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

November 16, 2022 updated by: Eric Lenze, Washington University School of Medicine
The purpose of this research study is to assess which antidepressants work the best in older adults who have treatment-resistant depression (TRD).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

742

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M6J-1H4
        • Centre for Addiction and Mental Health
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Late-Life Mood, Stress, and Wellness Research Program
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine Healthy Mind Lab
    • New York
      • New York, New York, United States, 10032
        • Columbia University Adult and Late Life Depression Clinic
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC Late-Life Depression, Evaluation, Prevention, and Treatment Program

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Aripiprazole Augmentation
Augment current antidepressant treatment with aripiprazole (tablets), titrated from 2-15 mg daily based on symptom severity and side effects.
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.
Other Names:
  • Abilify
Experimental: 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.
Drug: 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.
Other Names:
  • Wellbutrin
Experimental: 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.
Drug: 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.
Other Names:
  • Wellbutrin
Experimental: 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.
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
Other Names:
  • Pamelor,
Experimental: 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.
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.
Other Names:
  • Lithium carbonate
  • Eskalith

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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, SD=10).
Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks
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.
Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks
Serious Adverse Events
Time Frame: Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks
Life threatening illness, hospitalization, or need of medical care.
Step 1 (10 weeks), Step 2 (10 weeks), a period of up to 20 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Collaborators

Patient-Centered Outcomes Research Institute
National Institute of Mental Health (NIMH)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 24, 2017

Primary Completion (Actual)

September 28, 2020

Study Completion (Actual)

September 1, 2021

Study Registration Dates

First Submitted

October 28, 2016

First Submitted That Met QC Criteria

November 7, 2016

First Posted (Estimate)

November 10, 2016

Study Record Updates

Last Update Posted (Actual)

November 29, 2022

Last Update Submitted That Met QC Criteria

November 16, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201609085
  • TRD-1511-33321 (Other Grant/Funding Number: PCORI)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD 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.

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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