Depression
Conditions
Keywords
Major depressive disorder, MDD, Antidepressant
Brief summary
This study will use measurements of depression symptoms and brain activity to determine what factors may influence an individual's response to treatment for depression.
Detailed description
We are using depression symptom measurements and measurements of brain electrical activity (EEG) to determine what factors may influence whether a patient is likely to show a response to antidepressant medication, placebo, or only clinical visits (without the use of pills) during a treatment trial for depression.
Interventions
DRUGVenlafaxine (Effexor), Duloxetine (Cymbalta), Escitalopram (Lexapro)
Subjects assigned to the placebo (PBO) or medication (MED) condition will enter double-blind treatment with either venlafaxine XR, duloxetine, escitalopram, or placebo after lead-in. They will undergo the same schedule, structure, and intensity of visits as in the ICI condition, but also will be randomized to receive treatment with a pill. Subjects randomized to medication will be started on one tablet each morning of either venlafaxine XR 75 mg., duloxetine 30 mg., or escitalopram 10 mg. Dosages will be increased in a double-blinded manner by increasing the number of pills administered by one pill every three to five days until the final dose is achieved (225 mg., 90 mg., and 30 mg. respectively for venlafaxine XR, duloxetine, and escitalopram). In order to maintain blinding during dosage increase, the number of tablets of placebo will be increased every three to five days as well.
OTHERPlacebo
Subjects assigned to the placebo (PBO) or medication (MED) condition will enter double-blind treatment with either venlafaxine XR, duloxetine, escitalopram, or placebo after lead-in. They will undergo the same schedule, structure, and intensity of visits as in the ICI condition, but also will be randomized to receive treatment with a pill. Subjects randomized to medication will be started on one tablet each morning of either venlafaxine XR 75 mg., duloxetine 30 mg., or escitalopram 10 mg. Dosages will be increased in a double-blinded manner by increasing the number of pills administered by one pill every three to five days until the final dose is achieved (225 mg., 90 mg., and 30 mg. respectively for venlafaxine XR, duloxetine, and escitalopram). In order to maintain blinding during dosage increase, the number of tablets of placebo will be increased every three to five days as well.
BEHAVIORALInterpersonal Clinical Interaction (ICI)
Interaction with and assessment by clinical research personnel on a fixed schedule, with the pharmacotherapeutic alliance assessed both by research personnel and subjects.
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
Eli Lilly and Company
Wyeth is now a wholly owned subsidiary of Pfizer
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of unipolar major depression
Exclusion criteria
* Substance abuse * Psychotic disorder * History of severe head trauma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response as Assessed by Participants' Change in Depression Rating | Baseline, Week 8 | Comparison of treatment arms (Medication + ICI, Placebo+ICI, and ICI only). The Hamilton Depression Rating Scale (HAM-D-17) used here is a 17-item scale that measures severity of depression. Items are individually scored from 0-4 or from 0-2 depending on the item, and the individual scores for each item are added to comprise one score. Higher scores indicate greater severity of depression. Possible scores on the scale range from a minimum of zero (0) to a maximum of 52.Response is defined as a 50% decrease in HAMD-17 scoring. Remission defined as a HAMD-17 score of 7 or less. |
| Average Change in 3 Weeks of Participant Treatment Expectations | Averaged over 3 time points (Baseline, randomization, and end of lead-in) | Patient Attitudes and Expectations Form used for assessing expectation. The California Pharmacotherapy Alliance Scale, a measure associated with outcomes of antidepressant pharmacotherapy, used to measure participants' perceptions of: (a) participants' commitment to treatment; (b) participants' working capacity; (c) treatment providers' understanding and involvement; and (d) goal and working strategy consensus between participant and treatment provider. This is a 24-item questionnaire with a 7-point Likert scale (1 = not at all, 7 = very much so). Total score ranges from a minimum of 0 and a maximum of 120. The score is determined by a combination of negative and positive items. To assure negative items are reflected, subtract each of the negative item ratings from 8; for example, a rating of 1 becomes 7 (8 minus 1). The scores are computed by summing the items and dividing the total by 6 to procure the mean rating. A lower score indicates a worse outcome. |
| Change in Hamilton Depression Assessment Score | Baseline,Week 8 | Comparison of treatment arms (Medication + ICI, Placebo+ICI, and ICI only). The Hamilton Depression Rating Scale used here is a 17-item scale that measures severity of depression. Items are individually scored from 0-4 or from 0-2 depending on the item, and the individual scores for each item are added to comprise one score. Higher scores indicate greater severity of depression/worse outcome. Possible scores on the scale range from a minimum of zero (0) to a maximum of 52. |
Countries
United States
Participant flow
Recruitment details
133 subjects were screened for eligibility and 88 were eligible for enrollment between 8/19/05 - 8/7/08 at the UCLA Laboratory of Brain, Behavior, and Pharmacology. 88 participants were randomized however, n=67 for many of the measures as subjects who did not complete the Week 8 visit were not included in the analysis.
Pre-assignment details
Subjects were required to wash out of any other antidepressant medications for one week (30 days if washing out from fluoxetine).
Participants by arm
| Arm | Count |
|---|---|
| Medication Treatment (MED) MED 1-venlafaxine XR, MED 2-Duloxetine (Cymbalta), MED 3-Escitalopram (Lexapro) | 39 |
| Placebo | 29 |
| Interpersonal Clinical Interaction Subjects assigned to the interpersonal clinical interaction (ICI). Visits involve a session with a research nurse that will be approximately 20 minutes in length; visits at baseline, end of lead-in, and 1, 2, 4, and 8 weeks also will include a brief (5-10 minutes) meeting with a physician. | 20 |
| Total | 88 |
Baseline characteristics
| Characteristic | Medication Treatment (MED) | Interpersonal Clinical Interaction | Placebo | 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 | 39 Participants | 20 Participants | 29 Participants | 88 Participants |
| Age, Continuous | 41.67 years STANDARD_DEVIATION 13.63 | 43.1 years STANDARD_DEVIATION 12.7 | 41.75 years STANDARD_DEVIATION 14.35 | 41.96 years STANDARD_DEVIATION 13.74 |
| Region of Enrollment United States | 29 participants | 12 participants | 26 participants | 67 participants |
| Sex: Female, Male Female | 25 Participants | 12 Participants | 18 Participants | 55 Participants |
| Sex: Female, Male Male | 14 Participants | 8 Participants | 11 Participants | 33 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 / 29 | 0 / 26 | 0 / 12 |
| serious Total, serious adverse events | 0 / 39 | 0 / 29 | 0 / 20 |
Outcome results
Primary
Average Change in 3 Weeks of Participant Treatment Expectations
Patient Attitudes and Expectations Form used for assessing expectation. The California Pharmacotherapy Alliance Scale, a measure associated with outcomes of antidepressant pharmacotherapy, used to measure participants' perceptions of: (a) participants' commitment to treatment; (b) participants' working capacity; (c) treatment providers' understanding and involvement; and (d) goal and working strategy consensus between participant and treatment provider. This is a 24-item questionnaire with a 7-point Likert scale (1 = not at all, 7 = very much so). Total score ranges from a minimum of 0 and a maximum of 120. The score is determined by a combination of negative and positive items. To assure negative items are reflected, subtract each of the negative item ratings from 8; for example, a rating of 1 becomes 7 (8 minus 1). The scores are computed by summing the items and dividing the total by 6 to procure the mean rating. A lower score indicates a worse outcome.
Time frame: Averaged over 3 time points (Baseline, randomization, and end of lead-in)
Population: 88 participants who completed the first 3 time points in the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDICATIONS | Average Change in 3 Weeks of Participant Treatment Expectations | 3.55 units on a scale | Standard Deviation 0.78 |
| Placebo (PBO) | Average Change in 3 Weeks of Participant Treatment Expectations | 3.94 units on a scale | Standard Deviation 0.61 |
| Interpersonal Clinical Interaction (ICI) | Average Change in 3 Weeks of Participant Treatment Expectations | 3.17 units on a scale | Standard Deviation 1.16 |
Primary
Change in Hamilton Depression Assessment Score
Comparison of treatment arms (Medication + ICI, Placebo+ICI, and ICI only). The Hamilton Depression Rating Scale used here is a 17-item scale that measures severity of depression. Items are individually scored from 0-4 or from 0-2 depending on the item, and the individual scores for each item are added to comprise one score. Higher scores indicate greater severity of depression/worse outcome. Possible scores on the scale range from a minimum of zero (0) to a maximum of 52.
Time frame: Baseline,Week 8
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MEDICATIONS | Change in Hamilton Depression Assessment Score | Percent Change in HAM-D | -0.46 HAMD score | Standard Deviation 0.31 |
| MEDICATIONS | Change in Hamilton Depression Assessment Score | Change in HAM-D | -10.05 HAMD score | Standard Deviation 6.6 |
| Placebo (PBO) | Change in Hamilton Depression Assessment Score | Percent Change in HAM-D | -0.36 HAMD score | Standard Deviation 0.39 |
| Placebo (PBO) | Change in Hamilton Depression Assessment Score | Change in HAM-D | -7.59 HAMD score | Standard Deviation 7.98 |
| Interpersonal Clinical Interaction (ICI) | Change in Hamilton Depression Assessment Score | Percent Change in HAM-D | -0.05 HAMD score | Standard Deviation 0.27 |
| Interpersonal Clinical Interaction (ICI) | Change in Hamilton Depression Assessment Score | Change in HAM-D | -1.37 HAMD score | Standard Deviation 5.27 |
Primary
Response as Assessed by Participants' Change in Depression Rating
Comparison of treatment arms (Medication + ICI, Placebo+ICI, and ICI only). The Hamilton Depression Rating Scale (HAM-D-17) used here is a 17-item scale that measures severity of depression. Items are individually scored from 0-4 or from 0-2 depending on the item, and the individual scores for each item are added to comprise one score. Higher scores indicate greater severity of depression. Possible scores on the scale range from a minimum of zero (0) to a maximum of 52.Response is defined as a 50% decrease in HAMD-17 scoring. Remission defined as a HAMD-17 score of 7 or less.
Time frame: Baseline, Week 8
Population: Participants completing the Week 8 visit were included in the analysis (n=67)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDICATIONS | Response as Assessed by Participants' Change in Depression Rating | Responders | 17 Participants |
| MEDICATIONS | Response as Assessed by Participants' Change in Depression Rating | Remitters | 9 Participants |
| Placebo (PBO) | Response as Assessed by Participants' Change in Depression Rating | Responders | 11 Participants |
| Placebo (PBO) | Response as Assessed by Participants' Change in Depression Rating | Remitters | 9 Participants |
| Interpersonal Clinical Interaction (ICI) | Response as Assessed by Participants' Change in Depression Rating | Responders | 1 Participants |
| Interpersonal Clinical Interaction (ICI) | Response as Assessed by Participants' Change in Depression Rating | Remitters | 0 Participants |