Nebulized Ketamine for the Treatment of Major Depressive Disorder
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.
Severe Depression, Moderate Depression, Ketamine, Midazolam, Peripheral Nervous System Agents, Central Nervous System Agents, Neurotransmitter Agents, Physiologic Effects of Drugs, Sensory System Agents, Analgesics, Non-Narcotic, Anti-Inflammatory Agents, Non-Steroidal, Depressive Symptom, Hypnotics and Sedatives, Anti-anxiety Agents, Tranquilizing Agents, Psychotropic Drugs, Anesthetics Agent
About this study
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.
Interventions
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).
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).
Primary outcomes
Change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS) (8-10 days)
Eligibility information
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 locations
Maimonides Medical Center, Brooklyn, New York 11219 United States
Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.
Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-10-14.