Optimizing Outcomes of Treatment-Resistant Depression in Older Adults

Major Depressive Disorder Clinical Trial

— OPTIMUM  

Official title:

Optimizing Outcomes of Treatment-Resistant Depression in Older Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02960763
• Other study ID #: 201609085
• Secondary ID: TRD-1511-33321
• Status: Completed
• Phase: Phase 4
• Start date: February 24, 2017
• Est. completion date: September 1, 2021

Study information

• Verified date: November 2022
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 742
• Est. completion date: September 1, 2021
• Est. primary completion date: September 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Aripiprazole Augmentation
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.
• Bupropion Augmentation
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.
• Switch to bupropion
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.
• 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.
• 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

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health	Toronto	Ontario
United States	UCLA Late-Life Mood, Stress, and Wellness Research Program	Los Angeles	California
United States	Columbia University Adult and Late Life Depression Clinic	New York	New York
United States	UPMC Late-Life Depression, Evaluation, Prevention, and Treatment Program	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine Healthy Mind Lab	Saint Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
Washington University School of Medicine	National Institute of Mental Health (NIMH), Patient-Centered Outcomes Research Institute

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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