Original Title: Kétamine intraveineuse comme traitement aigu d’appoint de la dépression réfractaire aux thérapies usuelles optimisées chez l’adulte : modalités d’usage optimal

Authors' objectives: In May of 2025, the Institut national d’excellence en santé et en services sociaux (INESSS) published a report on the clinical relevance of parenteral ketamine in this context, based in particular on a rapid review of the efficacy and safety of this therapy. Several recommendations were made, including developing clinical tools to guide and standardize the use of ketamine. The Direction des affaires pharmaceutiques et du médicament of the Ministère de la Santé et des Services sociaux (MSSS) therefore asked INESSS to develop a standardized protocol and a standardized individual prescription template to implement the recommendations made in the report and to guide prescribers and health professionals responsible for administering intravenous ketamine in this context.

Authors' results and conclusions: RESULTS (#1 A TWO-STEP USER SELECTION PROCESS): The decision to proceed is based on the individual’s values and preferences, the advantages and limitations of the available treatment options, the communication of uncertainties regarding the medium- and long-term benefits of ketamine, and the risks of misuse, given its potential for dependence. (#2 MULTIPLE PRESCRIBING CONSIDERATIONS FOR A SAFE TREATMENT PLAN): The decision whether or not to use ketamine as an adjunctive therapy also depends on an assessment of the potential adverse effects, the absolute contraindications3, and situations where the precautionary principle applies4, which mainly involves the need for paraclinical tests. These evaluations include monitoring the vital signs, performing an electrocardiogram and ordering certain laboratory tests, depending on the individual’s condition. (#3 ADMINISTRATION CLOSELY MONITORED FOR A SAFE, OPTIMIZED EXPERIENCE ): Ketamine is administered intravenously in accordance with the prescription instructions regarding the dose and the duration of the infusion. During administration, the authorized professional continuously monitors the user closely. This includes checking their level of consciousness and sedation and vital signs and checking for any adverse effects. (#4 A FOLLOW-UP FOCUSED ON SUPPORT AND DATA-GATHERING): The discontinuation of adjunctive ketamine therapy is based on an individualized clinical decision guided by the person’s medical history, the observed effectiveness and safety, and the optimal dose or frequency of administration. The treatment is also discontinued when the individual requests this or if there is non-compliance with the safety commitments or instructions. (#5 ISSUES RAISED DURING THE PROJECT): Access to adjunctive ketamine therapy for depression resistant to optimized standard therapies presents certain operational challenges. Many facilities do not have suitable rooms or dedicated rooms for this treatment, and the shortage of nursing staff further strains the administration and monitoring capacity. CONCLUSION: While not a substitute for clinical judgment, this project should help standardize and guide the use of intravenous ketamine for depression resistant to optimized standard treatments, and facilitate interprofessional collaboration, particularly in second-line psychiatric units and among health professionals with mental health expertise. However, any practice changes that might result from this project will depend on the dissemination of the related clinical tools and on the uptake of the clinical information and the recommendations by the health professionals concerned.

Authors' recommendations: Upon completion of this project, and following an iterative process with the members of the advisory committee, during which the scientific data, the information and recommendations drawn from the reviewed literature, the contextual information, and the perspectives of the different stakeholders consulted were triangulated, a series of clinical recommendations were drawn up and incorporated into a tool intended for prescribers and administrators. In addition, an individual prescription template was created.

Authors' methods: This Guides and Standards project is based on INESSS’s rapid review guidelines and is a continuation of the work relating to the report. For this phase, a manual literature search was conducted in PubMed and other supplementary sources. The purpose was to identify new practice guides and clinical guidelines on the use of intravenous ketamine for treatment-resistant depression published since the end of the information watch carried out in the winter of 2025, in order to update the rapid review conducted at that time and to identify other information for answering the new assessment questions. A scientific professional contributed to the document selection process, and two professionals participated in extracting data and evaluating the methodological quality of these documents. In addition, narrative reviews were conducted to document specific targeted populational, clinical, organizational, and environmental aspects.

Authors' identified further research: The relevance of updating the recommendations will be determined in 4 years from the date of publication of these tools, based on the advancement of the scientific data, the changes in clinical practices, as well as the needs of the health and social services network.

Project Status: Completed

Year Published: 2026

URL for published report: https://www.inesss.qc.ca/fileadmin/doc/INESSS/Rapports/Usage_optimal/INESSS_Ketamine_GN_INESSS.pdf

English language abstract: An English language summary is available

Publication Type: Other

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: L'Institut national d'excellence en sante et en services sociaux (INESSS)