Ketamine for the acute treatment of severe suicidal ideation

Mocrane Abbar, chief of clinical department 1,  Christophe Demattei, statistician 2,  Wissam El-Hage, chief of clinical department 3,  Pierre-Michel Llorca, chief of clinical department 4,  Ludovic Samalin, assistant professor of psychiatry 4,  Pierre Demaricourt, chief of clinical department 5,  Raphael Gaillard, chief of clinical department 5,  Philippe Courtet, chief of clinical department 6 7,  Guillaume Vaiva, professor of psychiatry 8 9 ,Philip Gorwood, chief of clinical department 5,  Pascale Fabbro, methodologist 2,  Fabrice Jollant, professor of psychiatry 1 5  10 11 12


1Department of Psychiatry, Academic Hospital (CHU) Nîmes, University of Montpellier, Nîmes, France

2Department of Biostatistics, Epidemiology, Public Health and Innovation in Methodology, CHU Nîmes, University of Montpellier, Nîmes, France

3CHRU Tours, Research Unit (UMR) 1253, iBrain, University of Tours, National Institute for Health and Medical Research (INSERM), Tours, France

4Department of Psychiatry, CHU Clermont-Ferrand, University of Clermont Auvergne, UMR 6602, Institute Pascal, Clermont-Ferrand, France

5School of Medicine, University of Paris and Sainte-Anne Hospital, Paris, France

6INSERM, Centre for Epidemiological and Clinical Research in Psychiatry (PSNREC), University of Montpellier, CHU Montpellier, Montpellier, France

7Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France

8Department of Psychiatry, CHU Lille, Lille, France

9University of Lille, INSERM U1172 – LilNCog – Lille Neuroscience and Cognition, Lille, France

10Department of Psychiatry, McGill University, McGill Group for Suicide Studies, Montreal, QC, Canada

11Moods Team, INSERM, UMR-1178, Epidemiology and Population Health Research Centre (CESP), Le Kremlin-Bicêtre, France

12Department of Psychiatry and Psychotherapy, University Hospital Jena, Jena, Germany


Objective To confirm the rapid onset anti-suicidal benefits of ketamine in the short term and at six weeks, overall and according to diagnostic group.

Design Prospective, double blind, superiority, randomised placebo controlled trial.

Setting Seven French teaching hospitals between 13 April 2015 and 12 March 2019.

Eligibility criteria for participants Aged 18 or older with current suicidal ideation, admitted to hospital voluntarily. Exclusion criteria included a history of schizophrenia or other psychotic disorders, substance dependence, and contraindications for ketamine.

Participants 156 participants were recruited and randomised to placebo (n=83) or ketamine (n=73), stratified by centre and diagnosis: bipolar, depressive, or other disorders.

Intervention Two 40 minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (saline) were administered at baseline and 24 hours, in addition to usual treatment.

Main outcome measures The primary outcome was the rate of patients in full suicidal remission at day 3, according to the scale for suicidal ideation total score ≤3. Analyses were conducted on an intention-to-treat basis.

Results More participants receiving ketamine reached full remission of suicidal ideas at day 3 than those receiving placebo: 46 (63.0%) of 83 participants in the ketamine arm and 25 (31.6%) of 73 in the placebo arm (odds ratio 3.7 (95% confidence interval 1.9 to 7.3), P<0.001). This effect differed according to the diagnosis (treatment: P<0.001; interaction: P=0.02): bipolar (odds ratio 14.1 (95% confidence interval 3.0 to 92.2), P<0.001), depressive (1.3 (0.3 to 5.2), P=0.6), or other disorders (3.7 (0.9 to 17.3, P=0.07)). Side effects were limited. No manic or psychotic symptom was seen. Moreover, a mediating effect of mental pain was found. At week 6, remission in the ketamine arm remained high, although non-significantly versus placebo (69.5% v 56.3%; odds ratio 0.8 (95% confidence interval 0.3 to 2.5), P=0.7).

Conclusions The findings indicate that ketamine is rapid, safe in the short term, and has persistent benefits for acute care in suicidal patients. Comorbid mental disorders appear to be important moderators. An analgesic effect on mental pain might explain the anti-suicidal effects of ketamine.

Trial registration NCT02299440.

  Image Name  - Ketamine for the acute treatment of severe suicidal ideation

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