Optimizing Outcomes of Treatment-Resistant Depression in Older Adults

NCT02960763 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: 201609085TRD-1511-33321
• Study Type: interventional
• Target: 742
• Locations: 2 countries
• Sites: 5

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).

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (5)

Aripiprazole Augmentation

EXPERIMENTAL

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

Drug: Aripiprazole Augmentation

Bupropion Augmentation

EXPERIMENTAL

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

Switch to Bupropion

EXPERIMENTAL

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

Lithium Augmentation

EXPERIMENTAL

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

Switch to Nortriptyline

EXPERIMENTAL

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

Interventions

Aripiprazole Augmentation DRUG

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.

Also known as: Abilify

Aripiprazole Augmentation

Bupropion Augmentation DRUG

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.

Also known as: Wellbutrin

Bupropion Augmentation

Switch to bupropion DRUG

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.

Also known as: Wellbutrin

Switch to Bupropion

Lithium Augmentation DRUG

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

Also known as: Lithium carbonate, Eskalith

Lithium Augmentation

Switch to nortriptyline DRUG

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

Also known as: Pamelor,

Switch to Nortriptyline

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Patient-Centered Outcomes Research Institute: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (5)

UCLA Late-Life Mood, Stress, and Wellness Research Program

Los Angeles, California, 90095, United States

Location

Washington University School of Medicine Healthy Mind Lab

St Louis, Missouri, 63110, United States

Location

Columbia University Adult and Late Life Depression Clinic

New York, New York, 10032, United States

Location

UPMC Late-Life Depression, Evaluation, Prevention, and Treatment Program

Pittsburgh, Pennsylvania, 15213, United States

Location

Centre for Addiction and Mental Health

Toronto, Ontario, M6J-1H4, Canada

Location

Related Publications (3)

• Oughli HA, Ainsworth NJ, Butters MA, Brown PJ, Gebara MA, Gettinger TR, Karp JF, Lavretsky H, Lenard E, Miller JP, Mulsant BH, Nicol GE, Reynolds CF 3rd, Yingling M, Lenze EJ; OPTIMUM Research Group. Cognitive changes in older adults receiving pharmacotherapy for treatment-resistant depression: a secondary analysis of the OPTIMUM randomised controlled trial. Lancet Healthy Longev. 2025 Oct;6(10):100767. doi: 10.1016/j.lanhl.2025.100767. Epub 2025 Nov 11.

  PMID: 41237789 DERIVED

• Srifuengfung M, Lenze EJ, Roose SP, Brown PJ, Lavretsky H, Karp JF, Reynolds CF 3rd, Yingling M, Sa-Nguanpanich N, Mulsant BH. Alcohol and substance use in older adults with treatment-resistant depression. Int J Geriatr Psychiatry. 2024 Jun;39(6):e6105. doi: 10.1002/gps.6105.

  PMID: 38822571 DERIVED

• Lenze EJ, Mulsant BH, Roose SP, Lavretsky H, Reynolds CF 3rd, Blumberger DM, Brown PJ, Cristancho P, Flint AJ, Gebara MA, Gettinger TR, Lenard E, Miller JP, Nicol GE, Oughli HA, Pham VT, Rollman BL, Yang L, Karp JF. Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression. N Engl J Med. 2023 Mar 23;388(12):1067-1079. doi: 10.1056/NEJMoa2204462. Epub 2023 Mar 3.

  PMID: 36867173 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major

Interventions

Aripiprazole; Bupropion; Lithium Carbonate; Nortriptyline

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Propiophenones; Ketones; Organic Chemicals; Carbonates; Alkalies; Inorganic Chemicals; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds; Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Eric Lenze
• Organization: Washington University in St. Louis

lenzee@wustl.edu

314-362-5154

Study Officials

• Eric Lenze, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: October 28, 2016
• First Posted: November 10, 2016
• Study Start: February 24, 2017
• Primary Completion: September 28, 2020
• Study Completion: September 1, 2021
• Last Updated: October 3, 2024
• Results First Posted: May 24, 2022

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share

Locations

CA (1); US (4)