Lori Calabrese, MD

Tag: IV Ketamine Treatment for Bipolar Disorder

Family: Suffering Together With Psychiatric Disorders

“I don’t care what the &%@!* you think!! It’s all your fault!! I’m outta here!!!”

With that, Ben picked up the massive carved oak coffee table and threw it at the window. It hit the window and the wall with a thud, pushing the window frame in a contorted mangle of metal and glass out toward the garden, knocking a gash into the wall with the impact. Families that are suffering together with psychiatric disorders know this scene so well…

The table fell to the floor, unaffected by its collision, except for a few paint scrapes off the wall. The wall, however, didn’t do so well.

By then, Ben had already grabbed a china lamp and slung it toward another window. The shattering glass of the window and the shattering china in the lamp base formed a tinkling wind-chimes sort of symphony as they fell.

Ben beat his face with both fists, cursing his life.

Suffering Together

Little 6-year-old Sara shrank back into the shadows of the hallway. She knew not to cross her big brother at times like this. He was her hero and had been her best friend ever since she was born. He was kind, patient and included her even though he was 7 years older.

It scared her when he got like this, but she also instinctively knew he just couldn’t help it. She knew he’d probably cry again after this rage subsided, because he felt so helpless to control it and so sad about hurting the family.

She slipped back into her room and quietly closed the door to play with her dolls…and try to not hear what was happening.

Then her mom’s gentle voice sounded soothing and reassuring. She was helping him calm down, like she had so many times before. After 30 minutes or so (it was hard to tell time, but especially when every second seems like an eternity…) she heard Ben trying to talk through sobs… she knew what he was probably saying, and she wanted to go hug him. But she thought it was better to let mom do that right now. He might be embarrassed to know she heard all of that.

Each One Copes in His Own Way

Sara felt confident the “storm” had passed, but then the front door slammed so hard the house seemed to crack. She quietly opened her door to look and listen. Ben and Mom were talking in low tones in the living room…but she could see her older brother’s door was open.

Then a car started and screeched away outside.

Ohhhhh. I guess Ben’s episode made Gregory mad again. (Huge sigh) I wish everyone could just be happy. We must be the only family that goes through this..

Out of nowhere Scruffy, their mixed breed little dog, scooted between Sara’s legs and into her room for safety. She picked him up, and could feel him trembling…

Hugging Scruffy close to her, Sara withdrew back into her room and ever-so-quietly closed the door.

Quiet Distractions Provide Solace

She set up a tea party in her closet where it would be extra quiet… and brought in Baby Alive and Jenna to share it with her. hmmm….we need one more, she thought. She reached under her bed and pulled out Timothy, her cream-colored teddy bear…and took him into the “tea room” in her closet floor. With the light turned on, she pulled her closet door shut.

Shame Torments

Ben had stopped sobbing by now…and was looking at his feet. It’s never going to stop, he thought. What’s wrong with me?? I always ruin everything. I’m the black sheep of this family.

Why can’t I be like everyone else…? I’m so worthless, stupid, bad, and rotten to the core. I should never have been born… I’ll probably end up being a criminal…

“Whatcha thinking, Ben?” Ben’s mom waited patiently for Ben to gather his thoughts.

While Ben was searching for words, the front door opened.

Learning to Support Each Other In the Family

His dad was home from work. Ben tried to look pleasant.

“Hi Dad…”

“What’s going on…? Has something happened…?” Ben’s dad spotted the bashed windows and looked worried. Then his eyes fell on Ben’s swollen red face. Ben felt humiliated and didn’t know what to say.

“Hi Bill. How was your day?” Ben’s mom hated to bombard him with the latest family crisis when he’d just walked in from a stressful day. And she also hoped to give Ben a break from his dad’s scrutiny.

“It was fine, Lil. Is everything ok?”

The air in the room hung heavy with tension. But they were a family, and they needed to face times like these together, so Lily spoke up.

“Everything’s fine, honey. Ben had another episode today. It was terrible for him…well, for all of us. He’s feeling pretty discouraged right now. We were talking about what we could do to find a doctor that might help more than Dr. Mendolssohn has. Someone maybe who specializes in adolescent bipolar disorder?”

Ben focused on the pet hair on the rug. Bill nodded and stared at his feet, hands in his pockets. Lily stroked the sofa cushion. When a family is suffering together with psychiatric disorders…well, each one harbors his own secret pain.

A big part of that pain is helplessness.

Bill spoke first. “I noticed the car is gone…did Gregory leave?”

Ben sighed. Lily nodded.

“And Sara…?”

The NON-Squeaky Wheel Needs Attention, Too

Lily sprang up from the sofa and headed for Sara’s room. Her little girl had been so quiet…and with all the turmoil, she forgot to check on her. Guilt swelled up and threatened to choke her.

Tap, tap, tap. “Sara? May I come in please?” Lily tried to sound cheerful.

Tap-Tap-Tap. “Sara?”

Lily opened the door and didn’t see Sara.

“Sara??”

A tiny muffled voice squeaked, “yes, Mom?”

Lily got down on her knees and looked under the bed. Nothing.

She looked on the other side of Sara’s bed. Nothing but a couple stuffed animals.

“Sara? Where are you?”

The closet door opened. Sara’s hair was disheveled and the rims of her eyes were red. She’d been crying. Lily rushed over to her and swooped her up in a hug.

“Whatcha doing in your closet..?”

“Tea party…”

“Wanna help me cook supper?”

“Yeah!”

She swung Sara onto her hip and off they went to the kitchen, chattering about the tea party.

With Psychiatric Disorders, Symptoms Can Look Like Bad Behavior

Bill was sitting with Ben, helping him with his algebra homework. He knew a lecture about behavior wasn’t what Ben needed. He needed acceptance and support. Bill had made plenty of mistakes while he learned how to provide what his family needed in times like this.

So.

Another day. Once again they’d survived another major bump in the road. Tomorrow they’d call the insurance company about the damaged windows. But for now, they were thankful for peace.

He and Lily did their best to try to help Ben’s self-image remain strong…though they knew all too well that their best efforts might not be enough. They also tried to be sure Gregory had their time, support, and attention, too. It was easy in this household to be overlooked.

They were learning to avoid reacting with even more conflict or criticism. But rather to choose words and tone that soothed. Everyone needed it. And they believed their reactions were improving.

Family: Suffering Together with Psychiatric Disorders

Which brings up little Sara. They worked hard to try to protect her innocence and sweetness. But they couldn’t protect her from the frequent upheavals in her own home.

They also knew they had to be sure to communicate and make time for their relationship with each other. That was usually the first to be sacrificed.

Most of the time they were both stretched pretty thin.

Breathe.

Got anyone in your family with a psychiatric condition? It might be an eating disorder, bipolar disorder, severe depression, social anxiety (yes…that’s a disorder too), addiction, PTSD… there are lots of possibilities.

No matter what the condition, and whether it’s you or someone else, a family with a psychiatric disorder suffers together, feels helpless together, gets frustrated together… no one escapes.

And while it’s easy to blame, that doesn’t accomplish much, does it? It just makes the wounds infect.

When it gets right down to it, there is likely some genetic connection that links you all to the disorder. In this family, Ben drew the short straw. And bears the stigma.

But just as Bill isn’t to blame for the high blood pressure he inherited from his grandmother, and Lily isn’t to blame for her kidney stones, Ben inherited the tendency to develop his condition before he was ever born.

To try to manage his blood pressure, Bill either jogs or takes a brisk walk every night after work while Lily cooks dinner. Lily is careful to stay hydrated to avoid more stones. Ben tries to get out and play football in the afternoons and they work together to see that he eats balanced meals and gets to bed early. And they all take medication for these health problems.

When The Brain is Disordered, It Can Be Hard to Maintain Order At All

Not just for the person with the condition, but everyone close to him, too.

So don’t be fooled. The family tries to maintain these routines, but that’s not as easy as it sounds. It takes a concerted effort, and they try to support each other and understand when things don’t go as planned. Because, when a family is suffering together with psychiatric disorders, everything is more complicated, it seems.

Families like this have plenty of bad days. More days than they care to admit actually… where all the opportunities to manage their collective health slip through their fingers.

But they do try. And when things fall apart, they help each other get up and try again. Or at least they try to. Sometimes everyone just gets sick and tired of it all. So they retreat into their corners to recover a bit, then come together and face their life together again. At least that’s their intention.

Life Is Challenging on Some Level for Us All

If you don’t have a person in your family who has a health condition, maybe things go smoothly for you…? But I bet they don’t go as smoothly as you wish. Nobody’s life is perfect.

Still, if you do have one or more family members who endure chronic illness, (the genetics often strike multiple times in a family) you probably feel like no one can imagine what it’s like. You likely feel isolated and alone. Maybe you feel embarrassed, because your life isn’t perfect. And you’re right to some degree. No one knows what it’s like to live your life. But you don’t know what it’s like to live someone else’s either.

I can say this however… that if your family suffers with a member who has a brain or behavior disorder, we know it impacts the whole family. And our hearts are with you.

Is Your Outpost Suffering Together with Psychiatric Disorders?

Family is our most important outpost of support. No matter what the challenges a family faces, they don’t manage them well all the time. In fact, it’s fair to say there are LOTS of times the whole family seems to implode.

Some families have financial struggles. Other families have marriage struggles. And still other families have health struggles. But whatever the challenges, pulling together is the best way for everyone to come out in the best shape possible.

But then, that’s life, isn’t it?

It’s for you we work at Innovative Psychiatry to find better solutions, more effective treatments, and the compassion and support you need. And we’ve found extraordinary results for families like yours with ketamine treatment. You may have a family member with bipolar disorder, major depression, or PTSD. If so, call us.

She just might be a candidate for IV ketamine treatment. That also goes for social anxiety, addictions…and of course suicidal thoughts. ALWAYS take suicidal thoughts seriously. And let us help.

But don’t forget to take note of other family members who may be suffering in addition. They may need treatment, too, so they have the energy to conquer the days, weeks, and months of stress at home.

There is help available for your family. To feel better, with restored hope, and more harmony.

To the fresh emergence of your best selves,

Lori Calabrese, M.D.

July 29, 2019
Ketamine Restores Brain Circuitry Damaged by Depression – FAST

In a world where things go wrong and people get sick, every once in awhile something comes along that makes things right again. I’m talking about something that’s so dramatic in its solutions we’re tempted to call it a “miracle.”

But we won’t.

We’ll call it a game-changer.

Because IV ketamine treatment is changing history.

Nothing elicits our excitement like a tool that helps people to the degree this one does. So many people with complex co-morbid psychiatric disorders drop their shackles of symptoms …and discover they’re free to live rewarding lives.

IV Ketamine Restores Brain Circuitry

Ketamine does exactly that in the vast majority of those who were before hopeless in their condition. People whose severe illnesses prevented them from working, from building relationships, from enjoying anything. People whose lives were at risk because symptoms like suicidal thinking were made worse by their own despair.

The World Health Organization (WHO) declares depression and other severe mood disorders the leading cause of disability throughout the world. And yet, until the last several years, at least a third of these people could not be helped.

But, in the last decade, an often-abused anesthetic has emerged as a game-changer that millions were searching for.

Ketamine — so safe and effective that the WHO lists it as one of its 10 essential medicines — is now rising as one of most effective and extraordinarily restorative treatments we’ve ever had.

But to be clear — and to be fair — there are still some who don’t benefit. We continue to watch for more research that helps us understand why. And to look for and learn ways to possibly help them and more.

New Study Throws Open the Shutters on Synapse Restoration

Conor Liston, M.D., Ph.D

A study just released this month by Conor Liston of Weill Cornell Medicine, and colleagues, revealed yet more than we knew before about how ketamine works to achieve this remarkable restoration.

Dr. Liston is a leading researcher in the field of circuitry specific to the prefrontal cortex and its impact on cognitive and emotional processes. It’s the dedication of researchers like Dr. Liston, and a host of others, that has helped us understand and use the benefits of ketamine for our patients. We never take our neuroscience researchers for granted.

The combined effort of research teams like Dr. Liston’s in the U.S. and Tokyo resulted in expanded understanding of just what happens when ketamine reaches the brain in someone who’s stressed and depressed.

Of course their work is performed in the laboratory with lab animals, but gives insight about what happens in the brains of people, and how ketamine restores brain circuitry for them. Insights like this are changing the course of psychiatric treatment.

Ketamine’s Active Role with Neurons and Dendrites

The researchers used a “cutting-edge” technology that included light microscopes and allowed them to view the tiny dendrites and dendritic spines of synapses (in the medial prefrontal cortex) over time, so they could see what happens there over several hours, and then what happens after more than a day.

It turned out that the neuronal circuits changed first, with a readily observable change in behavior, in the initial 3 hours after ketamine. (Hold that thought: the circuit activity changes first.)

Then, over the next 12-24 hours, they saw that the number of spines had increased by well over half of those that had been lost during stress.

So they realized that the new spines and synapses were the result of the improved circuit activity.

Extraordinary.

New Technology Opens New Doors

This is the first time we’ve had an inkling into the timing of the effects and repair instigated by ketamine. The improvement seems to be a one-two punch. Once the spines survive a few days, they form new connections, and then within another 2-7 days, improved behavior and function became apparent.

This brand new discovery of ketamine’s effects helps us understand that there can be an immediate response to ketamine, and then a longer lasting reversal of symptoms that occurs a little later.

Both of these functions are important.

Old Treatment Replaced by New Insights

Remember that the old premise for treating depression was to increase the availability of neurotransmitters like serotonin to improve the movement of signals in the brain. For some people this was enough to help relieve the depression.

But in too many others, it did very little to relieve anything. We know now that stress prunes the signaling structures themselves. Stress from life, illness — whatever — breaks down, weakens, and destroys the synapses. The dendrites, dendritic spines, and synapses that are the highways the signals travel must be rebuilt. Without these structures, neurotransmitters like serotonin, dopamine, and norepinephrine can’t do their job.

Ketamine comes along and reverses this destructive process. It repairs damaged circuits, rebuilds new dendritic spines and synapses, increases connections, and lubricates signals with neurotransmitters … in the medial prefrontal cortex and in other key parts of the brain, too.

This revelation about how ketamine restores brain circuitry will most likely contribute to the ongoing development of new psychiatric drugs. We’re excited about the possibility that new medications can be designed to do all of this before they’re used by physicians for our patients.

Getting Closer to Bigger Breakthroughs

So we have a new paradigm, a new pattern to build upon. We may see over 80% response in patients with ketamine now, but we’re shooting for the time when researchers can improve upon this across the board… to be able to truly relieve psychiatric suffering — hopefully in our lifetime.

And we keep getting closer.

The Modes of Response Vary

As it stands now, there are some people who are so responsive to ketamine treatment that they feel remarkably better after the first infusion, and with each treatment, they become more and more hopeful, brighter, more joyful, more creative, and more resilient.

There are others who sense nothing for 3 or more infusions, then finally experience improvement, relief, and eventually joy just like the first group. These may require a few more than six infusions to reach that point.

Then there are those who may have 8 or 9 infusions. They may experience a few days of improvement throughout the process, but seem to keep losing the beneficial effects. In those cases, we explore other body systems and serum levels to find areas that need to be treated so the “treatment-resistance” can be penetrated, then with another infusion or two they finally achieve the same joy and resilience. We call it remission. And we fight for it.

Still, of course, there remains that small group who don’t seem to improve, so we continue to press on, to explore reasons…and possible solutions.

Science …and ART

IV ketamine treatment is the most remarkable treatment for mood disorders we’ve seen. And clinicians and researchers are looking beyond “mood disorders” all the time. Addictions and substance use disorders, for example, were considered to be disorders of motivated behaviors and treatment focused on teaching behavior control. We’ve learned so much, and while treating these disorders is complex, we’re finding IV ketamine can play a dramatic role in reducing craving and contributing to abstinence. “Dramatic” is an understatement.

Overall, the administration of IV ketamine treatment is both a science and an art.

Ketamine Treatment is a Process Toward Restoration

At Innovative Psychiatry in South Windsor, CT we encourage our patients to have patience with the process. To hold a commitment to see it through to fulfillment. And to consider a “booster” infusion if benefits subside or fade — whether it’s once every year or two, or twice a year…or every 3-4 months, if necessary.

Because every brain is different, and every life has its own unique character and pitfalls. It may be necessary to build and improve the infrastructure in your life. To accept yourself and others as they are, and learn to embrace the joys of life and ignore the stressors. All of this can help strengthen your remission and help it last longer.

If you’ve suffered the symptoms of a disorder without relief from treatments or medications, call us.

We’re committed to your restoration and eventual joy.

To the rediscovery of your best self,

Lori Calabrese, M.D.

April 29, 2019
Behind the Buzz: How Ketamine Changes the Depressed Patient’s Brain

The anesthetic-cum-party drug restores the ability to make connections among brain cells. The Food and Drug Administration’s approval last month of a depression treatment based on ketamine generated headlines, in part, because the drug represents a completely new approach for dealing with a condition the World Health Organisation has labelled the leading cause of disability worldwide. The FDA’s approval marks the first genuinely new type of psychiatric drug—for any condition—to be brought to market in more than 30 years.

Although better known as a party drug, the anesthetic ketamine has spurred excitement in psychiatry for almost 20 years, since researchers first showed that it alleviated depression in a matter of hours. The rapid reversal of symptoms contrasted sharply with the existing set of antidepressants, which take weeks to begin working. Subsequent studies have shown ketamine works for patients who have failed to respond to multiple other treatments, and so are deemed “treatment-resistant.”

Despite this excitement, researchers still don’t know exactly how ketamine exerts its effects. A leading theory proposes that it stimulates regrowth of synapses (connections between neurons), effectively rewiring the brain. Researchers have seen these effects in animals’ brains, but the exact details and timing are elusive.

A new study, from a team led by neuroscientist and psychiatrist Conor Liston at Weill Cornell Medicine, has confirmed that synapse growth is involved, but not in the way many researchers were expecting. Using cutting-edge technology to visualize and manipulate the brains of stressed mice, the study reveals how ketamine first induces changes in brain circuit function, improving “depressed” mice’s behavior within three hours, and only later stimulating regrowth of synapses.

As well as shedding new light on the biology underlying depression, the work suggests new avenues for exploring how to sustain antidepressant effects over the long term. “It’s a remarkable engineering feat, where they were able to visualize changes in neural circuits over time, corresponding with behavioral effects of ketamine,” says Carlos Zarate, chief of the Experimental Therapeutics and Pathophysiology Branch at the National Institute of Mental Health, who was not involved in the study. “This work will likely set a path for what treatments should be doing before we move them into the clinic.”

Another reason ketamine has researchers excited is that it works differently than existing antidepressants. Rather than affecting one of the “monoamine” neurotransmitters (serotonin, norepinephrine, and dopamine), as standard antidepressants do, it acts on glutamate, the most common chemical messenger in the brain. Glutamate plays an important role in the changes synapses undergo in response to experiences that underlie learning and memory. That is why researchers suspected such “neuroplasticity” would lie at the heart of ketamine’s antidepressant effects.

Ketamine’s main drawback is its side effects, which include out-of-body experiences, addiction and bladder problems. It is also not a “cure.” The majority of recipients who have severe, difficult-to-treat depression will ultimately relapse. A course of multiple doses typically wears off within a few weeks to months. Little is known about the biology underlying depressive states, remission and relapse. “A big question in the field concerns the mechanisms that mediate transitions between depression states over time,” Liston says. “We were trying to get a better handle on that in the hopes we might be able to figure out better ways of preventing depression and sustaining recovery.”

Chronic stress depletes synapses in certain brain regions, notably the medial prefrontal cortex (mPFC), an area implicated in multiple aspects of depression. Mice subjected to stress display depression-like behaviors, and with antidepressant treatment, they often improve. In the new study, the researchers used light microscopes to observe tiny structures called spines located on dendrites (a neuron’s “input” wires) in the mPFC of stressed mice. Spines play a key role because they form synapses if they survive for more than a few days.

For the experiment, some mice became stressed when repeatedly restrained, others became so after they were administered the stress hormone corticosterone. “That’s a strength of this study,” says neuroscientist Anna Beyeler, of the University of Bordeaux, France, who was not involved in the work, but wrote an accompanying commentary article in Science. “If you’re able to observe the same effects in two different models, this really strengthens the findings.” The team first observed the effects of subjecting mice to stress for 21 days, confirming that this resulted in lost spines. The losses were not random, but clustered on certain dendrite branches, suggesting the damage targets specific brain circuits.

The researchers then looked a day after administering ketamine and found that the number of spines increased. Just over half appeared in the same location as spines that were previously lost, suggesting a partial reversal of stress-induced damage. Depression-like behaviors caused by the stress also improved. The team measured brain circuit function in the mPFC, also impaired by stress, by calculating the degree to which activity in cells was coordinated, a measure researchers term “functional connectivity.” This too improved with ketamine.

When the team looked closely at the timing of all this, they found that improvements in behavior and circuit function both occurred within three hours, but new spines were not seen until 12 to 24 hours after treatment. This suggests that the formation of new synapses is a consequence, rather than cause, of improved circuit function. Yet they also saw that mice who regrew more spines after treatment performed better two to seven days later. “These findings suggest that increased ensemble activity contributes to the rapid effects of ketamine, while increased spine formation contributes to the sustained antidepressant actions of ketamine,” says neuroscientist Ronald Duman, of the Yale School of Medicine, who was not involved in the study. Although the molecular details of what happens in the first hours are not yet fully understood, it seems a restoration of coordinated circuit activity occurs first; this is then entrenched by neuroplasticity effects in synapses, which then maintain behavioral benefits over time.

[To prove that new synapses were a cause of antidepressant effects, rather than just coinciding with the improved behaviors, the team used a newly developed optogenetic technique, which allowed them to eliminate newly formed spines using light. Optogenetics works by introducing viruses that genetically target cells, causing them to produce light-sensitive proteins. In this case, the protein is expressed in newly formed synapses, and exposure to blue light causes the synapse to collapse. The researchers found that eliminating newly formed synapses in ketamine-treated mice abolished some of the drug’s positive effects, two days after treatment, confirming that new synapses are needed to maintain benefits. “Many mechanisms are surely involved in determining why some people relapse and some don’t,” Liston says, ” but we think our work shows that one of those involves the durability of these new synapses that form.”

And Liston adds: “Our findings open up new avenues for research, suggesting that interventions aimed at enhancing the survival of these new synapses might be useful for extending ketamine’s antidepressant effects.” The implication is that targeting newly formed spines might be useful for maintaining remission after ketamine treatment. “This is a great question and one the field has been considering,” Duman says. “This could include other drugs that target stabilization of spines, or behavioral therapies designed to engage the new synapses and circuits, thereby strengthening them.”

The study used three behavioral tests: one involving exploration, a second a struggle to escape, and a third an assessment of how keen the mice are on a sugar solution. This last test is designed to measure anhedonia—a symptom of depression in which the ability to experience pleasure is lost. This test was unaffected by deleting newly formed spines, suggesting that the formation of new synapses in the mPFC is important for some symptoms, such as apathy, but not others (anhedonia)—and that different aspects of depression involve a variety of brain circuits.

These results could relate to a study published last year that found activity in another brain region, the lateral habenula, is crucially involved in anhedonia, and injecting ketamine directly into this region improves anhedonia-related behavior in mice. “We’re slowly identifying specific regions associated with specific behaviors,” Beyeler says. “The factors leading to depression might be different depending on the individual, so these different models might provide information regarding the causes of depression.”

One caveat is that the study looked at only a single dose, rather than the multiple doses involved in a course of human treatment, Zarate says. After weeks of repeated treatments, might the spines remain, despite a relapse, or might they dwindle, despite the mice still doing well? “Ongoing effects with repeated administration, we don’t know,” Zarate says. “Some of that work will start taking off now, and we’ll learn a lot more.” Of course, the main caution is that stressed mice are quite far from humans with depression. “There’s no real way to measure synaptic plasticity in people, so it’s going to be hard to confirm these findings in humans,” Beyeler says.

[Read the Original Article]

April 23, 2019
Cerebral Folate Deficiency and Its Impact on Treatment-Resistance

“If I see far, it’s that I stand on the shoulders of giants.”

If you find yourself feeling alone and forgotten in your symptoms, feeling that there’s no one who really cares, please let me emphasize that there are hundreds, even thousands, of neuroscience researchers, medical doctors with PhDs, biochemists, psychopharmacologists, and psychiatrists who have been painstakingly searching for the answers you need for your suffering for generations, and millennia. You can feel alone, but there’s a host of people who have your back.

After eons of exploration, and hundreds of generations have suffered without remedy, we are living in an amazing time when solutions are emerging.

We’ve learned that the mild-mannered anesthesia medicine, ketamine hydrochloride, has been hiding in plain sight for nearly five decades, all along carrying within it the power to potentially transform your crippling depression, PTSD, and social anxiety into resilience, remission, fulfillment…and a rewarding life.

It was right under our noses, but we were missing it…

What else is lurking in plain sight that may hold the secret to relief for millions of people?

More to Learn to Relieve Psychiatric Disorders

While the vast majority of severely ill patients has been enjoying a life they’d not been capable of enjoying until they were treated with IV ketamine, there were still those who seemed to be unaffected and un-helped by it. We haven’t known why.

And even some of those who seemed unaffected and un-helped by ketamine treatment, began to improve in a slowly spreading glow until they too achieved remission months later.

And we learned about genetic alleles for BDNF that may indicate an individual’s responsiveness to treatment, and clinical indicators associated with treatment response.

Now we’ve been learning even more. About deficiencies of nutrients that can cause depression and other disorders. One of these deficiencies has been exposed as a key factor in autism. And when the deficiency was treated with high doses, the symptoms of autism diminished!

Who knew?

Right under our noses. Sometimes it takes generations of exploration passed down through generations of researchers to find the answers we’re looking for … which were lurking in plain sight.

We’ve talked about how a deficiency in testosterone can be a culprit blocking remission from depression.

Another BIG player is cerebral folate.

Cerebral Folate Deficiency

Folate is vitamin B-9, and provides important services throughout the body. In the brain, it plays an important role in neurotransmitter production. So when it’s deficient, the neurotransmitters tend to be produced more slowly.

You can read the label on your breakfast cereal box and see that it contains folic acid. But folic acid can’t cross the blood-brain barrier, which is there to protect the the brain from fluctuations that can interfere with its function.

Only in the form of folinic acid or methylfolate can folate reach the brain. And to do that it has to have a transport, called the folate receptor alpha, to take it there.

So to get B-9 into your brain to do its part in the neurotransmitter factory, it has to be in a certain form that can get through the security gate of the brain, known as the blood-brain barrier. Plus, it has to hitch a ride on a specific type of truck, and that truck has to be a specific model – the “low affinity folate transporter.”

It’s not hard to picture that a brain can get low on this stuff. So many hoops to jump through!

How Cerebral Folate Deficiency Can Affect You

And interestingly, most of the research about this has involved infants and children. In fact, the story of folate in the brain has a gripping history. It involves autistic children and infants with severe neurological disorders..but as those discoveries made their way into adult psychiatry.…

Well, we’re talking about it now because it turns out that adults have deficiencies too…and this is a deficiency that may contribute to why your depression seems treatment-resistant — but the problem is not that hard to treat. Which is good news…really good news.

In fact, if we find you’re treatment- resistant because of folate deficiency, we can prescribe folinic acid or l-methylfolate to treat the deficiency. Then, you may find you’re not treatment-resistant any more. Sound like a plan?

This is BIG news.

What this means is that some people who don’t get better with ketamine treatment, may just need their folate deficiency restored so their neurotransmitter factory can crank up again and turn out those much needed neurotransmitters.

Then, ketamine has what it needs on hand to help you get dramatically better.

Isn’t that amazing??

Researchers Paved the Way

In 2005, Dr. VT Ramaeker defined cerebral folate deficiency as “any neuropsychiatric disorder involving problems getting enough folate into the brain.” He was referring to the infants he treated. They had severe neurological illness, and happily, many of them responded to high doses of folinic acid.

Then, in 2013, Dr. Richard Frye studied 93 pediatric patients with autism and found that 75.3% had cerebral folate deficiency. He also found that those patients who had a cerebral folate deficiency also had antibodies to the folate receptor alpha — that specialized transport truck that takes the folate into the brain.

The following year, we’re back to Dr. Ramaeker, who measured cerebral folate in 18 patients with treatment-resistant schizophrenia…and you guessed it! 15 of them had cerebral folate deficiency. He treated 8 of them with high doses of folinic acid and 7of them got better.

Now, I should explain that finding the level of folic acid in the brain is a bit more involved than lab work. It requires a lumbar puncture so the folic acid in the cerebrospinal fluid can be measured. The measure of folic acid found in the cerebrospinal fluid is then multiplied by 1.5 to find the level in the brain.

Then, in 2017, Dr. Lisa Pan measured folic acid in 33 patients with treatment-resistant unipolar depression. 12 of these had cerebral folate deficiency and 10 out of those 12 responded after high doses of folinic acid.

Google’s Take on Folate and Cerebral Folate

When you google “folate,” you get all sorts of links about how folate is needed in your body. It helps make red and white blood cells in the bone marrow, convert carbohydrates into energy, and manufacture RNA and DNA.

(Hmmmm, makes you stop and think about BDNF. How it turns on mRNA to switch on DNA so the synapses proliferate and rebuild circuitry in the brain… interesting…)

But when you google “cerebral folate,” you find yourself reading about autism, and about treating it with folinic acid.

Cerebral Folate Deficiency Causes Tragedies

Cerebral folate is so important in the brain, that the lack of it causes all sorts of tragic results…. in infants, neural tube defects, spina bifida, cleft palate…

To think that autism, schizophrenia, and depression show links to cerebral folate deficiency — in at least some people — pushes us and the psychiatric and neuroscience research community to learn more about the central role that l-methylfolate and folinic acid play in the the central nervous system and in the genesis of psychiatric disorders.

These early important studies should prompt more extensive clinical studies. And they should prompt more interest in testing our patients with treatment-resistant disorders for this deficiency so that we can treat it sooner rather than later, don’t you think?

Unfortunately, that’s not as easy as it sounds. But it’s a start for us to realize this B vitamin is essential to our health and wellbeing. And just might be the key to your treatment-resistant disorder.

Treating Deficiencies in Vital Nutrients Helps You Thrive

At Innovative Psychiatry we test for cerebral folate deficiency when we suspect it could be a cause of treatment-resistance. We prescribe treatment for it to help improve your response to your treatment, including ketamine, and in turn, potentially improve your resilience and remission.

If you suffer from treatment-resistant depression, and think you might be a candidate for ketamine treatment, call us. We’ll do an evaluation to learn more about you and your illness. We can also order testing to help ensure your best outcome with IV ketamine treatment.

With so many who have gone before us, shining the light brighter so we can better see the obstacles to your joy, we’re here to help you find the life you ache to live.

April 22, 2019
Low T in Men Causing Your Treatment Resistant Depression..?

Since low testosterone in men has long been presumed to accompany aging, it can be overlooked as a cause of TRD in young men.

John had gained 75 lbs (!) through the stressful and exhausting project at work. He’d come to hate the way he looked.

Co-workers had turned on each other, undercutting rather than supporting each other as a team. John was a team player, and while his skill was beyond the skill of others on the team, he could feel himself slipping into depression…again. And his skills were slipping, too.

Because he was losing his edge, it was getting harder and harder to think through to solutions, much less articulate them to the others. He knew he was doomed. As long as his mind worked he could maintain his position in the department, but as depression returned, he became sluggish, he felt dense, and hopelessness rose like water in a submerged car.

To add insult to injury, his girlfriend was complaining that they never went out anymore, and that she felt he’d lost interest in her. He knew he hadn’t lost interest in her any more than anything else…he just didn’t have the energy to face restaurant crowds…or even show her what she meant to him. In fact, he hardly had the energy to get out of bed on lots of days.

And to make matters worse, his sex drive was shot. He just didn’t care about anything, but also felt like a failure as a man.

Before the project began, he had a few suicidal thoughts at night… But through the tormented road at work this year, the suicidal thoughts were cramming into each hour of the day at about 40/hour. He winced to himself… almost sounds like the speed of a car rather than an obsession to die.

This had been going on most of his adult life. Why couldn’t it be fixed? Why oh why did he keep trying…going to work…diving into the hopelessness again and again day after day? Why not just get off…?

What was wrong with him? Where could he find a doctor who could help him..??

Treatment Resistant Depression

Major Depressive Disorder (MDD) is complicated by a discouraging rate of relapse, even with those who achieve remission at some point. Studies of long duration have shown that patients who have residual symptoms after treatment have a worse prognosis. Which is why we do all we can to help our patients achieve remission, if possible.

Treatment resistant depression (TRD) causes immeasurable suffering. Because the symptoms don’t improve with traditional medicines, the ongoing struggle to find relief only seems to worsen symptoms. And untreated depressive symptoms that go on in spite of treatments can be debilitating and costly.

Treatment resistance occurs in 45% of depressed patients. These are patients whose symptoms have not improved after at least 2 medicine trials… or some combination…for 12-16 weeks each. This condition increases risks because of higher prevalence of suicidal thoughts, attempts, and tragically, death. Nearly a third of treatment resistant patients attempt suicide in their lifetime.

For years, most people thought that there were far more depressed women than men. That women are more prone to depression because they are more expressive of their emotions. But it turns out that isn’t true.

Depressed Men Don’t Act Like Depressed Women

However, studies emerged revealing that many men display different depression symptoms than women, and as a result their depression can be overlooked. Rather than sadness, they sometimes exhibit anger, irritability, and aggression. As such, those around them may pull away, rather than recognizing their loved one is actually depressed.

Another factor is that men are less likely to talk about how they’re feeling or seek help. So that creates the idea there aren’t as many depressed men as women, because their families can’t read their minds, right?

So a man who’s irritable and autocratic may actually be depressed, rather than just a difficult guy. (Surprising, sometimes.) This is good news for those friends and family members who love them. Because, if he is, he needs treatment… but he may not ask for it. Even if he does, there is a strong chance the treatment won’t help, or at least, not much.

If we’re to know what to do for him, we have to consider other things first.

So what causes depression in men?

Low T in Men

Honestly, the same things that cause depression in women, for the most part. Chronic stress, genetic factors, environmental factors, biological events like heart attack, stroke, chronic pain, or amputation, and other illnesses like diabetes, Parkinson’s, heart disease, or cancer.

But, there’s another condition that’s often overlooked. Low testosterone, or low T, is seen with hypogonadism.

The testes produce most testosterone (90-95%). But a small portion is produced in the adrenal gland. And studies have established that testosterone treatment can help men feel better emotionally, so a deficiency of testosterone can erode their mood and outlook.

Some men receive the diagnosis of hypogonadism. This is a condition that causes their bodies to produce too little testosterone.

It’s been said that hypogonadism, or low T, is a malady of elderly men. But, that’s a generalization that doesn’t take into account the many men between ages 18-40 whose testosterone level is below 10.4 nmol/L and who have treatment resistant depression.

Low T in YOUNG Men

Low testosterone is a leading cause of treatment resistant depression in older men, but many overlook that it’s a big cause of treatment resistant depression in younger (age 18-40) men, too.

Stanley Korenman, M.D., and his team published their work about the link between low T in young men (ages 18-40) and depression in a paper published November 2018 in the Journal of the Endocrine Society.

They studied 186 young men who made visits to a university medical center for any reason between the years 2013-2015. These men had symptoms of treatment resistant depression.

The prevalence of hypogonadism was present in 22.6% of these men.

The authors called for more research to determine if the hypogonadism causes the treatment resistant depression or if the treatment resistant depression causes the hypogonadism…maybe both?

Because to neglect this connection may be to ignore a condition that’s reversible. One that turns treatment resistant depression into treatable depression. And treatable depression can be transformed to remission.

We Strive to Treat YOU in YOUR Own Uniqueness

Our approach at Innovative Psychiatry is to treat each underlying condition and its own symptoms, then watch to see how the /improvements in function combine toward resilience and remission. It can be a tedious process but it’s all worth it when your symptoms finally dissipate.

A key component of your recovery may include IV ketamine treatment, if you have a treatment resistant disorder. Ketamine does its best work in patients with the most complex treatment resistant illnesses. But for ketamine to do its best work in restoring your brain cell connections prolifically, you need to treat other conditions like low T that may get in the way.

For this reason, we also may encourage you to see a specialist as we work on the process of treating your depression. We always love to work with your specialized health care team to help you get the most personalized care so you can feel really good again.

There is no one-size-fits-all remedy for everyone and every complexity of illnesses. But we must work together, exhaustively, and explore your disorders, your nutrient imbalances, your social and work life, your family life, your exercise, your diet…every aspect of your health…to tease apart those elements that may be contributing to the way you feel.

And while it may require an investment of time, effort, treatments, and re-evaluations for awhile, it will all be worth it when you look in the mirror and love the person you see there. Better days are ahead.

You will never hear me say, “There’s nothing more we can do.” Those days are over in psychiatry, I hope… but you will hear me ask, “What was the very best YOU you’ve ever been…? That’s the you we’re going to help you find again – together.”

To the restoration of your best self,

Lori Calabrese, M.D.

April 15, 2019
Ketamine May Relieve Depression By Repairing Damaged Brain Circuits

NPR Logo

Ketamine appears to restore faulty connections between brain cells, according to research performed in mice.

The anesthetic ketamine can relieve depression in hours and keep it at bay for a week or more.

Now scientists have found hints about how ketamine works in the brain.

In mice, the drug appears to quickly improve the functioning of certain brain circuits involved in mood, an international team reported Thursday in the journal Science. Then, hours later, it begins to restore faulty connections between cells in these circuits.

The finding comes after the Food and Drug Administration in March approved Spravato, a nasal spray that is the first antidepressant based on ketamine.

The anesthetic version of ketamine has already been used to treat thousands of people with depression. But scientists have known relatively little about how ketamine and similar drugs affect brain circuits.

The study offers “a substantial breakthrough” in scientists’ understanding, says Anna Beyeler, a neuroscientist at INSERM, the French equivalent of the National Institutes of Health, who wasn’t involved in the research. But there are still many remaining questions, she says.

Previous research has found evidence that ketamine was creating new synapses, the connections between brain cells. But the new study appears to add important details about how and when these new synapses affect brain circuits, says Ronald Duman, a professor of psychiatry and neuroscience at Yale University.

Studying ketamine’s antidepressant effects in mice presented a challenge. “There’s probably no such thing as a depressed mouse,” says Dr. Conor Liston, a neuroscientist and psychiatrist at Weill Cornell Medicine in New York and an author of the Sciencepaper.

So Liston and a team of scientists from the U.S. and Japan gave mice a stress hormone that caused them to act depressed. For example, the animals lost interest in favorite activities like eating sugar and exploring a maze.

Then the team used a special laser microscope to study the animals’ brains. The researchers were looking for changes to synapses.

“Stress is associated with a loss of synapses in this region of the brain that we think is important in depression,” Liston says. And sure enough, the stressed-out mice lost a lot of synapses.

Next, the scientists gave the animals a dose of ketamine. And Liston says that’s when they noticed something surprising. “Ketamine was actually restoring many of the exact same synapses in their exact same configuration that existed before the animal was exposed to chronic stress,” he says.

In other words, the drug seemed to be repairing brain circuits that had been damaged by stress.

That finding suggested one way that ketamine could be relieving depression in people. But it didn’t explain how ketamine could work so quickly.

Was the drug really creating all these new synapses in just a couple of hours?

To find out, the team used a technology that makes living brain cells glow under a microscope. “You can kind of imagine Van Gogh’s Starry Night,” Liston says. “The brain cells light up when they become active and become dimmer when they become inactive.”

That allowed the team to identify brain circuits by looking for groups of brain cells that lit up together.

And that’s when the scientists got another surprise.

After the mice got ketamine, it took less than six hours for the brain circuits damaged by stress to begin working better. The mice also stopped acting depressed in this time period.

But both of these changes took place long before the drug was able to restore many synapses.

“It wasn’t until 12 hours after ketamine treatment that we really saw a big increase in the formation of new connections between neurons,” Liston says.

The research suggests that ketamine triggers a two-step process that relieves depression.

First, the drug somehow coaxes faulty brain circuits to function better temporarily. Then it provides a longer-term fix by restoring the synaptic connections between cells in a circuit.

One possibility is that the synapses are restored spontaneously once the cells in a circuit begin firing in a synchronized fashion, says INSERM’S Beyeler, who wrote a commentary accompanying the study.

The new study suggests not only how ketamine works but also why its effects typically wear off after a few days or weeks, she says. “What we can imagine is that ketamine always has this short-term antidepressant effect, but then if the synaptic changes are not maintained, you will have relapse,” Beyeler says.

If that’s true, she says, scientists’ next challenge is to find a way to maintain the brain circuits that ketamine has restored.

[Read the Original Post Here]

April 12, 2019
Weekly Ketamine Infusions Show Initial, Repeated Depression Benefits

A new study shows that weekly ketamine infusions are associated with continued and maintained reductions in depressive symptoms among patients with treatment-resistant depression.

The findings, which are considered novel among studies assessing ketamine administration for patients with treatment-resistant depression, evidence the promising role the controversial drug could play in psychiatric care.

A team of investigators, led by Jennifer L. Phillips, PhD, an associate scientist in the Mood Disorders Research Unit at The Royal’s Institute of Mental Health Research, conducted a randomized, double-blind crossover comparison of single ketamine infusion versus active placebo control midazolam. The assessment, held with 41 participants with treatment-resistant depression at single treatment center, observed patients receive 6 open-label ketamine infusions 3 times per week over 2 once patients had a relapse of depressive symptoms.

Patients who reported a decrease of at least 50% in the Montgomery-Åsberg Depression Rating Scale (MADRS) received another 4 additional infusions once weekly in a maintenance phase.

Those administered a single ketamine infusion reported significantly reduced depressive symptoms at the primary efficacy endpoint of 24 hours post-care versus those treated with midazolam. The therapy showed cumulative antidepressant effects over repeated infusions, as well a doubling of antidepressant response rate in patients, according to linear mixed models.

Investigators found that 59% of patients met the response criteria following repeated infusions, with 3 infusions serving as the median dosage required to reach achieved response. In patients receiving weekly maintenance infusions, no further improvement in MADRS scores were reported.

The first-of-its-kind findings come just 1 month following the US Food and Drug Administration (FDA) approval of esketamine nasal spray (Spravato) for the treatment of patients with treatment-resistant depression. At the time, the therapy made history as the first novel treatment indicated for depression in 30 years—and headlines as one of the first hallucinogenic drugs to reach indication for a common condition.

Dennis Charney, MD, Dean of Icahn School of Medicine at Mount Sinai and a member of the Yale University team that led pioneering antidepressant ketamine trials in the 1990s, told MD Magazine® that microdosing or implementing controversial therapies for psychiatric care require what any other trial requires: control, safety, and a carefully-assessed standard for efficacy.

“No matter what treatment is being assessed, you have to follow those scientific approaches,” Charney said. “For conditions that don’t have effective treatments available, there should be an open mind.”

Adversely, Dan Iosifescu, MD, associate professor of Psychiatry at NYU School of Medicine, director of Clinical Research at Nathan S. Kline Institute for Psychiatric Research, and prominent ketamine investigator, told MD Mag that—among other reasons—ketamine will never reach at-home therapy use due to its prominent abuse as street drug Special-K. He anticipated the marketed therapy will be costly, and prescribed as long-term therapy for only a small depression patient population.

“For the majority of individuals that benefit from it, it will be essentially buying them time for other treatments—be them pharmacotherapies or device-based treatment, or psychotherapies, because those are beginning to work much more slower than ketamine does,” he said.

Whatever its marketed use entails, Phillips and colleagues concluded positively that ketamine showed both initial and repeated benefits for antidepressant effects as a once-weekly infusion.

“These findings provide novel data on efficacious administration strategies for ketamine in patients with treatment-resistant depression,” they wrote. “Future studies should further expand on optimizing administration to better translate the use of ketamine into clinical settings.”

The study, “Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial,” was published online in The American Journal of Psychiatry.

[Read the Original Article Here]

April 9, 2019
RESILIENCE! It’s the New Buzzword Among People with Mood and Anxiety Disorders

Too much screen time? Let yourself have 2 more minutes of it right now: because if you’ve been tooling around reading anything related to mood disorders or anxiety disorders, IV ketamine, and other advanced treatments, you’ve probably noticed that there’s buzz about resilience.

Because of the world that has opened up since IV ketamine began treating depressed patients with its ability to create new branches and connections, the expectations of these patients have soared.

No longer are patients satisfied to have a little relief from their depression. They’ve learned they can feel good. Feel “normal.” Enjoy participating in life the way others do.

So now the question you hear on the internet isn’t this: “Will any medicine help me feel at least a little bit better…?” No.. now it’s this: “Will this medicine help me feel resilient again?” Or “What can I do during this treatment to help it work… improve my chances of remission… develop more resilience?”

Now before we go on, I want to clarify that no doctor can promise or guarantee remission of symptoms from disorders like depression, bipolar disorder, PTSD, addiction,social anxiety, or to promise or guarantee that suicidal thinking will go away. There just isn’t any medicine in psychiatry that helps 100% of people get well.

But, even so, there are many people who’ve suffered for years, even decades, with these disorders who are now living lives they never dreamed possible. They’re painting, excelling at work, meeting the loves of their lives, enjoying their families, and contributing to their important relationships. They’re investing in hobbies, socializing with friends and family, and feeling good about themselves and their accomplishments.

This doesn’t happen overnight, but resilience has freed them to invest in their lives, and provides the energy for things they could never do before.

Resilience Protects You From Falling in the Ditch

And when hard times come along, they have the resilience to grieve a bit, then brush themselves off and keep moving forward. This may be the most remarkable change of all.

Resilience is the ability to adapt when a crisis comes along… to adapt to whatever the situation may be. To bounce back, recover, and move forward after an onslaught of difficulty.

Since psychiatric mood and anxiety disorders often develop as a response to some degree, to something environmental or an upsetting/traumatic event, if you can adapt to that event or force in your environment, you can remove that response from your psyche.

Adaptation is the way organisms throughout your world survive. When there’s a strong wind, if trees don’t bend under the wind they’ll be splintered and destroyed. But their ability to bend is their means of survival and the way they develop resilience.

The same is true of you.

If you have a continuous source of stress in your world, one that assaults your senses, emotions, or body, you can eventually be beaten down and weakened or destroyed by those assaults.

But if you can find a way to bend like a tree does, to adjust yourself to accommodate those assaults, hurts, and winds of fury without being damaged, it will help you avoid being traumatized. And that’s how you’ll develop resilience.

This brings up the story of a friend of mine.

Jillian grew up in a small town in the midwest, and was a faithful member of a tiny congregation there. The pastor had served in her church for 40 years, and unwittingly preached a serious sermon every Sunday that reflected the smallness of his own tiny world in that tiny town.

Jillian, like the rest of the church members, worked hard to live up to the expectations her pastor laid out in his sermons. Her town was small, her world was small, and those expectations left her view of life small, too.

Culture Shock – From Small Town to Big City

As she approached her thirtieth birthday, her husband broke the news to her. He’d been transferred to Chicago.

So they packed up their belongings, and moved into a pretty little apartment in that big, new city. Her birthday was anything but a celebration. The traffic overwhelmed her … the variety of people she saw at the grocery store, the post office, and everywhere else were just so different than any she’d ever seen before.

Hairstyles, clothing styles, and the way people just talked made her feel more like she was on another planet than just in a different city. She felt afraid to meet people or make friends. She was afraid she looked like a fool and she couldn’t imagine how you could trust anyone.

The more time she spent alone, the more isolated she felt. And the sadder she became. She was lonely. She missed the comfort of her home town.

Her husband asked her often if she was making any friends. But she just told him that the people she ran into on the street weren’t “her kind of people” — and she felt safer alone.

One day he arrived home from work and announced they’d been invited to dinner by one of his co-workers. She was excited to meet this co-worker and his wife. Surely they’d be a good match socially, too.

The following Friday, Jillian and her husband drove to the address her husband pulled from his pocket. The front yard was alive with a variety of blooms that reminded her of English gardens she’d seen in books at the library. It was just beautiful.

Jillian Adapts and Learns Resilience

They knocked on the door — and it was opened by the strangest-lookingpeople she’d ever seen. She immediately wanted to go home, but her husband held her hand firmly as he warmly greeted the couple.

Her husband’s co-worker had jet black hair that was shaved on the sides with a narrow path of hair from his forehead to his crown, pulled into a ponytail. His wife had bright pink hair with spikes on top enhanced by a shag that softly fell on the left side of her head; the right side was shaved from her temple to her ear.

Jillian’s alarm choked her. Then Cass, the pink-haired woman, spoke up and told her how glad she was to meet her. That most of her co-workers were middle- aged or nearing retirement, and she ached for friends her own age.

When she spoke, Jillian began to relax. What a warm and genuine person, she thought.

“May I help you in the kitchen?”

“Yes, I’d love the help!”

So the two of them disappeared into the kitchen to finish up with dinner, and their husbands settled in to talk shop and about their hobbies outside of work.

Jillian and Cass had so much more in common than she could have dreamed — and by the time they called the guys to sit down and eat, she had forgotten about the “strange” hairstyles. She realized that her perspective of the world in her small town had apparently been pretty sheltered. And she was thankful she had found someone who could be a true friend.

Resilience is Adapting to Your Situation, Which Helps You Bounce Back After Surprises, Disappointments, and Hardships

The point is, that Jillian adapted. She was experiencing a stressful situation, and it was affecting her emotionally. Sadness was growing as well as isolation and loneliness. If she’d remained unwilling to bend, she might have eventually plunged into depression.

But, after exposure to a stressor that felt threatening to her, she was instead willing to look beyond her distaste, and read the heart of a person who was ready and able to offer her real friendship. And many great adventures lay ahead as a result.

Resilience! It’s the new buzzword for a reason. Beyond reduced depression symptoms, resilience protects your life from being interrupted by a trauma or disappointment.

While this is an oversimplified example, it shows you how important it is to bend, rather than break. To change the way you think in a stressful situation so you can bounce back from disillusionment, disappointment, or betrayal.

Resilience! It’s the New Buzzword for Adapting and Growing Stronger

But, here’s the thing. Sometimes you face stressors that feel threatening to you when you don’t feel equipped to respond with resilience. In fact, sometimes you may not feel resilient at all.

Sound familiar?

Times when you’re drowning in depression or terrorized with PTSD. When you don’t have the energy to get out of bed, much less “bend with the wind.” What do you do then?

Ketamine Treatment Enhances Resilience

Well, that’s when you may need treatment. You need to get the help of your psychiatrist to get those symptoms under control. To empower resilience. And if the medications that have been prescribed for you haven’t helped, then you may need something more targeted, more potent.

One medicine we use at Innovative Psychiatry for exactly this is IV ketamine treatment. We’re experts in ketamine treatment and we’ve offered it for years–way before most doctors–and most people–ever even heard about it.

You may need something like that to help you enjoy resilience and to make it stronger. Because from its vantage point, ketamine has a list of actions that can help you develop the resilience that will see you through stressors and losses that may come along in the future.

Neuroplasticity Helps You Build Resilience

Ketamine stimulates neuroplasticity, which is the ability of the cells in the brain to change and adapt. That neuroplasticity can enhance your psychotherapy, especially when your therapy is 24 hours after your infusion.

It can also help you change your perspective of life and people. In doing that, it can help you learn how to “bend with the wind,” or whatever crosses your path. You can create and build up a level of resilience that empowers you to roll with the punches in life.

Numerous studies have shown that the more often you adapt to small stressors in your life, the stronger you’ll be at adapting to big calamities. And the more you change your thinking to adapt to difficulty, the stronger your resilience can be.

So, you can do things to strengthen your resilience…by choosing adaptive behaviors in smaller crises day by day.

For example, you don’t have to succumb to the same old habits when something frustrates you, or makes you angry. With the help of ketamine stimulating your neuroplasticity, you can choose to think a different thought. Then practice it.

I’m never going to get out of this job or this company. I’m doomed to a future of misery and mediocrity…

You have the choice to accept that thought…or to grab the wheel and change its direction, like so:

I’m not going to succumb to that thinking. I WILL excel at this job because I’m working hard to perform well. And I will be rewarded with promotions that will give me the resume that will promote me when I apply to new jobs. Bottom line, I’m not giving up..!

You have choices when thoughts come to you, and when your choice is empowered by the neuroplasticity of IV ketamine treatment, you CAN overcome.

Resilience helps you build a stronger remission of your symptoms... In fact, resilience is the reason so many people can undergo tremendous stressors, and bounce back.

People like you, and those you love. Because resilience isn’t something you’re born with or NOT born with. Resilience is something you can develop with practice, determination, and persistence.

That’s so important that I want to say it again: resilience is something that can be developed. You can develop it. And we can help you.

We want you to live as the best YOU, you can be. And you can with the ability to adapt, and to apply resilience.

April 8, 2019
PTSD in Trauma Survivors: Let’s Prevent More Suicide

Two survivors of the Parkland high school shooting on Valentine’s Day 2018 took their own lives a couple weeks ago.

Sydney Aiello, a senior and cheerleader at Marjory Stoneman Douglas High School, struggled to restore normalcy in her life after the terrifying experience.

Her trauma, of course, included the loss of friends who were killed in the shooting. She enrolled in college classes in the fall, but found it almost insurmountable to attend them, because of the terror she felt sitting in a classroom.

Sydney was diagnosed with Post Traumatic Stress Disorder (PTSD) in the months that followed that massacre, and struggled with guilt that she had survived the shootings, when friends like her close friend Meadow Pollack, had died.

This “survivor’s guilt” is a devastating symptom that makes survival after such a traumatic experience terribly painful. Sydney never reached out for help with her struggle, but suffered silently. On March 17, 2019…just a couple weeks ago…Sydney took her life.

A Second Suicide from PTSD in Trauma Survivors in Parkland, FL

Only 6 days later, Calvin Desir — a 16 year-old boy from the same high school — took his life. Calvin was a sophomore, and had also struggled silently… until that day. Little is known publicly about his story, but we can know those who are left to mourn his loss are as numerous and heartbroken as any of us would be after such a terrible loss.

Some of the students vented their terror, grief, and rage after the shooting by speaking out and forming March for Our Lives, that drew hundreds of thousands of protestors to Washington, DC and around the world.

It gave them a place to channel their energy, to at least try to prevent more shootings in the future.

But, far more students than those who participated in the protest, struggled with their pain, terror, grief, rage, and guilt in silence and isolation.

As time goes by, and they relive the memories of that terrible day, the fear of being found and shot, the horror of hearing their school mates scream…well, the stress of the memory can wear away at their confidence, their sense of safety, and their stability.

Don’t you wonder if PTSD in trauma survivors of the shooting could have been identified and whether these suicides might have been prevented? And most importantly now, is it possible to prevent any more?

Tragedies following Traumatic Events – Let’s Prevent More Suicides

While 3 of the 17 victims of the Parkland high school shootings were adult teachers, the other 14 were teenagers. How do teenagers, with their limited life experience and coping skills, resolve such fear, confusion, ill-founded guilt, anxiety, and pain?

Layer upon layer of tragedy, loss, and sorrow…eating at their security. The more time they spend alone, the more the memories loom, and the harder it is to break free of them. Anxiety and the stress of it all can drive their thoughts to despair and then sometimes desperation.

But… these students who grieve for their friends… they’re intelligent, resourceful people, right? Kind, smart, connected, well-spoken, artistic, athletic, healthy. Going places. So why didn’t these kids ask for help if they were becoming depressed, despondent, and so isolated and alone in that frame of mind?

But that’s the thing. When someone is traumatized, they may not show it like you would expect. The trauma of it all… in their thoughts… may be trapped in a cloak of private torment.

They may not have wanted to draw attention to themselves. They may have convinced themselves that they don’t “deserve” to live. If we don’t talk with them…listen to them…we can’t know what their thoughts were.

And that’s why it’s so important to engage the people you know who have been exposed to trauma — to the “big T” traumas and to the “little t” traumas…talk to them and listen. Help them open up about what they’re thinking and feeling — because more than likely, it’s not what you or I think they might be thinking and feeling.

Airing dark or haunting feelings just might be enough to lessen their torment and divert dangerous decisions.

Unbearable Guilt over Living Through the Event

For one thing, survivor’s guilt added to the suffocating, unrelenting grief, and elusiveness of relief. “I don’t deserve to live, if they had to die…Why wasn’t I shot? The pain of the loss I feel is so much worse than death…I wish I’d been shot, too!”

These are complex feelings, without clearly defined solutions. And though possibly not logical, they’re far too weighty for an adolescent mind and heart to untangle.

In short, these kids carried a load too large to manage. While it seems likely many of their parents got them into a psychiatrist’s care, that may not have helped enough soon enough.

We can’t conjecture on the parts of these two who’ve left us, but we can look for ways to prevent more suicides going forward by recognizing signs of PTSD in trauma survivors and helping them get treatment.

Because the chances are, all 3300 of the students at that high school were traumatized by the experiences of that day.

And they’re at risk. Not just in Parkland, FL, but in every high school across the country. Students are in pain, and are traumatized by events they hear on television or the internet, plus events that happen in their personal lives or the lives of others near them.

Helping Them Vent Their Private Pain

One thing to consider is that anyone who has undergone such a great shocking loss, probably needs to talk about it. To unload the confusion and uncertainties to a listening ear … and to do that, they probably need to be invited to do so.

It can be so difficult for a teenager to voice fears and dark secrets, especially if they include thoughts of suicide. They don’t know how the listener might respond.

If the listener is a peer, they may fear ridicule or betrayal of confidence.

If an adult, then maybe fear of anger, punishment, dismissal or hysterics.

No matter what they fear, it may seem easier to brood in silence about their thoughts, as well as possible plans.

The risk of divulging private thoughts also can move the thoughts from fantasy or vague consideration to full throttle. A move they may not want to feel rushed about.

So it’s important to ask. Just ASK.

“How have you been feeling lately? It would be easy to imagine that you’d struggle over your friend’s death… I’d like to listen when you feel like talking…”

“Do you ever think it would be a solution if you didn’t have to have worries like this anymore…?”

“Do you ever have any thoughts of ending your life, or hurting yourself in some way?”

“Have you thought of how or made any plans to end your life?”

Just ask.

What to Do with Their Answers

These questions can help give a direct, clear opportunity for conversation and expression of pain, loss, anger…

And their responses can clue you as to the next steps. If they have thought about it, or mention feeling less hope about the future, or less purpose…or increased rage, or wrecklessness… don’t leave them alone.

You can say, “let’s get help.” If you see or hear them express increased substance abuse, this can also be a sign of high risk. Again, seek help.

At the very least, write down this phone number for them.

National Suicide Prevention Lifeline

1-800-273-8255

But that’s just the first step.

How to Respond to PTSD in Trauma Survivors

Next, what can be done to relieve them of these tormenting thoughts, and protect them from an irreversible decision?

In my practice, the safest, most effective treatment of choice for serious suicidal risk is IV ketamine treatment. This can erase suicidal thoughts in as little as an hour and return someone who’s struggling with thoughts of suicide or thoughts of death as a relief to a state that’s safe for further treatment of depression, PTSD, and other psychiatric conditions.

But, no matter what, seek immediate psychiatric care. With parents, teachers, and friends of traumatized students on the alert for signs of suicidal thinking, we can all work together to avert tragedies and save lives.

Because of the limited life experience an adolescent has to draw from, as well as the impulsiveness that goes with a brain that’s not fully developed, irreversible decisions can be rampant during crisis.

The finality of death is difficult for these young people to grasp, and protecting them from making such decisions is paramount.

We can help protect them from these dangers.

It all starts with conversation. And trust.

To the highest hopes of your best self,

Lori Calabrese, M.D.

April 1, 2019
Misinformation about Esketamine (Spravato) and IV Ketamine

They’re different, but each can bring relief to those who suffer.

As word gets out that esketamine intranasal spray has been approved by the FDA, the internet is rippling with articles, posts, interviews, newsclips and press releases about ketamine — IV ketamine, esketamine, and ketamine nasal spray. And — online forums and meeting places are awash with misinformation on all counts.

We published a couple of articles here to lay the groundwork about the composition of esketamine compared to its relative ketamine — and about the requirements for esketamine use — to help to dispel misunderstanding.

But not everyone has read our posts, of course! And… some medical professionals have also stepped up to the mic to shed what we’ll call a tainted light on these medicines. It’s only been a couple weeks since the news broke, but things have already gotten a bit muddy in social media…

So let’s clean the windshield, and clear up some misunderstandings surrounding the news about these novel treatments, and the ground they stand on. Sound good?

Esketamine intranasal spray

First of all, esketamine intranasal spray (Spravato) is not ketamine intranasal spray. Esketamine is the left-facing enantiomer in the ketamine racemic moleduce, and as such possesses some of ketamine’s beneficial characteristics, but not nearly all.

(There’s a right-facing enantiomer, arketamine, that we’ll ignore for today. Together, both esketamine and arketamine make up what we refer to as “ketamine”–which we also refer to as racemic ketamine.)

The neuroscientists who developed esketamine for the pharmaceutical company Janssen (owned by Johnson & Johnson) worked with engineers to create a remarkable nasal sprayer to dispense it that gives a specific and controlled dose of esketamine with each spray.

Each dose of esketamine nasal spray comes in a box about the size of an iphone. The beginning dose is 56 mg, divided into two 28 mg sprayers. Each sprayer dispenses 2 sprays, one for each nostril to equal 28 mg. Then you open the second sprayer box 5 minutes later and use another sprayer that holds another 2 doses: one for each nostril.

So: one spray in each nostril, wait 5 minutes, and do it again. In your doctor’s office. With monitoring. For 2 hours. And then you can go home.

That’s for the starting dose of 56 mg.

If the dose is increased to 84 mg, you use 3 sprayers instead of 2.

While we all hope that esketamine intranasal spray is effective we won’t really know just how much it can do to relieve stuck depression until it’s been in use awhile and data emerges about the full extent of its effectiveness. Fingers crossed.

Insurance Coverage for the First FDA-Approved Novel and Advanced Depression Treatment

But here’s the thing. Insurance companies are scrambling to determine their own company’s coverage position.

They’re waiting to announce if they will cover esketamine (Spravato) right away, how much of the cost they will pay for, and if and how much they will pay for two hours of administration, clinical care and medical monitoring time. The sooner we know the answers to these questions for this FDA-approved medicine, the better.

So while we’re waiting, as confusing as it may seem to all of us, we can’t accurately refer to esketamine intranasal spray and ketamine intranasal spray interchangeably. They’re different.

Ketamine nasal spray has been around for a long time. (Bet you didn’t know that.) It was and is still the full racemic compound, and it has to be made up or “compounded” specially for individual patients by specialty compounding pharmacies.

A doctor can’t just write a simple prescription for it.

But there’s been no standardization in the compounding of it. The doses are individual and patient-specific, the dilutions can all be different, and there are literally dozens of sprayers a compounding pharmacy can choose to put it in. Testing to make sure that the exact dose needed is actually what is sprayed is, well, ….. ?

Racemic ketamine (the left and right molecules together) as a nasal spray can be less effective than IV ketamine because the nasal route isn’t as reliable as IV access, and the medication is not as bioavailable as it is when given IV.

One of the first psychiatrists who used ketamine intranasal spray in children is Dr. Demitri Papolos who has worked with children afflicted with the Fear of Harm phenotype of bipolar disorder. He reports striking results in these children consumed by fear when they are treated with ketamine nasal spray.

Racemic ketamine nasal spray has been offered by some doctors instead of IV ketamine, in addition to IV ketamine, after IV ketamine. And racemic ketamine has been used IM (intramuscularly) as an injection instead of IV ketamine, when IV access isn’t available, and for ketamine-assisted psychotherapy.

How to make sense of all of it?

IV Ketamine Treatment and its Side Effects

In general terms, IV ketamine treatment is a robust and rapid-acting antidepressant that can lift depressive symptoms even when all else has failed, and often helps patients achieve remission from their symptoms. Even if they’ve been symptomatic for years.

If you talk to an expert neuroscientist or physician who administers it to patients, you’ll often hear this medicine is the most extraordinary, remarkable medicine they’ve ever seen in psychiatry.

It just needs to be administered so its best benefits are maximized.

Of course, we’re learning more every day — and every week — about how to achieve the very best outcomes and help patients achieve remission.

And yet, there are times when it doesn’t seem to be effective in some people. We can’t explain that, but keep trying to learn more about why.

But it’s remarkably transforming in most people whose ketamine treatment is administered with wisdom, insight, and skill.

We can say that in recent years as we learn, our ability to work with ketamine and finely tune our patients’ responses has been growing, and more and more patients are achieving full remission.

Esketamine is the New Kid on the Block

This is one reason why it’s important that esketamine and ketamine mustn’t be considered interchangeable. Because esketamine intranasal spray has not had time to demonstrate what it can do. At least not yet.

Since esketamine (Spravato) has just been released, time is needed for psychiatrists to provide it to their patients, just as they provide IV ketamine, and compare the two. They need real life experience with both treatments to adequately speak about them from experience.

There has been no study published –yet– that compares racemic IV ketamine and esketamine intranasal spray head to head. So we’re hopeful … but we have to wait and see how well esketamine performs.

As far as IV ketamine treatment, the IV route gives us a very broad dose range, the ability to adjust the dose from moment to moment, to slow it or stop it immediately if a patient is fearful, to micromanage side effects like nausea, to extend the dissociative experience if necessary. It is completely customizable.

Nasal esketamine is not. It will be available in a very controlled, directed way without that type of flexibility, and only as a 28 mg 2-dose sprayer; you would use 2 or 3 spayers to equal 56 or 84 mg. No matter what you weigh. That means your dose is a standard, 2 sizes fit all. NOT calculated according to your weight.

The Issue of “Side Effects”

There are some side effects that have been reported with ketamine treatment, though they’re not widespread. Things like dizzyness, nausea, and blood pressure as well as heart rate elevations. All of these can be managed to keep you safe and comfortable during an infusion.

When the infusion ends, these transient effects tend to dissipate.

But there’s another effect that’s important to the work ketamine accomplishes, and rather than treating it, we want it to have full freedom to express itself.

That effect is dissociation.

Because the intensity of dissociation during an infusion is directly related to the improvement and remission of symptoms.

So write that down. When you see medical authorities who don’t know ketamine first-hand make statements about dissociation being a side effect to be avoided, remember that we not only don’t want to avoid it, but rather, we do give it the full stage. Because it’s associated with response.

Another case of misinformation about esketamine (Spravato) and IV ketamine.

Dissociation is one sign that ketamine is at work restoring those delicate brain systems that make you who you are.

And…the Naysayers

As surprising as it is at this point, there are still plenty of professors, psychiatrists, and other physicians who have read some negative reports about ketamine and stopped there. Those reports have turned out to be anomalies, rather than true evaluations of ketamine’s abilities to restore and transform.

Misinformation about esketamine (Spravato) and IV ketamine has been rampant the last few weeks.

So, surprising as it is, there are still those medical professionals who stand up and speak of their perception of ketamine, and declare it’s effects “patchy, spotty, or unreliable” when they don’t necessarily have the hands-on experience to understand what they’re referring to.

And so, with due respect intended, I encourage those who make statements like this to learn with us what we’ve learned in the last several years…

Because nothing could be further from the truth.

Each of those professionals who proclaim ketamine’s “placebo effect at best” need to shore up their courage, and interview the thousands who have been far more than relieved of severe symptoms.

So many have found themselves transformed, living in joy, and utterly free of the depression symptoms that have held them back for so many years.

People who think these treatments are bogus really should make the effort to talk to the thousands whose lives are working again.

Esketamine is building its track record now.

Since esketamine intranasal spray is new on the market, we’ll have to wait and see what it can do. We’re hoping it will be transforming, too. But when we speak of IV ketamine treatment, we’re not also referring to esketamine… at least not yet.

But so much has emerged about racemic ketamine treatment in the last few years. While we use it primarily at Innovative Psychiatry in a series of IV infusions to achieve remission, it’s being widely used in IM injections by psychiatric professionals across the country and internationally for ketamine-assisted psychotherapy with outstanding results, and as a compounded intranasal spray, and a compounded oral lozenge (or troche).

Are the effects temporary? Those who are lucky enough to find a doctor who understands the goals (remission) in ketamine treatment, may go for very long period without a maintenance treatment. Others find they need one or two at the 3-4 month and maybe the 7-8 month points …or at some other interval.

So no, when the treatment is administered properly, we’re not looking for temporary results. Some patients achieve remission easily, and others require a little more effort, or a few more infusions, to get there. But remission is remission. And the difference between depression and remission is…well everything.

Everyone is different. There is a wide variety of responses to ketamine, and some seem to need a maintenance or booster infusions every couple of months. And in their cases, they’re thankful that with those infusions they’re living again.

Not EVERYONE Responds to IV Ketamine Treatment the Same Way

It doesn’t work the same for everyone, because every brain is different and every life is different. Some lives are more laden with daily stress.

But it does result in remission for most. And you should hope and expect it to go the best way for you. And then you work to make it last.

Work on your infrastructure. Maintaining remission for the long term may require that you adjust and improve your personal infrastructure. Learn how to cope with major stressors and nurture peace in your life.

Is it possible the ones who go for extended periods in remission will reach a point they need a maintenance dose? Well sure… we can’t know until each person finds that the need arises down the road. Did their treatment fail??

NO! A thousand times no. Ask those patients how THEY feel about it. A full 18 months without a ketamine booster, living in joy, creativity, and hope…? Then a death in the family or a lost job or a divorce comes along, and they feel the need for another treatment. Because they want to maintain the solid creative life they’ve been enjoying.

Wonderful! Isn’t that wonderful???

And those very patients will likely move forward for another 2-3 years – or more – till they need another infusion. If ever.

Misinformation About Esketamine (Spravato) and IV Ketamine… And Moving Forward in the Latest Administration Methods is a Responsibility of The Physician in This Grassroots Field

We’re learning in this “ketamine for depression field” together. We don’t have the luxury of simply reading the pamphlet compiled by the pharmaceutical company who provides a medicine. Nor do we get to be lazy. We must keep learning, moving forward, exchanging data and experiences, and improving this treatment for our patients.

So you see, the method of administration matters.

The 0.5mg/kg doses we began with turns out to possibly be on the low end of average for therapeutic dosage. In our real-world practices, we must keep learning better ways to use IV ketamine treatment to help our patients achieve remission, one patient at a time.

Ketamine Dosage Just Can’t Be One-Size-Fits-All

Turns out there is no one-size-fits-all dose. It was a good place to start, but that was only the beginning. And doctors who are administering ketamine using that original set dosage, without watching for signs of dissociation then titrating the dose according to the patient’s response, may not be giving their patients the best chance for remission.

You may find someone in your town who can administer IV ketamine treatment in such an effective way that you enjoy remission for a long, long time. And when you do, you also want to send your friends to that doctor. The one that gets it.

The one that goes to the effort to titrate the dose, the rate, and the duration of the infusion. Who gets you scheduled for appointments no more than a few days apart.

With that doctor you achieved remission. You know you experienced deep and intense dissociation during every infusion. And now you know you’re better than you’ve been in a long, long time.

That’s the doctor you want to send your friends to,…right?

And you should.

Is Antidepressant Therapy Necessary During IV Ketamine Treatment?

That’s a good question, and another point of confusion these days. Antidepressant use while undergoing IV ketamine treatment is not necessary but is acceptable and in no way interferes with IV ketamine’s effectiveness. One of the beautiful things about ketamine (this doesn’t apply to esketamine…because it’s a different medicine, right?) is that it has its own actions.

If you’ve been taking an antidepressant, that’s no problem at all. Continue on your familiar medication, and move forward with a consult about IV ketamine treatment. Your medication and ketamine have different actions and won’t get in each other’s way.

At the same time, if you’ve stopped taking antidepressants because they didn’t help you at all, there is no need to start on a new one when you go for IV ketamine treatment.

Ketamine’s action is independent of traditional antidepressants and doesn’t require their actions to do its job. It’s a fast-acting, robust treatment that can restore and transform on its own.

This is unlike esketamine. Esketamine was FDA-approved with the condition that it be administered along with a new antidepressant that you have to start at the same time. Again, two different medicines.

Ketamine’s actions in the BDNF, prolific synapse formation, synaptic plasticity, the lateral habenula, and G cells on the lipid rafts of cell membranes, are fast and thorough.

This is no placebo, as some “experts” on the internet would have you believe. It’s transformative reconstruction in the brain.

One professional came forward and was interviewed. His knowledge about ketamine treatment was not first hand. He expressed that only 1 out of 9 subjects who were treated with ketamine for depression experienced any positive effects. And it was a very mild positive result. From his perspective, this was proof that ketamine had a placebo effect, at best.

To the untrained reader, it sounds like a dud, right?

Passing Judgment On a New Treatment Without Studying Its Use

There is more to this story we don’t know. Things like possibly improper administration of ketamine, or a poor understanding of medicines that interfere with its effects. Benzodiazepines or other medications, for example. Something was preventing those 9 patients from receiving ketamine’s benefits, and it could have been “user error,” as my computer says when I goof.

Bottom line, there is still so much we don’t know – but want to know – about IV ketamine treatment. But we do know a lot more than we did ten years ago.

And, authoritative comments made by people who aren’t themselves in the trenches with psychiatric patients and using ketamine as a psychiatric treatment, only create confusion for those seeking information.

We look forward to all we’ll learn about esketamine intranasal spray as we use it in the years to come, and watch what it can do for the lives of our patients and their families.

We’ve entered a new world in psychiatry — and with the help of ketamine and its derivatives, we’re closing the gap on the suffering from ineffective treatment of these disorders. We’re seeing patients who’ve been hopeless all their lives enjoy resilience and true remission.

This is amazing to see. We never take it for granted.

Innovative Psychiatry is pleased to provide esketamine (Spravato) intranasal spray and IV ketamine treatment for depression, suicidal thoughts, and other disorders.

If you suffer from symptoms that haven’t responded to treatment, call us. We can help you get the best treatment for your needs. There is hope ahead.

To the blooming of your best self this Spring,

Lori Calabrese, M.D.

March 25, 2019

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