Ketamine for Treatment-Resistant Depression

Ketamine for depression: how it works, side effects, and how it's used

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

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:

book cover: Managing the Depression Puzzle, 2nd Edition, by Ashley L. Peterson

Managing the Depression Puzzle takes a holistic look at the different potential pieces that might fit into your unique depression puzzle.

It’s available on Amazon and Google Play.

23 thoughts on “Ketamine for Treatment-Resistant Depression”

  1. Wow..sounds like a great drug. But I don’t like the side effects. However, when I am in a serious depression…as I know others can tend to fall into..maybe the pros could outweigh the cons. If only those side effects were not part of the dosage (the rapid heart rate, dissociative). If only a drug like this could work…without those serious risks. Looks like we are making progress I guess with meds like this. But not sure I am willing to take that risk right now.

  2. I am all for stuff like this, and it sounds very interesting. I’m hearing more and more about this sort of thing, so I hope it makes it way into mainstream treatment at some point in our lives…

  3. I think its interesting how there is research being done with certain drugs and how they help with different mental illness. I know there are some trials with good success going on right now with MDMA and PTSD. Heres hoping for more options!

    1. Revenge of Eve

      Doesn’t MDMA have a lot of bad effects on your brain? I used it for a long time and in recovery I have learned that is the reason I have a lot of memory loss. I’m not sure how accurate that is.

      1. I’ve also heard of positive results with MDMA for PTSD. I think the amount used is quite a bit lower than the amount that tends to be used recreationally.

  4. Revenge of Eve

    I’ve used it recreationally and it was wonderful but being that I am bipolar, it didn’t last.

  5. I have never tried ketamine, but then again after reading the side effects, I would stay clear. I’m very cautious as to what meds I am taking and future meds. After going through what I have with the withdrawals from Klonopin, I’m nervous to take anything.

  6. I’ve used Ketamine recreationally and I can tell you being someone diagnosed with bipolar depression the whole time I felt like I was falling. I was falling in what they call a, “K hole” its as if you’re falling down a rabbit hole and never going to hit a bottom, well until it wears off.

  7. I tried it and definitely had a positive result–though as a sober AA member, I’ve always liked all kinds of drugs. This one makes me feel awfully conflicted (which is why I set up a blog, hoping to meet other sober folks who’ve used ket for PTSD…..

  8. I’m trying IV Ketamine right now and it’s helping a little bit (I have pretty bad treatment-resistant depression, though). But they can’t K-hole me even when they try. They can’t get me to disassociate. So just putting that out there. I think I metabolize drugs really fast, hence the difficulty in treating me.

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