I love Canada, but sometimes we’re a little behind. Drugs are slower to get approved by Health Canada compared to the US, and we have fewer clinical trials going on here. I would be really interested in trying out ketamine, but it doesn’t have Health Canada approval for use in depression, there are no clinical trials in my neck of the woods accepting new patients, and going to a private clinic in the US would be extremely expensive. So for now, all I can do is dream of ketamine. But in the meantime, what is ketamine and how does it work?
Ketamine has been in use for some time as an anaesthetic drug, and it has been abused as the club drug Special K. In the last several years multiple research trials have shown that it has a rapid onset antidepressant effect (within about 24 hours). It increases rates of remission in major disorder, but the effect is not as pronounced for bipolar depression. It appears to have a protective effect against suicide, and unlike many antidepressants it doesn’t appear to trigger mania.
Mechanism of action
It has a different mechanism of action than other antidepressant medications. It acts on NMDA and AMPA receptors, affecting the balance between the calming neurotransmitter GABA and the excitatory/stress neurotransmitter glutamate. It also boosts production of BDNF (brain-derived neurotropic factor), which in turn promotes the formation of new synaptic connections in the brain. It has been suggested that people with depression may have abnormalities related to their NMDA receptors and experience what’s referred to “excitotoxicity” from glutamate overactivity.
Ketamine is typically given at a dose of 0.4-0.5 mg per kg of body weight, which is a lower dose than would be used for anaesthesia, with 1-2 doses per week. The effect from each dose typically lasts 3-7 days, but can last up to 15 days. It can be given as an intravenous infusion, or the esketamine version of the drug is available as a nasal spray.
Apparently side effects are generally mild and wear off within 2 hours. While harmful effects to the bladder can occur at high doses, this hasn’t been demonstrated at the doses used for depression treatment. It can have dissociative effects while the drug is being infused and in that 2 hours window after the dose, which could potentially limit the tolerability for some people. It can trigger spikes in heart rate and blood pressure, as well as headaches, dizziness, blurred vision, drowsiness, abnormal sensations, and perceptual disturbances. Patients remain in the clinic for a period of time following the dose so that they can be monitored.
What are your thoughts? Have you had any experience with ketamine?