Major Depressive Disorder
Conditions
Keywords
Late Life Depression, Psychotherapy, Mechanisms of Action, Positive Valence System, Social Reward
Brief summary
Abnormalities in the Positive Valence System (PVS) are associated with depressive symptoms and reduced behavioral activation in mid- and late-life. This study will investigate the engagement of the PVS during exposure to social rewards, part of a novel streamlined psychotherapy for mid- and late-life depression. Use of computational modeling will enable identification of neuroimaging and behavioral profiles associated with greater treatment response, and may guide future personalization of psychotherapy.
Interventions
BEHAVIORALEngage & Connect Psychotherapy
9-weeks of weekly psychotherapy sessions focused on social reward exposure
BEHAVIORALSymptom Review and Psychoeducation (SRP)
9-weeks of weekly psychotherapy sessions focused on symptom review and psychoeducation about depression and aging
Sponsors
National Institute of Mental Health (NIMH)
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
This is a randomized controlled trial. Participants will be randomly assigned to 9-weeks of either Engage-S Psychotherapy or Symptom Review and Psychoeducation (SRP) Psychotherapy
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Ages aged 50-85 \[stratified so that 50% are older than 65\] 2. Diagnosis of unipolar major depressive disorder without psychotic features, determined by the SCID 3. Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥ 20. 4. Mini Mental Status Exam (MMSE) ≤ 1 SD below the mean score for patient's age and education 5. Off antidepressants or on a stable dose of an antidepressant for 8 weeks and do not intend to change the dose in the next 10 weeks. 6. Capacity to provide written consent for research assessment and treatment.
Exclusion criteria
1. Intent or plan to attempt suicide in the near future. 2. History or presence of psychiatric diagnoses other than major depressive disorder without psychotic features, generalized anxiety disorder, or specific phobia. 3. Use of psychotropic drugs or cholinesterase inhibitors other than use of ≤ 0.5 mg of lorazepam daily up to seven times per week. 4. Neurological disorders (dementias, history of stroke, multiple sclerosis, Parkinson's disease, epilepsy, etc.); cardiac, renal, or respiratory failure; severe chronic obstructive pulmonary disease; metastatic cancer; or debilitated states or less common medical illnesses that may either influence brain systems of interest or ability to participate in the study. Dr. Alexopoulos or another research psychiatrist will review any medical illnesses that does not appear in the list above and determine whether it interferes with the study of positive valence system functions in depression. 5. Contraindications to MRI scanning including cardiac pacemaker, heart valve replacement, vascular stent, insulin pump, cochlear implant, any other metallic biomedical implant contraindicating to MRI, and claustrophobia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Resting State fMRI Connectivity of the Positive Valence System | Baseline, Mid-treatment (Week 5) and Post Treatment (Week 9) | Calculated from fMRI scan. Validation of target engagement (resting state functional connectivity (rsFC) within the right hemisphere orbital prefrontal cortex (OFC), specifically between the lateral and medial regions of the OFC). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montgomery Asberg Depression Rating Scale (MADRS) | Baseline, Mid-treatment (Week 5) and Post Treatment (Week 9) | 10-item Clinician rated measure of depression severity. Scores range from 0 (no depression) to 60 (severe depression). |
| Change in Behavioral Activation for Depression Scale (BADS) | Baseline, Mid-treatment (Week 5) and Post Treatment (Week 9) | 25-item measure self-report measure of behavioral activation. Scores range from 0 (very low behavioral activation) to 150 (high behavioral activation). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Engage & Connect Psychotherapy Engage & Connect, a modified adapted version of Engage. Its principal intervention is social reward exposure - facilitating engagement in rewarding and meaningful social activities with significant others. In Engage-S therapy, individuals with depression work with a therapist to develop action plans to pursue rewarding social activities of their choice.
Engage & Connect Psychotherapy: 9-weeks of weekly psychotherapy sessions focused on social reward exposure | 31 |
| Symptom Review and Psychoeducation (SRP) In this intervention, the therapist will review the participant's symptoms and provide literature-based clinical explanations and clarifications about the symptoms, the course, and the causes of depression. In SRP, the therapist reviews the depressed individual's symptoms, and level of information on depression, identifies misconceptions, and guides selection of educational material which could benefit the patient.
Symptom Review and Psychoeducation (SRP): 9-weeks of weekly psychotherapy sessions focused on symptom review and psychoeducation about depression and aging | 33 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Engage & Connect Psychotherapy | Symptom Review and Psychoeducation (SRP) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 15 Participants | 27 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 18 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 31 Participants | 57 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 | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 27 Participants | 26 Participants | 53 Participants |
| Region of Enrollment United States | 31 Participants | 33 Participants | 64 Participants |
| Sex: Female, Male Female | 25 Participants | 25 Participants | 50 Participants |
| Sex: Female, Male Male | 6 Participants | 8 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 33 |
| other Total, other adverse events | 7 / 31 | 4 / 33 |
| serious Total, serious adverse events | 0 / 31 | 0 / 33 |
Outcome results
Primary
Change in Resting State fMRI Connectivity of the Positive Valence System
Calculated from fMRI scan. Validation of target engagement (resting state functional connectivity (rsFC) within the right hemisphere orbital prefrontal cortex (OFC), specifically between the lateral and medial regions of the OFC).
Time frame: Baseline, Mid-treatment (Week 5) and Post Treatment (Week 9)
Population: Participants were excluded from analysis in the event no data were collected at baseline due to participant withdrawal, if the participants were clinically excluded during the study, technical issues with MRI data, or lost to follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Engage & Connect Psychotherapy | Change in Resting State fMRI Connectivity of the Positive Valence System | Baseline | 0.18 rsFC correlation coefficient | Standard Error 0.03 |
| Engage & Connect Psychotherapy | Change in Resting State fMRI Connectivity of the Positive Valence System | Week 5 | 0.24 rsFC correlation coefficient | Standard Error 0.02 |
| Engage & Connect Psychotherapy | Change in Resting State fMRI Connectivity of the Positive Valence System | Week 9 | 0.25 rsFC correlation coefficient | Standard Error 0.03 |
| Symptom Review and Psychoeducation (SRP) | Change in Resting State fMRI Connectivity of the Positive Valence System | Baseline | 0.18 rsFC correlation coefficient | Standard Error 0.02 |
| Symptom Review and Psychoeducation (SRP) | Change in Resting State fMRI Connectivity of the Positive Valence System | Week 5 | 0.29 rsFC correlation coefficient | Standard Error 0.02 |
| Symptom Review and Psychoeducation (SRP) | Change in Resting State fMRI Connectivity of the Positive Valence System | Week 9 | 0.24 rsFC correlation coefficient | Standard Error 0.03 |
Comparison: Functional connectivity within the orbital prefrontal cortex (OFC; specifically between lateral and medial OFC), significantly changed over time.p-value: 0.6249Mixed Models Analysis
Secondary
Change in Behavioral Activation for Depression Scale (BADS)
25-item measure self-report measure of behavioral activation. Scores range from 0 (very low behavioral activation) to 150 (high behavioral activation).
Time frame: Baseline, Mid-treatment (Week 5) and Post Treatment (Week 9)
Population: Participants were excluded from analysis in the event no data were collected at baseline due to participant withdrawal, if the participants were clinically excluded during the study, lost to follow-up, or did not complete the BADS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Engage & Connect Psychotherapy | Change in Behavioral Activation for Depression Scale (BADS) | Baseline | 71.24 score on a scale | Standard Deviation 21.36 |
| Engage & Connect Psychotherapy | Change in Behavioral Activation for Depression Scale (BADS) | Mid-treatment (Week 5) | 95.21 score on a scale | Standard Deviation 28.84 |
| Engage & Connect Psychotherapy | Change in Behavioral Activation for Depression Scale (BADS) | Post Treatment (Week 9) | 98.00 score on a scale | Standard Deviation 30.54 |
| Symptom Review and Psychoeducation (SRP) | Change in Behavioral Activation for Depression Scale (BADS) | Baseline | 70.00 score on a scale | Standard Deviation 18.4 |
| Symptom Review and Psychoeducation (SRP) | Change in Behavioral Activation for Depression Scale (BADS) | Mid-treatment (Week 5) | 88.21 score on a scale | Standard Deviation 20.73 |
| Symptom Review and Psychoeducation (SRP) | Change in Behavioral Activation for Depression Scale (BADS) | Post Treatment (Week 9) | 93.86 score on a scale | Standard Deviation 25.28 |
Comparison: Mixed effects model with a fixed effect for treatment and time, as well as time by treatment interaction, and a random effect for subject level.~F value for time by treatment interaction.p-value: 0.844Mixed Models Analysis
Secondary
Change in Montgomery Asberg Depression Rating Scale (MADRS)
10-item Clinician rated measure of depression severity. Scores range from 0 (no depression) to 60 (severe depression).
Time frame: Baseline, Mid-treatment (Week 5) and Post Treatment (Week 9)
Population: Participants were excluded from analysis in the event no data were collected at baseline due to participant withdrawal, if the participants were clinically excluded during the study, or lost to follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Engage & Connect Psychotherapy | Change in Montgomery Asberg Depression Rating Scale (MADRS) | Baseline | 23.66 score on a scale | Standard Deviation 4.62 |
| Engage & Connect Psychotherapy | Change in Montgomery Asberg Depression Rating Scale (MADRS) | Mid-treatment (Week 5) | 13.82 score on a scale | Standard Deviation 7.56 |
| Engage & Connect Psychotherapy | Change in Montgomery Asberg Depression Rating Scale (MADRS) | Post Treatment (Week 9) | 11.86 score on a scale | Standard Deviation 8.97 |
| Symptom Review and Psychoeducation (SRP) | Change in Montgomery Asberg Depression Rating Scale (MADRS) | Baseline | 24.81 score on a scale | Standard Deviation 3.39 |
| Symptom Review and Psychoeducation (SRP) | Change in Montgomery Asberg Depression Rating Scale (MADRS) | Mid-treatment (Week 5) | 18.62 score on a scale | Standard Deviation 7.03 |
| Symptom Review and Psychoeducation (SRP) | Change in Montgomery Asberg Depression Rating Scale (MADRS) | Post Treatment (Week 9) | 14.66 score on a scale | Standard Deviation 8.89 |
Comparison: Mixed effects model with a fixed effect for treatment and time, as well as time by treatment interaction, and a random effect for subject level.~F value for time by treatment interaction.p-value: 0.525Mixed Models Analysis