RCT of Neurocognitive and Neuroimaging Biomarkers: Predicting Progression Towards Dementia in Patients With Treatment-resistant Late-life Depression (OPTIMUM-Neuro RCT)
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Enrollment
- 87
- Locations
- 4
- Primary Endpoint
- Change in Psychological Well-Being
Study Overview
Brief Summary
The purpose of this study is to assess which antidepressants work the best in older adults who have treatment-resistant depression (TRD), and to test whether treatment-resistant late life depression is associated with declines in memory and attention and brain structure and function.
Detailed Description
Older adult participants with treatment-resistant depression will be randomly assigned to a Step 1 medication strategy.
- Adding aripiprazole to current antidepressant medication
- Adding bupropion to current antideprssant medication
- Replacing current antidepressant medication with bupropion
If depression is not relieved at the end of 10 weeks, or if participants do not qualify for Step 1, participants will be randomly assigned to a Step 2 medication strategy:
- Adding lithium to current antidepressant medication
- Replacing current antidepressant medication with nortriptyline
All medication strategies will be offered in collaboration with participants' own physicians with the the research team providing support and guidance.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 60 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Men and women aged 60 and older, with approximately equal proportions aged 60-70 and 70+.
- •Current Major Depressive Disorder (MDD), single or recurrent, as diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria.
- •Failure to respond adequately to two or more antidepressant treatment trials of recommended dose and length (approximately 12 weeks).
- •PHQ-9 score of 10 or higher.
Exclusion Criteria
- •Dementia; patients screened out due to possible dementia will be referred to a local Memory Clinic or back to their clinician for evaluation to clarify the presence or absence of dementia.
- •Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms.
- •High risk for suicide (e.g. active Suicidal ideations (SI) and or current/recent intent or plan)). Urgent psychiatric referral will be made in these cases.
- •Non-correctable, clinically significant sensory impairment (e.g., cannot hear well enough to cooperate with interview).
- •Unstable medical illness, including delirium, uncontrolled diabetes mellitus, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management.
- •Moderate to severe substance or alcohol use disorder, as determined by study physician.
- •Seizure disorder.
- •Parkinson's Disease
Arms & Interventions
Aripiprazole Augmentation
Augment current antidepressant treatment with aripiprazole (tablets), titrated from 2-15 mg daily based on symptom severity and side effects.
Intervention: Aripiprazole Augmentation (Drug)
Bupropion Augmentation
Augment current antidepressant treatment with bupropion once-daily extended release, titrated from 150-300 mg daily based on symptom severity and side effects.
Intervention: Bupropion Augmentation (Drug)
Switch to Bupropion
Taper from current antidepressant therapy. Start bupropion once-daily extended, titrated from 150-300 mg daily based on symptom severity and side effects.
Intervention: Switch to bupropion (Drug)
Lithium Augmentation
Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 mEq/L (milliequivalents/liter).
Intervention: Lithium Augmentation (Drug)
Switch to Nortriptyline
Taper from current antidepressant therapy. Start on nortriptyline tablets starting at 1 mg per kg of body weight daily, titrated per blood level to 80-120 ng/ml.
Intervention: Switch to nortriptyline (Drug)
Outcomes
Primary Outcomes
Change in Psychological Well-Being
Time Frame: Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks
Psychological well-being was assessed using the NIH Toolbox Psychological Wellbeing subscales of Positive Affect and General Life Satisfaction, with a T score calculated as the average of these two subscales. Higher scores indicate greater positive affect and life satisfaction. Reference T-score (mean=50, Standard Deviation (SD)=10.
Assessing the change in the Number of Participants With Remission From Depression
Time Frame: Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks
Remission defined as Montgomery Asberg Depression Rating Scale score ≤10. Scale ranges from 0-60 with higher scores indicating higher depressive symptoms.
Safety Outcomes Assessment for Serious Adverse Events
Time Frame: Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks
Assessing; Life threatening illness, hospitalization, or need of medical care over the duration of the study
To observe whether persistent (non-remitting) depression leads to greater cognitive decline (focusing on executive and episodic memory (EEM)-related cognitive domains
Time Frame: Baseline, 6-months, 24-months
Using baseline differences to compare if non-remitters demonstrate greater decline in EEM than remitters leading to greater cognitive decline using . Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Secondary Outcomes
No secondary outcomes reported