The Effect of Ketamine on Mechanises Underlying Suicidal Ideation and Drug-resistant Major Depression

Effects of Ketamine Treatment on Suicidal Ideation, Drug-resistant Major Depression, and Negative Emotional Experience. Clinical and fMRI Study

Suicide attempts are a serious concern worldwide. Currently, existing drugs take about three weeks to show effect on suicidal thoughts and drives. Recent evidence suggests that intravenous Ketamine exerts a rapid effect in suicidal patients, even after a single injection. We aim to examine whether oral Ketamine is a safe and effective treatment in suicidal patients. Following a suicide attempt, patients will be randomized into a group that will be given Ketamine for 21 days and one that will receive placebo, and assessed using questionnaires and brain scans. We expect early improvements in suicide scales in the Ketamine group.

As a secondary goal, this study will use IV ketamine in order to access the extent to which the experience of the embodied self mediate different levels of "embodied emotion". A better understanding of these relations will assist in unveiling the cognitive mechanism underlying the therapeutic effect of ketamine

Study Overview

• Status: Unknown
• Conditions: Suicidal Ideation; Major Depressive Disorder; Healthy Participants
• Intervention / Treatment: Drug: Saline; Drug: Ketamine

Detailed Description

Suicide is a leading cause of death worldwide. Current strategies rely mostly on prevention, as there is no pharmacotherapy that seems to benefit patients in the acute phase of suicidal ideation. Conventional medications exert a beneficial effect only after three weeks. However, recent evidence suggests that intravenous Ketamine, an NMDA receptor antagonist, has a rapid and direct beneficial effect on suicidal ideation, even after a single dose.

We hypothesize that daily oral administration of Ketamine in suicidal patients will prove a safe and effective outpatient treatment.

In a double blind, placebo-controlled trial, patients admitted to the emergency department after a suicide attempt will be randomized into two groups: one will be given a daily sub-anesthetic dose of oral Ketamine, while the second group will receive a daily dose of placebo. Participants will be followed-up for 21 days. Some of the subjects will also undergo functional MRI scans before and after the first Ketamine intake.

We expect significant early improvements in suicide and depression scales in the active treatment group. If daily oral Ketamine proves a safe, cost-effective, and beneficial treatment option for suicidal ideation, this will constitute a much needed new tool in preventing suicide ideation related morbidity and mortality.

The secondary goal, delineating the relation between sense of embodied self and embodied emotion, will be approached by recruiting 40 healthy participants that underwent a romantic relationship break-up. Each participant will undergo two sessions: one under the placebo and the other under Ketamine. Each session will involve two main tasks: a virtual version of the rubber hand illusion and a task comparing mental and physical pain perception. The vRHI will involve four conditions that will be induced by two independent variables, synchronicity (synchronous-asynchronous) and pleasantness (high/low). The mental/physical pain task will include four conditions as well: Physical pain (high/low) and mental pain (high/low)

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Talma Hendler, MD; Phone Number: 97236973953

Study Locations

• Israel
  • N/A = Not Applicable
    • Tel Aviv, N/A = Not Applicable, Israel, 64288
      • Recruiting
      • Tel Aviv Sourasky Medical Center
      • Contact: Haggai; Email: haggaisharon@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Suicidal Ideation group:

1. Any person admitted to the emergency room department after a suicide attempt , defined as requiring medical intervention - not just a psychiatrist ( surgical or pharmacological treatment but also the need for observation ) .
2. The need for medical intervention will be defined by the ER ED physician
3. Ages 18-65

For the depression group:

1. Diagnosed with major depression according to DSM VI.
2. Ongoing depression (according to DSM criteria) despite treatment with at least two antidepressants in adequate dosages and for longer than three weeks.
3. Ages 18-65

For the romantic relationship breakup:

1. Participants that have experienced a meaningful romantic relationship break-up within the past 12 months

-

Exclusion Criteria for all groups:

1. Psychotic state instate in the examination
2. Diagnosis of schizophrenia / schizoaffective disorder
3. Drug or alcohol abuse as is revealed in by blood/urine tests
4. Patient in which, according to the examiner, there is primary or secondary gain.
5. Patient , which, at the time of his admission , is without any pharmacological treatment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo for drug resistant depression; Patients will be treated for 21 days with daily oral placebo	Drug: Saline
Experimental: Ketamine for suicidal ideation; Patients will be treated for 21 days with daily oral Ketamine	Drug: Ketamine
Experimental: Ketamine for drug resistant depression; Patients will be treated for 21 days with daily oral Ketamine	Drug: Ketamine
Placebo Comparator: Placebo in suicidal ideation; Patients will be treated for 21 days with daily oral placebo	Drug: Saline
Experimental: Healthy Participants; Healthy participants that underwent a romantic relationship breakup will attend in tow experimental sessions, one with placebo and one with ketamine. Sessions will be separated within the range of 1 to 6 weeks	Drug: Saline; Drug: Ketamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Resolution of suicidal ideation	within 3 weeks of enrolement

Secondary Outcome Measures

Outcome Measure	Time Frame
Improvement in depression indices	within 3 weeks of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study adherence	How many patients quit the study due to side effects of the medication	within 3 weeks after commencing treatment
The visual analogue pain intensity scale	Reduction in subjective pain intensity	During the experiment session

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center

Publications and helpful links

General Publications

• Domany Y, Bleich-Cohen M, Tarrasch R, Meidan R, Litvak-Lazar O, Stoppleman N, Schreiber S, Bloch M, Hendler T, Sharon H. Repeated oral ketamine for out-patient treatment of resistant depression: randomised, double-blind, placebo-controlled, proof-of-concept study. Br J Psychiatry. 2019 Jan;214(1):20-26. doi: 10.1192/bjp.2018.196. Epub 2018 Sep 24.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Anticipated): May 1, 2020
• Study Completion (Anticipated): May 1, 2020

Study Registration Dates

• First Submitted: January 14, 2014
• First Submitted That Met QC Criteria: January 15, 2014
• First Posted (Estimate): January 16, 2014

Study Record Updates

• Last Update Posted (Actual): April 2, 2020
• Last Update Submitted That Met QC Criteria: April 1, 2020
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Self-Injurious Behavior; Suicide; Depressive Disorder; Suicidal Ideation; 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; Ketamine
• Other Study ID Numbers: TASMC-13-TH-0270-CTIL