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.”
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 needtreatment. 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.
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.
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 foryears.
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.
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.
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.
Transformative remission is inextricably linked to the quality, depth, and degree of dissociation during ketamine infusions.
Christopher trudged through the day, listless. He felt dead inside. Just couldn’t work up a care about what happened at the job interview. But practicality — the bills were piling up — drove him to go anyway.
He did his best in the interview, then got in the car to hurry home where he could retreat into his dark bedroom and sleep. He thought about death…about ways of ending his life… of making a plan that would work, before he could be interrupted. He knew he wouldn’t do it. But he’d been living with these thoughts all his life, and in the bad times it was the only way he could calm his mind and maybe fall asleep.
After months of research with studies she found online, his wife had been talking to him about ketamine treatment, and how it could not only wash away the suicidal thoughts but could help him feel good again, and find the energy to live. To care.
He wasn’t buying it. Just another antidepressant. They don’t work and never have. One more way to throw away money. A waste.
Still, she insisted, and he resigned himself to be a “guinea pig.”
How Dissociation Quality Determines Remission Lasting Power
The first two infusions were pleasant. Relaxing. Sort of “billowy.” But once each one ended he was back in the real world –, irritable, edgy, resigned. He thought to himself that surely his wife will now accept there’s nothing that will work, and leave him alone about it.
His wife, however, was determined. If ketamine could help others achieve remission, then it could help her husband.
When the doctor came in, she told him in no uncertain terms that nothing good was happening to Chris that she could see. She pressed the doctor to change something so this would not be a waste of money…and hope… Because his hope was gone. He needed success.
Increasing the Dose and Duration
The doctor agreed and increased the dose and extended the duration of the infusion to try to find that sweet spot between relaxation and overstimulation. Christopher’s “relaxing” experience was quite different this time.
Little by little, he lost his awareness of his chair, his presence in the room, and of his wife sitting nearby. He felt himself floating into another room…then another place…and then he lost awareness of himself and just let his mind float, and fly, and feel freedom. He didn’t care what was happening. Christopher thoroughly enjoyed the respite and relief of this vacation from his pain.
After his treatment ended, Chris felt a tinge of renewal. Of refreshing. Just a tinge…but it was unmistakable from the previous infusions where he soon returned to the same despair.
Now I get it, he thought. I see where this is trying to go. He set about googling and reading to find out how to prepare himself for the next infusion, to give it its best chance. He also picked back up a low stress hobby he’d enjoyed in the past and found he was enjoying it again. Did he feel happy? No. But there was something different.
Just a tinge of hope.
Christopher talked to the doctor about the first two infusions, who suggested that they keep doing infusions for awhile to make up for the lost ones. The doctor was willing to see where it took Chris, since he admitted he was learning what ketamine could do, too…
The 4th, 5th, 6th, 7th, and 8th infusions each enfolded Christopher in a deeper, more intense, and longer lasting dissociative experience then the one before.
By the end of the 8th infusion and for the weeks that followed, Christopher discovered life with a fresh new perspective.
He saw everything through more hopeful, optimistic goggles, and found more energy to create wondrous software programs in his work, enjoyed his wife like he never had before, and took up painting sunsets in a quest to truly capture the intensity of colors he saw.
Christopher has been enjoying his life and living it with gusto for the last 13 months since his ketamine treatment. He still looks back with gratitude on that day when his wife pressed him to let the doctor raise the dose, and the transformation with ketamine began…
…
In another blog, we discussed the role dissociation plays in remission from depression symptoms.
Let’s talk more about what that dissociation can be like.
Dissociation Quality Determines Remission Power
Since this last article about dissociation was written last fall, the field of ketamine for treatment resistant depression and other psychiatric disorders has grown by leaps and bounds. You can sample some of the reasons why here, here, and here.
Physicians, researchers, pharmacologists, and biochemists are in high gear exploring, testing, adapting, and learning at such a clip it’s hard to keep up.
But with so many brilliant neuroscientists constantly studying ketamine treatment — and so many dedicated physicians learning more and applying the new information to their patients’ treatments — growth was bound to happen.
So in the six months since our last blog on dissociation, we’ve learned that the standard dose of 0.5 mg/kg of ketamine is on the low end of average in effective antidepressant treatment. In our practice, a higher dose is needed in most patients before they experience deeper dissociation and remission of their hopelessness and depressive symptoms.
We’ve also learned that by clinging to the originally tested 0.5mg/kg for the full series of six or more infusions, many patients fall short of remission. So we’ve adopted flexible dosing and adapted infusions to the individual.
Because remember, as we keep saying, in a private real-world practice (as opposed to a research laboratory) our goal is to help each patient achieve remission from their symptoms. That means we remain open-minded to those things that may help our patients reach their goals.
We do what it takes.
And we’ve just submitted a paper for peer review describing this.
How Does Dose, Rate, and Duration of the Infusion Affect Remission?
So with that in mind, we seek to administer the ketamine infusions with remission as the target goal, and therefore adapt dosage, rate, and duration of the infusion based on each patient’s response to this medicine in each infusion.
Remember… 15 years ago, remission from treatment resistant disorders was pretty much unheard of. We’re exploring this frontier to find the best results for each patient.
This is the most personalized form of medical treatment available, and it’s vital for taking a long term illness from debilitation to remission.
So let’s go a little deeper.
What is dissociation and what isn’t..? Does it matter what happens in a patient’s brain during the infusion, as long as ketamine is infused into his or her body? Isn’t this medicine delivered through the IV based on the person’s weight, like most medicines?
These are great questions, so let’s take them one by one. The answer to the last question is NO.
Apparently, according to some studies between 2015 and 2018, the dissociative experience is explicitly connected to reduction in depressive symptoms. Which means dissociation helps you get well.
So it turns out that just infusing the body with ketamine isn’t enough. Something more is needed. Intense dissociation gives your brain what it needs to reboot… and feel joy.
In addition, that dissociative experience is not triggered by ketamine delivered in a standard dose based on body weight. It varies between individuals and needs to be titrated according to that individual’s response.
We see this first hand, every day. We know it.
Now, as far as dissociation, it’s the sense of being detached from yourself, or your body. We’re not talking about a disorder here, but rather a sense, or feeling, that occurs during the ketamine infusion.
You may experience a lovely floaty dreamy feeling, one where it’s like you’re daydreaming and relaxed. You may feel as if waves are splashing around you, but more in a metaphorical sense. But at the same time, you’re aware you’re sitting peacefully relaxed in a chair or recliner, but you’re not focusing on that. If someone speaks to you, you can easily respond. You’re aware of yourself, but not focused on yourself.
This isn’t dissociation, though it may be leading to it.
So What IS Dissociation?
Dissociation may be hard to describe but you’ll know it when you experience it. For lack of a better term, it’s a feeling of being separate from your body or yourself while still feeling relaxed. It may seem as though you’ve left your body and are floating above it, or in another place. It’s not an unpleasant or frightening feeling, but rather a relaxed sense of freedom… and it’s often accompanied by billowing relief.
In other cases, it may be a deep dive into your “inner workings,” your outlook and motives, your biases and self-imposed limitations… all in a flexible atmosphere where you can change the attitudes you want to change.
In still others, it may be more spiritual in nature, a transformative, almost metaphysical experience, focused on your spiritual self.
Remember, this is your brain. And yourexperience during dissociation will be uniquely yours.
No matter what the format of your dissociation, the importance of this is that it’s a direct sign that ketamine is at work in that moment repairing the signaling structures in your brain and all the damage that stress and depression have done. It doesn’t all happen at once, but the process does start right then.
For this reason, when you feel that “floating above your body” feeling or however it happens with you, we know it’s important that what you’re experiencing is sustained awhile.
This crucial time sees the repair work initiated and carried out and you may begin to feel a bit better within the hour. You may even find that you feel better and better through the next day and the day after that.
When your brain is functioning at full capacity, all the neurons are happily buzzing along carrying billions of signals all around your brain as you think about things, feel emotions, make decisions, sort through offenses, and figure out solutions.
Each neuron brandishes branches of buds that burst into connections with other neurons forming a dense and complex network.
You think the internet is complex? Ha! It’s a child’s toy compared to this. Every thought you form requires signals dashing around your brain pulling memory and feelings from the hippocampus and amygdala, managing impulses in the prefrontal cortex, and around and around it goes until your thought is formed.
And the beauty of it is that it can do that at the speed of light, while you memorize volumes of scientific theory, write a speech for a women’s conference, and compose music for your recital.
But when trauma or overwhelming stressors shove you into depression, those signaling pathways slow down, break apart, and thin out. Then, you find yourself left with something about as sophisticated as a string suspended between two tin cans. Remember those “telephones” when you were a child? Primitive. Impaired. Ineffective.
(You can hear some buzzing when someone talks to you but it’s hard to make sense of it. You can say something simple and try to make it heard by your friend in the tree house, but it won’t likely be the Gettysburg address.)
Your energy to try drains away. Your ability to think complex thoughts seems to all but disappear. The ability to perform becomes so “last year.”
You need a way to overcome this, but all the things they tell you to do just don’t help much at all.
It all seems futile, and you’re too weighed down to even try much anymore.
And then you hear about ketamine treatment and you go for your first infusion… (as in…how soon can you see me??)
What Happens During Your Ketamine Treatment
There is something significant that happened when Chris moved past the relaxed floaty feeling and advanced to “another room then another place…” and “let his mind float, and fly, and feel freedom.” That sensation is the outward signal that ketamine is repairing and restoring.
It triggers massive production of turbo-boosted brain-derived-neurotrophic-factor (BDNF) which causes the synapses to explode into branching and proliferating connections that spread across the brain in a sort of fast motion animation.
It happens at high speed and results in these sensations and impressions like floating then flying and swirling around.
Dissociation quality determines remission durability. And you want your remission to last and to be resilient, right? So be sure your doctor helps you experience intense and extended dissociation.
It seems possible – even likely – that some of those who are receiving the flat dosage of 0.5mg/kg without titration aren’t achieving sustained remission… Could it be this is why some of those are needing to return for maintenance doses every month or two?
We have studies that show that dosing below 0.5mg/kg doesn’t work well to decrease depression symptoms. And it might be that this dose decreases depression symptoms, but is not enough to bring on actual remission.
Is there a magic dose that always results in remission for everyone? Unfortunately, no …(wouldn’t that make things simpler?)
Is it possible that by titrating the dose, raising it a bit higher — according to a patient’s response — it could help a patient achieve remission? Well, it’s safe to say his or her chances are much better. What do you think? I’d love to read your comments!
With the new esketamine intranasal spray approved by the FDA, and with ketamine treatment becoming increasingly effective as we learn what it’s teaching us, hope is growing. People are getting well.
We’re learning. All of us are learning together. The field of ketamine for psychiatric disorders didn’t come with a manual, but we’re reading, and comparing notes, exchanging experiences, and watching our patients respond. And the more we learn, the more people get well.
Options are improving.
Watch for word from your own insurance company in coming months about their stance with esketamine. We expect to see more and more insurers get on board with esketamine intranasal spray.
But if you want treatment now, and you seriously seek remission, call us. And let’s work together to help you experience full and deep dissociation to the end that you may achieve remission. So you can build your life and your relationships. And work toward your dreams.
For years, ketamine clinics across the country have offered intravenous infusions as a fast-acting treatment for severe depression. But last week, the US Food and Drug Administration approved a version of ketamine, called esketamine, to do the same thing — so what’s the difference and what will this mean for newly interested patients?
Ketamine, sometimes known as the party drug Special K, is a compound made of two mirror-image molecules. It has long been approved as an anesthetic, isn’t covered by a patent, and is widely used — meaning it’s not going to make much money for a pharmaceutical company. So, Janssen patented the left part of the molecule, esketamine, and sent it through the FDA approval system as a potential cash cow called Spravato, legitimizing the use of ketamine for depression in the process.
“We deliver an off-label treatment that has the baggage of being known as a club drug,” says Steve Levine, the founder of Actify Neurotherapies, which runs 10 ketamine clinics around the country. “Now we’ve moved from ‘we deliver horse tranquilizer off-label’ to ‘we deliver FDA-approved Spravato’ and it’s just easier to talk to people about that.”
Still, FDA approval of esketamine for treating depression comes with plenty of caveats. The drug must be administered as a nasal spray, patients must be taking another antidepressant at the same time, and it can only be given to patients who have (unsuccessfully) tried two antidepressants before. Most notably, people won’t able to pick up Spravato at the local Rite Aid. Spravato will only be available in certified clinics.
Though Janssen, the maker of Spravato, has yet to officially announce what “certification” means, some psychiatrists have a head start on the process. Lori Calabrese, a psychiatrist who offers ketamine treatments at her clinic in Connecticut, is already certified because she contacted Janssen as soon as news of the approval went through. She had to go through a risk evaluation and mitigation strategy (REMS) program, which meant providing verification of all her medical licenses and showing that her clinic has been approved by the Drug Enforcement Administration for dispensing controlled substances. The next day, Calabrese was notified that she is cleared to administer Spravato. (A representative from Janssen was not available for comment.)
Doctors must order medication for a particular patient and pick it up at a specialty pharmacy. The patient will self-administer the nasal spray in the doctor’s office, stay in the office for two hours of monitoring, and then be taken home. The Spravato never leaves the facility. “It’s a very different kind of treatment model than anything we’ve seen in psychiatry before,” Calabrese adds. Janssen has told her that the first shipments of Spravato will be sent out on March 18th.
Plenty of excitement has greeted the Spravato news, but physicians caution that the requirement that it be taken nasally — instead of through IV, which is the typical method in clinics — may make it less effective. With an IV, all of the medicine is absorbed and the delivery is far more controlled, says Levine of Actify Neurotherapies. Though the nasal spray will help people who can’t (or don’t want to) take an IV, the process might be a little clunkier, especially because some of the drug might drift down people’s throats and it’s harder to control how much someone will get. There is also some evidence that nasal ketamine will be less effective than IV ketamine. Some studies have shown that more than 70 percent of those who try IV ketamine feel better; that number is closer to 45 percent for nasal ketamine.
It’s not cheap, either. Ketamine treatments usually cost a few hundred dollars per infusion, but the expense comes not from the generic drug, which is cheap, but from the doctors’ time and the clinic space. In contrast, just the Spravato drug alone can cost almost $900 per session, which would bring a monthly cost — at the recommended two sessions a week — to nearly $7,000, according to Stat News. The good news is that Spravato will be reimbursed at least partly by insurance, which will greatly increase access, says Bryan Clifton, chief medical officer of Kalypso Wellness Centers, another ketamine clinic. But as Calabrese points out, it’s going to be a challenge to figure out how much of the time and labor costs insurance will cover when the treatment alone is more expensive than the alternative, which already has those costs factored in.
For some, the approval of Spravato is more a story about the failures of the medical industry than great news about an exciting new treatment. “We’re very happy to see ketamine mainstream, but I’m distressed that this commodity medicine that’s so freely available got no interest until somebody could find a way to make more money from it,” says Steven Mandel, who runs Ketamine Clinics of Los Angeles. “It’s so thrilling to see this treatment endorsed publicly by mainstream institutions, but it’s one of the worst aspects of our medical system that this drug was scorned by all the big companies until they could find a way to get a piece of the action.”
Erik Messamore, a professor of psychiatry at Northeast Ohio Medical University, agrees. Messamore — who used to work with patients with treatment-resistant depression — wanted to administer ketamine for a patient, but was told that his insurance carrier would not protect him from liability because the drug was not FDA approved. We didn’t need esketamine, he argues. We needed channels for regular ketamine to be accepted in clinical practice. He maintains that instead of waiting for Janssen’s clinical trials, it would have been more helpful if the American Psychiatric Association, the National Institutes of Health, or another official board released guidelines that encouraged the use of ketamine for this kind of treatment.
That said, Messamore adds that if he were still working with severely depressed patients, he would absolutely offer Spravato. “I would be pressing my administration to get it offered to people as quickly as possible,” he says.
The newly approved drug, esketamine, is one half of the ketamine compound.
By Angela Chen@chengela Mar 11, 2019, 3:45pm EDTIllustration by Alex Castro/The Verge
For years, ketamine clinics across the country have offered intravenous infusions as a fast-acting treatment for severe depression. But last week, the US Food and Drug Administration approved a version of ketamine, called esketamine, to do the same thing — so what’s the difference and what will this mean for newly interested patients?
Ketamine, sometimes known as the party drug Special K, is a compound made of two mirror-image molecules. It has long been approved as an anesthetic, isn’t covered by a patent, and is widely used — meaning it’s not going to make much money for a pharmaceutical company. So, Janssen patented the left part of the molecule, esketamine, and sent it through the FDA approval system as a potential cash cow called Spravato, legitimizing the use of ketamine for depression in the process.
“We deliver an off-label treatment that has the baggage of being known as a club drug,” says Steve Levine, the founder of Actify Neurotherapies, which runs 10 ketamine clinics around the country. “Now we’ve moved from ‘we deliver horse tranquilizer off-label’ to ‘we deliver FDA-approved Spravato’ and it’s just easier to talk to people about that.”“THIS DRUG WAS SCORNED BY ALL THE BIG COMPANIES UNTIL THEY COULD FIND A WAY TO GET A PIECE OF THE ACTION”
Still, FDA approval of esketamine for treating depression comes with plenty of caveats. The drug must be administered as a nasal spray, patients must be taking another antidepressant at the same time, and it can only be given to patients who have (unsuccessfully) tried two antidepressants before. Most notably, people won’t able to pick up Spravato at the local Rite Aid. Spravato will only be available in certified clinics.
Though Janssen, the maker of Spravato, has yet to officially announce what “certification” means, some psychiatrists have a head start on the process. Lori Calabrese, a psychiatrist who offers ketamine treatments at her clinic in Connecticut, is already certified because she contacted Janssen as soon as news of the approval went through. She had to go through a risk evaluation and mitigation strategy (REMS) program, which meant providing verification of all her medical licenses and showing that her clinic has been approved by the Drug Enforcement Administration for dispensing controlled substances. The next day, Calabrese was notified that she is cleared to administer Spravato. (A representative from Janssen was not available for comment.)
Doctors must order medication for a particular patient and pick it up at a specialty pharmacy. The patient will self-administer the nasal spray in the doctor’s office, stay in the office for two hours of monitoring, and then be taken home. The Spravato never leaves the facility. “It’s a very different kind of treatment model than anything we’ve seen in psychiatry before,” Calabrese adds. Janssen has told her that the first shipments of Spravato will be sent out on March 18th.
Plenty of excitement has greeted the Spravato news, but physicians caution that the requirement that it be taken nasally — instead of through IV, which is the typical method in clinics — may make it less effective. With an IV, all of the medicine is absorbed and the delivery is far more controlled, says Levine of Actify Neurotherapies. Though the nasal spray will help people who can’t (or don’t want to) take an IV, the process might be a little clunkier, especially because some of the drug might drift down people’s throats and it’s harder to control how much someone will get. There is also some evidence that nasal ketamine will be less effective than IV ketamine. Some studies have shown that more than 70 percent of those who try IV ketamine feel better; that number is closer to 45 percent for nasal ketamine.
It’s not cheap, either. Ketamine treatments usually cost a few hundred dollars per infusion, but the expense comes not from the generic drug, which is cheap, but from the doctors’ time and the clinic space. In contrast, just the Spravato drug alone can cost almost $900 per session, which would bring a monthly cost — at the recommended two sessions a week —to nearly $7,000, according to Stat News. The good news is that Spravato will be reimbursed at least partly by insurance, which will greatly increase access, says Bryan Clifton, chief medical officer of Kalypso Wellness Centers, another ketamine clinic. But as Calabrese points out, it’s going to be a challenge to figure out how much of the time and labor costs insurance will cover when the treatment alone is more expensive than the alternative, which already has those costs factored in.
For some, the approval of Spravato is more a story about the failures of the medical industry than great news about an exciting new treatment. “We’re very happy to see ketamine mainstream, but I’m distressed that this commodity medicine that’s so freely available got no interest until somebody could find a way to make more money from it,” says Steven Mandel, who runs Ketamine Clinics of Los Angeles. “It’s so thrilling to see this treatment endorsed publicly by mainstream institutions, but it’s one of the worst aspects of our medical system that this drug was scorned by all the big companies until they could find a way to get a piece of the action.”
Erik Messamore, a professor of psychiatry at Northeast Ohio Medical University, agrees. Messamore — who used to work with patients with treatment-resistant depression — wanted to administer ketamine for a patient, but was told that his insurance carrier would not protect him from liability because the drug was not FDA approved. We didn’t need esketamine, he argues. We needed channels for regular ketamine to be accepted in clinical practice. He maintains that instead of waiting for Janssen’s clinical trials, it would have been more helpful if the American Psychiatric Association, the National Institutes of Health, or another official board released guidelines that encouraged the use of ketamine for this kind of treatment.
That said, Messamore adds that if he were still working with severely depressed patients, he would absolutely offer Spravato. “I would be pressing my administration to get it offered to people as quickly as possible,” he says.
Have you heard? In the “ketamine for depression” world we’re all a-buzz.
Esketamine nasal spray’s been added to our arsenal to fight refractory depression.
This is the first psychiatric medicine of its kind to win FDA approval. A medicine developed in a new brand new direction — glutamate modulation — to stimulate production of BDNF and to proliferate neurosynaptic branching and connection. It doesn’t just do some trivial thing. It repairs, and improves…and enriches.
Esketamine is the left-sided mirror image molecule — which in addition to the right-sided one makes up ketamine — and it may provide many of the same remarkable benefits of its parent, ketamine.
Because ketamine was approved by the FDA 50 years ago as a dissociative anesthetic, it’s generic, and not likely to be re-approved by the FDA for any other indication — like treatment resistant depression.
There was just no one to put the money into the expensive trials it takes to show efficacy and safety, despite the hundreds of scientific papers published about using ketamine for depression and other psychiatric conditions.
In 2006 (yes, 2006!), an important study revealed that ketamine was effective in treating depression.
Then, a few years ago, further research revealed that the temporary nature of ketamine’s antidepressant benefits could be extended by providing additional infusions.
And there were some doctors who began working with that data, and offered short series IV ketamine infusions over 2-3 weeks to help patients achieve, maintain, and extend their response and remission to ketamine. I was one of them.
Fast and Strong Antidepressant Medication
As revelations of IV ketamine’s rapid and robust antidepressant properties spread through journals, news outlets, and face-to -face discussions, a number of pharmaceutical companies set out to develop medicines that could act like ketamine and bring relief to more people… as well as win FDA approval.
Esketamine is the first medicine to accomplish this.
And there will be more to follow, for sure.
The days of relying on a monoamine hypothesis, and selective serotonin reuptake inhibitors (SRIs) and selective norepinephrine reuptake inhibitors (SNRIs) are behind us.
This is not to say these medicines are obsolete. Roughly 30-60% of people who suffer from depression are effectively treated by the oral antidepressants that are already available.
But for the rest who haven’t been helped –many of whom have become increasingly hopeless or suicidal — a medicine has been needed that does work. One that’s covered by insurance to help more people.
So researchers in pharmaceutical companies got to work to find compounds that would fit the bill.
Esketamine FDA Approval Will Lead to More Effective Medicines for Mood Relief
Instead, we’re enjoying the widespread, rapid, and robust effectiveness glutamate modulators can give. You know, the ones that dampen activity in the lateral habenula, dramatically proliferate signaling structures, and move G proteins off their lipid rafts in cell membranes to enhance communication across the brain.
Janssen Pharmaceuticals
The happy news is that esketamine is expected to be covered by insurance, and insurance companies have already begun negotiating with Janssen to provide this coverage.
Here’s what this means for you: the medicine will be covered by insurance, and the doctor’s office visit to provide it should also be covered by insurance. Given that it’s a 2 hour office visit, we expect the insurance reimbursement for that will make a dramatic difference for people and allow more people to come in for treatment.
Considering Aetna provided some of the funding for esketamine (Spravato) FDA trials, it seems likely they’ll be one of the companies that provides coverage for esketamine treatment. (Aetna, are you listening?) Blue Cross and Blue Shield as well as United Healthcare seem to be already involved and negotiating coverage, too.
We think all of them should get on board, and quickly and generously cover the drug and the physician expertise required for the office administration and monitoring.
Treatment resistant depression is extensive, leads to disability and life years lost, and can lead to suicide. Insurance companies need to step up quickly.
They can and should do better for you and for your family.
Since esketamine FDA approval only took place less than a week ago, it’ll take few weeks for us to get it — Janssen and their partners are working to produce, package and ship it, working out the certification, registration, and patient safety monitoring details.
And it may take up to 6 months for some insurance companies to decide what and how much of the cost of the drug and the office visit they’ll cover.
So we’re in a holding pattern. Watching, waiting, and preparing.
The Particulars of Esketamine FDA Approval
Now — let’s talk about what esketamine is, and what it isn’t.
The popular belief that esketamine nasal spray is ketamine runs rampant. It’s a relative of ketamine, but it isn’t ketamine.
As we’ve talked about before, ketamine is a racemic compound consisting of 2 mirror image molecules, like holding your two palms together: one on the right and one on the left. R-ketamine. And S-ketamine. In the world of science, many terms have Latin origins. The word for “left” in Latin is sinistra. Hence, the left-side mirror image molecule is called S-ketamine.
So these molecules are now often called by the phonetic spelling of their prefix: arketamine (R-ketamine) and esketamine (S-ketamine.)
This is important in understanding a little bit about this treatment. Each molecule in the ketamine compound contains different properties, and they share some as well. For instance, we think the left is the more psychoactive molecule — and many think it is a better antidepressant than the right; other researchers disagree or say they don’t know.
We know how robust the combination is, because we see it in IV ketamine treatment.
But we’ll all learn together what esketamine nasal spray will be like in the real world with real patients.
Esketamine nasal spray has not yet undergone a head-to-head comparison with IV ketamine in any published study. But with time, we’ll see how it performs to help you get better.
Esketamine FDA Approval: Requirements For Treatment
You need to know that you can’t just be prescribed esketamine.
When esketamine nasal spray is prescribed for you for treatment resistant depression, you need to show you’ve taken two antidepressants that have failed. In both cases, you must have taken the medicine for an adequate time at an adequate dose. And you will have start taking a new antidepressant when you start esketamine. (No ifs, ands, or buts about it. )
First, your doctor will register you with a special patient safety monitoring program.
Second, esketamine must stay in your doctor’s office. You’ll have to have your treatment in your doctor’s office, biweekly at first, then weekly, and then every 1-2 weeks for maintenance treatment.
Third, plan to stay in the office for 2 hours following treatment — for monitoring, and to ensure the side effects have subsided. In addition, you won’t be permitted to drive until the next day after a full and restful sleep.
Esketamine Side Effects
The FDA warns us about the side effects possible with esketamine. While they’re concerned with seeing proof that a medicine works, their greater concern is safety.
So, even though we don’t anticipate a serious safety hazard with esketamine, to protect your safety, the FDA warns of the potential for short-term cognitive impairment, and stresses that you not drive a car or operate machinery the day of your treatment, and also that you avoid making major decisions. They say the side effects may impair your attention, judgment, thinking, reaction speed, and motor skills. So — be cautious.
Esketamine nasal spray is not for pregnant and nursing women.
There’s been no testing at this point for esketamine’s effects on fetuses in the womb or infants.
The esketamine FDA approval has ushered in a new era of depression and anxiety medicines. Watch for updates about other ketamine-related medicines. We’ll be talking about them more as they begin to emerge.
To learn more about receiving esketamine (Spravato) treatment, please contact us here, and we’ll add you to our waiting list. We’ll contact you to come in for a consult to see if this is for you as soon as we’re able to begin ordering it from our specialty pharmacy, and we’ll work with your current doctors and therapist to ensure you get the most out of your treatment.
We’re on the cutting edge of treatment, to give you an edge over depression and suicidal thoughts.
We offer both IV ketamine treatment and esketamine nasal spray. And that means there’s help ahead for you.
The U.S. Food and Drug Administration today approved Spravato (esketamine) nasal spray, in conjunction with an oral antidepressant, for the treatment of depression in adults who have tried other antidepressant medicines but have not benefited from them (treatment-resistant depression). Because of the risk of serious adverse outcomes resulting from sedation and dissociation caused by Spravato administration, and the potential for abuse and misuse of the drug, it is only available through a restricted distribution system, under a Risk Evaluation and Mitigation Strategy (REMS).
“There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition,” said Tiffany Farchione, M.D., acting director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research. “Controlled clinical trials that studied the safety and efficacy of this drug, along with careful review through the FDA’s drug approval process including a robust discussion with our external advisory committees, were important to our decision to approve this treatment. Because of safey concerns, the drug will only be available through a restricted distribution system and it must be administered in a certified medical office where the health care provider can monitor the patient.”
Patients with major depressive disorder who, despite trying at least two antidepressant treatments given at adequate doses for an adequate duration in the current episode, have not responded to treatment are considered to have treatment-resistant depression.
The Spravato labeling contains a Boxed Warning that cautions that patients are at risk for sedation and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after administration of the drug. Because of the risk of sedation and dissociation, patients must be monitored by a health care provider for at least two hours after receiving their Spravato dose. The REMS requires the prescriber and the patient to both sign a Patient Enrollment Form that clearly states that the patient understands they should make arrangements to safely leave the health care setting to get home and that the patient should not drive or use heavy machinery for the rest of the day on which they receved the drug. Additionally, Spravato must be dispensed with a patient Medication Guide that outlines the drug’s uses and risks. The patient self-administers Spravato nasal spray under the supervision of a health care provider in a certified doctor’s office or clinic, and the spray cannot be taken home. The health care provider will instruct the patient on how to operate the nasal spray device. During and after each use of the nasal spray device, the health care provider will check the patient and determine when the patient is ready to leave.
The efficacy of Spravato was evaluated in three short-term (four-week) clinical trials and one longer-term maintenance-of-effect trial. In the three short-term studies, patients were randomized to receive Spravato or a placebo nasal spray. In light of the serious nature of treatment-resistant depresison and the need for patients to receive some form of treatment, all patients in these studies started a new oral antidepressant at the time of randomization and the new antidepressant was continued throughout the trials. The primary efficacy measure was the change from baseline on a scale used to assess the severity of depressive symptoms. In one of the short-term studies, Spravato nasal spray demonstrated statistically significant effect compared to placebo on the severity of depression, and some effect was seen within two days. The two other short-term trials did not meet the pre-specified statistical tests for demonstrating effectiveness. In the longer-term maintenance-of-effect trial, patients in stable remission or with stable response who continued treatment with Spravato plus an oral antidepressant experienced a statistically significantly longer time to relapse of depressive symptoms than patients on placebo nasal spray plus an oral antidepressant.
The most common side effects experienced by patients treated with Spravato in the clinical trials were disassociation, dizziness, nausea, sedation, vertigo, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, vomiting and feeling drunk.
Patients with unstable or poorly controlled hypertension or pre-existing aneurysmal vascular disorders may be at increased risk for adverse cardiovascular or cerebrovascular effects. Spravato may impair attention, judgment, thinking, reaction speed and motor skills. Patients should not drive or operate machinery until the next day after a restful sleep. Spravato may cause fetal harm and women of reproductive potential should consider pregnancy planning and prevention; women should not breastfeed while being treated.
Esketamine is the s-enantiomer of ketamine. Ketamine is a mixture of two enantiomers (mirror image molecules). This is the first FDA approval of esketamine for any use. The FDA approved ketamine (Ketalar) in 1970.
The FDA granted the approval of Spravato to Janssen Pharmaceuticals, Inc.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
A cause and affect relationship that’s a recipe for profound misery…is there hope?
Jarrod turned over. The room was dark except for the light of the clock. 3:45AM glowed brightly in the darkness. Jarrod sighed heavily. It had been 5 hours since he turned off the light. Exhaustion weighed him down like lead.
He hadn’t slept more than an hour all week. Why does it have to be so hard to just get some rest?? Rage was growing in a slow boil in his chest… He was afraid of what he might do if something didn’t break this maddening cycle. Sometimes he wanted to explode from the frustration. Sometimes he wanted to give up and die.
Much of the time, just after he dropped off, an alarm of sorts sounded inside his head and woke him wide awake again…
What is life if it has to be spent like this?
Months. Years. A lifetime.
None of his medicines worked. None. He felt defeated just thinking about it.
He tried to count sheep. His mind wandered fretfully slamming him with accusations, fears, uncertainty…hopelessness. Despair.
Buuuuzzzzzzz !!!
5:30AM. His alarm. He only slept maybe an hour and a half.
There was no choice but to drag himself out of bed and force himself to face another day… he knew he just couldn’t go on like this much longer… in fact, he wouldn’t.
Life-Threatening Misery
It’s not hard to connect the dots between insomnia and suicide. If you’ve suffered from chronic insomnia, you know the wretchedness of staring at the ceiling and watching the hours tick by.
And the longer it goes on, the more you worry about how you’ll get through the next day on 4 hours of sleep…or three hours… then 2 hours. Well, an hour and a half.
Have you ever experienced unrelenting insomnia for several nights in a row? If you have, you know that just as you’re getting sleepy, hoping you’ll drop off, suddenly you wake with a start and realize you had fallen asleep and woke up only 3 minutes later! It makes you want to chew nails.
In fact, it’s so terrible that prisoners of war are forcibly prevented from sleep as a torture to break down their resolve.
It’s not hard to see that prolonged insomnia can lead someone to want to die. Nor is it far-fetched to consider that having a desire to stop living could keep you from sleeping.
So which comes first? Well, it’s hard to know.
Sleep Disturbance is Treatable
Researchers have found that insomnia is an independent risk factor for suicidal thoughts, but a factor that’s not etched in stone. Because this is something that can be changed. And when it is, it relieves its influence on suicidal behaviors.
Genetics can’t be changed. Environment is hard to change. But insomnia..? It can usually be treated.
In addition, research has shown that insomnia is a risk factor and predictor for depression.
And among both adolescents and adults, those who seek treatment for problems with sleep experience more severe forms of depression than those who are depressed without sleep disturbance.
Insomnia Is An Independent Culprit
Traditionally, there has been an assumption that insomnia was a symptom of depression, but further research shows that sleep disturbance symptoms are experienced most often before the onset of depression, and continue longer after depression symptoms are relieved.
So is it the first symptom of depression that shows up long before other symptoms..? And the last to go after depression is resolved? Or is it a separate disorder that commonly accompanies other disorders?
You and I both know that when you go without sleep, or without enough sleep, 2-3 days in a row, it’s natural to find you’re more irritable and less able to control your mood.
When someone goes without sleep 5 days…or 8 days… their mental state becomes impaired, as well as coordination, cognition, and judgment. Often, at some point, they’ll finally sleep. Maybe for a few hours, maybe longer. And once they’re able to fall asleep once and remain asleep a few hours, they may have more success for the next few nights with more restful sleep.
Then the cycle begins again.
The Link Between Insomnia and Suicide Can Lead to Death
One recent study found that dysfunctional neuroplasticity may be to blame for insomnia. And that dysfunction can drive not only insomnia but other severe symptoms that are truly unbearable for you.
The theory is that neuroplasticity is a major mechanism in the cause of depression.
Neuroplasticity is the way the brain adapts to changes in the environment and to various stimuli.
Since sleep promotes synaptic neuroplasticity and a healthy ability to adapt and change, the lack of sleep reduces your ability to do that. Synaptic plasticity is also reduced in major depressive disorder.
Now think about this:
As many as 50% of people diagnosed with psychiatric disorders are never helped by medicines or therapies. Because of this, there’s been a need for a novel and advanced treatment to bring relief to their symptoms, as well as to their suicidal thoughts.
So it stands to reason that ketamine treatment can relieve both depressionandinsomnia. In fact, in a separate action, it can also erase suicidal thoughts in an hour or so.
Insomnia and Suicide
Stubborn long-term insomnia that doesn’t respond to medicines or therapy is not uncommon at all. But it contributes to your illness in ways that are so dangerous, it’s important to find effective treatment.
Suicidal thoughts are also life-threatening, and the longer they continue, the greater the risk to your survival.
If medicines and therapies haven’t relieved these symptoms, you may be a candidate for ketamine treatment. Ketamine treatment can restore your neuroplasticity and erase suicidal thoughts within 4 hours or less. Then, after that, you may find you can finally sleep.
At Innovative Psychiatry, patients walk out restored every week. They find they can do things they couldn’t do before, work through inner turmoil that they were unable to before, build relationships they lacked the energy and resilience to build before.
They can build rewarding lives and relationships.
And you can enjoy these breakthroughs, too.
Call us. You owe it to yourself to give your life and yourself the best advantage.
