Effectiveness of Ketamine Treatment for Three Consecutive Days in Depression

Effectiveness of Ketamine Treatment in Difficult-to-treat Depression Comparing With Midazolam: a Double-blind Randomized Controlled Trial and Its Cost Effectiveness Analysis

Inclusion criteria: 1. patient over 20 years old with depression diagnosed by a psychiatrist and MADRS >= 25 scores; 2. failed to improve by at least optimal dosage of two antidepressants for four weeks and one psychotherapy. Patients and outcome assessors will be blinded from intervention the patients have.

Participants will be randomized into two groups that are intervention (ketamine 0.5 mg/kg IV drip in 40 minutes) and control (midazolam 0.045 mg/kg IV drip in 40 minutes) groups. Participants will administer ketamine/midazolam once daily for three consecutive days. They will be evaluate MADRS changing, vital signs, dissociative symptoms, CGI, and quality of life (EQ-5D-5L) during the treatment, at 1 week and 4 weeks after treatment completion.

Study Overview

• Status: Completed
• Conditions: Depression
• Intervention / Treatment: Drug: Midazolam; Drug: Ketamine Hydrochloride

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10700
    • Keerati Pattanaseri

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• over 20 years old
• depression was diagnosed by a psychiatrist and having MADRS >= 25
• depression treated with 2 optimal dosage of antidepressants for 4 weeks and one psychotherapy
• stable dosage of current medications for 4 weeks
• fluently Thai

Exclusion Criteria:

• secondary depression
• PTSD
• current pregnancy
• history of increased intracranial hemorrhage, increased intracranial pressure, severe head injury, abnormal thyroid function, angina, heart failure, arrhythmia, aneurysm, uncontrolled hypertension, chronic lower tract respiratory disease, myasthenia gravis, glaucoma, dementia, acute porphyria, or cystitic (within 3 months prior to recruitment)
• allergy to ketamine or midazolam
• history of substance use disorder within 1 year prior to recruitment
• history of psychosis within 3 months
• history of bipolar disorder
• BMI over 35
• frail medical condition
• currently ECT or TMS

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine	Drug: Ketamine Hydrochloride; Ketamine hydrochloride 0.5 mg/kg intravenous administer in 40 minutes per day for 3 consecutive days
Placebo Comparator: Midazolam	Drug: Midazolam; Midazolam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery-Åsberg Depression Rating Scale (MADRS)	decrease more than 50% of scale from baseline is defined as remission	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
dissociation	The dissociative experiences measure, Oxford (DEMO)	immediately after administraion
health questionnaire	The 5-level EQ-5D version (EQ-5D-5L)	1 month

Collaborators and Investigators

• Sponsor: Mahidol University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Actual): July 31, 2022
• Study Completion (Actual): November 30, 2023

Study Registration Dates

• First Submitted: August 24, 2021
• First Submitted That Met QC Criteria: August 27, 2021
• First Posted (Actual): August 30, 2021

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Ketamine; Midazolam
• Other Study ID Numbers: 109/2564(IRB1)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No