Optimizing Outcomes of Treatment-Resistant Depression in Older Adults

Study Overview
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Brief Summary
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The purpose of this research study is to assess which antidepressants work the best in older adults who have treatment-resistant depression (TRD).

Detailed Description
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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 antidepressant 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. After treatment in Step 1 and/or Step 2, participants will enter the Continuation Phase to assess long term follow-up outcomes for 12 months. Participants in this clinical trial will also be asked to participate in an additional study to gather imaging and biomarker data.

Official Title
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Optimizing Outcomes of Treatment-Resistant Depression in Older Adults

Conditions
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Treatment Resistant Depression, Major Depressive Disorder, Treatment-Refractory Depression, Late Life Depression, Geriatric Depression

Intervention / Treatment
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* Drug: Aripiprazole Augmentation
* Drug: Bupropion Augmentation
* Drug: Switch to bupropion
* Drug: Lithium Augmentation
* Drug: Switch to nortriptyline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 60 and older Current Major Depressive Disorder (MDD) Failure to respond adequately to two or more antidepressant treatment trials of recommended dose and length Patient Health Questionnaire-9 (PHQ-9) score of 10 or higher Exclusion Criteria: Inability to provide informed consent Dementia Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms High risk for suicide and unable to be managed safely in the clinical trial Contraindication to proposed study medications, as determined by study physician including history of intolerance or non-response to proposed medications. Non-correctable, clinically significant sensory impairment interfering with participation 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

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aripiprazole Augmentation<br>Augment current antidepressant treatment with aripiprazole (tablets), titrated from 2-15 mg daily based on symptom severity and side effects. | Drug: Aripiprazole Augmentation<br>* Augment current antidepressant treatment with aripiprazole (tablets). Start at 2 mg daily; increase every two weeks (i.e., to 5, 7, 10 mg) to a maximum of 15 mg daily based on symptom severity and side effects.<br>* Other names: Abilify;|
| Experimental: Bupropion Augmentation<br>Augment current antidepressant treatment with bupropion once-daily extended release, titrated from 150-300 mg daily based on symptom severity and side effects. | Drug: Bupropion Augmentation<br>* Augment current antidepressant treatment with bupropion once-daily extended release, starting at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects.<br>* Other names: Wellbutrin;|
| Experimental: Switch to Bupropion<br>Taper from current antidepressant therapy. Start bupropion once-daily extended, titrated from 150-300 mg daily based on symptom severity and side effects. | Drug: Switch to bupropion<br>* Taper from current antidepressant therapy. Start bupropion once-daily extended release at 150 mg daily; titrated after four weeks to 300 mg daily based on symptom severity and side effects.<br>* Other names: Wellbutrin;|
| Experimental: Lithium Augmentation<br>Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L. | Drug: Lithium Augmentation<br>* Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L.<br>* Other names: Eskalith;|
| Experimental: Switch to Nortriptyline<br>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. | Drug: Switch to nortriptyline<br>* 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<br>* Other names: Pamelor,;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychological Well-Being | 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, SD=10). | Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks | 
| Number of Participants With Remission From Depression | Remission defined as Montgomery Asberg Depression Rating Scale score ≤10. Scale ranges from 0-60 with higher scores indicating higher depressive symptoms. | Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks | 
| Serious Adverse Events | Life threatening illness, hospitalization, or need of medical care. | Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Comparative Effectiveness Research, Pragmatic Clinical Trials, Patient-Centered Outcomes Research