Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder
Brief summary
Do functional brain changes occur during Venlafaxine ER (extended release) versus Fluoxetine treatment and do changes in selective structures, such as the amygdala, predict treatment response?
Detailed description
This is a single site, controlled, double-blind study of outpatients. There are two arms: 1. Forty participants who have a current Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revised (DSM-IV-TR) diagnosis of Major Depression will be recruited. These subjects will be randomized to receive one of two antidepressant medications: Fluoxetine or Venlafaxine ER for the duration of the study. Subjects will gradually be titrated onto the medications and will be seen in the clinic up to 18 times for medication checks, to monitor side effects and depressive symptoms, including suicidal ideation. In the event of suicidal ideation, subjects will be withdrawn from the study and referred for immediate treatment. 2. Twenty normal control subjects with no current or past DSM-IV-TR diagnosis and will receive no medication. Normal control subjects will have up to 5 visits while in the study. Subjects will contact study staff to complete a phone screen and then eligible subjects will complete a clinic screen. Subjects will then be scheduled to attend the magnetic resonance imaging (MRI) simulation visit and if subjects continue to meet entrance criteria, they will be scheduled for the first MRI. Following the first MRI, subjects in the medication conditions will begin receiving medication. All subjects will undergo 3 functional magnetic resonance imaging (fMRI)s during the study: at the beginning of the study, approximately 8 weeks and 26 weeks later. During the MRI, subjects will view slides with positive and negative emotional content. Subjects will complete various clinical interviews or rating scales assessing mood and side effects at each of the visits.
Interventions
DRUGVenlafaxine ERT
Titrated to a minimum dose of 75mg. Further titration based on clinician assessment at followup visits. Intervention to continue through completion of study (180 days). Initial titration: Days 1-7: 37.5 mg; Days 7-14: 75 mg; Days 15-180: 75-300mg based on clinician assessment. Titration rate is a maximum of 75mg/7d.
DRUGFluoxetine
Titrated to a minimum dose of 20mg. Further titration based on clinician assessment at followup visits. Intervention to continue through completion of study (180 days). Initial titration: Days 1-7: 20mg; Days 7-14: 20mg; Days 15-180: 20-80mg based on clinician assessment. Titration rate is a maximum of 20mg/7d
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Intervention Group: * Right-handed, * Be able to lie still on their back for about 120 minutes, * Meet DSM-IV criteria for major depression (single or recurrent), * Have had depressive symptoms for at least 1 month prior to screen visit, * Must score an 18 or above on the Hamilton-D at both the initial screening visit and first fMRI scanning session, * Able to understand and speak English. * Control Group: same as above with the exception of no diagnosis of psychiatric disorder.
Exclusion criteria
* Any history of seizures, * Current medical disorders that might make interpretation of scan data difficult, * Diabetes requiring insulin treatment, * A serious heart disorder or subjects who have had a heart attack within the last 3 months, * Subjects who meet DSM-IV criteria for alcohol/drug abuse or dependence within the last six months, * Other current DSM-IV Axis I or Axis II diagnoses, * A personal or family history of bipolar disorder, * Current use of medication that affects central nervous system (CNS) function, * Participation in the last 30 days in a clinical study involving an investigational drug, * A subject with metallic implants, such as prostheses, shrapnel or aneurysm clip-S, or persons with electronic implants, such as cardiac pacemakers. The magnetic field generated by the MRI machine can cause a displacement or malfunctioning of these devices. * A subject who is claustrophobic, * Female subjects who are pregnant, * A subject at serious risk for suicide, * Diagnosis of cancer in the past 3 years and/or has active neoplastic disease, * Nonresponse to 2 adequate trials of antidepressant treatment, * Nonresponse to 2 adequate trials of an empirically supported psychotherapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | Study entry, 2 months, and at end of study (6 mos) | Hamilton Depression rating scale is a clinician assessment tool to measure severity of depression symptoms. Minimum score is 0 (no symptoms); maximum score is 52 (severe symptoms of depression). Hamilton Anxiety rating scale is a clinician assessment tool to measure severity of anxiety symptoms. Minimum score is 0 (no symptoms); maximum score is 56 (severe symptoms of anxiety). |
| Functional Magnetic Resonance Imaging (fMRI) Response to an Emotional Regulation Task. | At study entry, 2 months and end of study (6 months) | Depressed participants were scanned while viewing a sequence of positive and negative images; they were instructed to enhance or supress their emotional response to the image or to continue to attend. To examine brain function when regulating negative affect, we created contrast maps for each participant at all 3 time points by subtracting the attend condition from the suppress condition in response to negative stimuli. Data from all 3 scan sessions were used to assess treatment-induced change in brain activity when regulating emotion. Analyses examining change using difference scores (end vs. starting points), we subtracted initial HAMD score from final HAMD score. For fMRI analyses, in a voxelwise manner, we subtracted initial negative suppress vs attend from final negative suppress vs attend. Control subjects were not depressed, repeat scans to assess change were not completed. Reported results are from BA10, one of our areas of interest. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Currently Depressed Subjects: Venlafaxine Currently depressed subjects; Randomized medication treatment with Venlafaxine ERT
Venlafaxine ERT: Titrated to a minimum dose of 75mg. Further titration based on clinician assessment at followup visits. Intervention to continue through completion of study (180 days). Initial titration: Days 1-7: 37.5 mg; Days 7-14: 75 mg; Days 15-180: 75-300mg based on clinician assessment. Titration rate is a maximum of 75mg/7d. | 15 |
| Currently Depressed Subjects: Fluoxetine Currently depressed subjects; Randomized medication treatment with Fluoxetine
Fluoxetine: Titrated to a minimum dose of 20mg. Further titration based on clinician assessment at followup visits. Intervention to continue through completion of study (180 days). Initial titration: Days 1-7: 20mg; Days 7-14: 20mg; Days 15-180: 20-80mg based on clinician assessment. Titration rate is a maximum of 20mg/7d | 14 |
| Control (Non-psychiatric Subjects) Non-psychiatric subjects with no past or current history of depression. Subjects will receive no medication | 21 |
| Total | 50 |
Baseline characteristics
| Characteristic | Currently Depressed Subjects: Fluoxetine | Control (Non-psychiatric Subjects) | Currently Depressed Subjects: Venlafaxine | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 21 Participants | 15 Participants | 50 Participants |
| Age, Continuous | 33.14 years STANDARD_DEVIATION 10.71 | 31.31 years STANDARD_DEVIATION 14.22 | 30.74 years STANDARD_DEVIATION 11.46 | 31.65 years STANDARD_DEVIATION 12.31 |
| Region of Enrollment United States | 14 participants | 21 participants | 15 participants | 50 participants |
| Sex: Female, Male Female | 8 Participants | 13 Participants | 8 Participants | 29 Participants |
| Sex: Female, Male Male | 6 Participants | 8 Participants | 7 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 0 / 14 | 0 / 21 |
| serious Total, serious adverse events | 0 / 15 | 0 / 14 | 0 / 21 |
Outcome results
Primary
Functional Magnetic Resonance Imaging (fMRI) Response to an Emotional Regulation Task.
Depressed participants were scanned while viewing a sequence of positive and negative images; they were instructed to enhance or supress their emotional response to the image or to continue to attend. To examine brain function when regulating negative affect, we created contrast maps for each participant at all 3 time points by subtracting the attend condition from the suppress condition in response to negative stimuli. Data from all 3 scan sessions were used to assess treatment-induced change in brain activity when regulating emotion. Analyses examining change using difference scores (end vs. starting points), we subtracted initial HAMD score from final HAMD score. For fMRI analyses, in a voxelwise manner, we subtracted initial negative suppress vs attend from final negative suppress vs attend. Control subjects were not depressed, repeat scans to assess change were not completed. Reported results are from BA10, one of our areas of interest.
Time frame: At study entry, 2 months and end of study (6 months)
Population: Depressed subjects were treated with an SSRI or an SNRI, and assessed at 3 time points on an fMRI emotional response task. Differences in depression scores and changes in the fMRI responses were analyzed for changes to better understand the association between emotion regulation, depression, and treatment response.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Currently Depressed Subjects: Venlafaxine | Functional Magnetic Resonance Imaging (fMRI) Response to an Emotional Regulation Task. | -0.042666667 fMRI signal change | Standard Deviation 0.291892646 |
| Currently Depressed Subjects: Fluoxetine | Functional Magnetic Resonance Imaging (fMRI) Response to an Emotional Regulation Task. | 0.0414 fMRI signal change | Standard Deviation 0.332904397 |
Primary
Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales
Hamilton Depression rating scale is a clinician assessment tool to measure severity of depression symptoms. Minimum score is 0 (no symptoms); maximum score is 52 (severe symptoms of depression). Hamilton Anxiety rating scale is a clinician assessment tool to measure severity of anxiety symptoms. Minimum score is 0 (no symptoms); maximum score is 56 (severe symptoms of anxiety).
Time frame: Study entry, 2 months, and at end of study (6 mos)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Currently Depressed Subjects: Venlafaxine | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMD T0 | 20.07 units on a scale | Standard Deviation 1.94 |
| Currently Depressed Subjects: Venlafaxine | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMA T0 | 14.07 units on a scale | Standard Deviation 3.37 |
| Currently Depressed Subjects: Venlafaxine | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMD 2months | 8.86 units on a scale | Standard Deviation 4.5 |
| Currently Depressed Subjects: Venlafaxine | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMA 2months | 7.5 units on a scale | Standard Deviation 4.55 |
| Currently Depressed Subjects: Venlafaxine | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMD 6months | 5 units on a scale | Standard Deviation 3.67 |
| Currently Depressed Subjects: Venlafaxine | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMA 6months | 4.25 units on a scale | Standard Deviation 3.36 |
| Currently Depressed Subjects: Fluoxetine | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMA 6months | 5.89 units on a scale | Standard Deviation 3.86 |
| Currently Depressed Subjects: Fluoxetine | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMD T0 | 21.36 units on a scale | Standard Deviation 2.71 |
| Currently Depressed Subjects: Fluoxetine | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMA 2months | 8.54 units on a scale | Standard Deviation 4.86 |
| Currently Depressed Subjects: Fluoxetine | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMD 6months | 7.33 units on a scale | Standard Deviation 4.92 |
| Currently Depressed Subjects: Fluoxetine | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMA T0 | 15.57 units on a scale | Standard Deviation 3.82 |
| Currently Depressed Subjects: Fluoxetine | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMD 2months | 10.15 units on a scale | Standard Deviation 4.52 |
| Control (Non-psychiatric Subjects) | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMA T0 | NA units on a scale | — |
| Control (Non-psychiatric Subjects) | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMD 2months | 1.25 units on a scale | Standard Deviation 1.34 |
| Control (Non-psychiatric Subjects) | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMA 6months | NA units on a scale | — |
| Control (Non-psychiatric Subjects) | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMA 2months | NA units on a scale | — |
| Control (Non-psychiatric Subjects) | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMD T0 | 1 units on a scale | Standard Deviation 1.55 |
| Control (Non-psychiatric Subjects) | Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales | HAMD 6months | 1.64 units on a scale | Standard Deviation 1.22 |