Major Depressive Disorder, Post Traumatic Stress Disorder
Conditions
Brief summary
In the Investigator's ongoing studies of Posttraumatic Stress Disorder (PTSD) in older adults, it has been found that older adults with PTSD frequently meet the criteria for comorbid Major Depressive Disorder (MDD). Moreover, relative to trauma-exposed healthy controls (TEHCs), elders with PTSD manifest executive function deficits, fatigability, and mobility and physical function deficits that are consistent with what the investigator has observed in depressed older adults. Yet, the investigator has found that very few older adults with combined PTSD/MDD have received appropriate antidepressant treatment for their condition. These findings give rise to the questions of (1) how effective is antidepressant treatment for depressive symptoms in the context of PTSD/MDD and (2) are cognitive and physical function deficits in PTSD/MDD patients reversible with effective antidepressant treatment?
Detailed description
Chronic PTSD in older adults leads to increased risk of mortality from cardiovascular disease, metabolic syndrome, diabetes mellitus, and ulcerative gastrointestinal disease. PTSD appears to promote aging-associated syndromes such as frailty, and older patients with PTSD exhibit faster cognitive decline and have twice the risk of dementia compared to individuals without PTSD. In addition, laboratory studies report accelerated biological signatures of aging in PTSD patients, including shortened leukocyte telomere length, increases in pro-inflammatory cytokines, and increased oxidative stress. PTSD is associated with similar anatomical brain changes to those occurring with cognitive aging, including bilateral hippocampal volume reductions, specifically affecting the dentate gyrus (DG) and CA3 subregion, and increased microvascular lesions (white matter hyperintensities \[WMH\]). These observations suggest that the adverse health and functional outcomes associated with chronic PTSD in older patients may be explained by a deleterious interaction between pathophysiologic changes underlying PTSD and the biology of aging, the end result of which is to accelerate senescence throughout the body and particularly in the brain. However, no prior study has explicitly tested this hypothesis by examining indices of aging in older adults with and without PTSD. In our ongoing IRB #7489, The investigator hypothesize that chronic PTSD, over and above other contributing factors, accelerates biological aging in the brain and body, leading to adverse behavioral consequences such as frailty and cognitive decline. To test these hypotheses, 150 individuals are being recruited who are aged≥50and diagnosed with PTSD. A control group of 150 age-, sex-, and trauma exposure-matched subjects without PTSD are being recruited and assessed. Included subjects undergo comprehensive neuropsychological assessment and cerebral blood volume functional magnetic resonance imaging (CBV-fMRI) to assess regional hippocampal metabolic activity and function. Structural MRI is performed to quantify WMH, regional brain volume, and cortical thickness while resting-state fMRI measures functional connectivity within hippocampal networks. PTSD subjects and controls are compared on measures of aging within the following domains: neural (DG CBV, WMH, morphology), cognitive (processing speed, memory, executive function, pattern separation), somatic (peripheral inflammatory markers, leukocyte telomere length, and measures of oxidative stress), and behavioral (grip strength, gait speed, fatigue levels). By elucidating the interaction of chronic PTSD with aging processes, data from this project may contribute to the development of rationally designed, personalized, and age-appropriate novel treatments. Interim analyses of PTSD subjects in this study demonstrate a high degree of comorbidity with MDD. Among participants with PTSD enrolled to date, 67.1% meet the criteria for MDD and the mean Hamilton Rating Scale for Depression (HRSD) is 18.1. The most prominent cognitive differences observed to date in our study between PTSD and TEHC subjects is executive dysfunction, which is common in late-life depression. PTSD subjects have dramatically increased fatigability and prevalence of frailty criteria compared to TEHCs, abnormalities which are also frequently seen in our older MDD samples. Yet, the investigator has found that less than 25% of these individuals are currently receiving an adequate dose and duration of first-line pharmacotherapy for MDD, while only one-third report any past medication treatment. These data raise the question of whether patients with combined PTSD/MDD could benefit from adequate antidepressant medication treatment and to what degree their cognitive and physical function deficits would be reversible with this therapy.
Interventions
DRUGEscitalopram
The participant will be begun on either escitalopram 10mg or duloxetine 30mg. Subjects will begin escitalopram 10mg, continue this dosage for 4 weeks, then if the HRSD \>7 at Week 4, he/she will have their dosage increased to 20mg for the remainder of the 8 week study.
DRUGDuloxetine
Participants who have not responded to or not tolerated escitalopram in the current depressive episode will be started on duloxetine. They will take 30mg for the first 2 weeks, then, contingent on clinical assessment that the 30mg dose is sufficiently well tolerated, be increased to 60mg for the remaining 6 weeks of the study.
Sponsors
New York State Psychiatric Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to 105 Years
Healthy volunteers
No
Inclusion criteria
1. Individual has completed IRB 7489 2. Diagnosed with DSM 5 MDD 3. HRSD \>=18 4. Willing to and capable of providing informed consent and complying with study procedures.
Exclusion criteria
1. History of allergic or adverse reaction to 2. Non-response to adequate trial of escitalopram (at least 4 weeks at dose of 20mg) and duloxetine (at least 4 weeks at dose of 60mg)during the current episode. 3. Current treatment with psychotherapy, antidepressants, or other psychotropic medications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hamilton Rating Score for Depression (HRSD) From Baseline to Week 8 | Baseline and Week 8 | Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluating recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score above 16 is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity. The change in Hamilton Rating Score for Depression (HRSD) from baseline to week 8 was calculated as Week 8 HRSD - Baseline HRSD. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment With Escitalopram or Duloxetine Participant will be begun on either escitalopram 10mg or duloxetine 30mg. The default medication will be escitalopram. Subjects will begin escitalopram 10mg, continue this dosage for 4 weeks, then if the Hamilton Rating Score for Depression (HRSD) \>7 at Week 4, he/she will have their dosage increased to 20mg for the remainder of the 8 week study. Participants who have not responded to or not tolerated escitalopram in the current depressive episode will be started on duloxetine. They will take 30mg of duloxetine for the first 2 weeks, then, contingent on clinical assessment that the 30mg dose is sufficiently well tolerated, be increased to 60mg for the remaining 6 weeks of the study.
Escitalopram: he participant will be begun on either escitalopram 10mg or duloxetine 30mg. Subjects will begin escitalopram 10mg, continue this dosage for 4 weeks, then if the HRSD \>7 at Week 4, he/she will have their dosage increased to 20mg for the remainder of the 8 week study.
Duloxetine: Participants who have not responded to or not tolerated escitalopram in the current depressive episode will be started on duloxetine. They will take 30mg of duloxetine for the first 2 weeks, then, contingent on clinical assessment that the 30mg dose is sufficiently well tolerated, be increased to 60mg for the remaining 6 weeks of the study. | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Treatment With Escitalopram or Duloxetine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | NA years |
| Hamilton Rating Score for Depression (HRSD) | 23 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Change in Hamilton Rating Score for Depression (HRSD) From Baseline to Week 8
Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluating recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score above 16 is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity. The change in Hamilton Rating Score for Depression (HRSD) from baseline to week 8 was calculated as Week 8 HRSD - Baseline HRSD.
Time frame: Baseline and Week 8
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment With Escitalopram or Duloxetine | Change in Hamilton Rating Score for Depression (HRSD) From Baseline to Week 8 | 3 score on a scale |