Clinical TrialMajor Depressive Disorder (MDD)KetamineCompleted

Ketamine Treatment Effects on Synaptic Plasticity in Depression

Single-group, Phase IV study (n=9) of four 0.5 mg/kg IV ketamine infusions over two weeks in adults with current MDD to measure synaptic density changes using [11C]UCB-J PET.

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

Detailed Description

This study evaluates ketamine's effects on synaptic density in adults with current major depressive disorder using [11C]UCB-J PET before and after a course of four subanesthetic IV ketamine infusions (0.5 mg/kg each) administered over two weeks.

Primary aims are to quantify changes in synaptic density following ketamine treatment and to explore synaptic density as a mediator and predictor of sustained antidepressant response; participants undergo inpatient admission for imaging and treatment at NYSPI.

Outcomes include PET measures of SV2A binding, clinical depression ratings (HAM-D), and safety/tolerability assessments; imaging uses [11C]UCB-J with robust test-retest reliability to detect longitudinal changes.

Study Protocol

Preparation

sessions

Dosing

4 sessions
40 min each

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

Open single-group treatment with four IV ketamine infusions over two weeks in adults with current MDD.

Interventions

  • Ketamine0.5 mg/kg
    via IV• four infusions over 2 weeks• 4 doses total

    Slow continuous IV infusion over ~40 minutes; two infusions per week for two weeks.

Participants

Ages
18 – 55
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Unipolar, major depressive episode (MDE), with 17-item Hamilton Depression Rating Scale score ≥16. Patients may be psychiatric medication-free, or if currently taking psychiatric medication, not responding adequately as evidenced by current MDE.
  • 18-55 years old
  • Female patients of child-bearing potential must be willing to use an acceptable form of birth control during study participation such as condoms, diaphragm, oral contraceptive pills.
  • Must be enrolled in division's umbrella research protocol
  • Able to provide informed consent
  • Agrees to voluntary admission to an inpatient research unit at The New York State Psychiatric Institute (NYSPI) for baseline PET imaging and Magnetic Resonance Imaging (MRI), ketamine infusion, and repeat PET imaging

Exclusion Criteria

  • Exclusion Criteria:
  • Unstable medical or neurological illness including: A) baseline hypertension (BP>140/90); B) significant history of cardiovascular illness; C) Platelet count < 80,000 cells/uL; and D) Hemoglobin < 11 g/dL for females and < 12 g/dL for males
  • Significant electrocardiogram (ECG) abnormality (e.g., Ventricular tachycardia, evidence of myocardial ischemia, symptomatic bradycardia, unstable tachycardia, second degree (or greater) atrioventricular (AV) block).
  • Pregnancy, currently lactating, or planning to conceive during the course of study participation.
  • Diagnosis of bipolar disorder or current psychotic symptoms.
  • Current or past ketamine use disorder (lifetime); any drug or alcohol use disorder within past 6 months
  • Inadequate understanding of English.
  • Prior ineffective trial of or adverse reaction to ketamine.
  • A neurological disease or prior head trauma with evidence of cognitive impairment.
  • Subjects who endorse a history of prior head trauma and score ≥ 1.5 standard deviations below the mean on the Trailmaking A & B will be excluded from study participation.
  • Metal implants or paramagnetic objects contained within the body which may present a risk to the subject or interfere with the MRI scan.
  • Current, past, or anticipated exposure to radiation that may interfere with PET/MRI participation.
  • Claustrophobia significant enough to interfere with MRI scanning
  • Weight that exceeds 325 lbs or inability to fit into MRI scanner
  • Individuals taking prescribed opioid medication, using opioids recreationally, or taking naltrexone at the time of enrollment
  • Daily use of benzodiazepine, zolpidem (Ambien), zaleplon (Sonata), or eszopiclone (Lunesta) for ≥2 weeks at time of consent

Study Details

Locations

New York State Psychiatric Institute/Columbia University — New York, New York, United States

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