Optimizing Outcomes of Treatment-Resistant Depression in Older Adults

Phase 4

Completed

• Conditions: Treatment Resistant Depression; Major Depressive Disorder; Treatment-Refractory Depression; Late Life Depression; Geriatric Depression
• Interventions: Drug: Aripiprazole Augmentation; Drug: Switch to bupropion; Drug: Lithium Augmentation; Drug: Bupropion Augmentation; Drug: Switch to nortriptyline

• Registration Number: NCT02960763
• Lead Sponsor: Washington University School of Medicine

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2016-10-28
• Study First Submitted QC: 2016-11-07
• Study First Posted: 2016-11-10
• Study Start: 2017-02-24
• Primary Completion: 2020-09-28
• Study Completion: 2021-09-01
• Results First Submitted: 2022-02-01
• Results First Submitted QC: 2022-05-20
• Results First Posted: 2022-05-24
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-18
• Last Update Posted: 2024-10-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 742

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aripiprazole Augmentation	Aripiprazole Augmentation	Augment current antidepressant treatment with aripiprazole (tablets), titrated from 2-15 mg daily based on symptom severity and side effects.
Switch to Bupropion	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.
Lithium Augmentation	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.
Bupropion Augmentation	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.
Switch to Nortriptyline	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.

Primary Outcome Measures

Name	Time	Method
Psychological Well-Being	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, SD=10).
Number of Participants With Remission From Depression	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.
Serious Adverse Events	Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks	Life threatening illness, hospitalization, or need of medical care.

Trial Locations

Locations (5)

Centre for Addiction and Mental Health; 🇨🇦 Toronto, Ontario, Canada

Washington University School of Medicine Healthy Mind Lab; 🇺🇸 Saint Louis, Missouri, United States

UCLA Late-Life Mood, Stress, and Wellness Research Program; 🇺🇸 Los Angeles, California, United States

UPMC Late-Life Depression, Evaluation, Prevention, and Treatment Program; 🇺🇸 Pittsburgh, Pennsylvania, United States

Columbia University Adult and Late Life Depression Clinic; 🇺🇸 New York, New York, United States