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

The Washington University

Status and phase: Completed; Phase 4

Conditions: Major Depressive Disorder; Treatment Resistant Depression; Geriatric Depression; Late Life Depression; Treatment-Refractory Depression

Treatments: Drug: Aripiprazole Augmentation; Drug: Switch to nortriptyline; Drug: Switch to bupropion; Drug: Bupropion Augmentation; Drug: Lithium Augmentation

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02960763

201609085 (Other Identifier)

TRD-1511-33321

Details and patient eligibility

About

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

Full 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.

Enrollment: 742 patients

Sex: All

Ages: 60+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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742 participants in 5 patient groups

Aripiprazole Augmentation

Experimental group

Description:

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

Treatment:

Drug: Aripiprazole Augmentation

Bupropion Augmentation

Experimental group

Description:

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

Treatment:

Drug: Bupropion Augmentation

Switch to Bupropion

Experimental group

Description:

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

Treatment:

Drug: Switch to bupropion

Lithium Augmentation

Experimental group

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.

Treatment:

Drug: Lithium Augmentation

Switch to Nortriptyline

Experimental group

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.

Treatment:

Drug: Switch to nortriptyline