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. 2021 Feb;66(2):113-125.
doi: 10.1177/0706743720970860. Epub 2020 Nov 11.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder: Recommandations Du Groupe De Travail Du Réseau Canadien Pour Les Traitements De L'humeur Et De L'anxiété (Canmat) Concernant L'utilisation De La Kétamine Racémique Chez Les Adultes Souffrant De Trouble Dépressif Majeur

Jennifer Swainson  1 , Alexander McGirr  2 , Pierre Blier  3 , Elisa Brietzke  4 , Stéphane Richard-Devantoy  5 , Nisha Ravindran  6 , Jean Blier  7 , Serge Beaulieu  5 , Benicio N Frey  8 , Sidney H Kennedy  6 , Roger S McIntyre  6 , Roumen V Milev  4 , Sagar V Parikh  9 , Ayal Schaffer  6 , Valerie H Taylor  2 , Valérie Tourjman  10 , Michael van Ameringen  8 , Lakshmi N Yatham  11 , Arun V Ravindran  6 , Raymond W Lam  11
Affiliations

The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder: Recommandations Du Groupe De Travail Du Réseau Canadien Pour Les Traitements De L'humeur Et De L'anxiété (Canmat) Concernant L'utilisation De La Kétamine Racémique Chez Les Adultes Souffrant De Trouble Dépressif Majeur

Jennifer Swainson et al. Can J Psychiatry. 2021 Feb.

Erratum in

Abstract
in English, French

Objective: Patients with major depressive disorder often have limited response to first-line and second-line medications; hence, novel pharmacological treatments are needed for treatment-resistant depression (TRD). Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, has demonstrated rapid antidepressant effects in patients with TRD. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence for efficacy and safety of racemic ketamine and to provide recommendations for its use in clinical practice.

Methods: A systematic review was conducted with computerized search of electronic databases up to January 31, 2020 using combinations of search terms, inspection of bibliographies, and review of other ketamine guidelines and consensus statements. The level of evidence and lines of treatment were assigned according to CANMAT criteria. Recommendations were given in question-answer format.

Results: Intravenous (IV) racemic ketamine given as a single infusion has Level 1 evidence for efficacy in adults with TRD. The evidence for multiple infusions, given as an acute series or as ongoing maintenance treatment, is limited to Level 3. Adverse events associated with ketamine infusions include behavioral (e.g., dissociative symptoms) and physiological (e.g., hypertension) events. There is only Level 3 or 4 evidence for non-IV formulations of racemic ketamine. Consensus recommendations are given for clinical administration of IV ketamine including patient selection, facility and personnel issues, monitoring, and maintaining response.

Conclusions: Single-dose IV racemic ketamine is a third-line recommendation for adults with TRD. The need for repeated and maintenance ketamine infusions should be carefully assessed on a case-by-case basis with consideration of potential risks and benefits. Because of limited evidence for efficacy and risk for misuse and diversion, the use of oral and other formulations of racemic ketamine should be limited to specialists with ketamine-prescribing expertise and affiliations with tertiary or specialized centers.

Objectif:: Les patients souffrant de trouble dépressif majeur (TDM) ont souvent une réponse limitée aux médicaments de première et de deuxième intention, donc de nouveaux traitements pharmacologiques sont nécessaires pour la dépression réfractaire au traitement (DRT). La kétamine, un antagoniste des récepteurs N-méthyl-D-aspartate (NMDA), a démontré des effets antidépresseurs rapides chez les patients de la DRT. Le Réseau canadien pour les traitements de l’humeur et de l’anxiété (CANMAT) a formé un groupe de travail pour examiner les données probantes de l’efficacité et de la sécurité de la kétamine racémique et pour en recommander l’usage dans la pratique clinique.

Méthodes:: Une revue systématique a été menée avec une recherche informatique des bases de données électroniques jusqu’au 31 janvier 2020, à l’aide de termes de recherche combinés, de l’inspection des bibliographies, et de l’examen d’autres directives sur la kétamine et d’énoncés de consensus. Le niveau des données probantes et des intentions de traitement était affecté selon les critères de CANMAT. Les recommandations ont été données sous forme de question-réponse.

Résultats:: La kétamine racémique intraveineuse administrée en une seule perfusion a des données probantes de niveau 1 pour ce qui est de l’efficacité chez les adultes de la DRT. Les données probantes pour de multiples perfusions, administrées en série aiguë ou comme traitement d’entretien constant, se limitent au niveau 3. Les événements indésirables associés aux perfusions de kétamine sont notamment des effets comportementaux (p. ex., symptômes dissociatifs) et physiologiques (p. ex., hypertension). Il n’y a que des données probantes de niveau 3 ou 4 pour des formulations de kétamine racémique non intraveineuse. Des recommandations consensuelles sont données pour l’administration clinique de kétamine intraveineuse, elles portent notamment sur la sélection des patients, le contexte et les questions liées au personnel, la surveillance et le maintien de la réponse.

Conclusions:: La kétamine racémique intraveineuse en une seule perfusion est une recommandation de troisième intention pour les adultes réfractaires au traitement. Le besoin de perfusions de kétamine répétées et d’entretien devrait être soigneusement évalué selon le cas par cas en tenant compte des risques et avantages potentiels. En raison des données probantes limitées en matière d’efficacité et du risque d’abus et de déviation, l’utilisation de formulations orales et autres de la kétamine racémique devrait se limiter aux spécialistes qui ont l’expertise de prescrire la kétamine et qui ont des affiliations aux centres tertiaires ou spécialisés.

Keywords: antidepressants; depression; esketamine; glutamate; ketamine; major depressive disorder; treatment-resistant depression.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest: Jennifer Swainson has received honoraria from Bausch, Janssen, Lundbeck, Otsuka, Sunovion, and Eisai. Alexander McGirr has no disclosures. Pierre Blier has received honoraria or research funds from Allergan, Bristol Myers Squibb, Janssen, Lundbeck, Pierre Fabre Médicaments, Pfizer, Sunovion, CIHR, Ontario Brain Institute, and Otsuka. Elisa Brietzke has received honoraria or research funds from Queen’s University School of Medicine, SEAMO, CNPq-Universal Grant, Otsuka, Daiichi-Sankyo, and FAPESP. Nisha Ravindran has received grants from Janssen. Serge Beaulieu has received honoraria or research funds from Pfizer, Otsuka, Lundbeck, Sunovion, Allergan, Janssen-Ortho, and Takeda. Benicio N. Frey has received research funds from Pfizer. Sidney H. Kennedy has received honoraria or research funds from Abbott, Alkermes, Allergan, BMS, Brain Canada, CIHR, Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research Fund, Otsuka, Pfizer, Servier, Sunovion, Xian-Janssen, and Field Trip Health. Roger S. McIntyre has received honoraria or research funds from Lundbeck, Janssen, Shire, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Minerva, Stanley Medical Research Institute, CIHR, GACD, and National Natural Science Foundation of China. Roumen V. Milev has received honoraria or research funds from Ontario Brain Institute, Allergan, Janssen, Lallemand, Kye, Lundbeck, Nubiyota, Otsuka, Pfizer, and Sunovion. Sagar V. Parikh has received honoraria or research funds from Assurex, Takeda, Janssen, Mensante, Aifred, Sage. Ayal Schaffer has received honoraria from Allergan, Janssen, Lundbeck, Otsuka, and Sunovion. Valerie H. Taylor has received honoraria or research funds from DiaMentis, Janssen, Lundbeck, Otsuka, Purdue, Shire, and Takeda. Valérie Tourjman has no disclosures. Michael van Ameringen has received honoraria or research funds from Allergan, Almatica, Brainsway, Lundbeck, Myriad Neuroscience, Otsuka, Purdue, Janssen, Canadian Foundation for Innovation, Hamilton Academic Health Sciences Organization, and Pfizer. Lakshmi N. Yatham has received honoraria or research grants from Allergan, CANMAT, Lundbeck Institute, Otsuka, DSP, and Sanofi. Arun V. Ravindran has received grants from Janssen. Raymond W. Lam has received honoraria or research funds from Allergan, Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, CIHR, CANMAT, Canadian Psychiatric Association, Hansoh, Healthy Minds Canada, Janssen, Lundbeck, Lundbeck Institute, MITACS, Ontario Brain Institute, Otsuka, Pfizer, St. Jude Medical, University Health Network Foundation, and VGH-UBCH Foundation. Other authors have no disclosures.

Comment in

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