Research
Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial BMJ 2022; 376 doi: https://doi.org/10.1136/bmj-2021-067194
(Published 02 February 2022) Cite this as: BMJ 2022;376:e067194
Linked Editorial
Ketamine for 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
Author affiliations
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
Correspondence to: F Jollant jollantf@gmail.com
Accepted 3 December 2021
Abstract
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 ClinicalTrials.gov NCT02299440.
Acces article : https://www.bmj.com/content/376/bmj-2021-067194.full