I love Canada, but sometimes we’re a little behind. Drug approval by Health Canada is slower than in the US, and fewer clinical trials are done here. I’d 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 with treatment-resistant depression. I could go to a private clinic in the US, but that 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 around for some time as an anesthetic. It’s also a potential drug of abuse 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 depressive 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.
Ketamine’s mechanism of action
Ketamine’s mechanism of action is different from 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 the production of BDNF (brain-derived neurotrophic factor), which in turn promotes brain health and neuroplasticity. This mechanism may be why ketamine has antidepressant effects when other drugs that act on the same receptors don’t have the same effects.
Some research suggests that people with depression may have abnormalities related to their NMDA receptors. This can produce glutamate overactivity, leading to hyperexcitation in the brain, known as excitotoxicity.
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 anesthesia, with 1-2 doses per week. It’s given as an intravenous infusion. The effect from each dose typically lasts 3-7 days, but it can last up to 15 days.
There’s also a nasal spray formulation that delivers esketamine. Ketamine consists of two mirror-image molecules, abbreviated as S and R. Esketamine is the S-ketamine molecule only.
Side effects are supposed to be generally mild and wear off within 2 hours. While harmful effects on the bladder can occur at high doses, this hasn’t been demonstrated at the doses used for depression treatment. Dissociative effects can occur during the infusion and in that 2-hour 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.
Ketamine’s role in treating depression
Ketamine is still in its relatively early days in treating depression. It’s labour-intensive, as patients need to remain in the clinic for at least 2 hours to let the dissociative effects wear off. This is true whether it’s administered by IV or nasal spray.
Ideally, researchers will come up with another drug that has the same kind of therapeutic effect as ketamine without the anaesthetic/dissociative effects. Hopefully, that will be coming down the pike sooner rather than later.
In the meantime, I’m hoping that I’ll be able to have reasonable access to ketamine soon, because being treatment-resistant sucks, and I need something that works in a different way from all the stuff I’ve already tried.
Have you had any experience with ketamine?
For more posts on psychiatric medications, check out the Psych Meds 101 series, which covers: