Major Depressive Disorder
Conditions
Keywords
Depression, Neuroimaging biomarkers, MDD, Neurofeedback
Brief summary
The proposed work aims to examine the neural changes associated with fast-acting antidepressant treatments in order to develop imaging-based biomarkers of treatment response for depression.
Detailed description
Over the past decade, neuroimaging tools have rapidly advanced the field of neural biomarkers of treatment response in depression. Still, despite obvious scientific progress in this field, the ability to implement neuroimaging biomarkers of antidepressant treatment response in clinical trial settings is lacking. In order to objectively assess the neural bases of treatment response in depression, the investigators will use a Real-time Neurofeedback fMRI task, specifically designed to record and modulate mood improvement by providing neurofeedback in the context of the administration of an antidepressant treatment. In a pilot study, positive neurofeedback during the administration of the drug was associated with significant acute mood improvement and increased blood oxygen level dependent (BOLD) responses in the rostral anterior cingulate cortex (rACC), a common neural target of antidepressant treatments. The central hypothesis is that antidepressant effects in depression are mediated by increased neural activity in the rACC (AIM1), which can be used in clinical trials of antidepressant treatment to predict antidepressant effects (AIM 2) and assess the effect of antidepressant treatment on antidepressant-induced rACC neural responses (AIM 3). The results obtained from this project are expected to have an important impact on our ability to understand the cognitive and neural mechanisms implicated in antidepressant treatment responses in patients with depression, as well as on the ability to implement neuroimaging biomarkers of treatment response in the clinical trial settings.
Interventions
DRUGEscitalopram
Selective Serotonin Reuptake Inhibitor (SSRI)
DRUGPlacebo
Placebo
BEHAVIORALReal-time Neurofeedback fMRI task pre- and post-RCT
Placebo experiment during an fMRI scanning session
Sponsors
Marta Peciña, MD PhD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* A man or woman age of 18 or older. * Currently experiencing a depressive episode as part of Major Depressive Disorder. * Able to tolerate lying still on your back for 60 minutes at a time. * Have had no more than one failed antidepressant trial of adequate dose and duration. * Have been antidepressant medication-free for at least 21 days prior to collection of imaging data (5 weeks for fluoxetine)
Exclusion criteria
* Are currently taking any psychiatric medication, or any potentially augmenting or sedative drugs. * Have a history of inadequate response/tolerability to escitalopram; or history of resistant depression * Pregnant or breastfeeding or plan to become pregnant over the duration of the study. * Have a history (lifetime) of psychotic depressive, schizophrenic, bipolar, schizoaffective, or other Axis I psychotic disorders. * Meet criteria for substance dependence in the last 6 months, except nicotine, or substance abuse in the last 2 months. * Have a medical condition that contradicts treatment with escitalopram. * Are currently receiving psychotherapy or any other treatment for your depression.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Scores | baseline and week 8 | The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. It was designed in 1979 by British and Swedish researchers as an adjunct to the Hamilton Rating Scale for Depression (HAMD) which would be more sensitive to the changes brought on by antidepressants and other forms of treatment than the Hamilton Scale was.\[2\] There is, however, a high degree of statistical correlation between scores on the two measures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quick Inventory of Depressive Symptomatology (QIDS) Scores | baseline and 8 weeks | The Quick Inventory of Depressive Symptomatology (QIDS) is a 16-item, self-reported measure of depression that ranges from 1 (no depression) to 27 (very severe depression). |
| Neural Responses During the Sham Neurofeedback fMRI Task. | Baseline | Voxel-wise BOLD changes during the expectancy condition of the Sham Neurofeedback fMRI task. |
Countries
United States
Participant flow
Pre-assignment details
Six participants were excluded after enrollment for the following reasons: leaving the study site without informing study team, asking for extra-time to consider the study, feeling uncomfortable in the fMRI and asking to exit the scanner, testing positive for pregnancy tests, feeling indecisive, and not responding to contact attempts.
Participants by arm
| Arm | Count |
|---|---|
| Antidepressant Treatment 20mg of escitalopram will be taken over an 8-week period, starting with 10mg for the first week.
Escitalopram: Selective Serotonin Reuptake Inhibitor (SSRI) | 25 |
| Placebo A placebo pill will be taken over an 8-week period.
Placebo: Placebo | 29 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Antidepressant Treatment | Placebo | 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 | 25 Participants | 29 Participants | 54 Participants |
| Age, Continuous | 25.44 years STANDARD_DEVIATION 6.33 | 23.45 years STANDARD_DEVIATION 5.65 | 24.18 years STANDARD_DEVIATION 5.76 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 29 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 6 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 8 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 15 Participants | 29 Participants |
| Region of Enrollment United States | 25 participants | 29 participants | 54 participants |
| Sex: Female, Male Female | 20 Participants | 26 Participants | 46 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 29 |
| other Total, other adverse events | 22 / 25 | 18 / 29 |
| serious Total, serious adverse events | 0 / 25 | 0 / 29 |
Outcome results
Primary
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Scores
The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. It was designed in 1979 by British and Swedish researchers as an adjunct to the Hamilton Rating Scale for Depression (HAMD) which would be more sensitive to the changes brought on by antidepressants and other forms of treatment than the Hamilton Scale was.\[2\] There is, however, a high degree of statistical correlation between scores on the two measures.
Time frame: baseline and week 8
Population: Scores can range from 0-60, with higher scores meaning greater the depression severity. The greater the change in MADRS scores from baseline, the better the outcome. 46 participants were analyzed, with 8 participants lost to follow up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Changes in MADRS Scores From Baseline to Week 8 Within the Antidepressant Treatment Arm | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Scores | 11 score on a scale | Standard Deviation 9 |
| Changes in MADRS Scores From Baseline to Week 8 Within the Placebo Arm | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Scores | 12 score on a scale | Standard Deviation 9 |
p-value: 0.58Regression, Linear
p-value: 0.05Correlation
Secondary
Change in Quick Inventory of Depressive Symptomatology (QIDS) Scores
The Quick Inventory of Depressive Symptomatology (QIDS) is a 16-item, self-reported measure of depression that ranges from 1 (no depression) to 27 (very severe depression).
Time frame: baseline and 8 weeks
Population: Scores can range from 0-27, with higher scores meaning greater the depression severity. The greater the change in QIDS scores from baseline to week 8, the better the outcome. 46 participants were analyzed, with 8 participants lost to follow up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Changes in MADRS Scores From Baseline to Week 8 Within the Antidepressant Treatment Arm | Change in Quick Inventory of Depressive Symptomatology (QIDS) Scores | 6.82 score on a scale | Standard Deviation 6.01 |
| Changes in MADRS Scores From Baseline to Week 8 Within the Placebo Arm | Change in Quick Inventory of Depressive Symptomatology (QIDS) Scores | 5.54 score on a scale | Standard Deviation 5.45 |
p-value: 0.8Regression, Linear
Secondary
Neural Responses During the Sham Neurofeedback fMRI Task.
Voxel-wise BOLD changes during the expectancy condition of the Sham Neurofeedback fMRI task.
Time frame: Baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Changes in MADRS Scores From Baseline to Week 8 Within the Antidepressant Treatment Arm | Neural Responses During the Sham Neurofeedback fMRI Task. | 1.1 BOLD signal change |
Comparison: At the group-level, a random-effects analysis determines the main effects of the regressors of interest (e.g., high vs. low expectancy) resulting in statistical parametric maps (t or F statistics). To control for potential confounders, sex and depression severity will be entered as covariates in statistical models.p-value: <0.05t-test, 2 sided