Ketamine

Overview

Our program offers intravenous ketamine treatment for individuals with treatment resistant depression. Treatment resistant depression is a form of depression in which there has been no improvement in symptoms after trying at least two pharmacological therapies. Ketamine is an N-methyl-D-aspartate receptor antagonist, which has long been used as an anesthetic medication. Recent evidence shows that subanesthetic doses of ketamine have rapid and robust antidepressant and anti-suicidal effects, which can have potentially life-saving relief for many individuals. Ketamine appears to work by mediating the glutamatergic system, which leads to changes in neural signaling and connectivity in relation to emotion and cognition in the brain. These changes in brain pathways result in improved depressive symptoms.

Ketamine FAQ for patients

  1. What is ketamine?
  2. How does ketamine work to improve depression?
  3. Will ketamine work for me?
  4. Who is eligible for ketamine treatment?
  5. Do I have to pay for this treatment?
  6. How is ketamine administered?
  7. What dose of ketamine will be used?
  8. What are the side effects of ketamine?
  9. How quickly does IV ketamine treatment begin to work?
  10. How many sessions of treatment will I need?
  11. How long do the effects of ketamine last?
  12. Can I continue taking my antidepressant medication while getting ketamine treatment?

What is ketamine?

Ketamine has been used as an anesthetic medication for the last 50 years. It is on the World Health Organization’s list of Essential Medications for its safety and efficacy as an anesthetic. More recently, over the past two decades, sub-anesthetic doses of ketamine have been used to treat psychiatric disorders including major depressive disorder (MDD).

There have been many clinical trials that have demonstrated the efficacy and safety of ketamine in reducing depressive symptoms and reducing suicidal ideation in treatment resistant depression compared to another drug or no drug at all.

How does ketamine work to improve depression?

In depression and other forms of persistent mood disorders, chronic stress results in changes in the signaling pathways within the brain. Ketamine works by blocking the N-methyl-D-aspartate (NMDA) receptor. By binding to the NMDA receptors, ketamine increases the amount of a neurotransmitter called glutamate within the brain, which leads to the activation of other molecules that help neurons communicate through new signaling pathways. This process is called synaptogenesis. This effect on signaling pathways likely results in changes in cognition and mood which are impacted by depression.

Will ketamine work for me?

Ketamine treatment helps

Who is eligible for ketamine treatment?

Individuals who are aged 18 and older with a diagnosis of moderate to severe depression who have not benefited from other forms of treatment are eligible for ketamine treatment.

Individuals who are not eligible for ketamine treatment include those who have active substance use disorders or have psychotic symptoms.

Do I have to pay for this treatment?

No, there is no cost to you to receive ketamine treatment. Ketamine is not currently covered by OHIP, however our clinic has funds available to cover the cost of treatment.

How is ketamine administered?

The most extensively studied route of administration of ketamine is intravenous, thus it is the most commonly used in clinical practice. Oral, sublingual, transmucosal, intranasal, intramuscular, and subcutaneous routes have also demonstrated an antidepressant effect in clinical trials, however more evidence is needed before being recommended over the intravenous route.

Intravenous ketamine is a mixture of two molecules, R- and S-ketamine. There is another type of ketamine, which uses only the S-ketamine molecule. It is called Esketamine or Spravato, which has Health Canada approval for use in treatment resistant depression, and is administered as a nasal spray. However, there is not enough evidence to suggest which form of ketamine is safer or more effective at this time. Given the depth of evidence-based research available, our program utilizes intravenous ketamine.

 What dose of ketamine will be used?

Intravenous ketamine is most commonly administered at a dose of 0.5mg/kg infused over 40 minutes. Your psychiatrist will determine whether a different dose may be needed for you.

 What are the side effects of ketamine?
The doses of ketamine that are used for depression are much lower than the dose used for anesthesia, which makes it relatively safe and tolerable. The potential side effects of ketamine appear to be dose-dependent and peak within 2 hours of infusion and resolve within 4-24 hours of infusion.

The most common short term side effects of subanesthetic doses of ketamine administered intravenously include a sense of dissociation (feeling disconnected from yourself or surroundings), increased blood pressure, and increased heart rate, which appears during treatment and disappears shortly after the infusion. Other potential side effects are anxiety, blurred vision, dizziness, headache, nausea, vomiting. These are known to be self-limited. We will monitor for these symptoms throughout the treatment.

In terms of long term side effects, studies of prolonged use of higher doses of ketamine have identified urinary symptoms, cognitive impairment, and risks for abuse and addiction. However, the duration of ketamine infusion within our program is not prolonged. The treatment dose used for depression is non-addictive.

How quickly does IV ketamine treatment begin to work?

The antidepressant effects of ketamine have been demonstrated to occur within 24 hours of a single administration. Some patients may see relief within a few days and some may need repeated treatments.

How many sessions of treatment will I need?

You will receive your IV ketamine treatment two times per week for three weeks. In total, you will receive 6 treatments over three weeks.

How long do the effects of ketamine last?

The antidepressant effects of ketamine appear to wear off within 3-12 days after treatment, although some patients remain well for a couple of months. The effects can be maintained with repeated doses of ketamine or other treatment modalities, including pharmacology, psychotherapy, or neurostimulation. However, there is not enough evidence to suggest the best route of administration, treatment interval, or dose of ketamine for maintenance treatment.

Can I continue taking my antidepressant medication while getting ketamine treatment?

Ketamine treatment is safe to receive when taking concurrent conventional antidepressants. There has been some evidence which suggests that concurrent use of some medications such as benzodiazepines and NMDA receptor antagonists may affect the effects of ketamine. Your psychiatrist will review your medications prior to determining if you are eligible for treatment with ketamine.

What are the contraindications for ketamine?
Ketamine should not be given to individuals who suffer from psychotic disorders or have psychotic symptoms. Ketamine is contraindicated in those who have uncontrolled or inadequately controlled elevated blood pressure and those who have shown hypersensitivity to the drug.

Do I need a referral for ketamine treatment?
You will require a referral from a physician

Where do I go for my intake assessment?
Your intake appointment may be conducted in-person or virtually. Our administrative team will let you know what type of appointment you will have prior to your visit. For virtual appointments, you will receive information about how to join your session virtually from the comfort and safety of your home. For in-person appointments, please come to St. Michael’s Hospital and go to the 17th floor of the Cardinal Carter South wing. Please check in at our reception desk. Please arrive 15 minutes early for your appointment to complete questionnaires which you will receive from the reception desk.

What can I expect before coming to the intake assessment?
You will be seen by a Psychiatrist and Physician Assistant to complete an initial 60-minute intake assessment to determine eligibility for the ketamine program. Once eligibility has been determined, you will be provided with information for your treatment schedule, which involves two in-person appointments per week for three weeks.

What can I expect before coming to my treatment sessions?
You will meet with the psychiatrist and physician assistant prior to receiving your treatment. You will meet an anesthesiologist who will be administering the intravenous ketamine treatment. The ketamine will be infused for 40 minutes.You will be  monitored for ___ after receiving the treatment. The entire session will take an average of ____.

Since St. Michael’s Hospital is a teaching hospital and is affiliated with research, you may meet other team members who may ask if you are interested in participating in any existing research trials.

What can I expect after completing the ketamine treatment program?

After completing treatment within our program, you will be referred back to the referring physician with further treatment recommendations and for ongoing care. We will continue to monitor you at regular scheduled follow-up appointments for up to ___ weeks.

In case of an emergency

If you are having thoughts of harming yourself at any time, please call the Greater Toronto Distress Centre Helpline 416-408-HELP (4357) or visit your nearest emergency department. In this situation, please do not use the clinic voicemail or email, as it may not be possible to provide an immediate response.


Anesthesia team to add specific details about treatment day eg. where to go, process

Eligibility criteria for referral form

Eligibility criteria:

  • Age 18-65
  • Individuals who have been diagnosed with moderate to severe Major Depressive Disorder or Bipolar Disorder
  • Individuals who are experiencing a Major Depressive Episode as defined and operationalized in the DSM-V
  • Individuals must have received at least 2 guideline concordant pharmacotherapeutic treatment trials

Exclusion criteria:

  • Individuals who meet DSM-V criteria for substance use and/or alcohol use disorder or have met criteria in the last three months
  • Individuals who are experiencing psychotic symptoms
  • Individuals who are experiencing a current manic episode
  • Individuals with symptomatic traumatic brain injury
  • Uncontrolled medical disorders (i.e. uncontrolled or insufficiently treated hypertension)
  • Individuals who are pregnant
  • Medical contraindications, allergies, or previous intolerability to ketamine
  • Individuals who cannot provide consent to treatment
  • Individuals who cannot commit to biweekly in-person treatments for duration of treatment

References

1. Andrade C. Ketamine for Depression, 1: Clinical Summary of Issues Related to Efficacy, Adverse Effects, and Mechanism of Action: (Clinical and Practical Psychopharmacolgy). J Clin Psychiatry. 2017;78(04):e415-e419. doi:10.4088/JCP.17f11567

2. Andrade C. Ketamine for Depression, 2: Diagnostic and Contextual Indications: (Clinical and Practical Psychopharmacology). J Clin Psychiatry. 2017;78(5):e555-e558. doi:10.4088/JCP.17f11629

3. Andrade C. Ketamine for Depression, 3: Does Chirality Matter?: (Clinical and Practical Psychopharmacology). J Clin Psychiatry. 2017;78(06):e674-e677. doi:10.4088/JCP.17f11681

4. Andrade C. Ketamine for Depression, 4: In What Dose, at What Rate, by What Route, for How Long, and at What Frequency?: J Clin Psychiatry. 2017;78(7):e852-e857. doi:10.4088/JCP.17f11738

5. Andrade C. Ketamine for Depression, 5: Potential Pharmacokinetic and Pharmacodynamic Drug Interactions: (Clinical and Practical Psychopharmacology). J Clin Psychiatry. 2017;78(7):e858-e861. doi:10.4088/JCP.17f11802

6. Andrade C. Ketamine for Depression, 6: Effects on Suicidal Ideation and Possible Use as Crisis Intervention in Patients at Suicide Risk: (Clinical and Practical Psychopharmacology). J Clin Psychiatry. 2018;79(2):18f12242. doi:10.4088/JCP.18f12242

UHN ECT v Ketamine protocol

UHN rTMS FAQ for formatting

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