Ketamine and major depressive disorder

Note: This article has been updated to include clarification on the College requirements for intranasal esketamine. The original published article can be found here.

Ketamine is a dissociative anesthetic agent usually administered intravenously. It has been an emerging treatment for major depressive disorder. 

Ketamine is capable of producing amnesia, analgesia, and all levels of sedation including general anesthesia though not anticipated in the doses used to treat depression, provided these doses are not exceeded. Regardless of the route of administration, it has a serious side effect and risk profile. It can cause significant hypertension requiring frequent monitoring of blood pressure and treatment if indicated. It may also cause serious dissociative effects that may require intervention. Due to its psychotogenic properties, it is susceptible to misuse and abuse, requiring careful inquiry into past history of drug use or addiction. 

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.

Parenteral administration of ketamine, including subcutaneous (SQ), intramuscular (IM), and intravenous (IV) as off-label use for depression and chronic pain management continue to only be permitted in accredited non-hospital facilities. 

The College does not explicitly prohibit the off-label uses of medications including other formulations of ketamine as this may fall under research in approved clinical trials, evolving clinical practice and, occasionally, complementary and alternative medicine. The College does not take action against a physician unless the physician practises a therapy that departs from prevailing medical practice and it can be demonstrated that the therapy posed a greater risk to patient health or safety than did prevailing medical practice. It is always expected that patients be fully informed of the risks, benefits (and unknown nature of risks and benefits) of any off-label or non-conventional treatments and this is adequately documented in the consent process. Greater scrutiny must be applied when this involves pediatric patients.

Questions may be directed to Health Canada at, or the Janssen Journey Program at 1-833-257-7191 or online at