Major Depressive Disorder
Conditions
Keywords
depression, major depressive disorder, mental health, mood disorder, geriatric, late-life
Brief summary
The goal of this study is to learn about changes in the brain that occur during Engage, a psychotherapy for depression in older adults, and how they may differ from changes that occur during supportive therapy. Older adults with depression will receive 9 weeks of either Engage or supportive therapy and will complete research assessments before the therapy begins and at weeks 3, 6, and 9 of treatment. Research assessments will include questionnaires, computer tasks, and recordings of electrical brain activity (also called electroencephalography or EEG).
Detailed description
Late-life depression is prevalent and devastating, and response rates to even the most effective treatments are low. Outcomes may be improved by developing targeted interventions such as Engage - a new, easily disseminated, neurobiologically informed psychotherapy for late-life depression designed to restore impaired function of neural reward systems. This study will use event-related potentials and a panel of other reward system measures to assess target engagement in depressed older adults receiving Engage therapy, with a comparison group of depressed peers receiving supportive therapy. Participants will be randomly assigned to either Engage or supportive therapy and will complete research assessments at baseline and weeks 3, 6, and 9 (end of treatment).
Interventions
BEHAVIORALEngage Therapy
Engage therapy is designed to help individuals with depression become involved in activities they previously enjoyed but have not been participating in since developing depression. In Engage therapy, individuals with depression work with a therapist to develop action plans to pursue rewarding activities of their choice.
BEHAVIORALSupportive Therapy
Supportive therapy is designed to provide a warm and supportive environment in which individuals with depression can feel comfortable expressing their thoughts and feelings. In supportive therapy, therapists help patients identify themes in their thinking, provide reassurance, emphasize coping skills, and provide guidance as needed.
Sponsors
National Institute of Mental Health (NIMH)
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age greater than or equal to 60 years. * Diagnosis of unipolar major depressive disorder without psychotic features, determined by Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (SCID). * Montgomery-Asberg Depression Rating Scale (MADRS) score greater than or equal to 20. * Mini Mental State Exam (MMSE) score greater than or equal to 24. * Off antidepressants or on a stable dose of an antidepressant for 12 weeks and no intent to change the dose in the next 10 weeks. * Capacity to provide written consent for both research assessment and treatment.
Exclusion criteria
* Intent or plan to attempt suicide in the near future. * Presence of current psychiatric diagnoses other than major depressive disorder without psychotic features, generalized anxiety disorder, or specific phobia. * History of past psychiatric diagnoses other than major depressive disorder without psychotic features or anxiety disorders (separation anxiety disorder, specific phobia, social phobia, panic disorder, agoraphobia, or generalized anxiety disorder). * Use of psychotropic drugs or cholinesterase inhibitors other than use of less than or equal to 0.5 mg of lorazepam daily up to five times per week. * 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 neural systems of interest or ability to participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Late Positive Potential to Rewarding Stimuli | Change from baseline to week 9 | The late positive potential (LPP) is an electroencephalographic (EEG)-derived measure of emotional engagement with positively valanced images. |
| Change in the Reward Positivity | Change from baseline to week 9 | The reward positivity (RewP) is an electroencephalographic (EEG)-derived response to rewarding feedback from a guessing task. |
| Change in P1 | Change from baseline to week 9 | The P1 is an electroencephalographic (EEG)-derived measure of early visual attention that is elicited by visual stimuli. |
| Change in Behavioral Activation | Change from baseline to week 9 | Behavioral activation will be measured using the Behavioral Activation for Depression Scale (BADS), a 25-item measure of behaviors targeted in behavioral activation therapies such as Engage. Scores range from 0 to 150, where higher scores on this measure indicate more participation in activities and social interactions, and lower scores indicate more social isolation, rumination, and avoidance of activities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Anhedonia | Change from baseline to week 9 | Anhedonia will be measured by the clinician-rated Snaith-Hamilton Pleasure Scale (SHAPS-C). The SHAPS-C measures pleasure and enjoyment experienced in response to a variety of situations. Scores range from 14 to 56, where higher scores indicate greater severity of anhedonia and lower scores indicate lower severity of anhedonia. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited through community referrals, physical ads posted in locations frequented by older adults, a depression screening hotline maintained by the Weill Cornell Institute of Geriatric Psychiatry, and via ads posted on social media. The first participant was enrolled on 3/14/2019, and the last participant was enrolled on 9/26/2023.
Participants by arm
| Arm | Count |
|---|---|
| Engage Therapy Participants receive Engage therapy for 9 weeks.
Engage Therapy: Engage therapy is designed to help individuals with depression become involved in activities they previously enjoyed but have not been participating in since developing depression. In Engage therapy, individuals with depression work with a therapist to develop action plans to pursue rewarding activities of their choice. | 32 |
| Supportive Therapy Participants receive supportive therapy for 9 weeks.
Supportive Therapy: Supportive therapy is designed to provide a warm and supportive environment in which individuals with depression can feel comfortable expressing their thoughts and feelings. In supportive therapy, therapists help patients identify themes in their thinking, provide reassurance, emphasize coping skills, and provide guidance as needed. | 33 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Engage Therapy | Supportive Therapy | Total |
|---|---|---|---|
| Age, Continuous | 67.79 years STANDARD_DEVIATION 6.34 | 72.75 years STANDARD_DEVIATION 7.64 | 70.31 years STANDARD_DEVIATION 7.41 |
| Anhedonia | 30.30 units on a scale STANDARD_DEVIATION 6.91 | 32.31 units on a scale STANDARD_DEVIATION 6.35 | 31.34 units on a scale STANDARD_DEVIATION 6.65 |
| Behavioral Activation | 82.72 units on a scale STANDARD_DEVIATION 21.52 | 77.75 units on a scale STANDARD_DEVIATION 15.77 | 80.11 units on a scale STANDARD_DEVIATION 18.73 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 33 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Late Positive Potential | 4.84 microvolts STANDARD_DEVIATION 3.13 | 6.78 microvolts STANDARD_DEVIATION 4.87 | 5.86 microvolts STANDARD_DEVIATION 4.22 |
| P1 | 1.92 microvolts STANDARD_DEVIATION 3.8 | 2.41 microvolts STANDARD_DEVIATION 3.09 | 2.18 microvolts STANDARD_DEVIATION 3.42 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 27 Participants | 29 Participants | 56 Participants |
| Region of Enrollment United States | 32 Participants | 33 Participants | 65 Participants |
| Reward Positivity | 2.15 microvolts STANDARD_DEVIATION 2.37 | 2.26 microvolts STANDARD_DEVIATION 3.8 | 2.21 microvolts STANDARD_DEVIATION 3.15 |
| Sex: Female, Male Female | 25 Participants | 24 Participants | 49 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 33 |
| other Total, other adverse events | 1 / 32 | 7 / 33 |
| serious Total, serious adverse events | 0 / 32 | 0 / 33 |
Outcome results
Primary
Change in Behavioral Activation
Behavioral activation will be measured using the Behavioral Activation for Depression Scale (BADS), a 25-item measure of behaviors targeted in behavioral activation therapies such as Engage. Scores range from 0 to 150, where higher scores on this measure indicate more participation in activities and social interactions, and lower scores indicate more social isolation, rumination, and avoidance of activities.
Time frame: Change from baseline to week 9
Population: Two participants dropped out before baseline and some data points are missing due to poor data quality or missed study assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Engage Therapy | Change in Behavioral Activation | 12.88 units on a scale | Standard Deviation 14.64 |
| Supportive Therapy | Change in Behavioral Activation | 18.93 units on a scale | Standard Deviation 23.51 |
p-value: 0.39Mixed Models Analysis
Primary
Change in Late Positive Potential to Rewarding Stimuli
The late positive potential (LPP) is an electroencephalographic (EEG)-derived measure of emotional engagement with positively valanced images.
Time frame: Change from baseline to week 9
Population: Two participants dropped out before baseline and some data points are missing due to poor data quality or missed study assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Engage Therapy | Change in Late Positive Potential to Rewarding Stimuli | 0.80 microvolts | Standard Deviation 3.24 |
| Supportive Therapy | Change in Late Positive Potential to Rewarding Stimuli | 0.07 microvolts | Standard Deviation 3.25 |
p-value: 0.08Mixed Models Analysis
p-value: 0.14Mixed Models Analysis
Primary
Change in P1
The P1 is an electroencephalographic (EEG)-derived measure of early visual attention that is elicited by visual stimuli.
Time frame: Change from baseline to week 9
Population: Two participants dropped out before baseline and some data points are missing due to poor data quality or missed study assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Engage Therapy | Change in P1 | -0.24 microvolts | Standard Deviation 1.39 |
| Supportive Therapy | Change in P1 | 0.43 microvolts | Standard Deviation 1.61 |
p-value: 0.69Mixed Models Analysis
Primary
Change in the Reward Positivity
The reward positivity (RewP) is an electroencephalographic (EEG)-derived response to rewarding feedback from a guessing task.
Time frame: Change from baseline to week 9
Population: Two participants dropped out before baseline and some data points are missing due to poor data quality or missed study assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Engage Therapy | Change in the Reward Positivity | -0.46 microvolts | Standard Deviation 3.66 |
| Supportive Therapy | Change in the Reward Positivity | -0.60 microvolts | Standard Deviation 4.85 |
p-value: 0.69Mixed Models Analysis
Secondary
Change in Anhedonia
Anhedonia will be measured by the clinician-rated Snaith-Hamilton Pleasure Scale (SHAPS-C). The SHAPS-C measures pleasure and enjoyment experienced in response to a variety of situations. Scores range from 14 to 56, where higher scores indicate greater severity of anhedonia and lower scores indicate lower severity of anhedonia.
Time frame: Change from baseline to week 9
Population: Two participants dropped out before baseline and some data points are missing due to poor data quality or missed study assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Engage Therapy | Change in Anhedonia | -3.37 units on a scale | Standard Deviation 5.96 |
| Supportive Therapy | Change in Anhedonia | -2.07 units on a scale | Standard Deviation 6.13 |
p-value: 0.58Mixed Models Analysis
p-value: 0.96Mixed Models Analysis