February 2021

By:  Dr. Werner Oberholzer, Deputy Registrar, CPSS

CPSS Position on Ketamine Off-Label Use

Re: Ketamine/Esketamine administered in any form IV/Oral/Sublingual/Intranasal as treatment for mental health and chronic non-cancer pain diagnoses. 

The CPSS has received questions regarding the prescribing and administration of Ketamine to patients with treatment-refractory depression and as a treatment modality for chronic non-cancer pain.  Download official letter 

This treatment is not yet fully supported by professional consensus or established clinical evidence, however, the College does not explicitly prohibit the off-label uses of medications, including Ketamine, as this may fall under research in approved clinical trials, evolving clinical practice and, occasionally, complementary and alternative medicine.
Physicians are reminded not to prescribe or practice a therapy that departs from prevailing medical practice unless they are able to demonstrate that the potential benefits of the therapy outweigh the risks.

Parenteral administration of Ketamine, including subcutaneous (SQ), intramuscular (IM), and intravenous (IV) as off-label use for depression and/or chronic pain management outside of a hospital or emergency room continues to only be permitted in accredited non-hospital facilities setting under the CPSS Regulatory Bylaw 26.1 Operation of Non-Hospital Treatment Facilities in the Province of Saskatchewan if the treatment produces sedation:

(e) a non-hospital treatment facility is one in which any of the following are performed:

(i) the use of drugs which are intended or which may induce general anaesthesia or sedation requiring the monitoring of vital signs, including all uses of intravenously administered sedatives or narcotics, except in emergency circumstances;

For all other forms of Ketamine (oral/sublingual/intranasal), caution is advised due to potential safety risks associated with off-label or inappropriate use of these products and others containing Ketamine. The College’s Complementary and Alternative Therapies policy applies to physicians who prescribe or administer such treatment.

Please be aware that certain products like intranasal esketamine have manufacturer specific guidelines. For example the guidelines for Spravato® state:

Intranasal esketamine (SPRAVATO®) has been approved for use in Canada following a Notice of Compliance from Health Canada. SPRAVATO® is indicated for use in combination with an oral antidepressant (that is either a SSRI or SNRI) for the treatment of major depressive disorder (MDD) in adults who have not responded adequately to at least two separate courses of treatment with different antidepressants, each of adequate dose and duration, in the current moderate to severe depressive episode. Psychiatrists may prescribe SPRAVATO® to patients who meet the appropriate criteria in a community setting, as long as they have appropriate training and knowledge and are doing so in accordance with requirements set out by Health Canada and the SPRAVATO® Canadian product monograph. In settings where there is limited availability of psychiatry specialist care, and complex TRD patients are managed by family practitioners in consultation with a psychiatrist, the family practitioner could provide treatment under the same requirements.

Pursuant to the Canadian product monograph, SPRAVATO® is only available through a controlled distribution program called the Janssen Journey™ Program. The goal of the Janssen Journey™ Program is to mitigate the risks of adverse outcomes related to sedation, dissociation, blood pressure changes, and the risk of misuse and abuse.

  • SPRAVATO® can only be prescribed by a physician who is experienced and proficient in the management of major depressive disorder and enrolled in the Janssen Journey™ Program.
  • Only pharmacists enrolled in the Janssen Journey™ Program can dispense SPRAVATO®.
  • Physicians who prescribe SPRAVATO® and pharmacists who dispense SPRAVATO® must complete training on the risks of the product and agree to adhere to the requirements of the Janssen Journey™ Program.
  • Prior to being prescribed SPRAVATO®, patients must be enrolled in the Janssen Journey™ Program.
  • Prescribers must ensure that the patients are informed of and understand the conditions of use and risks of treatment with SPRAVATO®.
  • SPRAVATO® can only be dispensed to sites of care where patients self-administer the product under the direct supervision of a health-care professional and are monitored by a health-care professional post-administration.
  • Questions may be directed to Health Canada at hcinfo.infosc@canada.ca, or the Janssen Journey Program at 1-833-257-7191 or online at www.JanssenJourneyHCP.ca.

It is expected that the physician not only observe the patient, but have the necessary equipment and competence to manage any adverse reactions.

It is expected that patients be fully informed of the risks, benefits (and unknown nature of risks and benefits) of any off-label treatments, and particular attention should be paid to informed consent in these circumstances. Clear documentation with details of such discussions should be available on the patient’s medical record.

Ketamine also falls under the list of monitored drugs of the College’s Regulatory bylaw 18.1 The Prescription Review Program and physicians are reminded about the risk for abuse, misuse and diversion.

We wish to remind physicians about the expectations that physicians only prescribe a drug if:

  • they have the knowledge, skill and judgment to do so safely and effectively,
  • they have appropriate training and competence, and
  • they have immediate access to equipment used to manage any adverse events.

Physicians are encouraged to contact the CMPA for advice before proceeding with therapies that are not considered conventional treatment options.

The College of Physicians and Surgeons of Saskatchewan has consulted with the College of Physicians and Surgeons of Alberta (CPSA), as they are currently evaluating standards for the prescribing and administration of Ketamine. The results are not expected for at least another 6 months. The College of Physicians and Surgeons of British Columbia’s (CPSBC’s) approach is generally the same as what the CPSS is advising. Should further evidence become available regarding the use of Ketamine, the CPSS may consider revising this guidance.

The CPSS acknowledges the use of the communique of the College of Physicians and Surgeons of 
British Columbia CPSBC (Ketamine and major depressive disorder and  Interim Guidance ).

The CPSA has a clinical toolkit, 
Ketamine and Esketamine: Key considerations, which may be helpful in decision making.