Effects of Ketamine in the Acute Phase of Suicidal Ideation (KETIS)

Evaluation of the Effects of Ketamine in the Acute Phase of Suicidal Ideation: a Multicenter Randomized Double-blind Trial

The primary objective of this study is to assess the efficacy of ketamine versus a placebo for the short-term (at 72h, i.e. 24h after the last perfusion) relief of suicidal ideation, measured using the BSS hetero questionnaire, in patients hospitalized for suicide risk.

Study Overview

• Status: Completed
• Conditions: Suicidal Ideation
• Intervention / Treatment: Other: Baseline evaluation; Drug: 1st perfusion of ketamine; Other: Follow-up between perfusions; Drug: 2nd perfusion of ketamine; Drug: 1st perfusion of saline; Drug: 2nd perfusion of saline

Detailed Description

The secondary objectives of this study are to assess:

A. The maintenance of medium-term effectiveness of ketamine on the resolution of suicidal ideation

B. The evolution of the full spectrum of suicidality under ketamine compared to placebo

C. The evolution of psychic and physical pain scores under ketamine compared to placebo

D. The evolution of Beck Hopelessness score which is a predictor of long-term suicide risk, under ketamine compared to placebo

E. The early antidepressant efficacy of ketamine in depressed, uni- or bipolar patients

F. The somatic and psychological tolerance of ketamine

G. An overall improvement in the clinical condition of the patient by the practitioner

H. Creation of a biological collection for future ancillary studies dedicated to genetic analysis (microRNA and mRNA).

I. The efficacy of ketamine versus a placebo for the short-term (at 72h, i.e. 24h after the last perfusion) relief of suicidal ideation, measured using the BSS self-report questionnaire, in patients hospitalized for suicide risk.

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • CHU de Clermont Ferrand - Hôpital Gabriel-Montpied
  • Lille, France, 59037
    • CHRU de Lille - Hôpital Michel Fontan
  • Montpellier, France, 34295
    • CHRU de Montpellier - Hôpital Lapeyronie
  • Nîmes, France, 30000
    • Clinique Les Sophoras
  • Nîmes, France, 30029
    • CHRU de Nîmes - Hôpital Universitaire Carémeau
  • Paris, France, 75010
    • APHP - Hôpital Lariboisière
  • Paris, France, 75674
    • CMME Centre Hospitalier Sainte Anne
  • Paris, France, 75674
    • Centre Hospitalier Sainte-Anne
  • Saint-Cyr-sur-Loire, France, 37540
    • CHRU de Tours - Clinique Psychiatrique Universitaire

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• French speaking patients freely hospitalized for prevention of suicide and who have a medium or high suicide risk score according to a MINI structured interview
• The patient is able to understand how the study is carried out and the tests performed
• The patient is deemed capable of giving his/her informed consent
• The patient has been correctly informed
• The patient must have given his/her informed and signed consent.
• The patient must be insured or beneficiary of a health insurance plan.
• Presence of suicidal ideation according to the SSI score (score > 3)
• Negative pregnancy test for women of childbearing age

Exclusion Criteria:

• The patient is participating in another interventional study
• Within the past three months, the patient has participated in another interventional study
• The patient is in an exclusion period determined by a previous study
• The patient is under judicial protection
• The patient is an adult under guardianship
• The patient refuses to sign the consent
• The patient is not able to understand the informed consent
• Pregnancy or breastfeeding
• History of schizophrenia or other psychotic disorders
• Presence of psychotic symptoms at initial interview
• Schizoid or schizotypic personality disorder
• Positive urine screening for illicit substances, excluding cannabis
• Substance dependence in the preceding month (excluding nicotine or caffeine)
• Concomitant treatment with electroconvulsive therapy
• Unstable somatic pathology
• Clinically significant anomalies found during clinical examination, biological test or ECG
• Non-stabilized hypertension or hypertension > 180/100
• Known or suspected contra-indication for ketamine (includes interactions): hypersensitivity to ketamine, hypertension, class IV cardiac insufficiency, history of stroke, hepatic or cutaneous porphyria, history of intracranial hypertension

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; Patients randomized to this group will be treated via Ketamine infusion. Intervention: Baseline evaluation Intervention: 1st perfusion of ketamine Intervention: Follow-up between perfusions Intervention: 2nd perfusion of ketamine Intervention: Follow-up after perfusions	Other: Baseline evaluation; Before perfusions begin, each patient will have a baseline evaluation including the following: the Columbia Suicide Severity Rating Scale (CSSRS), the Beck Scale for Suicide Ideation (BSSI), a physical pain VAS (visual analog scale), a mental pain VAS, the Clinical Global Impressions Scale (CGI-S), Beck's Hopeless scale (BHS), the Inventory of Depressive Symptomatology for the Clinician (IDS-C30), the Patient Rated Inventory of Side Effects (PRISE), the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS).; Drug: 1st perfusion of ketamine; A 1st perfusion of ketamine is performed: 0.5 mg/kg diluted in saline, administered over 40 minutes by intravenous (IV) pump and cardiorespiratory monitoring. (Day 0); Other: Follow-up between perfusions; Patients will be re-evaluated with a selection of questionnaires at 40 minutes, 120 minutes, 4 hours, and 24 hours after the end of the first perfusion, and then again at 48 hours after the end of the first perfusion and right before the second perfusion and then again Day 3, Day 4, Week 2, Week 4 and Week 6.; Drug: 2nd perfusion of ketamine; A 2nd perfusion of ketamine is performed: 0.5 mg/kg diluted in saline, administered over 40 minutes by intravenous (IV) pump and cardiorespiratory monitoring. (Day 2)
Placebo Comparator: Placebo/Control; Patients randomized to this group will be treated via saline solution infusion. Intervention: Baseline evaluation Intervention: 1st perfusion of saline Intervention: Follow-up between perfusions Intervention: 2nd perfusion of saline Intervention: Follow-up after perfusions	Other: Baseline evaluation; Before perfusions begin, each patient will have a baseline evaluation including the following: the Columbia Suicide Severity Rating Scale (CSSRS), the Beck Scale for Suicide Ideation (BSSI), a physical pain VAS (visual analog scale), a mental pain VAS, the Clinical Global Impressions Scale (CGI-S), Beck's Hopeless scale (BHS), the Inventory of Depressive Symptomatology for the Clinician (IDS-C30), the Patient Rated Inventory of Side Effects (PRISE), the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS).; Other: Follow-up between perfusions; Patients will be re-evaluated with a selection of questionnaires at 40 minutes, 120 minutes, 4 hours, and 24 hours after the end of the first perfusion, and then again at 48 hours after the end of the first perfusion and right before the second perfusion and then again Day 3, Day 4, Week 2, Week 4 and Week 6.; Drug: 1st perfusion of saline; A 1st perfusion of saline is performed: the same volume of saline as in the ketamine arm, administered over 40 minutes by IV pump and cardiorespiratory monitoring. (Day 0); Drug: 2nd perfusion of saline; A 2nd perfusion of saline is performed: the same volume of saline as in the ketamine arm, administered over 40 minutes by IV pump and cardiorespiratory monitoring. (Day 2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BSSI score	A suicidal ideation score measured using the BSS (Beck et al. 1979) in its hetero questionnaire form ≤ 3 at 24 hours after the second infusion of ketamine or placebo (yes/no). A threshold ≤ 3 separates the resolution of suicidal ideas from their persistence (Holi et al. 2005; DiazGranados et al. 2010).	Day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The occurrence of a suicide attempt or a completed suicide (yes/no)		6 weeks
Evaluation of the full spectrum of suicidality using the CSSRS		Baseline (Day-2 to Day 0)
Evaluation of the full spectrum of suicidality using the CSSRS		Day 1
Evaluation of the full spectrum of suicidality using the CSSRS		Day 2
Evaluation of the full spectrum of suicidality using the CSSRS		Day 3
Evaluation of the full spectrum of suicidality using the CSSRS		Day 4
Evaluation of the full spectrum of suicidality using the CSSRS		Week 2
Evaluation of the full spectrum of suicidality using the CSSRS		Week 4
Evaluation of the full spectrum of suicidality using the CSSRS		Week 6
The BSSI score		Baseline (Day-2 to Day 0)
The BSSI score		40 min after end of 1st perfusion (Day 0)
The BSSI score		120 min after end of 1st perfusion (Day 0)
The BSSI score		4 hours after end of 1st perfusion (Day 0)
The BSSI score		Day 1
The BSSI score		Day 2
The BSSI score		Day 4
The BSSI score		Week 2
The BSSI score		Week 4
The BSSI score		Week 6
Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		Baseline (Day-2 to Day 0)
Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		40 min after end of 1st perfusion (Day 0)
Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		120 min after end of 1st perfusion (Day 0)
Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		4 hours after end of 1st perfusion (Day 0)
Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		Day 1
Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		Day 2
Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		Day 3
Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		Day 4
Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		Week 2
Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		Week 4
Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		Week 6
Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		Baseline (Day-2 to Day 0)
Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		40 min after end of 1st perfusion (Day 0)
Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		120 min after end of 1st perfusion (Day 0)
Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		4 hours after end of 1st perfusion (Day 0)
Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		Day 1
Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		Day 2
Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		Day 3
Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		Day 4
Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		Week 2
Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		Week 4
Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		Week 6
Evaluation of despair using the Beck Hopelessness Scale		Baseline (Day-2 to Day 0)
Evaluation of despair using the Beck Hopelessness Scale		Day 1
Evaluation of despair using the Beck Hopelessness Scale		Day 2
Evaluation of despair using the Beck Hopelessness Scale		Day 3
Evaluation of despair using the Beck Hopelessness Scale		Day 4
Evaluation of despair using the Beck Hopelessness Scale		Week 2
Evaluation of despair using the Beck Hopelessness Scale		Week 4
Evaluation of despair using the Beck Hopelessness Scale		Week 6
Evaluation of depression by the clinician (IDS-C30)		Baseline (Day-2 to Day 0)
Evaluation of depression by the clinician (IDS-C30)		4 hours after end of 1st perfusion (Day 0)
Evaluation of depression by the clinician (IDS-C30)		Day 1
Evaluation of depression by the clinician (IDS-C30)		Day 2
Evaluation of depression by the clinician (IDS-C30)		Day 3
Evaluation of depression by the clinician (IDS-C30)		Day 4
Evaluation of depression by the clinician (IDS-C30)		Week 2
Evaluation of depression by the clinician (IDS-C30)		Week 4
Evaluation of depression by the clinician (IDS-C30)		Week 6
Evaluation of somatic tolerance of ketamine using the Patient Rated Inventory of Side Effects (PRISE) throughout follow-up		Baseline (Day-2 to Day 0)
Evaluation of somatic tolerance of ketamine using the Patient Rated Inventory of Side Effects (PRISE) throughout follow-up		Day 1
Evaluation of somatic tolerance of ketamine using the Patient Rated Inventory of Side Effects (PRISE) throughout follow-up		Day 2
Evaluation of somatic tolerance of ketamine using the Patient Rated Inventory of Side Effects (PRISE) throughout follow-up		Day 3
Evaluation of somatic tolerance of ketamine using the Patient Rated Inventory of Side Effects (PRISE) throughout follow-up		Day 4
Evaluation of psychic tolerance using the Young Mania Rating Scale (YMRS)		Baseline (Day-2 to Day 0)
Evaluation of psychic tolerance using the Young Mania Rating Scale (YMRS)		Day 1
Evaluation of psychic tolerance using the Young Mania Rating Scale (YMRS)		Day 2
Evaluation of psychic tolerance using the Young Mania Rating Scale (YMRS)		Day 3
Evaluation of psychic tolerance using the Young Mania Rating Scale (YMRS)		Day 4
Evaluation of psychic tolerance using the Brief Psychiatric Rating Scale (BPRS)		Baseline (Day-2 to Day 0)
Evaluation of psychic tolerance using the Brief Psychiatric Rating Scale (BPRS)		Day 1
Evaluation of psychic tolerance using the Brief Psychiatric Rating Scale (BPRS)		Day 2
Evaluation of psychic tolerance using the Brief Psychiatric Rating Scale (BPRS)		Day 3
Evaluation of psychic tolerance using the Brief Psychiatric Rating Scale (BPRS)		Day 4
Presence/absence of abnormal monitoring values throughout the study: hypertension	Any abnormal hypertension, pulse oxymetry or cardiac frequency values observed during the study will be noted.	6 weeks
Presence/absence of abnormal monitoring values throughout the study: pulse oxymetry	Any abnormal hypertension, pulse oxymetry or cardiac frequency values observed during the study will be noted.	6 weeks
Presence/absence of abnormal monitoring values throughout the study: cardiac frequency	Any abnormal hypertension, pulse oxymetry or cardiac frequency values observed during the study will be noted.	6 weeks
Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		Baseline (Day-2 to Day 0)
Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		40 min after end of 1st perfusion (Day 0)
Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		120 min after end of 1st perfusion (Day 0)
Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		4 hours after end of 1st perfusion (Day 0)
Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		Day 1
Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		Day 2
Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		120 min after end of 2nd perfusion (Day 2)
Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		Day 3
Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		Day 4
Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		Week 2
Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		Week 4
Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		Week 6
The BSSI score	A suicidal ideation score measured using the BSS (Beck et al. 1979) in its self report questionnaire form ≤ 3 at 24 hours after the second infusion of ketamine or placebo (yes/no). This scale is validated in French (de Man, Balkou & Iglesias 1987); a threshold ≤ 3 separates the resolution of suicidal ideas from their persistence (Holi et al. 2005; DiazGranados et al. 2010)	24 hours after the last perfusion

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Study Director: Mocrane Abbar, MD, Centre Hospitalier Universitaire de Nīmes

Publications and helpful links

General Publications

• Witt KG, Hetrick SE, Rajaram G, Hazell P, Taylor Salisbury TL, Townsend E, Hawton K. Psychosocial interventions for self-harm in adults. Cochrane Database Syst Rev. 2021 Apr 22;4(4):CD013668. doi: 10.1002/14651858.CD013668.pub2.
• Abbar M, Demattei C, El-Hage W, Llorca PM, Samalin L, Demaricourt P, Gaillard R, Courtet P, Vaiva G, Gorwood P, Fabbro P, Jollant F. Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial. BMJ. 2022 Feb 2;376:e067194. doi: 10.1136/bmj-2021-067194.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): November 21, 2019
• Study Completion (Actual): November 21, 2019

Study Registration Dates

• First Submitted: November 20, 2014
• First Submitted That Met QC Criteria: November 20, 2014
• First Posted (Estimated): November 24, 2014

Study Record Updates

• Last Update Posted (Actual): December 1, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: ketamine; low-dose ketamine; treatment of acute suicidal ideation
• Additional Relevant MeSH Terms: Behavioral Symptoms; Self-Injurious Behavior; Suicide; Behavior; Suicidal Ideation; 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: PHRC-N/2013/MA-01; 2014-001324-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO