Using a Low Dose of Ketamine vs. Active Placebo in Treating Severe Depression and Suicide

A Double-blind, Randomized-controlled Trial Using a Low Dose of Ketamine vs. Active Placebo in Treating Severe Depression and Suicide

Depression and suicide are two leading mental health and public health issues in Taiwan. However, until now, the optimal treatment for refractory depression and suicide is still lacking. Previous USA studies suggested a low dose NMDA antagonist Ketamine infusion can significantly reduce depression and suicide. In our study, we firstly investigate the anti-suicide and anti-depressive effects of ketamine in Taiwan. If we can find the similar antidepressant and anti-suicide of ketamine in Taiwanese, this result will have a great influence in the current suicide and depression prevention programs.

Study Overview

• Status: Unknown
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Ketamine; Drug: Midazolam

Detailed Description

Depression and suicide are major issues of public health worldwide. However, there is time-lag for current available antidepressants to have therapeutic effective. In fact, if partial responses were also included, up to 50% of depressed patients showed little or no response to traditional antidepressant medication treatments. In addition, suicide is also a prevalent mental health problem worldwide and still has no optimal and effective treatment now. In Taiwan, the annual suicide rate increased gradually despite of the suicide prevention program. Ketamine, a kind of N-methyl-D-aspartate receptor (NMDAR) antagonist, is a FDA-approved anesthetic agent. One single sub-anesthesia dose of ketamine infusion can rapidly improve refractory depression without side effects of dependence, and its antidepressant effects have been proved by some double-blind and randomized controlled trials in other countries. However, it has not been investigated and validated in Han Chinese population. The mechanism of rapid antidepressant effects is still unknown. Besides, much less studies assessed the anti-suicide efficacy of a low dose of ketamine infusion.

Under the support of NSC 101-2314-B-010-060 and NSC 101-2314-B-010-061, we finished the study of a single dose ketamine infusion in the treatment of refractory major depression (TRD) using a double blind randomized placebo-controlled fashion. Three groups with each 24 patients of TRD received 0.5mg/kg, 0.2mg/kg and placebo (PBO) respectively. The primary outcome assessed by MADRS and HAMD depression ratings disclosed about 40~45% response. Also, a single low dose of ketamine could reduce approximately 50% suicide-related symptoms based on the subanalysis of ketamine treatment efficacy for specific suicide item.

In current study, we plan to recruit 48 subjects of TRD within two years in double-blind, randomized - controlled fashion with each year 24 subjects, who will receive 0.5mg/kg vs. active placebo (0.045mg/kg Midazolam) equally. Mood symptom changes by MARDRS and HAMD ratings, suicide scales, and impulsivity and loneliness scales will be conducted at different time points from baseline to the 14th day. We will elucidate the exact efficacy of a low dose of ketamine infusion for the rapid anti-depression and anti-suicidal ideations. If it is successful, it would be able to generalize to benefit for the huge population of Chinese in the world.

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 111
    • Recruiting
    • Taipei Veterans General Hospital
    • Contact: Mu-Hong Chen, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Major depression including unipolar and bipolar depression, according to DSM-IV criteria and MINI (MiniInternational Neuropsychiatric Interview;MINI) diagnostic interview.
2. Age ≧ 20y/o < 65 y/o
3. voluntary patients with signed informed consent proved by institutional review board (IRB)

Exclusion Criteria:

1. Major medical conditions (e.g., head injury, epilepsy, severe renal diseases and cancer).
2. Other axis I psychiatric disorders such as schizophrenia, delusional disorder, organic brain syndrome, and dementia.
3. Pregnancy.
4. Substance abuse in previous 6 months such as cocaine, marijuana, opium, ketamine, PCP (phencyclidine)。
5. Current use of NMDA receptor antagonist (Amantadine, Rimantadine, Lamotrigine, Memantine, Dextromethorphan)
6. Alcohol abuse / dependence within 6 months.
7. Attempt suicide in hospital.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.5mg/kg Ketamine; Anesthesia	Drug: Ketamine; We will elucidate the exact efficacy of a low dose of ketamine infusion for the rapid anti-depression and anti-suicidal ideations.; Other Names: Ketalar
Active Comparator: 0.045mg/kg Midazolam; Benzodiazepine	Drug: Midazolam; We will elucidate the exact efficacy of a low dose of ketamine infusion for the rapid anti-depression and anti-suicidal ideations.; Other Names: Dormicum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction rate of suicide symptom	Reduction rate of suicide symptom postinfusion of ketamine	4 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 14 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction rate of depression symptom	Reduction rate of depression symptom post-infusion of ketamine	4 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 14 days.

Collaborators and Investigators

• Sponsor: Taipei Veterans General Hospital, Taiwan
• Investigators: Principal Investigator: Mu-Hong Chen, M.D., Taipei Veterans General Hospital, Taiwan

Study record dates

Study Major Dates

• Study Start (Anticipated): September 10, 2018
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: September 9, 2018
• First Submitted That Met QC Criteria: September 10, 2018
• First Posted (Actual): September 11, 2018

Study Record Updates

• Last Update Posted (Actual): September 19, 2018
• Last Update Submitted That Met QC Criteria: September 17, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: ketamine; suicide; treatment refractory depression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Self-Injurious Behavior; Depression; Depressive Disorder; Suicide; Depressive Disorder, Major; 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: 107-2314-B-075-063-MY3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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