That Floating Sensation May Predict Ketamine’s Healing At Work
Know anyone who’s depressed?
I don’t mean someone feeling blue or disappointed, but really depressed. The hard-to- function type of depression. The hard-to-think-hard-to-get-out-of bed kind of depression. Where everything looks dark and hopeless, and you doubt yourself and your value…and it continues and gets worse for months or years.
Severe depression. The kind that makes you want to die, and you can’t see any value in your life…and those thoughts start coming… that everyone who knows you would be so relieved if you were gone. Lies that kill.
Depression like this messes with your outlook, your decisions, your abilities, your energy, your motivation, your perception of your own value… and it’s almost insurmountable to get out of bed.
We Call Your Disorder “Treated” Only If You Feel Better
In some cases we call this Major Depressive Disorder, or MDD. In others, it 
may be the depressive part of the cycle in bipolar disorder. Depression of this magnitude can be debilitating. And it needs to be treated effectively. In fact, no matter what treatment is used, if you don’t feel better, then it’s the same as if your depression weren’t treated at all.
No matter how many pills you’ve swallowed or how many therapy sessions you’ve attended —
Treatment must produce results you can feel and confirm. Or else it’s not effective. And if you aren’t feeling better and functioning better … well, what’s the point?
Ketamine is a medicine that was developed in the 1960’s and ’70’s as an anesthesia medicine. It’s been used for 50 years safely with children, adults, and senior citizens. It regulates glutamate in the brain, and blocks the NMDA receptor which prevents it from causing you to feel depressed.
AMPA Gives You Power to Adapt and Develop Flexibility
It also fires up AMPA , which is another glutamate receptor that is responsible for most of the fast excitatory transmission in the brain.
In other words, it’s the AMPA receptors that are behind the synaptic plasticity, 
which means they empower the connections between brain cells to grow and flourish and move signals around the brain much more rapidly.
Plasticity basically means changeability. Or…changeableness. (Are those even words…?)
So, synaptic plasticity changes the connections in your brain and makes them grow and bud and sprout like crazy…which helps you to develop more and more ability to adapt the way you think, the way you respond, the way you see events and circumstances so you can develop flexibility, healthier thinking habits and more resilience, too.
This is one big part of what makes ketamine work so well.
Ketamine’s Antidepressant Response
Then it tells the cell to make more and more AMPA fast, so you feel better and better rapidly. And this is just one action ketamine performs to fight depression. There are lots of others, but let’s focus on this one for now.
We’ve talked often about ketamine treatment, provided in tiny doses roughly equal to 0.5mg/kg given IV over 40 minutes by a psychiatrist who is adept with psychopharmacological methods that make the most of each infusion.
Ketamine is a molecule that modulates the excitatory neurotransmitter glutamate.
We’ve talked about how important close supervision by a psychiatrist is to determine the rate and dose needed specifically for you, and your brain, so you have the quality of response to the medicine that will provide the best outcome for you.
And…we’ve pointed out that some providers have popped up in the landscape who give the same dose to every patient, or the same protocol, or varying doses to every patient with little attention to precision rate or infusion length. This is super easy for the provider, easy for the clinic. There is no infusion pump, and the only rate control is the rolling wheel on the IV tubing.
You see where I’m going.
Care in Ketamine Administration Yields Better Results for You
We’ve hypothesized that this less precise administration of ketamine may be the
reason that non-psychiatrists and psychiatrists alike who use this one-size-fits-all method for treating depressed patients was resulting in a lower percentage of remission from mood disorders across the board.
We know that we’ve seen an 80% response in treatment-resistant patients by using this precise and remission-focused approach.
Well, researchers published a study in February this year in the Journal of Affective Disorders along this line. It demonstrated how the various dissociative effects can predict how much antidepressant effect a person will receive from a ketamine infusion.
Led by Mark J. Niciu, a team of researchers including Carlos Zarate (a leader in ketamine research), conducted a followup study to their previous work to determine whether the quality of dissociation was correlated to a positive antidepressant response.
Dissociation…and Ketamine’s Antidepressant Response
We’ve all been interested in this. Is dissociation “just a side effect,” or does it 
MATTER? Is it necessary to have dissociation for ketamine to “work?” Or for depression to lift? For anxiety to dissolve? For trauma to heal? And what dissociative features, exactly? How intense are we talking about? And for how long?
The researchers took a group of 126 people from 18 to 65 with mood disorders – 84 with major depression and 42 with bipolar disorder and asked them to complete rating scales just after their treatment about what they experienced during their ketamine infusion.
Dissociation is basically a detachment from reality, but it can include detachment from yourself (depersonalization), detachment from your surroundings (derealization)…and sometimes a sense of amnesia.
The Study:
Now, each patient involved in the study was currently experiencing a full episode of depression that had been going on at least 2 weeks. Prior treatments had failed all of these subjects. In some cases just one, but many had tried multiple treatments.
Researchers selected the subjects very carefully. None of them had psychotic symptoms and none of them had dissociative symptoms at baseline.
Some patients received a ketamine infusion (yep, just one, not a series) at a prescribed dose of 0.5mg/kg over 40 minutes and others received a placebo…
And guess what?
People who experienced dissociation during their ketamine infusions had much more improvement in their depressive symptoms – the more intense the dissociation, the better the improvement.
And the specific dissociative feature (remember there are 3: depersonalization, derealization and amnesia) that was most strongly associated with responding to ketamine? Depersonalization.
The antidepressant effect was strongest at Day 7, not 3-4 hours
after or a day later.
You Can’t Know Without Testing – There’s So Much to Learn
Isn’t that interesting? You’d think the response would have been strongest during the first 24 hours, but not so in this study. You know… the miracle WOW that everyone seems to expect. (Boy, do we have to explain and help reset expectations here.) When you think about how ketamine restores signaling structures as well as all the other things it does, it does stand to reason that as the structures in the brain improve, so would the antidepressant effects.
The research team encouraged more studies to pin down and confirm their findings. And we do, too. But it’s exciting to consider that the very dissociative experience you feel during a ketamine infusion is actually connected to the wonderful restoration it does.
Understanding Your Treatment and Your Healing
It’s important to know that the experience itself is important… important for your improvement and healing.
When you understand this, it’ll help you not be afraid.
And it’ll help you understand that the dissociative experience during treatment is not something we see as bad or unwanted or as an adverse event that needs to be avoided or abolished. It’s an integral part of the treatment itself, and something that we have come to understand is critical for transformation.
With proper treatment, and fine control of the dose and rate of your infusion, we work towards just the right place for you … where your treatment, and your dissociative experience during your treatment, fuse together in the best possible way, to give you the best possible outcome.
Now that’s a sweet spot!
When you’ve felt trapped by a disorder, you’ll do just about anything to live a fulfilling life and wake up every morning with hope.
Every single step of research that shines another light on ketamine’s 
extraordinary impact on depression and other mood disorders brightens the path for all of us who treat patients with ketamine, and for those who suffer from all these mood disorders and haven’t been helped by anything else before.
There really is hope!
We Want You to Enjoy a Rewarding Life
Here at Innovative Psychiatry we continue to see people like you who suffer and have given up. Then, after a ketamine treatment series, we often see them achieve remission and enjoying their restored ability to create, to invest themselves, to build relationships, and to savor life’s moments. We see this everyday.
If you’re struggling with a psychiatric mood disorder that has not improved with other treatments, call us. We’re here to help you find the relief thousands of others have found.
This is a new era, and you really can feel better…you can even feel well. Kick that disorder to the curb… let’s work together to help you live again.
To the reinvigoration of your best self,
Lori Calabrese, MD