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

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

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

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

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

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

How is the study designed?

Design Details

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

Number of Arms

5

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	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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Patient-Centered Outcomes Research Institute; National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Eric Lenze, MD, Washington University School of Medicine

Study record dates

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 (Estimated): November 10, 2016

Study Record Updates

• Last Update Posted (Actual): October 3, 2024
• Last Update Submitted That Met QC Criteria: September 18, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Comparative Effectiveness Research; Pragmatic Clinical Trials; Patient-Centered Outcomes Research
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Antimanic Agents; Cytochrome P-450 CYP2D6 Inhibitors; Dopamine Uptake Inhibitors; Adrenergic Uptake Inhibitors; Aripiprazole; Bupropion; Lithium Carbonate; Nortriptyline
• 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