Antidepressant Response in Older Adults With Comorbid PTSD and MDD

April 12, 2022 updated by: Bret Rutherford, New York State Psychiatric Institute
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?

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • New York State Psychiatric Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

60 years to 105 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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
Drug: Escitalopram
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.
Other Names:
  • lexapro
Drug: 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 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.
Other Names:
  • cymbalta

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Hamilton Rating Score for Depression (HRSD) From Baseline to Week 8
Time Frame: 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.
Baseline and Week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
New York State Psychiatric Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Bret R Rutherford, MD, New York State Psychiatric Institue

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 3, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 20, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 20, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 4, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 5, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 6, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 11, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 12, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 8111

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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