Clinical TrialTreatment-Resistant Depression (TRD)KetamineCompleted

Ketamine for Older Adults Pilot

This pilot completed single-group study (n=25) assessed safety and feasibility of IV ketamine (0.5 mg/kg infused over 40 minutes) in older adults with treatment-resistant depression, with twice-weekly infusions for 4 weeks and optional weekly continuation for responders.

Target Enrollment
25 participants
Study Type
Phase IV interventional
Design
Non-randomized

Detailed Description

Single-group interventional pilot in adults ≥65 with treatment-resistant unipolar depression testing IV ketamine 0.5 mg/kg infused over 40 minutes. Acute phase: twice-weekly infusions for 4 weeks; responders/remitters offered weekly continuation infusions for 4 weeks.

Outcomes include feasibility, safety (vitals, adverse events), depressive symptoms (PHQ-9), executive functioning, and daily mobile health symptom surveys to evaluate precision-medicine approaches.

Assessments at baseline, end of acute phase, and end of continuation phase; study developed methods for mobile health and precision approaches in late-life depression.

Study Protocol

Preparation

sessions

Dosing

12 sessions
40 min each

Integration

sessions

Study Arms & Interventions

Ketamine IV

experimental

Intravenous ketamine infusions for acute and continuation phases (single-group).

Interventions

  • Ketamine0.5 mg/kg
    via IVtwice weekly then weekly12 doses total

    Infused over 40 minutes; acute: twice weekly for 4 weeks (8); continuation: weekly for 4 weeks (4).

Participants

Ages
6599
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Community-living men and women age 65 years and older;
  • 2. Treatment-resistant depression: defined as unipolar major depressive disorder, non-delusional (diagnosed by SCID-5) that persists despite ≥ 2 adequate antidepressant trials of different classes in the current episode; including at least one evidence-based second-line treatment in the current episode (including serotonin norepinephrine reuptake inhibitors, bupropion, tricyclics, monoamine oxidase inhibitors, or augmentation with an atypical antipsychotic, stimulant, bupropion, lithium, or triiodothyronine);
  • 3. Persistent moderate to severe depressive symptoms determined by Patient Health Questionnaire 9-item (PHQ-9) score ≥15 at baseline;
  • 4. Able to provide informed consent.

Exclusion Criteria

  • Exclusion Criteria:
  • 1. Dementia per history, score < 24 on the Montreal Cognitive Assessment (MoCA), or determined by clinical interview with geriatric psychiatrist to have high likelihood of dementia;
  • 2. Psychotic spectrum or bipolar disorder or severe personality disorder that at the PIs discretion would interfere with safe participation. Anxiety disorders are not an exclusion;
  • 3. Unstable medical conditions such that IV ketamine is not safe or tolerated or that would interfere with participation in a long-term study (i.e., poorly controlled hypertension, life expectancy < 1 year because of terminal illness, unstable angina);
  • 4. Baseline systolic BP > 165 or diastolic > 100 at evaluation;
  • 5. Current alcohol or substance use disorder or lifetime recreational ketamine use or other dissociative agent (e.g., PCP);
  • 6. Use of naltrexone, memantine, or any medication that could be considered contraindicated with ketamine;
  • 7. Taking more than 2 adequately-dosed oral antidepressants;
  • 8. High acute risk for suicide and unable to be managed safely in the clinical trial.

Study Details

Locations

UCLA Late-Life Mood, Stress, and Wellness Research ProgramLos Angeles, California, United States
Washington University School of Medicine Healthy Mind LabSt Louis, Missouri, United States
Columbia University Adult and Late Life Depression ClinicNew York, New York, United States
UPMC Late-Life Depression, Evaluation, Prevention, and Treatment ProgramPittsburgh, Pennsylvania, United States
University Health NetworkToronto, Ontario, Canada

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