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:
-
- 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.


Ketamine Can
and performed well in school…receiving all sorts of academic awards.
answering the telephone. School became an insurmountable mountain to climb. She began to hide under her bed for the school day so no one would know she didn’t go. She couldn’t go.
Finally, she was placed on
The verbal abuse and horrific scenes deteriorated to physical abuse, but just reminded her that she knew what it was to suffer. And he’d been alone without support, so she was determined to be that support and “help him heal.”
Bangkok she suffered a gargantuan panic attack. She couldn’t think to find her luggage, her gear, or her phone. Finally, she called her family collect and asked them to help her get home. Knowing her fragile state, they readily complied.
shoulders that left her left shoulder 3 inches shorter than her right one. She was unable to move her upper body without extensive treatment.
she got out of the hospital.
months. Then she began to feel the old depression returning, the critical thoughts, the anger, the hopelessness…but for the first time since she was a little girl…
her through the illnesses and surgeries, and life is working for her now on an exciting new level.
dangerous depression can be.
Ketamine Treatment Shows It’s Effectiveness with Treatment-Resistant Adolescent Depression
high. He’d been invited to a magnet school focused on science and technology for his high school years. After winning a pile of awards for his debate team, as well as in math and science competitions, he couldn’t continue.
person’s normal social, mental, and academic development. It colors the way he or she sees the world, and the people in it.
round of treatment, and only half respond to the second round. We’ve talked before about how failed treatment affects teens with
for its effectiveness with
patients require a higher dose than adults to achieve a dissociative state, which is an important aspect of ketamine treatment.
suffer from treatment-resistant depression, and watch them emerge from ketamine treatment with joy, 
Smash Treatment-Resistant Mood Disorders with Rapid-Acting Antidepressants: Like Ketamine Treatment
Through a series of leaks and improprieties however, it began to drift onto the streets as an illegal substance. The drug was phencyclidine, or PCP. Remember 
with thoughts of suicide, if those thoughts can’t be eradicated quickly, the risk of death is high.
and instead prolong them. As we’ve moved forward in clinical practice, we’ve found that increasing the number of infusions in some cases can ensure remission. That is, if the initial six fell short of that goal. And we’ve worked with different infusion protocols over 2-3 weeks.
with many new medicines that operate quickly to treat mood disorders. But that’s the way of progress.
Trauma: Don’t Beat Yourself Up – Allow Your Loved Ones to Lift You UP
may not have shattered him like the next guy. People go through divorce. One ex-wife gets thoroughly angry and surges forward like a steam engine to overcome the heartbreak she feels about her husband’s infidelity. But another one may be so shattered, so disillusioned she can’t work, can’t function, and trembles or vomits when she sees her errant ex-husband or drives by their favorite restaurant.
she has reason to be heartbroken and deeply shaken. The fact that another woman lost her infant child in a sweeping illness does not trump the widow’s pain.
person is different
elp you move forward.
from the ashes, you’ll likely gain strength and resilience through the processes you endure, and the storms you weather.

years with undiagnosed depression. Not that her parents were aware. Quite to the contrary, they were proud of their talented and intelligent daughter. As long as she continued to perform, they were happy.
swallowed up by a hole. How could she face the 8th grade boys when she felt so ugly?
DHA and EPA are long chain omega 3 fatty acids that account for 97% of the omega 3 fatty acids in the brain. They’re vital for optimum brain function and development.
mother’s depression during pregnancy, showed inflammation and depression in adulthood.
Psychiatric Disorders and Creativity: Is there a link?
performing arts, politics, business, religion, literature, music, and science translate to exceptional people all around you in school, work, and everywhere in between, it’s worth another look.
developing symptoms of schizophrenia.
patients we treat. Ketamine treatment is
psychiatrists deeply experienced in treating life-threatening psychiatric disorders as well as
a precise infusion pump and monitoring equipment to ensure the most thorough and effective treatment experience. 


the
have been prevented if everyone knew about ketamine’s
this one and inform yourself. It’s no longer necessary to suffer under the burden of a seemingly untreatable disorder. 
Postpartum Depression and Paternal Postpartum Depression
seem to be responding like you thought she would. In the first few months, she’s noncommittal and has nothing much to say. In case something goes wrong.
period is interrupted, it can cause a cascade of suffering in both mother and child. The cooing and cuddling a mother does with her newborn stimulates the growth of neurons and synapses in the brain.
enough for the
Clinical and Diagnostic Research. They included 92 women scheduled for caesarean section, to determine the safety and effectiveness of using a combination of ketamine and propofol to manage pain after surgery. Researchers hoped to address the problem of pain that delayed initial breastfeeding after caesarean section. (Stay with me here — it’s relevant.)
tested to find more medicines that act quickly like ketamine does. In the future, we may find that they can be used postpartum to bring a mom to remission quickly so she can bond with her baby.


operating system in the human body. It is absolutely the “last frontier” in medicine. And it has as much credibility as any other body system…and is as real as Saturn or Jupiter…two planets we can see but can not yet touch.
processes and tight control of the protein “expression” of these genes. Genetic expression basically involves turning on the protein or RNA that the DNA creates to fulfill that gene’s blueprint. 
lays another row of bricks in the foundation of our understanding of the causes of different psychiatric conditions, and opens up new directions to improve treatment.