Misinformation about esketamine (Spravato) discourages patients from receiving treatment.

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

Misinformation about esketamine (Spravato) can discourage someone who needs treatment when treatment can remit her symptoms.

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

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

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

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

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

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

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

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

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

How to make sense of all of it?

IV Ketamine Treatment and its Side Effects

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

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

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

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

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

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

Woman twirling in relief from remission of depression.
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”

Misinformation about esketamine (Spravato) and IV ketamine's side effects cause confusion.

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

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

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

That effect is dissociation.

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

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

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

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

And…the Naysayers

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

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

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

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

Because nothing could be further from the truth.

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

Man with guitar soaking up peace after IV ketamine treatment.

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

This man is grateful for hope after esketamine (Spravato) and IV ketamine infusion.

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

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

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

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

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

And you should.

Is Antidepressant Therapy Necessary During IV Ketamine Treatment?

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

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

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

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

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

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

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

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

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

Passing Judgment On a New Treatment Without Studying Its Use

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

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

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

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

Misinformation about esketamine (Spravato) and IV ketamine can confuse patients who suffer.

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

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

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

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

To the blooming of your best self this Spring,

Lori Calabrese, MD offers innovative psychiatric treatment like IV Ketamine
Lori Calabrese, M.D.
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