Clinical TrialMajor Depressive Disorder (MDD)KetaminePlaceboCompleted

Ketamine as a Rapidly-Acting Antidepressant in Depressed Emergency Department Patients

Randomised, triple‑blind, parallel‑group ED study (n=21) comparing a single IV bolus of ketamine 0.25 mg/kg versus diphenhydramine 25 mg for rapid antidepressant effects in patients with severe MDD.

Target Enrollment
21 participants
Study Type
Phase II interventional
Design
Randomized, triple Blind

Detailed Description

Randomised, triple‑masked, parallel trial testing a single sub‑anesthetic IV ketamine bolus (0.25 mg/kg) versus an equivalent volume of diphenhydramine (25 mg) in Emergency Department patients presenting with severe major depressive disorder.

Primary analyses compare mood measures pre‑ and post‑infusion; secondary measures include heart rate and heart‑rate variability, serum inflammatory cytokines (IL‑1, IL‑2, IL‑6, IL‑8, IL‑10, IL‑12, TNF‑α), BDNF, and serum magnesium to explore biological correlates of response.

Aim is to determine the rapidity and persistence of ketamine's antidepressant effects in ED patients to potentially reduce need for inpatient admission and provide a safety bridge to outpatient care.

Study Protocol

Preparation

sessions

Dosing

1 sessions
2 min each

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

Single sub‑anesthetic IV ketamine bolus for rapid antidepressant effect in ED patients with MDD.

Interventions

  • Ketamine0.25 mg/kg
    via IV• single dose• 1 doses total

    IV bolus over 1–2 minutes; single infusion.

Diphenhydramine

active comparator

Active comparator (diphenhydramine 25 mg IV) used as blinding/control.

Interventions

  • Placebo25 mg
    via IV• single dose• 1 doses total

    Diphenhydramine 25 mg IV (Benadryl) delivered as equivalent volume; encoded as active comparator in notes.

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Medically stable as determined by the medical physician
  • Meets criteria for Major Depressive Disorder (MDD) based on a structured clinical Interview (MINI International Neuropsychiatric Interview).
  • Reports symptoms of severe depression at the time of presentation, defined as a score of 24 or greater on the MADRS.
  • Patients for whom a psychiatric evaluation and disposition decision has been made by emergency psychiatry staff to admit to an inpatient psychiatric unit at Bellevue Hospital Center or NYU Tisch Hospital.
  • Each subject must have a level of understanding sufficient to sign an informed consent stating that the treatment being offered is not FDA approved for the treatment of depression and is being provided as an off-label option.

Exclusion Criteria

  • Exclusion Criteria:
  • Pregnancy
  • Inability to read or understand English
  • Current clinical signs of intoxication or delirium at time of study intervention
  • Overdose, within previous 24 hours, of any agent which would impair ketamine metabolism
  • Lifetime misuse/abuse of ketamine, phencyclidine (PCP),or related substances
  • Lifetime history of psychotic spectrum illness
  • First-degree relative with history of psychotic illness
  • Lifetime diagnosis of borderline personality disorder, or as confirmed by assessment using items #90-104 of the SCID-II (for DSM-IV).
  • Subjects with clinically significant abnormal findings as determined by medical history, physical examination, vital signs (blood pressure, heart rate, and respiration rate), O2 saturation measure, 12-lead ECG, clinical laboratory tests (CBC, chemistry panel, thyroid function tests), urine drug screen, and urine pregnancy test (for females of childbearing potential only).
  • Clinically unstable medical, surgical or neurological conditions at ED presentation
  • History of stroke or intracranial hypertension
  • History of glaucoma
  • Subjects with one or more seizures without a clear and resolved etiology
  • Current NMDA antagonist medications (eg. Amantadine, Rimantadine, Lamotrigine, Memantine, Dextromethorphan)
  • Known hypersensitivity to ketamine or amantadine
  • Anti-psychotic medications (Typicals or Atypicals), with the exception of low-dose quetiapine (total daily dose of 100mg or less).
  • Actively trying to commit suicide, even in a hospital setting
  • Current homicide risk
  • Unable or unwilling to give informed consent according to HIC guidelines
  • Unable or unwilling to provide 2 contact phone numbers or be followed up per study protocol.
  • Previous enrollment in this study.
  • Concurrent enrollment in a research protocol investigating experimental pharmacologic treatments for depression at this or any other institution.

Study Details

Locations

Bellevue Hospital Center — New York, New York, United States
NYU Langone Medical Center/Tisch Hospital — New York, New York, United States

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