The Big Question
Is dissociation needed? Is it necessary? Can you get better without it, or with “just a little bit” of dissociation? Does the kind of dissociative experience you have during a ketamine infusion predict whether ketamine is going to work? Or how much it will help? …. or If it will help faster? If it will work better….? Will it be scary? Will it be negative? Can it set you back….or make you worse? Can you do anything to shape it (yep, the dissociative experience) to get the most out of it? Boy, what IS dissociation anyway? And is dissociation important for ketamine to work?
I’m tellin’ ya, that is the question of the hour. Every hour. (Or every 90 minutes, I should say. Because that’s the time we set aside for you, when you receive a ketamine infusion. )
When you come in for ketamine, we dive deep. We look for what you used to be like at your best self—really like. Or… if it feels like you never had a best self, we go back further still. And then we look at all of the factors that have contributed to where you are today: what happened, how it happened, what the interplay is genetics, experiences, people in your life, work and the things you love, symptoms and how they’ve spiraled out of control, treaters and treatments that didn’t work out for you.
We want to understand your narrative. Because if you are a candidate for treatment with IV ketamine, we want to offer you the hope and the possibility to change that narrative….and write a new one moving forward.
So the question is what does that? What moves you forward? Ketamine itself? the racemic molecules, the NMDAR antagonism and disinhibition? glutamate activation? the multiple downstream effects involving AMPA activation, and g-protein fast action sliding off lipid rafts? The production of BDNF (brain-derived neurotrophic factor), and the growth of new branches on neuronal trees that leads to synaptic plasticity and flexibility of thought?
There is a lot of action that ketamine creates (and a lot that we are still exploring because we don’t have all the answers yet about exactly how it works). And it is all very wonderful and scientific. We love the molecular, we love the granular….we love translational neuroscience. But more than that, we love the transformation that we see when science blooms deep in the mind.
And that’s what happens in dissociation.
Science blooms in the mind.
Let me tell you what that means.
Dissociation has been described with all kinds of terms, including feeling dreamy, floaty, spaced out …. Detached from yourself or not a part of yourself, feeling detached from your surroundings. Having changes in your sense of self and where you are–feeling like you’re not yourself but a collection of thoughts or a mind/heart somewhere in the universe.
You’ll hear people describe it as feeling weird, loopy, or really trippy, with visual experiences, or feeling that time expands or contracts. Feeling an ineffable sense of awe. Or sometimes feeling like something dark is trying to intrude.
Early reports with IV ketamine for depression suggested that dissociation was associated with a good response to ketamine. Not that it was to be avoided, but that it was actually OK. More than OK, it was part of the treatment and part of what might be helping lift depression.
More recent clinical research, and the experience of countless ketamine clinicians and thousands of patients suggests not only that is it welcomed, but that the dissociative experience during your treatment could be necessary, maybe even IMPORTANT for you to experience, to remember, to analyze and to integrate into your life’s experience as your move forward…and AWAY from your depression, your anxiety, your trauma.
We think dissociation is incredibly important, and that the way that you recall your experiences during dissociation, interpret them, and look for meaning will help you grow, develop flexibility of thought, open you up to new possibilities and reawaken old loves (like the love of music, or sports, or the outdoors) or invite you to seek out new ones. The biological changes that lay the structure, and the ineffable and sometimes spiritual or mystical experiences that can occur during dissociation can be absolutely transformative. Stunningly effective. In a way nothing else we have is.
Is it important?
You betcha.
Can we prove it?
Ah. That’s another story.
Prominent Ketamine Researchers Seek Answers
Recently, two veteran neuroscience researchers in this exciting “ketamine for depression” saga, Elizabeth D. Ballard, Ph.D. and Carlos A. Zarate, M.D., published a groundbreaking paper in Nature Communications. They addressed the question about whether dissociation is important for ketamine’s antidepressant effects.
To do that, they scoured over 76 papers — peer-reviewed published reports and clinical trials of IV ketamine used in the treatment of depression, reviews, psychedelic research.
There are physicians who offer 6 ketamine infusions at a “standard dose” of 0.5 mg/kg over 40 minutes. This was the early protocol used in early research trials. And there are certainly many who haven’t veered from it.
There are others who have taken a more flexible path to help more people achieve remission. We’ve hinted about how we titrate the dose, the rate, and the number of infusions, in an effort to evoke a better response. Getting better is what matters. Living better is what sings.
Still, there has been some controversy about the role dissociation plays in ketamine achieving that response, especially remission from severe depression. So, we applaud Elizabeth Ballard, PhD and Carlos Zarate, MD for their diligence in trying to find answers to the questions.
Let’s talk about their paper, and address the current position ketamine holds among treatments for depression and other disorders, and how far it’s come.
This beautifully written manuscript highlights the immediate antidepressant effects ketamine treatment produces, along with the short-term dissociative effects that often occur during the infusion itself.
So… is dissociation important for ketamine’s antidepressant benefits? Let’s see…
They say the primary purpose for their publication is to scrutinize other studies and to learn — through a close examination of other research — and figure out the answer to this question. Is the side effect of dissociation necessarily a requirement of the antidepressant impact that is so restorative to so many… you could even say most…patients?
Oral antidepressants have a slow onset of relief, taking at least weeks, and often months, to bring relief. In fact, after all that waiting, sometimes those medicines don’t improve symptoms much at all. (If you’re reading, you probably know this firsthand.)
Ketamine, in contrast, can create rapid improvements in many symptoms within hours or a day. Ketamine treatment is not for everyone (for a variety of reasons). But for those who are good candidates, ketamine usually provides more relief and more remission than any other medicine we use.
Extraordinary Restoration in Treatment Resistant Conditions
Ketamine shows its greatest effectiveness and rapid responses in treatment resistant depression, bipolar depression, PTSD, OCD, social anxiety disorder, substance dependence, and suicidal thoughts.
As we’ve also talked about before, in a separate action, ketamine has become known for rapid eradication of suicidal thoughts. We’ve reported our own real world results about how ketamine can stop suicidal thoughts in an afternoon in the office, preventing visits to the emergency department and hospitalizations.
Chemists originally developed ketamine as an anesthetic to replace phenylcyclidine (known as PCP) in the ’60’s because PCP caused delirium, agitation, hallucinations…and violence. So it was taken off the market. Those chemists set out to develop ketamine in the same laboratory to initiate anesthesia. Ketamine didn’t illicit violent behaviors, thankfully. But dissociation and out-of-body experiences accompanied it and it was labeled a dissociative anesthesia.
Then, in the early part of the 21st century, studies began to explore what ketamine might do for people with treatment resistant depressive disorders using small doses…and the results were eye opening.
As far as the connection between dissociation and an effective antidepressant response to ketamine:
A study in 2014 found that the other side effects of ketamine, such as systolic blood pressure changes, diastolic blood pressure changes, pulse changes, or manic symptoms, weren’t associated with improvement in depressive symptoms…not at 230 minutes, or at 7 days after the infusion.
On the other hand, dissociative symptoms were associated with antidepressant improvement at 230 minutes, and at 7 days after the infusion.
Another finding of note was that some subjects with treatment resistant depression respond enthusiastically to their rapid improvement. But, when healthy subjects received the infusions, some of them experienced a transient period of dysphoria, feeling uncomfortable and ill at ease, after a ketamine infusion.
Beyond various side effects — including dissociation — that others have experienced, there’s more to consider. Let’s talk about the importance of a patient having the ability to access a “non-ordinary state” of mind to fully benefit from the work that ketamine does.
This “non-ordinary state of consciousness” can usher in neuroplasticity in the brain. Where the synaptic connections are growing, proliferating, changing… and this state of change can open your mind to think new thoughts, and to think differently about things that happen.
Like how you feel about a trauma, or a stressor, and to change your response to that experience.
The experiences, the meaning, the imagery often open up new and deeper ways of thinking about the experiences in your life in new ways, and give you an opportunity to perhaps forge a new path.
How exhilarating that can be!
So now, ketamine treatment…a series of infusions over a few weeks….is building a reputation for effectiveness with treatment resistant depression, bipolar depression, social anxiety, PTSD, OCD, and substance dependence. And by a separate action, ketamine has shown it can eradicate suicidal thoughts rapidly.
Because ketamine’s effects have been so remarkably effective in those it helps, it’s inspiring the development of new medicines in hopes of discovering more wonderful treatments for people who suffer.
So what is dissociation, really?
According to one expert, dissociation is defined as a discontinuity in the normal integration of consciousness, memory, identity, emotion, perception, body representation, motor control, and behavior. These veteran researchers acknowledge that it would be beneficial if ketamine could be as effective without the side effects of such things as dissociation. But it is not yet clear whether the dissociation is a core feature of the antidepressant response. Or, it could be just a side effect. Ballard and Zarate point out that the evidence is just not conclusive or clear.
Yes…but what’s important about dissociation??
Well, that depends on who you are…and where you’re coming from. The early researchers showed it was important because it was associated with a better response to ketamine treatment. Ballard and Zarate, in the paper we talked about above, question that because their analysis of the literature to date suggests the findings are inconsistent. They conclude that “the relationship between dissociation and ketamine remains an open question.” Part of the question may be that the rating scale used in most of the the studies to “measure dissociation,” the CADSS, might not be the right one. It was designed to measure dissociation just before and after the recall of traumatic memories in patients with PTSD. But it might not really be the best scale to capture the rapid dissociative experience that happens during a ketamine infusion and the range of experiences —like perceptual changes, peacefulness, bliss. (There are other scales out there that might capture these better.)
So…if you’re a researcher, “important” means predictive of, or statistically associated with, or prognostic for. Then “is dissociation important?” means “is it necessary for response or remission?”
Stick with us here.
However, if you’re a pharmaceutical company, you might see dissociation as just a weird and hard to quantify experience. Troublesome. You list it as an adverse effect. (Because it’s not the primary goal of treatment–remission is.) It could get in the way of your FDA approval, and of allowing your newly developed drug to be approved for at-home use. It can affect your sales. It might get in the way, it might push you to test and produce low doses and leave it at that.
BUT…if you’re the one sitting in the chair, what you want to know is this: Is what I experience during an infusion important for ME? How can I make sense of it? For me? How can I use the experience… to help me? Can dissociation—and the whole experience—actually help me?
What ketamine infusions can do for you is what is important to you. The whole experience — from start to finish, from the beautiful serene setting to your mindset and your intentions (and your hopes and your fears) as the infusion begins — can and should be integrated so that you can move forward and into a better, richer, life.
Infusion. Infused with hope.
There really is hope.
At Innovative Psychiatry, ketamine treatment continues to be the best treatment we offer for rapid relief and remission of depression and suicidal thoughts, and for rapid relief in so many of the conditions we’ve discussed. We look forward to following the research — and working with our own patients, who are often our finest teachers — and to learning from all of it as the field moves forward.
We’re also set and ready to provide ketamine treatment for you in our safe offices. We’ve installed a system that destroys bacteria and viruses, including coronavirus, from the air and lifts them from hard and soft surfaces so you can get treatment, even in the midst of a pandemic, without hesitation or fear.
We titrate your dose and adjust your infusion rate to make your treatment comfortable, productive, and effective. We want you to get better. We want you to find your joy again…to embrace bliss.
If you’ve found that your medicine for your disorder isn’t helping, call us.
We’ll talk about your history, your symptoms, your needs… and determine if ketamine treatment is a good fit for you.
Although we can’t guarantee your outcome (no one can), we’ll offer you our best judgment, and all of our clinical expertise. This treatment is very effective for the majority of our patients, and it could be transformative for you.
Call us and let’s work together to see what ketamine treatment can do for you.
To the restoration of your best self,
