Erasing The Stigma: The Facts Surrounding Intranasal Esketamine

Anyone who has personal experience with mental illness knows that there is a frustrating

amount of stigma surrounding depression and ailments and the treatments used to ease their

symptoms. Too often, people experiencing clinical depression will hear, “Just try to be happy,”

or, “It’s not that bad.” 

While many people are still resistant to taking medication for depression (according to the NIH, 49% of psychiatric patients did not adhere to their medication regimen,)more people are open about their mental illnesses now than they were in the past according to a Harris Poll for the American Psychological Association. 87% of American adults said that having a mental health disorder is nothing to be ashamed of, while 86% believed that people with mental health disorders can get better. That’s why it’s easy to believe the CDC numbers that say the percentage of adults who had received any mental health treatment increased from 19.2% to 21.6% from the years 2019 to 2021.

Nexium, Lunesta and Celexa… If any of these drugs sound familiar to you, it is because they are

widely used and without much controversy. They also happen to function in the same way as

intranasal Spravato, the form of ketamine Dr. Blair prescribes and monitors his patients as they

take it.

While this procedure has risks, the professionals working at Optimum TMS and clinics nationwide abide by a code referred to as the Risk Elimination and Mitigation Strategy (REMS). They monitor you until the Spravato has worked its way out of your system. REMS even dictates that you are not allowed to drive or operate heavy machinery until you’ve had a full eight hours of sleep. Need a ride home? Optimum will call a Lyft or Uber for you on your phone if you cannot rely on a trusted friend or relative.

I sat down and spoke with Dr. Blair, a psychiatrist at Optimum TMS right here in Columbus, Ohio, about intranasal ketamine therapy and a of other treatments also unfortunately laced with unpleasant stigma.

 

Q. Can you tell me what exactly esketamine is?

Dr. Blair: “So, esketamine is actually a purified form of ketamine that was FDA approved in March of 2019 for Treatment-Resistant Depression and also depression associated with acute suicidal thoughts or behavior. It is somewhat different than the ketamine you might find on the streets or, ketamine infusion therapy, or IV ketamine, which is offered. The main difference is that esketamine is the more potent form of ketamine. So, ketamine that you find on the streets or IV actually is a mixture of esketamine and arketamine. That’s basically two different mirror image molecules, the same molecular structure, but they’re what’s called enantiomers. It’s almost like your right and left hand. The more potent form is esketamine. The manufacturers of Spravato, which is intranasal esketamine, actually isolated that more potent esketamine formulation and did all the research necessary to suggest its safety, but also its efficacy in treating depression. It is only FDA approved, though, when given in a clinician’s office or a doctor’s office.” 

Q. Roughly estimating, what kind of success do you feel you see with esketamine among patients who come to you with treatment-resistant depression?

Dr. Blair: “Roughly 65% of people have a dramatic response or improvement in their depressive symptoms, which may not sound all that great, but for those who’ve really tried, in many cases, numerous antidepressant medications and numerous types of talk therapy or psychotherapy, it actually is quite a high response rate. Another advantage of esketamine versus some of the other strategies that we have in psychiatry is that for those who respond they tend to respond much more rapidly than some of the other treatment modalities, such as individual talk therapy or even classic antidepressants, which can take six to eight weeks or more to get their full benefits.”

Q. What is Risk Evaluation and Mitigation Strategy?

Dr. Blair: “It was set up by the FDA to ensure that ketamine is administered safely by doctor’s offices, and also to make sure that the ketamine is actually going to who it’s supposed to go to. So, basically, the risk evaluation medication program requires the clinic to be registered. It requires the prescribing doctor to be registered. Still, it also requires the patient receiving the treatment to be registered to ensure that not only the patient’s tolerating the medicine. Okay. And that the side effects are being monitored, if there are any, and if so, that those side effects are being addressed appropriately, but also that, again, that this Spravato or intranasal esketamine is actually delivered specifically to who it’s supposed to go to. What occurs is that this is a type of medicine that you can’t just go to any pharmacy and pick up and take home and administer yourself. This is a program that requires the intranasal esketamine to be sent directly to the clinician’s office, where then it is placed into a safe. It’s not removed from that safe until an individual who’s receiving the treatment arrives for therapy. Then it’s been directly given to the individual, and then they self administer the treatment and then are observed over 2 hours worth of time to ensure that they’re tolerating the treatment.”

Q. What is the maximum dose a person can receive under a doctor’s care, following the rules of REMS?

Dr. Blair: “So, the maximum dose is 84 milligrams per session, which is technically three intranasal devices to typically spread out anywhere from five to nine minutes per administration. In most cases, the maximum frequency is twice weekly, which is typically started in the very first month of treatment. An individual will titrate to 84 milligrams as long as they tolerate it and receive that twice weekly, and then eventually space that out to once weekly by the second month. For those who are good responders, many of them engage in some type of maintenance strategy to improve their long-term prognosis. Maintenance therapy can be as frequently as once weekly to every other week. When they’re doing extremely well, they’ll even successfully be able to space it out longer than that.”

Q. What risks is a person taking while receiving that dose of esketamine under the care and observation of a team like the one here?

Dr. Blair: “There are multiple potential side effects that can occur, especially during the 2 hours following self-administration of intranasal esketamine. The most common is dissociation. Dissociation is almost like feeling outside of yourself or disconnected from reality. Now, much of the time, the dissociation is not deemed as subjectively extremely scary or anything for the individuals. There are some people who identify it as almost like a spiritual experience or a deep meditative state, but for some, it could be a somewhat scarier, unpleasant experience that’s followed by nausea and, in some cases, even vomiting or sedation. We try to minimize the risk associated with nausea or vomiting by recommending holding off food 2 hours before a treatment session and even holding off liquids 30 minutes before. We do, though, if any of those side effects come about, have as-needed medicine to help with nausea. Another thing that can occur is elevated blood pressure. One of the things we do to mitigate those risks is check blood pressure before and after treatment, and also about 440 minutes into treatment, where typically the blood pressure spikes following administration. And if the blood pressure ever gets to unsafe levels, there’s a protocol that we follow to either administer a medication that can rapidly bring down the blood pressure or, if the individual is having certain symptoms that are worrisome, that their blood pressure is so high, such as severe headaches or other kind of high blood pressure risk factors such as visual changes or things like that, then we could also implement a strategy to try to get them to an emergency department if necessary. So, we definitely have protocols in place to help mitigate the risk. But again, intranasal esketamine is a very potent type of treatment, and we’re giving a dose that is meant to be effective but also has risks associated with it. That’s why REMS requires a two-hour monitoring period to ensure that an individual does well with it. And if any of those side effects do occur, that we’re doing what we should be doing appropriately to help a person get through it without any long-term negative outcomes.”

Q. Do you feel there is a risk of becoming addicted to esketamine at the dose you receive in

treatment?

Dr. Blair: “Although ketamine itself can certainly become habit forming, the dose that individuals receive in therapy would be a dose that would be very low likelihood of ever  becoming physiologically dependent, especially due to the frequency that it’s administered. So even at the highest frequency of administration, which is that first month where individuals receive twice weekly therapy, there’s still a very low risk of addiction. Now, for those who struggle with addiction, I always give the warning that because of the potential for habit- forming nature, for some, the experience can kind of trigger the feelings that they may have experienced when they were using whatever their drug of choice was. It could potentially be a risk to trigger cravings for whatever their drug of choice was, or could even potentially trigger their desire to go and try to find, like, ketamine on the streets or something like that, for the in- between times. But the question was specific for the dose that we administered. So it is very low likelihood to become physiologically dependent on ketamine at what is administered according to the REMS protocol.”

Q. Weighing the risks and benefits, do you believe esketamine is a favorable treatment for

people experiencing severe depression who have tried numerous prescription drugs and talk

therapy?

Dr. Blair: “I certainly do. I believe by the time individuals show up to my clinic, they’re usually  really struggling because they typically tried so many different types of treatments, including talk therapy and multiple different types of antidepressants. And so by the time they show up here, many times feeling like, this is my last chance. So, the treatments that our clinic attempts to offer are strategies that have a higher response rate than the traditional strategies. And even many of those who have been deemed treatment resistant, which means they’ve tried antidepressants and talk therapy, yet still struggle, do respond to this. Again, for ketamine, it’s about 65% response. TMS is about 70% to 80% response, depending on the studies. So both of these could be potentially helpful and worth the potential risk associated with them for those who are really suffering.”

Q. Can you tell me a little more about TMS?

Dr. Blair: “So TMS stands for transcranial magnetic stimulation. It is FDA-approved for treatment-resistant depression. It’s been FDA-approved for depression since 2008, but it’s also received other indications, including FDA indications for treatment-resistant obsessive-compulsive disorder, smoking cessation, and anxious depression, meaning depression with coexisting anxiety. There’s a lot of different mental health indications out there, different than what used to be called shock therapy, which is now called electroconvulsive therapy. Shock therapy, or ECT, is actually very effective, but what it does is it uses electricity administered to the brain with the goal actually to induce a seizure. And that seizure is believed to provide a very rapid therapeutic benefit for those who respond to it. However, ECT is very invasive, requires anesthesia, but it also is very rapid acting and effective as well. About one in two people have short-term memory deficits with ECT. Still, it is a gold standard treatment for those who haven’t responded to anything else, including things like Spravato or intranasal esketamine or TMS. So, very effective but very invasive. An analogy for ECT is like jump-starting a car battery that’s not functioning well or rebooting a computer that’s stuck—so very rapid acting but very invasive. TMS and analogy are more like physical therapy for the brain or a workout for the brain because instead of administering electricity, it administers MRI-strength magnetic field pulses in a repetitive fashion. And every time a pulse is administered to the targeted areas of the brain, the. The goal is to cause the neurons to become active. The technical term is the neurons depolarize, but when you do that repetitively, when you pulse them repetitively, it’s going to cause those neurons to fire and wire together. The whole concept of a person who’s been struggling with depression for a very long time is certain parts of their brain tend to be underutilized while other parts of the brain tend to be overutilized. The part of the brain that’s underutilized tends to be the same part of the brain that can be helpful for focus, concentration, energy, motivation, the ability to feel sustained pleasure. So, with TMS, we actually target that underutilized part of the brain to increase the interconnectivity of the neurons and overall robustness of neural pathways to eventually help people have a better fighting chance of feeling better. So it does have a similar response rate to intranasal esketamine. About 75% to 80% respond, and about one in two achieve full remission. The difference, though, is that it takes longer, basically, because it works like physical therapy for the brain. Most people need anywhere from 20 to 30 sessions before they start feeling dramatically better. And when you do five sessions a week anywhere from three to 20 minutes a session, depending on the protocol. That can be pretty time-intensive. And a lot of times, people want to feel better sooner, especially when they’re in the midst of a crisis. Another thing with the TMS is it does take longer, but the cool thing is it’s more durable than other types of treatment. For those who respond, it tends to last longer, and most people don’t do maintenance TMS versus ECT and the same thing with intranasal ketamine.” 

Q. Do you think there is a stigma surrounding various treatments for mental illness?

Dr. Blair: “Yeah, I certainly do. I believe that there’s a stigma associated with mental illness in general, and many people are less likely to actually receive treatment for mental health-related disorders versus medical conditions or non-mental health-related medical conditions. And so that’s unfortunate. I do think that in some circles of society, different types of treatment are becoming more socially acceptable. Now, recently, there’s been a lot of concerns, especially in the media portrayal of different types of treatments such as ketamine, is that this is an extremely high-risk type of treatment, probably because there are people who have overdosed on ketamine and had bad outcomes with it, and that just, again, can worsen the stigma for potentially life-changing treatments when bad outcomes occur. So, yeah, unfortunately, not only for mental illnesses, there’s stigma, but there’s stigma around different types of treatment as well, including the ketamine.”

 

Blair laid out the details for me in terms I could understand, and I felt reassured that these

treatments were being safely performed, with rules and protocols in place to keep patients

from coming to harm. While he did acknowledge the existence of stigma even in the modern

world against mental illness and treatment for mental illness, he told me that he believes the

more mental illness is spoken about positively on social media, the more likely it is that we will

be able to battle that stigma. Indeed, with tools like TMS and intranasal ketamine on our side,

we’ll have more happy endings to share on our timelines.