Nebulized Ketamine for the Treatment of Major Depressive Disorder

April 21, 2026 updated by: Theresa Jacob, PhD, MPH

Nebulized Ketamine for the Treatment of Major Depressive Disorder in an Inpatient Setting: A Midazolam-controlled Randomized Controlled Trial

This is a double-blind active placebo controlled clinical trial for individuals with moderate to severe depression. The purpose of this study is to assess if nebulized ketamine can reduce depressive symptoms.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The objective of this study is to evaluate the effect of ketamine formalized to be dispensed via inhalation, as an adjunct to concomitant medications and therapies on those with moderate to severe depression currently in an inpatient psychiatric unit. Investigators will examine the effects of nebulized ketamine on depressive symptoms.

This is a prospective double-blind placebo controlled study in which an active placebo, Midazolam, will be used. Participants will commit to either 4 visits or 5 visits depending on which treatment arm they are randomized into. All visits can be done remotely, however, days in which the participant will be dosed will have to be in person. During dosing days, the participant will be monitored for a minimum of two hours. Study participant's vitals will be collected at regular intervals during the observation period.

Adult psychiatry inpatients who are 18 years and older with a diagnosis of moderate to severe depression will be screened for enrollment by the study.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • New York
      • Brooklyn, New York, United States, 11219
        • Recruiting
        • Maimonides Medical Center
        • Sub-Investigator:
          • Theresa Jacob, PhD, MPH
        • Contact:
        • Principal Investigator:
          • Jessica Poster, MD
        • Principal Investigator:
          • Simran Ailani, MBBS
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • All individuals 18 years and older with a Montgomery-Asberg Depression Rating Scale score (MADRS) ≥ 20
  • Must have a diagnosis of moderate to severe Major Depressive Disorder (MDD)
  • Structured Clinical Interview for DSM-5 (SCID-5) will be performed to confirm MDD diagnosis

Exclusion Criteria:

  • Adult patients with an allergy to Ketamine
  • Adult patients with an allergy to Midazolam
  • Individuals with a history of mania/hypomania or diagnosis of bipolar disorder
  • Patients on lithium and/or lamotrigine therapy
  • Recent or current homicidal ideation with an intent to act
  • MDD with psychotic features or current or past diagnosis of a psychotic disorder
  • No substance use disorder in the preceding 3 months except nicotine or caffeine or a positive urine screen for substances (except cannabis)
  • Diagnosis of obsessive-compulsive disorder, antisocial personality disorder, borderline personality disorder, posttraumatic stress disorder, intellectual disability, altered mental status, pregnant or breastfeeding patients,
  • Patients on > 2 medications for hypertension
  • Patients with uncontrolled hypertension (BP >140 mm Hg systolic and/or >90 mm Hg diastolic on two separate readings at the time of screening)
  • Body weight of > 150kg
  • Patients with history of congestive cardiac failure
  • Day of presentation, patients with unstable vital signs (systolic blood pressure <90 or>160 mm Hg, pulse rate <50 or >150 beats/min, and respiration rate <10 or >30 breaths/min)
  • Consumption of opioids within 24 hours of drug administration
  • Acutely intoxicated patients will also be excluded

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nebulized Ketamine
Ketamine dosage calculated by body weight at 1.5mg/kg
Drug: nebulized ketamine
The formulation of the study drug is administered via nebulizer in which the participants inhales the study drug. The dosage is calculated by body weight (1.5mg/kg).
Other Names:
  • Ketalar
Active Comparator: Nebulized Midazolam
Midazolam used as active comparator. Dosage calculated by body weight at 0.03mg/kg
Drug: nebulized midazolam
The formulation of the active comparator drug is administered via nebulizer in which the participant inhales the study drug. The dosage is calculated by body weight (0.03mg/kg).
Other Names:
  • Midazolam

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS)
Time Frame: 8-10 days
Montgomery-Asberg Depression Rating Scale (MADRS) has a range from 0 to 60, where the lower score indicates the better health status. Change in mean total Montgomery Asberg Depression Rating Scale (MADRS) score from the baseline (pre-dose day 1 ), Day 2 and last day of assessments (Day 8 or Day 10)
8-10 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinician-Administered Dissociative States Scale (CADSS)
Time Frame: 8-10 days
Measurement of dissociative symptoms. Clinician Administered Dissociative States Scale (CADSS) comprises 23 subjective items, each on a 5 point scale, a "0" represents absence of any adverse events and "4" represents a severely bothersome side effect. A total score ranges from 0-92, a lower score indicates a better health status.
8-10 days
Side Effect Rating Scale for Dissociative Anesthetics (SERSDA)
Time Frame: 8-10 days
Overall side effects as measured by the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). SERSDA has 9 items, each graded on a five point scale, with "0" representing the absence of any adverse effects and "4" representing a severely bothersome side effect.
8-10 days
Maximal sedative effects using Modified Observer's Assessment of Alertness and Sedation ( MOAA/S)
Time Frame: 8-10 days
Modified Observer's Alertness/Sedation Scale ( MOAA/S) uses a 6 point scale. A "0" indicates failure to respond to painful stimulus, "5" represents fully alert. .
8-10 days
Richmond Agitation-Sedation Scale (RASS)
Time Frame: 8-10 days
Measurement of participant's consciousness with a rating ranging from +4 to -5. +4 represents "combative", +3 represents "Very agitated", +2 represents "Agitated" , +1 represents restless, 0 represents "Alert and calm", -1 represents "Drowsy", -2 represents "Light sedation", -3 represents "Moderate sedation", -4 represents "Deep sedation", and -5 represents "Unarousable".
8-10 days
A change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS) from the baseline (pre-dose on day 1) and 2 hours post-medication administration
Time Frame: 8-10 days
Montgomery-Asberg Depression Rating Scale (MADRS) has a range from 0 to 60, where the lower score indicates the better health status. Change in mean total MADRS prior to dose administration on Day 1, 2 hours after dose administration for each day.
8-10 days
Change in Beck Scale for Suicide Ideation
Time Frame: 24 hours
Beck Scale for Suicide Ideation (SSI) has a range from 0 to 42, where the lower score indicates the better health status. SSI score of ≥4, response which would be defined as SSI ≥50% below baseline - 2 hours post medication administration and remission defined as SSI score of ≥50% and lower than 4 - 24 hrs after medication administration of follow-up
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Theresa Jacob, PhD, MPH

Investigators

  • Study Director: Theresa Jacob, PhD, MPH, Maimonides Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 16, 2024

Primary Completion (Estimated)

September 30, 2027

Study Completion (Estimated)

September 30, 2027

Study Registration Dates

First Submitted

December 23, 2024

First Submitted That Met QC Criteria

December 23, 2024

First Posted (Actual)

December 31, 2024

Study Record Updates

Last Update Posted (Actual)

April 24, 2026

Last Update Submitted That Met QC Criteria

April 21, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-06-05-MMC

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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