for people ages 60 years and up (full criteria)
study started
estimated completion
Principal Investigator
by Helen Lavretsky, MD (ucla)



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


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.


Treatment Resistant Depression Major Depressive Disorder Treatment-Refractory Depression Late Life Depression Geriatric Depression Comparative Effectiveness Research Pragmatic Clinical Trials Patient-Centered Outcomes Research Depression Depressive Disorder Depressive Disorder, Major Depressive Disorder, Treatment-Resistant Aripiprazole Lithium Carbonate Bupropion Nortriptyline Aripiprazole Augmentation Bupropion Augmentation Switch to bupropion Lithium Augmentation Switch to nortriptyline


You can join if…

Open to people ages 60 years and up

  • 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 CAN'T join 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


  • UCLA Late-Life Mood, Stress, and Wellness Research Program accepting new patients
    Los Angeles California 90095 United States
  • Washington University School of Medicine Healthy Mind Lab accepting new patients
    Saint Louis Missouri 63110 United States

Lead Scientist at University of California Health

  • Helen Lavretsky, MD (ucla)
    Professor-in-Residence, Psychiatry and Biobehavioral Sciences. Authored (or co-authored) 121 research publications.


accepting new patients
Start Date
Completion Date
Washington University School of Medicine
Phase 4
Study Type
Last Updated