Treatment for Psychiatric Mood Disorders Has Been Quietly Waiting To Do Its Magic for 50 Years
He was 48, in the midst of a booming career, and like some others who demonstrate that special kind of genius, he had periods when depression came over him unexpectedly…and made it extremely difficult to function.
Because of his star-level performance most of the time, his boss gave him some room during these times to find “whatever he needed to find” to get back on his feet. It was humiliating…and he felt powerless to change it. He wished he could disappear into a hole and never come out.
After a lifetime of trying to physically and mentally brute his way through the days, training himself to function anyway no matter what…using muscle memory...he was growing weary of the battle.
Prolonged Years Fighting a Mood Disorder – Demoralizing
These long bouts made him feel foolish and stupid…like he couldn’t find two thoughts to rub together, and anyone who knew him could certainly see the pain and vulnerability in his face.
His productivity and accomplishments tanked during these times, and co-
workers made insensitive and cruel remarks.
“They’re jealous, honey,” his wife tried to soothe him. “Because they can’t keep up with you most of the time. You’ll be yourself again…just hang on.”
Finally, in desperation, he decided to pick up the card his sister had given him six months ago for a psychiatrist she really liked, and make a call. He didn’t know what he’d say…but at least he was calling.
…You Have to Take the First Step
Mary answered the phone. She had a soft voice, and she didn’t sound rushed. And at the end of her greeting, she asked him, “How may I help you?” It blew his mind. He didn’t know.
So he hesitated. He hadn’t called a doctor’s office in years.
“Uh. I’m wondering if I could have an appointment. I’m in bad shape. A couple times a year I get like this. Depressed, I think, but it makes me feel dumb, and weak.
“May I ask your name?”
“James.”
“Thank you, James. I think you’d really give yourself a chance to feel better if you met with the doctor as soon as possible. She has a number of advanced forms of treatment for depression that might make a real difference for you.”
“Well, I ran out of hope a long time ago.”
“Not today you didn’t–you called!”
When James arrived at the office, it was his Hail Mary last ditch effort. He sat 
down in the waiting room and spotted beautiful binders with The Ketamine Library on the front.
They were filled with articles and studies about ketamine treatment. It seemed the more he browsed, the more the articles answered any question he could think of…Something new for depression. hmmm. As he began to read the articles, he was astonished at the reports people gave and how much better they felt…
The articles also referred to esketamine, something about mirror images … and said it wasn’t yet available. He wondered why it was advertised when it wasn’t yet available. And he wondered how the two were related… so he kept reading…until his name was called. He stood up and walked into the office, hoping beyond hope that this time would be different…
Why Ketamine Over Esketamine (Still Testing for FDA Approval)
As esketamine nears completion of its FDA trials, and crawls closer to the 
coveted approval status, people all over the US who suffer from mood disorders are clamoring for more information.
Why Ketamine Over Esketamine?
The answer is rather logical.
Recently, I was asked some questions about the behavior of s-ketamine and r-ketamine, the two enantiomer Siamese twins that you get when you divide the ketamine molecule. S- stands for left, and it’s the left half of the ketamine molecule that has been named esketamine.
Someone said he had been excited about esketamine, but as he understands more about it, his enthusiasm is waning. So he asked:
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- What is an AMPA receptor?
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- Is it a part of the NMDA receptor, or a separate thing itself?
- And is it possible that there could be a synergistic effect of ketamine (Dextro + Levo) combined — meaning is it necessary to have both halves of the ketamine molecule to get the full benefits when ketamine is used for depression and other psychiatric disorders?
Why Ketamine Over Esketamine? Because It Works…and It’s Available NOW
This was my response:
“Thanks! Wow–these are great questions!
“There are 3 kinds of glutamate receptors: NMDA receptors, 
AMPA receptors, and kainate receptors. (Each kind has variants.) So AMPA receptors are just one of the 3 kinds of glutamate receptor and they’re different from NMDA receptors. They exist independently of NMDA receptors but they can be on the same cells next to NMDA receptors–and they often are.
“Even though there is so much interest in glutamate receptors, it’s the AMPA receptors that are really responsible for the majority of FAST excitatory transmission in the brain.
“And it’s the changes in AMPA receptors that are really at the core of synaptic plasticity.
The Nitty-Gritty On NMDA vs. AMPA Receptors – Clearing the Fog
“And long-term synaptic plasticity can last from minutes to a lifetime–a brilliant phrase that’s well known in neuroscience. Hold that thought.
“Here’s where it gets so exciting: a molecule (let’s think medicine) can bind to an NMDA receptor or to an AMPA receptor.. or to either or to both. Sometimes, a molecule can bind to an NMDA receptor and when it does, the NMDA receptor tells the neuron to make more AMPA receptors and bring them up to the surface quickly –
“Then, the numbers can increase rapidly, dramatically, and can stay high. 
This helps create quick responsiveness, flexibility, growth and change….and it can be for the long-term.
“Ketamine binds to NMDA receptors. And for a long time, people thought this was why it helped with depression. But then a lot of other drugs that bind to the same place failed when tested in depression and function as antidepressants.
“Hmmm…
The More We Learn, The Better It Gets
“What we now know is that ketamine directly binds to AMPA receptors and directly increases their numbers and the phosphorylation of those receptors (i.e., the activation of them) — wow! If AMPA is a major player in plasticity (and it is!) and AMPA production, activation, and movement in neuronal members increases long-term synaptic plasticity (and it does!), it may help you understand why we are all so incredibly excited about using sub-anesthetic doses of ketamine for depression: because it not only directly activates NMDA receptors (which can up the number and the location of AMPA receptors on the same cells), and because it also directly activates AMPA.
“More action, more firing, more growth… more opportunity for flexibility of thought, more opportunity for the kinds of changes that people with depression want to see in their lives.
“We see this every day in my office.
“Finally, it’s possible that there is a synergistic effect when both the r- and s- forms (the dextro- and levo- forms) of the ketamine molecule are present — which is what we use in our IV ketamine infusions. I need to explore this more, and we need more research into which form of ketamine — the r-, the s- or the racemic compound — best activates AMPA.
“Calling all neuroscientists!”
Another Question: Why Aren’t All Doctors Seeing Equal Results?
Truth be told, this is only a smattering of questions we’re all asking about ketamine, about esketamine, and about what might be the best treatment for the majority of patients who suffer with symptoms of major depressive disorder, panic disorder, social anxiety, bipolar disorder, PTSD, OCD, and substance use disorder…not to mention suicidal thinking.
Because there are a variety of ways doctors are administering ketamine, and 
because research is going on in laboratories and hospitals around the world to better understand what ketamine does, how it works, and what its limitations are, there are mixed reports coming from all directions.
Outstanding Outcomes Emerging in Private Practice
My intent in telling you what I see is to inform you to make the best decisions for your health. And at Innovative Psychiatry, we’re seeing the majority of our patients with treatment-resistant disorders enter remission daily, weekly, and all the time in between.
Now it’s true that there are some patients who don’t seem to be helped by ketamine, and we don’t yet know why. But. We’ve found that even some who weren’t helped initially…and went home disappointed…later responded to the treatment and entered remission within a few months. We can’t explain that….
It does matter how this medicine is administered, and we adhere to the best
research, the best recommendations, and the best psychiatry we can offer — and we see outstanding… really extraordinary… results with IV ketamine treatment. We know that all doctors, and all clinics, aren’t getting the best results. But those of us who are … well, we know at least part of the reason why.
The only thing that motivates us here at Innovative Psychiatry — and always has — is finding solutions that help our patients get better. So they can live and enjoy their lives, their work, and their families.
If you’ve tried at least two traditional antidepressant treatments with no relief, ketamine treatment may be the solution. It has been for over 80% of our treatment-resistant patients up till now. No other medicine for mood disorders has come close.
If you haven’t been helped by other treatments, call us.
This is National Suicide Prevention month, and we’re here to tell you that ketamine treatment can stop suicidal thinking in just a few hours. Often less. So that when those obsessive thoughts of death and dying stop, you can use the freedom that gives you to really dive into treatment and therapy that can help you save and rebuild your life.
Find out how much better you can feel.
To the reinvigorating of your best self,
Lori Calabrese, M.D.