Major Depressive Disorder
Conditions
Keywords
platelet function, childhood abuse, depression, antidepressants, immune function, stress response
Brief summary
Men and women who have suffered sexual and/or physical abuse before the age of 12 are at increased risk for anxiety and mood disorders, other serious psychiatric disorders, and likely medical illnesses. What is not known is whether adult survivors of childhood adversity experience heightened negative emotions and increased physical responses due to altered norepinephrine or serotonin systems in their brains and bodies. The investigators expect to see that survivors of childhood adversity experience heightened negative emotions and increased physical responses to stress.
Interventions
DRUGEscitalopram
10 mg of Escitalopram, and titrated up to 20 mg of Escitalopram after day 22 of intervention
DRUGDesipramine
25 mg of Desipramine for day 1-3, 50 mg of Desipramine for day 4-7, 75 mg of Desipramine for day 8-14, 100 mg of Desipramine for day 15-21. Titrated between 125 mg to 200 mg of Desipramine for day 22-56 of intervention
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
\-
Exclusion criteria
* Individuals who are suicidal, psychotic, or with bipolar depression * alcohol or substance abuse or * regularly use medications which alter mood or blood vessel function (zolpidem or zalpelon, aspirin, nonsteroidal antiinflammatory drugs, sympatholytics, theophylline, central acting agonists, beta-blockers, coumadin, nitrates, triazolobenzodiazapines, or use steroids (testosterone-patch or pill form), use tryptophan or monoamine oxidase inhibitors (MAOIs), * have narrow-angle glaucoma, liver disease, * severe allergies (especially to antidepressants similar to escitalopram or desipramine) * seizures, or a serious medical disorder (e.g. hypothyroidism) that is unstable or is untreated. * Depressed patients with a prior history of severe adverse events associated with SSRIs or TCAs will not be accepted into the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response of Participants, Defined by Change in the 21-item Hamilton Depression Rating Scale (HDRS) From Baseline to Week8 | Baseline, Week 8 | Number of subjects that showed no response, partial response, and response based on scores from baseline and week 8. The 21-item HDRS measures depression severity. The scoring is sum the total of all 21 items to arrive at the total score, with a range of 0 to 60, where higher scores indicated greater severity. Nine items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Eleven items are scored from 0 - 2 (0 = absent and 2 = severe). The last item is scored on a 4-point scale of 0-3 (0 = absent and 3 = severe). The HDRS at week 8 was compared to the baseline HDRS and each participant's response was calculated using the below table: No Response = \< 25% change in Depression Rating Scale Score Partial Responder = \< 50% to \>25% change in Depression Rating Scale Score Responder = 50% or greater change in Depression Rating Scale Score |
Countries
United States
Participant flow
Recruitment details
Subjects recruited from Emory Psychiatry Clinic outpatient population
Participants by arm
| Arm | Count |
|---|---|
| Escitalopram Subjects received 10 mg of Escitalopram for 22 days and then were titrated up to 20 mg of Escitalopram after day 22 until day 56 | 21 |
| Desipramine Subjects received 25 mg of desipramine for day 1-3, 50 mg of desipramine for day 4-7, 75 mg of desipramine for day 8-14, 100 mg of desipramine for day 15-21. Subjects titrated between 125 mg to 200 mg of desipramine for day 22-56 of intervention | 19 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Protocol Violation | 2 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 4 |
Baseline characteristics
| Characteristic | Escitalopram | Desipramine | 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 | 21 Participants | 19 Participants | 40 Participants |
| Region of Enrollment United States | 21 participants | 19 participants | 40 participants |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Male | 13 Participants | 13 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 21 | 18 / 19 |
| serious Total, serious adverse events | 1 / 21 | 0 / 19 |
Outcome results
Primary
Response of Participants, Defined by Change in the 21-item Hamilton Depression Rating Scale (HDRS) From Baseline to Week8
Number of subjects that showed no response, partial response, and response based on scores from baseline and week 8. The 21-item HDRS measures depression severity. The scoring is sum the total of all 21 items to arrive at the total score, with a range of 0 to 60, where higher scores indicated greater severity. Nine items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Eleven items are scored from 0 - 2 (0 = absent and 2 = severe). The last item is scored on a 4-point scale of 0-3 (0 = absent and 3 = severe). The HDRS at week 8 was compared to the baseline HDRS and each participant's response was calculated using the below table: No Response = \< 25% change in Depression Rating Scale Score Partial Responder = \< 50% to \>25% change in Depression Rating Scale Score Responder = 50% or greater change in Depression Rating Scale Score
Time frame: Baseline, Week 8
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Escitalopram | Response of Participants, Defined by Change in the 21-item Hamilton Depression Rating Scale (HDRS) From Baseline to Week8 | Response | 5 participants |
| Escitalopram | Response of Participants, Defined by Change in the 21-item Hamilton Depression Rating Scale (HDRS) From Baseline to Week8 | No or Partial Response | 2 participants |
| Desipramine | Response of Participants, Defined by Change in the 21-item Hamilton Depression Rating Scale (HDRS) From Baseline to Week8 | Response | 9 participants |
| Desipramine | Response of Participants, Defined by Change in the 21-item Hamilton Depression Rating Scale (HDRS) From Baseline to Week8 | No or Partial Response | 4 participants |
Comparison: Chi Square test was performed comparing actual vs. expected non- and partial response or response to either escitalopram or desipramine treatment.p-value: 0.918Chi-squared