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Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM)

Primary Purpose

Treatment Resistant Depression, Major Depressive Disorder, Treatment-Refractory Depression

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Aripiprazole Augmentation
Bupropion Augmentation
Switch to bupropion
Lithium Augmentation
Switch to nortriptyline
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Treatment Resistant Depression focused on measuring Comparative Effectiveness Research, Pragmatic Clinical Trials, Patient-Centered Outcomes Research

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UCLA Late-Life Mood, Stress, and Wellness Research Program
  • Washington University School of Medicine Healthy Mind Lab
  • Columbia University Adult and Late Life Depression Clinic
  • UPMC Late-Life Depression, Evaluation, Prevention, and Treatment Program
  • Centre for Addiction and Mental Health

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Aripiprazole Augmentation

Bupropion Augmentation

Switch to Bupropion

Lithium Augmentation

Switch to Nortriptyline

Arm Description

Augment current antidepressant treatment with aripiprazole (tablets), titrated from 2-15 mg daily based on symptom severity and side effects.

Augment current antidepressant treatment with bupropion once-daily extended release, titrated from 150-300 mg daily based on symptom severity and side effects.

Taper from current antidepressant therapy. Start bupropion once-daily extended, titrated from 150-300 mg daily based on symptom severity and side effects.

Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L.

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.

Outcomes

Primary Outcome Measures

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).
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.
Serious Adverse Events
Life threatening illness, hospitalization, or need of medical care.

Secondary Outcome Measures

Full Information

First Posted
October 28, 2016
Last Updated
November 16, 2022
Sponsor
Washington University School of Medicine
Collaborators
Patient-Centered Outcomes Research Institute, National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT02960763
Brief Title
Optimizing Outcomes of Treatment-Resistant Depression in Older Adults
Acronym
OPTIMUM
Official Title
Optimizing Outcomes of Treatment-Resistant Depression in Older Adults
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
February 24, 2017 (Actual)
Primary Completion Date
September 28, 2020 (Actual)
Study Completion Date
September 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Washington University School of Medicine
Collaborators
Patient-Centered Outcomes Research Institute, National Institute of Mental Health (NIMH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Treatment Resistant Depression, Major Depressive Disorder, Treatment-Refractory Depression, Late Life Depression, Geriatric Depression
Keywords
Comparative Effectiveness Research, Pragmatic Clinical Trials, Patient-Centered Outcomes Research

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
742 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Aripiprazole Augmentation
Arm Type
Experimental
Arm Description
Augment current antidepressant treatment with aripiprazole (tablets), titrated from 2-15 mg daily based on symptom severity and side effects.
Arm Title
Bupropion Augmentation
Arm Type
Experimental
Arm Description
Augment current antidepressant treatment with bupropion once-daily extended release, titrated from 150-300 mg daily based on symptom severity and side effects.
Arm Title
Switch to Bupropion
Arm Type
Experimental
Arm Description
Taper from current antidepressant therapy. Start bupropion once-daily extended, titrated from 150-300 mg daily based on symptom severity and side effects.
Arm Title
Lithium Augmentation
Arm Type
Experimental
Arm Description
Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L.
Arm Title
Switch to Nortriptyline
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Aripiprazole Augmentation
Other Intervention Name(s)
Abilify
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Bupropion Augmentation
Other Intervention Name(s)
Wellbutrin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Switch to bupropion
Other Intervention Name(s)
Wellbutrin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Lithium Augmentation
Other Intervention Name(s)
Lithium carbonate, Eskalith
Intervention Description
Augment current antidepressant treatment with lithium carbonate tablets starting at 300 mg daily, titrated per blood level to 0.4-0.6 meQ/L.
Intervention Type
Drug
Intervention Name(s)
Switch to nortriptyline
Other Intervention Name(s)
Pamelor,
Intervention Description
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 Measure Information:
Title
Psychological Well-Being
Description
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).
Time Frame
Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks
Title
Number of Participants With Remission From Depression
Description
Remission defined as Montgomery Asberg Depression Rating Scale score ≤10. Scale ranges from 0-60 with higher scores indicating higher depressive symptoms.
Time Frame
Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks
Title
Serious Adverse Events
Description
Life threatening illness, hospitalization, or need of medical care.
Time Frame
Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Lenze, MD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCLA Late-Life Mood, Stress, and Wellness Research Program
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Washington University School of Medicine Healthy Mind Lab
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Columbia University Adult and Late Life Depression Clinic
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
UPMC Late-Life Depression, Evaluation, Prevention, and Treatment Program
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Centre for Addiction and Mental Health
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6J-1H4
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
A cleaned, complete, and de-identified copy of the final data set including administrative and technical metadata records will be made available through a Washington University in St. Louis (WUSTL) secure repository and registered at clinicaltrials.gov.

Learn more about this trial

Optimizing Outcomes of Treatment-Resistant Depression in Older Adults

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