Esketamine FDA Approval Marks a New Era in Psychiatric Medicine

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.

So why work with something that isn’t ketamine?

History of Esketamine’s Father

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.

And since then, a grass-roots movement by researchers and psychiatrists around the world swelled to study ketamine’s significant impact on depression, bipolar depression, PTSD, suicidal thoughts, social anxiety, OCD, and addiction.

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.

There are several medicines that continue to be tested, but esketamine nasal spray (Spravato) is the first out of the gate.

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.

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.

To the emerging of your very best self,

Lori Calabrese, M.D.