, per clinical judgment, are not appropriate candidates for CBT or SSRIs. * History or current diagnosis of the following DSM-IV psychiatric illness: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, patients with mood congruent or mood incongruent psychotic features, patients with substance dependence disorders, including alcohol, active within the last 3 months. * Serious suicide or homicide risk, as assessed by the evaluating clinician or a score of 4 on the third item of the HAM-D. * Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Rating Scale (HAM-D-17) Scores | 12 weeks | The Hamilton Depression Rating Scale is a clinician-rated scale used to rate depression severity. The maximum score is a 50 and the minimum score is a 0, where higher scores indicate greater severity. Scores from 14 to 18 indicate moderately severe depression. |
| Change in Absolute Beta Power in Channel 4 | 12 weeks | Change between baseline and LOCF in absolute power of the beta wave recorded from channel 4 of the EEG |
| Change in Absolute Theta Power From Channel 1 | 12 weeks | Change between baseline and LOCF in relative power of the theta wave recorded from channel 1 of the EEG. Relative power refers to the percentage of power in the theta wave compared with the total power in the patient's EEG. |
| Change in Relative Theta Power Channel 3 | 12 weeks | Change between baseline and LOCF in relative power of the theta wave recorded from channel 3 of the EEG. Relative power refers to the percentage of power in the theta wave compared with the total power in the patient's EEG. |
| Change in Relative Theta Power From Channel 4 | 12 weeks | Change between baseline and LOCF in relative power of the theta wave recorded from channel 4 of the EEG. Relative power refers to the percentage of power in the theta wave compared with the total power in the patient's EEG. |
| Change in Relative Beta Power From Channel 4 | 12 weeks | Change between baseline and LOCF in relative power of the beetawave recorded from channel 4 of the EEG. Relative power refers to the percentage of power in the beta wave compared with the total power in the patient's EEG. |
| Change in Absolute Beta Power From the Ear Channel | 12 weeks | Change between baseline and LOCF in absolute power of the beta wave recorded from the ear channel of the EEG. The ear channel refers to the average of channels 3 and 4. |
| Change in Relative Theta Power From Temporal Channel | 12 weeks | Change between baseline and LOCF in relative power of the theta wave recorded from the temporal channel of the EEG. Relative power refers to the percentage of power in the theta wave compared with the total power in the patient's EEG. The temporal channel refers to the average of channels 1 and 2 |
| Change in Relative Theta Power From Ear Channel | 12 weeks | Change between baseline and LOCF in relative power of the theta wave recorded from the ear channel of the EEG. Relative power refers to the percentage of power in the theta wave compared with the total power in the patient's EEG. The ear channel refers to the average of channels 3 and 4 |
| Percent Change in Relative Theta Power From Week 1 of the Ear Channel | 1 week | Percent change between baseline and week 1 in relative power of the theta wave recorded from the ear channel of the EEG. Relative power refers to the percentage of power in the theta wave compared with the total power in the patient's EEG. The ear channel refers to the average of channels 3 and 4 |
Countries
United States
Participant flow
Recruitment details
The first patient was screened on January 6, 2009, and the last patient was screened on October 26, 2010. The study was completed at the Depression Clinical and Research Program at Massachusetts General Hospital.
Participants by arm
| Arm | Count |
|---|---|
| Cognitive Behavioral Therapy (CBT) The CBT group will receive weekly 50-minute individual sessions over the course of 12 weeks conducted by experienced therapists who are trained in manual based CBT. | 23 |
| Escitalopram The medication group will receive open label treatment of escitalopram, 10-20 mg/day, flexible dose, for 12 weeks, and will be seen every two weeks by a study physician. | 16 |
| Total | 39 |
Baseline characteristics
| Characteristic | Cognitive Behavioral Therapy (CBT) | Escitalopram | Total |
|---|---|---|---|
| Age, Continuous | 44.8 years STANDARD_DEVIATION 14.2 | 43.3 years STANDARD_DEVIATION 15.5 | 43.9 years STANDARD_DEVIATION 14.8 |
| Age, Customized <=18 years | 0 participants | 0 participants | 0 participants |
| Age, Customized >=65 years | 3 participants | 1 participants | 4 participants |
| Age, Customized Age unknown | 1 participants | 1 participants | 2 participants |
| Age, Customized Between 18 and 65 years | 19 participants | 14 participants | 33 participants |
| Region of Enrollment United States | 23 participants | 16 participants | 39 participants |
| Sex: Female, Male Female | 12 Participants | 9 Participants | 21 Participants |
| Sex: Female, Male Male | 11 Participants | 7 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 23 | 9 / 16 |
| serious Total, serious adverse events | 0 / 23 | 0 / 16 |
Outcome results
Primary
Change in Absolute Beta Power From the Ear Channel
Change between baseline and LOCF in absolute power of the beta wave recorded from the ear channel of the EEG. The ear channel refers to the average of channels 3 and 4.
Time frame: 12 weeks
Population: EEG data only available for 11 participants from CBT arm and 11 participants from Medication arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Behavioral Therapy (CBT) | Change in Absolute Beta Power From the Ear Channel | .0537 Hz | Standard Deviation 0.08943 |
| Escitalopram | Change in Absolute Beta Power From the Ear Channel | -.0167 Hz | Standard Deviation 0.07461 |
| Non Responders in Medication Arm | Change in Absolute Beta Power From the Ear Channel | .0670 Hz | Standard Deviation 0.14412 |
| Responders in Medication Arm | Change in Absolute Beta Power From the Ear Channel | -.01401 Hz | Standard Deviation 0.08307 |
Primary
Change in Absolute Beta Power in Channel 4
Change between baseline and LOCF in absolute power of the beta wave recorded from channel 4 of the EEG
Time frame: 12 weeks
Population: EEG data only available for 11 participants from CBT arm and 11 participants from Medication arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Behavioral Therapy (CBT) | Change in Absolute Beta Power in Channel 4 | .0930 Hz | Standard Deviation 0.13602 |
| Escitalopram | Change in Absolute Beta Power in Channel 4 | -.0102 Hz | Standard Deviation 0.09301 |
| Non Responders in Medication Arm | Change in Absolute Beta Power in Channel 4 | .0683 Hz | Standard Deviation 0.151 |
| Responders in Medication Arm | Change in Absolute Beta Power in Channel 4 | .0056 Hz | Standard Deviation 0.1084 |
Primary
Change in Absolute Theta Power From Channel 1
Change between baseline and LOCF in relative power of the theta wave recorded from channel 1 of the EEG. Relative power refers to the percentage of power in the theta wave compared with the total power in the patient's EEG.
Time frame: 12 weeks
Population: EEG data only available for 11 participants from CBT arm and 11 participants from Medication arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Behavioral Therapy (CBT) | Change in Absolute Theta Power From Channel 1 | .225 Hz | Standard Deviation 0.02765 |
| Escitalopram | Change in Absolute Theta Power From Channel 1 | -.0455 Hz | Standard Deviation 0.07683 |
| Non Responders in Medication Arm | Change in Absolute Theta Power From Channel 1 | .0075 Hz | Standard Deviation 0.0734 |
| Responders in Medication Arm | Change in Absolute Theta Power From Channel 1 | .003 Hz | Standard Deviation 0.0535 |
Primary
Change in Relative Beta Power From Channel 4
Change between baseline and LOCF in relative power of the beetawave recorded from channel 4 of the EEG. Relative power refers to the percentage of power in the beta wave compared with the total power in the patient's EEG.
Time frame: 12 weeks
Population: EEG data only available for 11 participants from CBT arm and 11 participants from Medication arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Behavioral Therapy (CBT) | Change in Relative Beta Power From Channel 4 | .0483 Hz | Standard Deviation 0.0356 |
| Escitalopram | Change in Relative Beta Power From Channel 4 | .0173 Hz | Standard Deviation 0.02921 |
| Non Responders in Medication Arm | Change in Relative Beta Power From Channel 4 | .0063 Hz | Standard Deviation 0.03758 |
| Responders in Medication Arm | Change in Relative Beta Power From Channel 4 | .0179 Hz | Standard Deviation 0.02929 |
Primary
Change in Relative Theta Power Channel 3
Change between baseline and LOCF in relative power of the theta wave recorded from channel 3 of the EEG. Relative power refers to the percentage of power in the theta wave compared with the total power in the patient's EEG.
Time frame: 12 weeks
Population: EEG data only available for 11 participants from CBT arm and 11 participants from Medication arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Behavioral Therapy (CBT) | Change in Relative Theta Power Channel 3 | .0362 Hz | Standard Deviation 0.0446 |
| Escitalopram | Change in Relative Theta Power Channel 3 | -.0090 Hz | Standard Deviation 0.0859 |
| Non Responders in Medication Arm | Change in Relative Theta Power Channel 3 | .0015 Hz | Standard Deviation 0.02993 |
| Responders in Medication Arm | Change in Relative Theta Power Channel 3 | .272 Hz | Standard Deviation 0.06577 |
Primary
Change in Relative Theta Power From Channel 4
Change between baseline and LOCF in relative power of the theta wave recorded from channel 4 of the EEG. Relative power refers to the percentage of power in the theta wave compared with the total power in the patient's EEG.
Time frame: 12 weeks
Population: EEG data only available for 11 participants from CBT arm and 11 participants from Medication arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Behavioral Therapy (CBT) | Change in Relative Theta Power From Channel 4 | .0336 Hz | Standard Deviation 0.04428 |
| Escitalopram | Change in Relative Theta Power From Channel 4 | -.0009 Hz | Standard Deviation 0.0321 |
| Non Responders in Medication Arm | Change in Relative Theta Power From Channel 4 | .0076 Hz | Standard Deviation 0.03678 |
| Responders in Medication Arm | Change in Relative Theta Power From Channel 4 | .0070 Hz | Standard Deviation 0.04429 |
Primary
Change in Relative Theta Power From Ear Channel
Change between baseline and LOCF in relative power of the theta wave recorded from the ear channel of the EEG. Relative power refers to the percentage of power in the theta wave compared with the total power in the patient's EEG. The ear channel refers to the average of channels 3 and 4
Time frame: 12 weeks
Population: EEG data only available for 11 participants from CBT arm and 11 participants from Medication arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Behavioral Therapy (CBT) | Change in Relative Theta Power From Ear Channel | .0349 Hz | Standard Deviation 0.0444 |
| Escitalopram | Change in Relative Theta Power From Ear Channel | -.0050 Hz | Standard Deviation 0.03487 |
| Non Responders in Medication Arm | Change in Relative Theta Power From Ear Channel | .0046 Hz | Standard Deviation 0.02858 |
| Responders in Medication Arm | Change in Relative Theta Power From Ear Channel | .0171 Hz | Standard Deviation 0.04103 |
Primary
Change in Relative Theta Power From Temporal Channel
Change between baseline and LOCF in relative power of the theta wave recorded from the temporal channel of the EEG. Relative power refers to the percentage of power in the theta wave compared with the total power in the patient's EEG. The temporal channel refers to the average of channels 1 and 2
Time frame: 12 weeks
Population: EEG data only available for 11 participants from CBT arm and 11 participants from Medication arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Behavioral Therapy (CBT) | Change in Relative Theta Power From Temporal Channel | .0182 Hz | Standard Deviation 0.02003 |
| Escitalopram | Change in Relative Theta Power From Temporal Channel | -.0159 Hz | Standard Deviation 0.03422 |
| Non Responders in Medication Arm | Change in Relative Theta Power From Temporal Channel | .0125 Hz | Standard Deviation 0.07914 |
| Responders in Medication Arm | Change in Relative Theta Power From Temporal Channel | .0027 Hz | Standard Deviation 0.03688 |
Primary
Hamilton Depression Rating Scale (HAM-D-17) Scores
The Hamilton Depression Rating Scale is a clinician-rated scale used to rate depression severity. The maximum score is a 50 and the minimum score is a 0, where higher scores indicate greater severity. Scores from 14 to 18 indicate moderately severe depression.
Time frame: 12 weeks
Population: The number of participants for analysis was based on the number of participants who completed treatment (12 weeks of CBT or medication)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Behavioral Therapy (CBT) | Hamilton Depression Rating Scale (HAM-D-17) Scores | 10.64 units on a scale | Standard Deviation 6.44 |
| Escitalopram | Hamilton Depression Rating Scale (HAM-D-17) Scores | 13.78 units on a scale | Standard Deviation 9.4 |
Primary
Percent Change in Relative Theta Power From Week 1 of the Ear Channel
Percent change between baseline and week 1 in relative power of the theta wave recorded from the ear channel of the EEG. Relative power refers to the percentage of power in the theta wave compared with the total power in the patient's EEG. The ear channel refers to the average of channels 3 and 4
Time frame: 1 week
Population: EEG data only available for 11 participants from CBT arm and 11 participants from Medication arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Behavioral Therapy (CBT) | Percent Change in Relative Theta Power From Week 1 of the Ear Channel | 44.1809 percent | Standard Deviation 42.17256 |
| Escitalopram | Percent Change in Relative Theta Power From Week 1 of the Ear Channel | 8 percent | Standard Deviation 27.45993 |
| Non Responders in Medication Arm | Percent Change in Relative Theta Power From Week 1 of the Ear Channel | 7.5180 percent | Standard Deviation 29.37028 |
| Responders in Medication Arm | Percent Change in Relative Theta Power From Week 1 of the Ear Channel | 23.3718 percent | Standard Deviation 41.25936 |