Lori Calabrese, MD

Author: Lori Calabrese, M.D.

IV Ketamine + Neuroplasticity = Relief, Relaxation, and Relishing Life

I could use some of that. We hear that all the time. Relief, relaxation and relishing your life can sound so far away … but it doesn’t have to be. As word gets out about IV ketamine treatment for depression and other psychiatric mood disorders, more and more studies are emerging.

New information is surfacing about the effectiveness of this medication. And it’s inspiring more discussion, more research, and deeper understanding of the causes of depression.

And there’s more.

As evidence grows through research and clinical data, it seems clear that depression interferes with the neuroplasticity in the brain. Including diminished neurogenesis in the hippocampus and diminished synaptogenesis in the prefrontal cortex. In other words, depression messes with the growing neurons or brain cells and the synapses or connections that allow the neurons to communicate with each other.

A big factor in this is that stress reduces an important growth factor called BDNF, or Brain Derived Neurotrophic Factor. Sort of a “compost” for neurons. Without BDNF, your neurons become tattered and sparse.

They diminish in size and number … and thin out.

When you’re depressed, these measly neurons with their poor synaptic connections just have a much tougher time communicating with each other … so there is less creative thought, if any. Well-being tanks. And your world becomes darker, less hopeful, and without future. It’s a bad place to be in.

A brain that is well-connected is a brain that experiences creative thought and well-being. A brain in the dark is a depressed brain.

IV Ketamine + Neuroplasticity

Here’s where neuroplasticity comes in. (Don’t let the word shut you down.)

In this context, plasticity refers to the brain’s ability to change at any age … whether for better or for worse. So the term “neuroplasticity” refers to the ability of your neurons to adapt and remodel themselves. In the past 10 years or so, neuroscientists have come to understand that your brain is constantly remodeling itself throughout your life. And when it remodels itself, it remodels its networks, And because of that, it remodels how it works.

So, to put it briefly, when you think dark and despairing thoughts, or angry and vindictive thoughts, day after day after month after year, this thinking actually reshapes and remodels your brain. It’s kind of shocking, really.

The brain remodels itself. Your brain remodels itself.

Dark, negative and hopeless thoughts have a detrimental impact on your brain’s structure and on how it functions. Your brain changes to fit your thought processes … to respond to your stressors. By the same token, if you read inspiring and creative books, spend time with joyful people, and create joyful experiences, your brain can change over time for the better.

The very structure of your neurons can change — in a lush way. Richly. For the better. For your good.

Wow.

This is where people say, “I want some of that.”

Well, this is an oversimplification, of course. It doesn’t account for all of the different factors, illnesses, and environmental influences that shape the way your neurons look and act — grow and function — but it IS an illustration of one way the brain can change. At any rate, It appears that one reason IV ketamine treatment is so effective for so many different psychiatric symptoms is because of the way it enhances neuroplasticity in the brain.

Growing Your Brain Structure Garden

For example, when you take the time to learn a new language as an adult, you’re putting parts of your brain to work that respond by growing to accommodate.

A study of taxi drivers in London revealed that through the process of memorizing the streets of London to pass certification, that a specific structure in the brain enlarges to manage that information. The hippocampus is the memory center in the brain, and this study revealed that drivers who’d been driving taxis for decades had the largest hippocampi of the group.

Just an example to show how the brain changes with the right type of stimulation.

By the same token, the amygdala is the fear center in the brain, and it’s been studied extensively in childhood trauma, and in adult anxiety, depression, and bipolar disorder. The newest research shows that the size of the amygdala can change rapidly in response to recent stressors — even in people who’ve never had any of the these conditions. The left amygdala was smaller in people who’d had a recent stressor — it didn’t even have to be longstanding or chronic. And the shrinkage was enough to be seen on an MRI.

So here’s the point.

Ketamine’s Rapid Action

Ketamine acts rapidly in numerous ways, and its fast action is changing lives, as well as saving them. It stimulates changes in the brain that affect its structure and its function.

One example is that it quickly matures new neurons so they’re functionally mature and doing their job within 2 hours. Traditional antidepressants just can’t do this. As more neurons proliferate, mature, and migrate from the hippocampus into far-reaching brain regions, ketamine also stimulates the formation of more synapses, especially in the prefrontal cortex. The greater the communication throughout the brain, the better functioning the brain, and the greater the well-being of the individual. You.

The more synapses that are generated, the more neuroplasticity, or ability to change and grow, the brain will enjoy. And a growing, adapting brain provides a higher level of living and learning for you to experience. Plus a greater sense of joy and well-being.

Let the Sunshine In

It’s as if the proliferation of neurons – and the synaptic connections that empower them to communicate – opens doors and windows in the brain to let the light and fresh air in. This wonderful circulation of signaling gives the brain new thoughts, new hope, new relief.

Basically, IV ketamine + neuroplasticity = relief, relaxation, and relishing your life.

If you’d like to know more about innovative treatments for your psychiatric symptoms, please call for an appointment so we can evaluate what’s going on.

Innovative Psychiatry is committed to help you find and develop your best self. Let’s work together.

Joining forces with you to discover your best self,

Lori Calabrese, M.D.

April 18, 2017
Ketamine Wannabe Drugs … of the Future

Ever have somebody copy you? You know, try to be like you? Imitate what you do, where you go? try to get what you have? They wannabe like you. Well, maybe not just exactly like you — kind of like you and better than you all at the same time.

It’s happening with ketamine.

We’ve been talking for awhile now about the breakthrough of low dose IV ketamine. In fact, everybody’s been talking about ketamine for treatment-resistant mood disorders. We’ve expounded on its effectiveness in relieving suicidal thinking, treatment-resistant depression, and other psychiatric disorders. Did you catch the discussion about which route is most effective and why we use it? Check it out here.

You should know about all the ways it’s changing the horizon for psychiatric treatment. Like how it stops suicidal thinking within hours, rather than weeks. And how people who have lived with depression and despondency for years — no matter what medication they were taking — can feel depression just lift within hours. Maybe you’ve been there yourself, or you know someone who has.

But there’s more to talk about.

The discovery of ketamine’s therapeutic effects on depression has opened doors to more revelations of the chemical sort. Mechanisms of action. Delivery systems. Ways of leveraging the funding of pharmaceutical companies to develop more versions of ketamine, maybe with the same or similar benefits, but without any side effects …

Think of it like this:

Ketamine wannabes want to “be like” ketamine and wannado like ketamine — except better, without side effects, for longer.

But it turns out that’s easier said than done.

Since ketamine is no longer under patent, it’s unlikely that a pharmaceutical company would be interested in investing the necessary funds to conduct extensive trials and research about its effectiveness to treat mood disorders at this stage … at least on ketamine specifically.

Or that a company would shell out time and money to study long-term response and remission rates, or long-term safety, for a well-known generic like ketamine — even if it is being used in a new way in new settings to treat new conditions. There just wouldn’t be the return on investment in the long term.

However, by making changes in the molecules and targets that provide the therapeutic results for ketamine, new versions of the drug in the form of ketamine wannabe compounds that specifically target mood disorders are being designed and developed, and are in the race for FDA approval.

Ketamine Wannabe Drugs

So grab your chemistry lab goggles, and let’s explore some of these molecular discoveries among ketamine-wannabe molecules.

Ketamine is a racemic compound — it has two parts that are mirror images of each other joined together like Siamese twins. If we split it right down the middle where the mirror images join — presto! — we have two “new” drugs. One faces right and the other faces left. We call the left-facing one “S” or in the world of pharmaceuticals, “es–” as in esketamine. So it turns out in this case that changing the structure of ketamine slightly could give us the same benefit, hopefully fewer side effects, and easier use. In other cases, molecules like ketamine are coming down the pike that act on similar targets or in similar ways to help with depression without some of the potential side effects of ketamine.

They both wannabe and don’t wannabe like ketamine. They wannado better.

Esketamine

Esketamine has been approved in Europe for a decade and a half – specifically for anesthesia – and Janssen Pharmaceuticals has acquired a patent to utilize it in the US as an intranasal spray for treatment-resistant depression.

The Food and Drug Administration has awarded “breakthrough” status to esketamine to zoom its advancement through to approval with less interference from various obstacles and the usual red tape that slows everything down.

They plan to specify it for use it in a clinical setting (as opposed to at home) for the sake of controlling the dosage, as well as to prevent sale on the street.

Rapastinel

Another pharmaceutical company – Allergan in Dublin, Ireland – has designed a peptide in this same “ketamine-like” category. You may know that a peptide is a chain of amino acids bonded together in a specific way, and this one looks pretty effective as an adjunctive treatment in depression. It has characteristics like being fast-acting and long-lasting and it’s given as an IV infusion, like ketamine.

Ketamine’s action with NMDA receptors is to block ion channel activity. Here’s where rapastinel is different. It binds to the glycine site on the receptor and regulates or modulates it by changing the shape of that site. Pretty cool. The result is that rapastinel reportedly has a minimum of dissociative or out-of-body side effects that are sometimes experienced with IV ketamine infusions.

Rapastinel is in Phase III trials in the US as an adjunctive treatment for major depressive disorder, and more trials are expected in Europe and Japan. Soon, it’ll be ready for FDA approval for use in the clinical setting to treat depression.

AV-101

Still another pharmaceutical company in San Francisco is working to create a small molecule drug that possesses all the good traits of ketamine without its potential dissociative side effects: VistaGen Therapeutics.

This molecule is one that’s back on the scene from over 30 years ago. At that time, it couldn’t cross the blood-brain barrier to do its work. And consequently, couldn’t impact the depressive symptoms a person was experiencing.

But now, the molecule (which is considered to be a “pro-drug”) has been revamped and this current version does cross the blood brain barrier, And when it does, it’s metabolized from a pro-drug into an active drug that modulates a certain glycine binding site at the NMDA receptor — unlike ketamine and different from rapastinel.

So while ketamine completely blocks certain NMDA receptor ion channels, AV-101 just sort of regulates the receptor gently…which seems to result in gentler side effects.

A New Frontier – Ketamine and Ketamine Wannabe Drugs

There are plenty more versions of modified “ketamine wannabe” molecules in the wings, developing to hopefully even replace ketamine at some point. Hoping to improve on ketamine’s action. Aspiring to lesser side effects. Working towards easier administration. We’ll just have to see how that goes.

And one day this miraculous breakthrough medication – ketamine – may become obsolete like so many cornerstone discoveries of the past.

But right now, boy are these exciting times! We’re on the threshold of a brave new world in psychiatry. A world where people who’ve suffered without relief for years, even decades, can finally experience relief and build a fulfilling life.

One last thought…

All of the companies working with these small molecule drugs are investing in priceless research that’s opening more doors and windows of understanding –. which will, in turn, only increase the benefits for people who just haven’t responded to or tolerated anything else.

For example, we know that ketamine, rapastinel, and AV-101 all work at the NMDA receptor site. So it’s been assumed that that action is the key to their effectiveness. However, when researchers blocked the AMPA receptor, none of these drugs worked. I’ll say it again. None.

Which revealed that the AMPA receptor needs to be activated for the drugs to deliver their fast antidepressant, anti-suicidal results.

And this revelation may lead to more breakthroughs for more who suffer … through ketamine wannabe drugs.

We’re on this. We stay up at night. We watch closely to glean all we can from the research that’s exploding, so we can continue to provide the most up-to-date, cutting edge, fresh discoveries that neuroscience offers.

And…we’ll be here to help you find your best self.

So call us, and let’s find the right innovative solution for you.

To the emerging of your best self,

Lori Calabrese, M.D.

April 12, 2017
IV Ketamine and Treatment-Resistant Mood Disorders

IV Ketamine and Treatment-Resistant Mood Disorders

After reading today about a beautiful young man – let’s call him Tom – whose life ended tragically at the crossroads of despair, I started thinking.

Like many of my own patients, he had a wondrously warm and giving heart — and a compassionate heart the size of Montana for homeless animals.

His talent for music generated moving, exquisite collections of melody and lyrics that stunned listeners with its charm.

Such sensitivity, such beauty for the world to enjoy.

But his life ended far too soon, because he could find no relief for his illness.

Bipolar disorder.

Tragedy Without IV Ketamine

I’ve treated many people with similar stories in my office. I’ve offered the best that we had–medications, combinations, the latest research, the newest adjunctive treatment, supplements, recommendations for lifestyle changes, collaboration with the the best therapists in the area, resources, articles, support–everything I had. I never stop trying. But until a few years ago, we had little to offer those who didn’t respond to traditional treatment. Or who were just sick of it.

And that’s tragic. Really, really tragic. But more common than we can bear to think.

It’s not just about bipolar disorder or treatment-resistant depression. We’re talking about postpartum depression, PTSD, and other psychiatric mood disorders.

I thought about Jacie. Jacie wasn’t expecting to get pregnant when she did, but she was happy about it, and enjoyed the feelings of wonder about this tiny new person growing inside her.

But around the time her second trimester began, she noticed her initial lilting emotions weren’t lilting anymore. In fact, she felt gray…dull…and couldn’t seem to relate to the idea of a baby.

Once the baby was born, everything was a struggle. She felt angry, frustrated, and exhausted beyond belief. And guilty that she wasn’t enjoying this innocent baby girl. In desperation, she talked to her doctor honestly about how she had been feeling. And her fear she might do something to hurt herself or her child.

He referred her to a psychiatrist he trusted, and she began seeing her. Her depression had gone on a long time — untreated.

IV Ketamine and Treatment-Resistant Mood Disorders

When depression comes during pregnancy, it can be so much worse than postpartum depression that begins after the baby is born … and so hard to treat. In Jacie’s case, her depression didn’t budge, and the persistence of it affected her relationship with her baby, and her marriage.

She was surrounded with people who loved her. She was fortunate in that sense. But nothing seemed to ease the agitation and misery she endured. Or her self-hatred and guilt that she resented her baby and didn’t know how to change it, or feel better. To be the kind of mom her baby needed.

Traditional antidepressants and psychotherapy just aren’t effective for some people. If you’re one of them, or you know one of them, you know what I mean. Since depression is caused by a complexity of changes in the brain, there’s no simple solution.

And in my musings, another man came to mind — Dan. He’d suffered with PTSD for over 15 years. War time trauma, loss of friends in combat and the powerlessness he felt to save or protect them; it all tormented him.

He’d been told he should be “getting over this” by his friends and his family. Oh, they meant well. But they had no idea what they were saying. And suggestions like those didn’t help. Not at all.

He struggled just to get through the day … to have a relationship with his wife … to work at a job, to pay the bills.

He wanted to be productive, but every time he had a few good days or weeks, it didn’t last because of the dreams, the night terrors…the reactions to noises or touch. Then he’d lose his confidence, walk off the job, and withdraw again.

The loss of life, of peace, of relationships, of fulfillment, for people like these has been unavoidable till now.

For those who couldn’t benefit from the traditional treatments for mood disorders, there just weren’t any solutions. IV ketamine and treatment-resistant mood disorders went to war.

Your treatment-resistant mood disorder won’t win over IV ketamine.

These stories are just examples, but they represent multitudes of individuals whose lives have been interrupted, oppressed, tormented, or in some cases cut short, by symptoms of disorders that remained unaffected by traditional treatment.

And that’s why I thought of all of these people.

Because the ineptness of so many antidepressants left me feeling powerless to help; too many of my patients were crippled by their disorders, but desperately wanted the same chance at building happiness and fulfillment as anyone else.

Too many.

And that’s why I’m excited now and so full of hope.

That’s why I talk so often and so enthusiastically about this emerging frontier of new therapeutic uses for that anesthetic-turned-antidepressant, IV ketamine.

Because for all all the Toms, Jacies, and Dans who found no help at all from previous treatments, 80% now experience relief, restoration, and often total remission after IV ketamine treatment.

We’re still working to find solutions for that other 20%, and we won’t stop. But we’re helping 80% of those for whom we had nothing, nada, zip…zero… that would help.

All my training didn’t prepare me for the heartbreak of those who are so desperate for relief and can’t find it. But hope is growing, and ideas are flourishing for ways to use this new knowledge to spawn more solutions.

Relief and Solutions are RISING

So after my musings about those who weren’t helped, and the sadness I feel that we didn’t find solutions soon enough, it’s exhilarating to know there’s an entire frontier opening. A new world of treatment for those who weren’t helped before, through the discoveries surrounding ketamine for depression and other new solutions that will spring from it.

IV ketamine and treatment-resistant mood disorders … it’s a fight to the finish, and ketamine is winning.

Are you wondering if you’ll ever be able to have a life…? If you’ll ever get to feel stable — emotionally, financially, socially?

You really aren’t alone. Sometimes you just can’t see there’s support at your fingertips… help just beyond your line of sight.

Reach out and let’s talk about the things in your life and feelings that interfere with the power to live life the way you want to.

Power to find your best self, and share it with those around you.

Power to enjoy.

To the power for finding your best self,

Lori Calabrese, M.D.

April 3, 2017
NBC News: “Doctors Say ‘Club Drug’ Ketamine Rescues Suicidal Patients”

“Special K,” a psychedelic drug popular in dance clubs, is being used to treat severe depression when nothing else works. Watch the video below!

March 30, 2017
PTSD Has a New Predator: IV Ketamine

PTSD Has a New Predator: IV Ketamine

He’d seen active combat in Iraq and Afghanistan.

His unit had grown close. Tight. Trusted each other with their lives.

They’d cheered when word came that Jarrett’s baby had been born.

They’d gotten drunk with Ben when his mom died.

They had each other’s back, and knew each other in a way civilians couldn’t comprehend.

Then one day, an explosion.

He’d looked up and both of Ben’s hands were blown off.

Jarrett’s legs were 10 feet away, and he was shrieking.

He held him, tried to stop the bleeding. He couldn’t think but his mind was screaming — he had to save him.

Somehow.

He’s stateside now. Trying to work a “normal” job. But a friendly slap on the back puts him back in that desert. It should have been him, not Jarrett, that didn’t make it home.

Someone drops a tray in the kitchen, and he’s surrounded with mortar shells, blood, and Jarrett’s legs.

It’s tough to hold any job for long, and he doesn’t feel like he fits in anywhere he tries. At times, the simplest of tasks seems to be more than he can manage.

And it’s getting worse …

PTSD Knows No Favorites, No Gender

She was a friendly, warm, and fun-loving girl.

She’d worked at a wings place near the beach. She met him at a friend’s party. His flashy smile, his rugged good looks … wow! She couldn’t resist.

In a couple of weeks, they were living together. It seemed like they’d known each other forever.

But … then their first fight. It was cruel, dirty, and it broke all the rules. Demeaning, and anything but loving. She cried, and wondered what she’d gotten herself into. But she couldn’t stay away long.

Things went smoothly at first.

Then, a worse fight … that started with accusations, then escalated to a choke hold, bruises, a bruised and bloody face.

But she couldn’t bring herself to leave. She believed his “recovery” depended on her faithful and patient loyalty.

Until, one day, she was sure he would kill her.

She passed out from asphyxiation with her neck in the vise of his clamped arm. When she woke up, he was raping her.

The blows from his fist slammed her to alertness, and when his guard was down, she ran from the house.

Now she’s staying with her sister, her nights filled with nightmares of all the terrors she had endured. She wakes breathless, covered in sweat, and deeply shaken. The next day is a loss. She can’t pull herself together.

During the day, she panics at the smallest frustration, is volatile, reacts to unexpected sounds as if she’s under attack.

She doesn’t trust anyone, and believes everyone she encounters is purposely humiliating her, lying to her, or out to hurt her in some way.

Four years with a violent abuser shattered her trust. Her confidence. Her ability to even function. She wonders if she’ll ever find herself again.

How Can You Heal?

Two examples of people with PTSD. Both experienced traumatic, even devastating, events. How can you heal from the terrible memories that torment you?

PTSD affects more than 3 million Americans a year. The Lone Survivor Foundation says that 1 in 3 of all veterans suffer from PTSD.

Post-traumatic stress disorder (PTSD) is serious and potentially debilitating. It occurs in some people who have experienced or witnessed a natural disaster, serious injury or loss of friends in an active combat zone, a terrorist event, or personal and violent assault such as battering or rape.

While most people who experience the traumatic events that cause PTSD recover eventually, for many that can take years. And years.

The symptoms can be so severe you may be unable to work, unable to participate in healthy, loving relationships, and unable to sleep. Your nightmares can trigger memories that are so real that you may be overcome by intense and painful emotional and physical reactions.

Night after night.

Day after day.

IV Ketamine Erases PTSD Triggers

Then there’s the depression and anxiety, and the flashbacks, and amplified reactions to certain music, or smells, or types of touch, sounds, or flashes of light. The triggers are sometimes unpredictable, out of the blue. You can’t relax, and neither can those who love you.

While the standard of treatment for decades has been psychotherapy and medication, But for you, treatment may not be that effective. The torment goes on, and your loved ones are often left alone, baffled, shaken.

Until recently.

In 2014, the US Army funded a study to learn about the effects of IV ketamine on combat veterans with PTSD.

“Our results provide the first evidence that a single dose of IV ketamine was associated with rapid reduction of core PTSD symptoms and reduction in comorbid depressive symptoms . . . ,” the authors wrote.

And hundreds, maybe thousands, of individuals with PTSD have been successfully treated since then. We’ve seen it over and over at Innovative Psychiatry, as have other psychiatrists through the US who offer their patients this groundbreaking, almost miraculous, treatment.

PTSD has a new predator: IV ketamine.

And as we’ve said often lately, there’s still so much to be learned. But IV ketamine infusions are changing lives, changing traumatized men and women, and giving them the freedom to build a life free from terror.

Society’s stigma overshadows you if you have PTSD, and the war of images and terror inside you makes healing and recovery so difficult. But IV ketamine infusions bring rapid and immediate relief, liberating you to live in peace, free from fear of memories or triggers.

If you suffer from PTSD and wish for peace, a sense of safety, and the breathing room to relax and build relationships, call for an appointment. We’re Innovative Psychiatry because we leave no stone unturned to find solutions for you.

Your best self is just ahead. Don’t stop looking till you find the quality of life you’ve wished for.

To the discovery of your best self,

Lori Calabrese, M.D.

March 29, 2017
Low-Dose Ketamine In Treating Depression: An Outsider’s Perception

Mother and Healthcare Professional Discusses Her Child’s Experience with Low-Dose Ketamine for Treatment Resistant Depression

As both a healthcare professional and a parent of a child who suffers from treatment resistant depression and anxiety, I have been quite attentive to the changes that arise in an individual after receiving low-dose ketamine. I thought it would be helpful to share my observations with others who are contemplating offering this innovative treatment in their practices or for those that may be exploring ketamine as an option in treating their own depression.

Though low-dose ketamine can alleviate suicidal thoughts immediately and lift an individual from feelings of despair which many have suffered for years, it does not cure one’s depression indefinitely. Ketamine, in my experience, has worked in a way that it offers hope to individuals and provides a new found resilience in dealing with life stressors. As an outsider looking in, I have watched my child develop the drive and passion to discover new approaches to help improve her mental health and overall well-being. – Ann Corcoran RN, MSN, Nurse Consultant, Mental Health Care Advocate

[Read the Full Article Here]

March 23, 2017
IV Ketamine: Doing What Prozac Can’t

Excitement about IV Ketamine

Recently, I shared my perspective about the consensus statement released by the American Psychiatric Association’s Council of Research on Novel Biomarkers and Treatments Task Force. Their statement was about the use of IV ketamine for treating mood and other psychiatric disorders.

That Task Force, in its consensus statement, assured members of the APA that there’s compelling evidence that IV ketamine has the ability to provide rapid and robust antidepressant effects in patients with treatment-resistant mood disorders.

Well, I was delighted to see that NPR published an article this past Monday, March 20, 2017, about Gerard Sanacora, M.D., Ph.D., Professor of Psychiatry at Yale School of Medicine, and his personal reflections on IV ketamine for mood disorders. You should read the article, too.

Gerard Sanacora is a member of the same Task Force. He says he’s treated hundreds of patients who are severely depressed with IV ketamine and is excited about the results in these patients’ lives.

He says doctors have asked him how he can use a medication when there is still unknown data about long-term use.

What Would You Do?

His answer?

“If you have patients that are likely to seriously injure themselves or kill themselves within a short period of time, and they’ve tried the standard treatments, how do you not offer this treatment?” he says.

Well, that’s how I feel, too, and why I offer IV ketamine infusions. In good conscience, with what I know about ketamine, how could I not? It’s what growing numbers of other psychiatrists are feeling, too.

Ketamine has an effect no other medicine has had before. Within hours it can erase the suicidal thoughts of someone who’s been on the verge of suicide for some time.

It removes the self-destructive thoughts, and the terrible mental images of death. And it happens fast.

This one extraordinary effect is changing the way we approach severely depressed individuals. There is something we can do to bring our patients relief from this dangerous, life-threatening symptom. And it succeeds in bringing them relief in 80% of cases.

Dozens of doctors responded to surveys in the US and Canada, reporting that over 3,000 patients have been treated for mood disorders with ketamine. The good news is spreading, as well it should be!

Even so, as we’ve discussed before, IV ketamine treatment has still not been studied in enough depth to answer some questions that remain unanswered. And that’s because of the lack of large-scale trials. Large-scale trials are needed. And with the attention ketamine is receiving from pharmaceutical companies, I expect those trials are just ahead.

More Questions

James Murrough, M.D. at Icahn School of Medicine at Mt Sinai in New York, worries that because of the lack of large trials, it’s not yet known how long a treatment regimen can be continued safely. And it’s true that it will take years of studies to establish that.

From his perspective, that’s troubling because IV ketamine can wear off in a few days or a few weeks. Repeat infusions are necessary to prevent the return of depression. So, unless a form of ketamine is developed that lasts a great deal longer, we’ll need to continue giving those treatments to those who need them… until they achieve remission.

But in spite of that, he strongly feels the case for IV ketamine is warranted and justified…much stronger than a few years ago. And so do we.

Most Promising Since Prozac

“There’s warranted caution that’s balanced with an optimism that says we’ve never had a new medication for depression since the era of Prozac,” Murrough says.

IV Ketamine: Doing what Prozac Can’t

No new medication for depression since Prozac!!!

So just a quick review: Prozac emerged in the 1980’s and was the first of a “new class” of depression drugs targeting serotonin, one of the neurotransmitters.

Prozac opened a world of possibilities in psychiatric treatment. But there have been far too many who suffered from mood disorders and were never helped by Prozac and its offshoots.

Since then, sure, there have been new medications and new neurotransmitters that have caught our fancy — mine, too. But no drug has has been more effective, more rapid, and more transformative — with an entirely novel mechanism of action — than IV ketamine.

Period.

IV Ketamine – Doing What Prozac Can’t

Because ketamine acts on a different neurotransmitter than Prozac and other common antidepressants. Instead of Prozac’s focus on serotonin, ketamine acts on glutamate, another neurotransmitter that acts on a different system. Murrough says that because ketamine’s been so remarkably successful, the pharmaceutical companies are pulling old drugs off the shelf that act on the glutamate system.

They’re as excited as we are at the possibility of creating a whole new class of more effective drugs for depression.

So, there is actually a possible contender in the ring for ketamine being developed. Related to ketamine chemically, it’s called esketamine and is in testing. It’s not been considered by the FDA yet, but that’s not far off.

And it’s one of a mountain of medicines in development that are related to ketamine, according to Gerard Sanacora.

He also said, “This is probably the most interesting and exciting new development that I’ve seen in my career, and probably going back over the past 50 to 60 years.”

And that’s certainly the case for me, too. For all of us who are seeing our patients doing better, looking better, and feeling better – after decades in practice.

These are such exciting times in psychiatric medicine. I’m so thrilled to be a part of this life-changing and life – saving historical time. And I’m thrilled you are too.

Until recently, our patients with treatment-resistant mood disorders weren’t getting better.

Now they are.

IV Ketamine is Changing – and Saving – Lives

They’re living again, building fulfilling lives again, looking to the future with HOPE.

If you know someone who’s been lost, sad, full of shame and despair, and just doesn’t seem to get better, there’s new hope now.

Encourage them to call us, or call us yourself for an in-depth evaluation. There is specific lab work we can do that will actually help us know if IV ketamine is likely to work and work quickly. It’s been successful with about 80% of our patients who have received infusions.

IV Ketamine isn’t for everyone, but with appropriate screening, it may be exactly right right for you. It may be exactly what you’ve been waiting for. And if you’re struggling with a treatment-resistant mood disorder, you owe it to yourself to find out.

You can feel better.

Much, much better.

To the release of your best self,

Lori Calabrese, M.D.

March 22, 2017
Treatment-Resistant Depression Meets Its Match

Do you know someone who’s been listless and hopeless for a really long time? More than weeks or even months … someone who’s been taking antidepressants for years, and has never really felt better?

Have you noticed how years of despair affects a person’s outlook so deeply that their personality seems to change?

Clare’s story

Take Clare. She began feeling more and more overwhelmed when she was in 8th grade. A string of unfortunate events seemed to pound her down further and further, until she’d lost her ability to recover.

It was as if life formed a dark tunnel around her and she couldn’t face it any more. She started avoiding school because facing it was too hard.

She came to believe it would never, ever get better. And she became volatile at times, and subdued at times. She grew to have a generally defeated attitude, and overreacted to small frustrations.

Treatment – Resistant Depression Leads to Overwhelm and Failure

This once cheerful, go-getter teenage girl withdrew into a place where she could no longer function, no longer face others, no longer spend time with friends.

After high school she tried to go to college, and her psychiatrist changed her medications to something that he hoped would help more.

But she’d try her hardest and do well for a semester, then fail the following semester. So she’d work up all the energy she could to succeed and do well again, then fall apart a few weeks into the next semester.

Eventually, she dropped out of college because her grade point was no longer high enough to stay.

Failure, Despondency, and No Reason to Live

Clare thought about dying often. On a few occasions, her mom or a roommate walked in to find her with a pile of pills in her lap and a big glass of water, about to carry out a plan…

This is what treatment-resistant depression looks like. In the beginning, the despair seems justified after a series of overwhelming or heartbreaking events. But, eventually, the unchanging, unrelenting despair washes away hope. Any reason to live seems to erode away.

Neurotransmitters Play the Culprit

Neuroscientists have discovered that there are multiple brain-based and physical causes for depression. Large networks of neurons can be affected by cascades of inflammation that affect many systems and many neurotransmitters.

Neurotransmitters are chemicals in the brain that help one part of the brain communicate with other parts. In most cases, the more neurotransmitters in the brain communicate with other areas throughout the brain, the better you feel.

For some people, SSRIs may help. But if they don’t, we start thinking about whether we should try an approach that might stimulate GABA, dopamine, or norepinephrine activity.

In addition, the weeks or months that are required to determine whether an SSRI is effective mean that the one suffering is left to endure in a seemingly untreated state. If you talk to someone who’s been handicapped by crippling depression, and tell them you have a new drug to try, but it may be months before we know if it will help, his response will likely be dripping with despair.

And that despair sometimes ends in loss of life.

Gaining Understanding

Psychiatrists didn’t realize years ago that all depression can’t be successfully treated with SSRIs, so only a portion of the depressed patients they treated were actually being helped.

But, we’re learning.

Thanks to continued study, we’ve learned more and more about what areas of the brain are involved in depression, and the various neurotransmitters that are involved, as well.

Without question, there’s been a critical need for rapidly acting and effective treatments that provide relief for people who suffer from treatment-resistant depression, and have for a long time.

Why IV Ketamine?

And in searching for such treatments, IV ketamine – the decades old anesthesia drug – has risen to the task and is shining.

Because in addition to treating treatment-resistant depression, IV ketamine is also demonstrating its exciting effectiveness in successfully treating bipolar depression, post-traumatic stress disorder, and acute suicidal thinking in about 80% of cases in our clinic.

To take it a step further, the action of IV ketamine with suicidal thinking is independent of the antidepressant action. Many patients receiving IV ketamine infusions find the suicidal thinking disappears before the infusion has even finished!

Never before have we had a medication so fast and effective for people tormented by suicidal thoughts.

So many start ketamine infusion treatments in a dark and despondent place. Then at the end of the infusion, a look of amazement and relief floods their face. And they tell you things like, “this moment is the first time in 7 years” they’ve felt relieved and hopeful.

To me, it’s pretty miraculous.

And if you’re burdened with treatment-resistant depression, bipolar depression, or PTSD, it could feel like a miracle to you, too.

I hope you’ll take the time to read the other articles linked in this post. Information is your link to feeling better.

The more you learn, the more your hope can grow, and the sooner you can take action.

We believe in you, and the life you can live. A fulfilling and satisfying life is possible, with the right treatment.

Make an appointment for a complete evaluation, and let’s work together to find the right treatment for you. We want you better, so you can restore your best self.

To the release of your best self,

Lori Calabrese, M.D.

March 15, 2017
JAMA Psychiatry Weighs In: The “Ketamine for Depression” Buzz
JAMA: “Ketamine for Depression” Buzz

The mental health community is all a-buzz about IV ketamine for treating depression and other psychiatric disorders, and for good reason. For the first time, people who’ve been treated without success for years are experiencing relief and enjoying their lives.

For anyone who has suffered from psychiatric disorders without relief for a prolonged time, the possibility of a breakthrough treatment that actually works can mean the difference between life or death. Or utter misery vs. hope. Most folks would go for hope … wouldn’t you?

This anesthetic-turned-street-drug has returned to the scene to restore its reputation by providing a remarkably successful, and fast, reversal of depression in patients who’ve not experienced relief in a very long time– some of them for decades.

In addition, these infusions in single doses or in a series of doses, reverse suicidal thinking, often within hours, if not before the IV infusion is even completed. Now that’s lifesaving.

What’s more, suicidal thoughts disappear immediately in many cases, whether the depression is relieved or not.

So yes, some of us in the psychiatry community are excited about what IV ketamine can do.

Psychiatrists Containing Enthusiasm

But … we know we have to contain ourselves, and maintain a scientific approach to this “off-label” use of the anesthetic ketamine. So we read the research, keep up with the published studies, and pore over the data to be sure our enthusiasm doesn’t get ahead of us.

We talk to each other endlessly, scour the journals, go to conferences, stay up late, stay at the office late, pull together every shred of published research, every letter to the editor, every blog and YouTube video.

Then, we watch TED talks. And we tweet, we message, we write. And we see dozens of people every day who are depressed. Sick of it. Suicidal. We offer many treatments. And we offer hope. Some of us offer off-label treatment with IV ketamine. And some of us have seen hundreds of ketamine patients, and administered nearly 1000 infusions. (That’s us.) We’re in the trenches. Deep.

Now comes this timely release to further illuminate the path for psychiatrists who are moving forward to help their patients with this breakthrough treatment.

So what does the APA (American Psychiatric Association) and JAMA Psychiatry (Journal of the American Medical Association Psychiatry) have to say about this unexpected surprise that treats psychiatric disorders?

In the March 1, 2017 issue of JAMA Psychiatry online, a consensus statement was released by the American Psychiatric Association (APA) Council of Research Task Force on Novel Biomarkers and Treatments regarding the off-label use of ketamine in the treatment of mood and other psychiatric disorders. The best and brightest are on that Task Force.

The Task Force made the point that there is compelling evidence that IV ketamine has the ability to provide rapid and robust antidepressant effects in patients with mood disorders who had previously displayed resistance to treatment.

Limited “Ketamine for Depression” Data

They acknowledged the sample sizes were small in these studies. And use of low dose ketamine for psychiatric disorders has increased at such a rapid rate that there’s a lot we still don’t know.

So, one point they made is that there’s limited data. The strongest data about the use of ketamine in the treatment of psychiatric disorders is for the treatment of major depressive episodes where there are no psychotic features.

Their concern was that even in the case of major depression, some of data that was evaluated had been collected from only the first week following one dose of ketamine treatment.

Again, limited studies, limited number of patients, limited information about outcomes, side effects, impact of long-term use.

Still, we know that anesthesiologists have been using this drug for decades and have found it to be quite safe in controlled settings. But the APA Task Force’s statement isn’t intended to decrease the use of ketamine in treating psychiatric disorders. But instead to highlight where we are and the most critical things to consider for keeping its use safe while research on ketamine proceeds.

Criteria for Ketamine Treatment

So, initially, the Consensus Statement recommends we take several steps when we see a patient to help determine if ketamine treatment might be appropriate for him or her. They include:
- Performing a comprehensive evaluation to determine that the patient meets appropriate diagnostic criteria for depression
- Ensuring the patient has completed adequate courses of FDA-approved antidepressants before considering ketamine
- Thoroughly reviewing the psychiatric and medical history as well as the patient’s potential risk factors for ketamine treatment
- Carefully evaluating any history of substance abuse, including baseline urine toxicology screens
In addition, they said the physician should thoroughly discuss ketamine treatment with the patient before use. The possible benefits of it, as well as the possible risks associated with its use for any given patient. This empowers the patient to make a truly informed decision about whether the benefits are greater than the risks. Of course — that makes sense. It’s the very basis of collaborative treatment in medicine and the basis of informed consent. Then, like with any medical procedure, we should obtain written consent before beginning the infusion.

Precautions with Ketamine

Next, in terms of specifics, spikes in blood pressure sometimes occur with ketamine infusions, so patients receiving ketamine therapy ought to be in a facility setting where we can manage any unexpected medical incident.

Even so, ketamine is considered “reasonably safe” at the recommended dosage of 0.5mg/kg over 40 minutes.

Because of ketamine’s natural action, patients experience dissociative effects that should pass momentarily. Or some may have short-lived vivid experiences of heightened perceptions, or intense ideas or memories.

Understandably, patients who experience effects like this may react with behaviors unlike their usual personality. So, physicians must be prepared to treat episodes of that nature. Which is why we want to see ketamine administered in specially prepared clinical settings, instead of at home.

Suicide Prevention

Also, as effective as ketamine is with suicidal thinking, there’s still the risk that the self-destructive thoughts or plans won’t lift for some patients. So it’s vital that physicians evaluate their patients after ketamine treatment before discharging them home.

Overall, psychiatrists must form a comprehensive plan for managing the patient’s depression along with needed followups. Ketamine is a highly effective drug to be incorporated into the overall treatment and management of depression.

The APA Task Force strongly advised that psychiatrists develop a standard operating procedure for administration of ketamine.

At the very minimum, it should incorporate these points:
- Signed informed consent and pre-procedure evaluation
- Baseline assessment of vital signs: blood pressure, heart rate, O2 saturation
- Continual evaluation of patient’s mental and physiologic status throughout the infusion
- Management of side effects that may occur during the treatment
Studies are lacking to evaluate the efficacy of long-term use of ketamine treatment for depression.

The most useful data to date indicate that infusions given up to twice a week and within four weeks are effective. Patients should be monitored with a rating instrument to assess changes in mood.

Avoid Abuse or Dependence

The Task Force also recommends that dosing of ketamine be discontinued if infusions can’t be reduced to one per week.

The committee members agreed that ketamine is an incredibly promising treatment but must be used with standards that ensure the highest level of safety.

Ketamine is the most abused drug in Asia. So the widespread use of it in the US – for therapeutic purposes – must be surrounded in safeguards to avoid the advent of abuse or dependence, in spite of its benefits.

JAMA: Ketamine for Depression – The Buzz

All in all, the buzz is that ketamine is the most promising new treatment to date for depression. The data is limited, it’s true. There’s much to be explored. But, we’re working rapidly to pull together all of the available evidence and all of the best practice recommendations as we proceed. This treatment is bringing hope where there was very little before.

We’re thrilled to be on the forefront, and we’ve developed our protocols for IV ketamine very carefully. Not only to set the bar for the standard of practice in our field but to exceed the standard.

At Innovative Psychiatry, our protocols comply with the recommendations of APA Council of Research Task Force on Novel Biomarkers and Treatments published in JAMA Psychiatry. But, we go above and beyond those. We educate you. Then, provide you with the research articles that we read ourselves. And ensure that we offer IV ketamine infusions as a psychiatric treatment — not simply as a medical procedure.

To that end, we work with you and your physicians and therapists for the best possible results. And we pull out every stop to help you feel better and enjoy life again when nothing else has helped.

Call for an appointment, and let’s work together to help you rediscover your best self.

To your emerging best self,

Lori Calabrese, MD
March 9, 2017
Ketamine IV, IM, or IN for Depression: Which is Best? (Does It Matter?)
Why do we always talk about IV ketamine for treatment-resistant depression, rather than just ketamine? Can’t we give it any old way…ketamine IV, IM, or IN for depression?

Why is it so important that it be given as an intravenous infusion, rather than as an intramuscular injection or an intranasal spray?

Ketamine IV, IM, or IN for Depression

Like lots of medications, ketamine can be given in a variety of ways. But are they all advantageous to you?

We don’t think so.

Not all physicians insist upon IV administration of ketamine, if they offer ketamine as a treatment for psychiatric disorders at all. But at Innovative Psychiatry, this is the only way we provide this medication.

We’re finicky. We’re perfectionists. We want to make sure we know the exact dose your brain receives so that we make sure you get the absolute best possible results from your treatment.

Did I say that right? Exact. Absolute. Best. That’s what intravenous ketamine offers as an advantage over any other method. It makes your best – or getting back to your best self – possible.

This is where we start swimming with sharks. And this is where the research and the experience and the opinions about what to do and how to do it get interesting.

Bioavailability

What’s bioavailability anyway??

It’s the amount of medication that your body is actually able to use. Not how much you’re given, but how much your body sees and can use.

So … it means the active portion that reaches your blood stream and that can actually be useful to you. The portion that treats what’s bothering you. The rest is altered, digested, excreted, or otherwise discarded by your body.

Make sense?

Why IV Ketamine?

OK. Basically, we want to be sure we know the exact dosage you receive, so we can know you’ll get the very best results. And intravenous infusion is the ONLY route where 100% of the ketamine you are given is 100% available to your body and 100% able to get to your brain. Which is exactly where it needs to be.

So how can we predict the exact dosage your brain will see?

Well, with an IV infusion, your ketamine dose is determined by your body weight that day and calculated down to a tenth of a milligram. Then it’s mixed with saline and slowly “infused” directly into your blood stream the same way that fluid is given to someone who’s dehydrated. (We love the word infusion — as in “infused with hope.”)

With an IV infusion, there are no obstacles preventing that perfect entry into your bloodstream and on to your brain. Anesthesiologists have known this for decades. Ketamine was designed to be given IV.

Why Intranasal Ketamine Is Unpredictable

But that’s not the case for other routes, which do present obstacles to the drug before it reaches the blood stream. I’ll show you what I mean.

When ketamine is given as an intranasal spray, it has to pass through your mucous membranes to reach your bloodstream. So first, it has to be suspended perfectly and evenly in a mist, and then the mist has to evenly saturate the mucous membranes of your nostril. And — it has to land high enough to not drip out your nose so that you don’t lose it and straight enough not to not run down the back of your throat. On top of that, it must be well-aimed enough to not get wasted on plain air and gentle enough to not get sneezed back out.

If that weren’t tricky enough, in addition to that, the ketamine spray delivers a mist that gives a concentrated dose over just a very few brief seconds of contact with mucous membranes, and just minutes of contact with critical and delicate brain systems … systems that need time to change for the better.

It’s just a bit too iffy …  whereas intravenous infusions are slow and precise and we can calculate, predict, and control. They allow very slow, controlled exposure of critical pathways to a medicine that stimulates neuronal growth and rearborization.

IM Ketamine: The Problems with Timing and Side Effects

In the case of intramuscular, or IM injections, ketamine must enter the muscle then find its way to the blood vessels and be absorbed.

Because the muscles contain dense blood vessels, a large portion of the drug makes it to the blood stream, but not all. There’s no way to determine how much time it will take the ketamine to leach out of the muscle, or how much of it will leach out, and reach your bloodstream so it can reach your brain.

From the time it’s injected, it depends on the circulation in that muscle and the condition of that muscle in terms of fitness.

To put it simply, your guess is as good as mine as to the total amount that makes it to the bloodstream and the rate at which it reaches the tissues in the brain to effect the changes we want to see.

Once again…way too iffy.

For ketamine, you need a route that ensures that ketamine reaches its target effectively, and you need a dose that will deliver the precise amount your brain needs to receive the optimum benefit from it. You also need it to reach the brain in a slow, controlled way. It needs to work, not frighten.

Because that’s another problem we’ll talk about in a bit. SIde effects … they just can’t be controlled once the medicine is in the muscle.

Bioavailability Comparison

Take a look at the differences in bioavailability of ketamine through these different routes:

Intravenous   100%

Intramuscular approximately 93%

Intranasal approximately 45%

Sublingual approximately 19-50%

Approximately?? For your brain??

As you can see, a range of 19-50%, as seen with sublingual use, is just far too uncertain. And approximating the dose, as seen with IM and intranasal ketamine, especially when we’re seeing numbers as low as 45%, just isn’t the best way to ensure solid, safe, predictable benefits.

Exquisite IV Ketamine

But when the ideal low dose of ketamine is precisely measured and administered directly into your bloodstream by an intravenous infusion, you get the benefit of all its anxiety-smashing, depression-relieving qualities in full measure.

There is none lost through dripping, sneezing, swallowing, digestion — or sloppy spraying or poor coordination. There’s just nothing getting in the way.

It’s a beautiful thing.

Add to that the fact that IV ketamine has been used in anesthesia since the early 1960’s. It’s backed by decades of data confirming its bioavailability, safety, and tolerability.

Effectiveness

Now think about this:

When you take ibuprofen for a headache, how long do you expect to wait to experience relief? 30 minutes? 45?

Have you ever been given an IV medication in the hospital? If so, you know that you start to feel relief pretty quickly. It can be a lifesaver when you really need it.

That’s because medications given by IV are available to the body so quickly … faster than any other route. There’s some benefit almost immediately, and it continues until you feel better and better as the medication circulates. With IV ketamine, the benefits keep growing.

Another factor is that the physician should give ketamine at a controlled rate. This is to create certain conditions in the brain to trigger a waterfall of actions…like the proverbial falling dominoes… that relieve the symptoms of the psychiatric disorders we’re treating.

Ketamine Research

Ketamine for depression has been a topic of scientific and clinical study for some time. The best research on ketamine over the past few years for the treatment of suicidal thoughts, depression, bipolar depression, PTSD, and OCD has used very precise IV infusion protocols.

It’s IV ketamine which–over and over–has been so startlingly effective. Intranasal sprays are being studied now, and one pharmaceutical company is sponsoring studies on a version of a ketamine spray it wants to turn into a brand-name patent, but there’s just not enough research on the spray technology, effective dose, or protocol for administering it to know what’s effective. One spray or two? one nostril or two? how strong? exactly how much? and how often? every 10 minutes? or every 15? why not every day? twice a week?

And intramuscular ketamine injections–forget about it. They can be such a nightmare of erratic absorption and side effects that can persist for hours that there’s no clear way to judge what dose might be effective or tolerable for you.

But by giving ketamine IV, we’re able to give
- - the most precise dose (recalculated to a tenth of a milligram each time you lose or gain a pound)
- - the most precise rate (calculated down to the minute using sophisticated infusion pumps)
- a drug your body can utilize 100%
We create optimum conditions. You experience the most benefits in the fastest way possible. It’s a win-win.

Safety

Two words: Side effects and drug abuse. (OK, so it’s 4 words.)

We associate ketamine with potential side effects, no matter how it’s given. This is the case with the majority of medicines. But the range and severity and duration of those side effects vary tremendously depending on whether ketamine is given IV, IM or intranasally.

Keeping an Eye on Side Effects – Just in Case…

In an outpatient office setting, low dose IV ketamine infusions can be administered in a beautiful, comfortable environment. High tech. Soft touch. Low lights and warm blankies (our patients love this!) with all of the medical monitoring and all of the important safeguards in place. Not the least of which is having a psychiatrist and infusion nurse right there to address any possible side effects.

In case of side effects, the psychiatrist can stop the infusion within seconds.Then she can administer a small dose of medication to treat the problem. Within minutes after the infusion, you can be ready for tea, snacks, conversation, and the ride home.

This isn’t true with intramuscular ketamine. In this case the full dose is administered in about a minute instead of slowly over 45, and there is no way to stop or slow the absorption once it’s already been injected into the muscle. And if strong dissociative side effects occur, as they often do with IM, the continued absorption of ketamine from the muscle can’t be interrupted– and the nightmare can last for hours. In one report, patients were kept lying down for at least 4 hours after an IM injection of ketamine for depression…just for monitoring.

If you use an intranasal spray mist at home, you administer it to yourself. There is no physician right there to address side effects.

Preventing Abuse

Unfortunately, ketamine has been shanghai’d by those seeking illicit experiences. It’s not just necessary, it’s critical to guard the way it’s distributed. It’s a shame, but a fact of life in the world we live in.

Think about this: If patients have ketamine available as a nasal spray for “as needed” use, what’s the risk? Clearly, if ketamine spray is available at home, there’s a much higher risk of outright abuse, sharing, or sale on the street.

It’s just so clear: right now, IV ketamine infusions are the best and most reliable approach we have. They allow precision dosing, instant responsiveness by the physician, almost-instant control of any potential side effects, and no risk of drug abuse or sharing in the community. .

At Innovative Psychiatry, we provide ketamine exclusively by IV infusion because it’s the best method for providing rapid, maximum benefits in the safest environment for you.

If you have not experienced relief from antidepressants, or if you’re tired of trying one thing after another, give us a call and let’s work together to evaluate what might be more effective for you.

To the recovery of your best self,

Lori Calabrese, M.D.
March 2, 2017

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