Dr. Grammer: “So really cool. This is one of the neat things about nasal esketamine was the effect began to differentiate from a placebo in as early as the first treatment, so it actually has a fairly rapid onset of action, which is unlike anything else we have in psychiatry, right, everything takes, you know, 4, 6, 8 weeks, this is one that can actually start working really, really quickly.”

[Life to Live by Grace Mesa (Instrumental Version) begins]

Beyond Depressed is a mental health podcast for people who want to know the science behind emerging treatments and if those treatments are right for them or a loved one. New therapies using psilocybin, magnetic stimulation, ketamine and medical marijuana are bringing people much needed relief. Together, we’ll take a deep dive into depression and how therapy, medications and drugs can help you feel better.

Beyond Depressed is hosted by Dr Geoffrey Grammer. Dr. Grammer is a decorated retired Colonel with the United States Army and is currently serving as the Chief Medical Officer for Greenbrook TMS. He has experience in psychiatry, internal medicine, and behavior neurology.

Disclaimer: The following podcast is for information and educational purposes only and should not be considered official medical advice.

[Life to Live by Grace Mesa (Instrumental Version) ends]

Dr. Grammer 

Welcome back to the podcast. Have you seen those ads on social media for ketamine treatment for depression? That’s what we’re going to talk about today. I’m joined by my co host, Joe. Hi Dr. Grammer, how are you? Good, good. Thank you for coming back. So Joe, have you seen these ads pitching ketamine online?

Joe Clements 

I have seen them and I’ve had people mention to me that they are seeing them. Ketamine doesn’t have to me… like if you said ketamine to me, I wouldn’t immediately think, oh, you know, medical treatment for depression, I would think, maybe like street drugs. So how did we come from I think of ketamine as a street drug to ketamine is now a effective legitimate treatment for depression in a clinical context.

Dr. Grammer 

Yeah, it’s a good question, because I think in the next several series of podcasts we’re gonna do here, we’re gonna talk about different, you know, what had been used as recreational drugs and how now they’re coming back into the fold as potentially therapeutic modalities for treating different neuropsychiatric conditions. Ketamine is kind of interesting, because ketamine was actually FDA approved, years and years ago, like back in the 70s, I believe, and it was approved as an anesthetic agent. And it’s even still used today sort of in pediatric emergency medicine as sort of a relatively short term anesthesia. It’s also used in veterinary medicine. So some people unflatteringly will kind of refer to it as horse tranquilizer, or what have you. But what people have found is that, you know, there were some reports that when people received ketamine, for anaesthesia, they would sometimes be a lifting of mood, and that got people into investigating whether or not it might be helpful as an antidepressant agent. Now, like a lot of medications that can cause alterations in mental status, it is a drug of abuse, and so people have probably heard of it on the street as Special K. To be clear, the doses used, the frequency used, and so forth of people who use street ketamine is completely different than the very controlled setting of using it as an antidepressant. So, one of the challenges with ketamine is that it has a very difficult time getting a steady serum level that then impacts the brain.

Joe Clements 

What is a serum level?

Dr. Grammer 

How much is in your blood?

Joe Clements 

Okay.

Dr. Grammer 

Yeah, so, like some other psychiatric medications, ketamine is one of those where too little or too much, is actually a bad thing. You have to get the dose just right. And ketamine, if we were to ingest it, actually will have to go through the liver, before it diffuses into your bloodstream, it gets to your brain, and the liver chews it up pretty efficiently. So historically, the only method that was reliable to get that exact amount of ketamine in someone was using an IV formulation. And for the past half decade or so there have been clinics that have popped up that will bring people in, they’ll do the monitoring, they’ll give the IV drug and then see if that can relieve their symptoms. There were problems with that, though. One was there was no established standard because there’s no FDA approval for depression. No one ever did that definitive study saying this is exactly how much you give how frequently you give it to fix depression.

Joe Clements 

So can I jump?

Dr. Grammer 

Yeah.

Joe Clements 

It seems like there’s a common thread in some of the treatments we’ve discussed previously in the podcast, and that I know will be coming up, that a lot of the things that are effective for depression or OCD and PTSD are discovered has side effects of other procedures, other treatments that were being given. And you’ve mentioned this a couple times that there’s this issue with getting a full scale control study done on those because it’s essentially a repurposed medication or a repurposed drug is that yeah, is that the term? So what? What would be the hang up very often in getting… So somebody realizes like a ketamine or something else actually works for mood enhancement for depression treatment? What are the barriers to getting those controlled studies done?

Dr. Grammer 

Well, and this is unfortunate to say, but with IV ketamine, one of the biggest problems was, it’s no longer under patent to generic medication. And it’s actually relatively cheap, you know, vials less than 10 bucks or something. So no one’s gonna pay to get that FDA cleared because it costs millions of dollars to do essentially an FDA study, because then anyone can say, well, I too, will sell ketamine, so you have no intellectual property protection, to make it valuable return on investment. And the other problem too is once you make a med IV only, its ability to be widely disseminated out there in the community becomes somewhat problematic. And just think about it. I mean, anytime you’ve had to get an IV, there’s a labor intensity to that that exceeds other kind of easy treatments where you kind of go in and get something done. Also, the other problem with IV ketamine is if you overshoot the mark, you move from essentially causing some mild intoxication to general anesthesia. Right, which could be extremely bad, right? So you want something that that you would be able to deliver that has some built in protections, so that you don’t accidentally overdose somebody. And so where we got from that was the evolution of something called esketamine or Spravato. And that’s a nasal form of a part of the ketamine molecule. So, a lot of molecules in nature essentially have two mirror images of each other called enantiomers and one half of that is, you know, essentially the essence is what makes up Spravato, that molecule, and then they put it into essentially a carrier that you can squirt into your nose and it gets absorbed by the mucous membranes. Now, that molecule is actually very important because what I have seen out there some some providers doing to try to bypass the complexities of Spravato. We’ll talk about that a bit more down the road, but they’re giving compound ketamine and it’s just essentially the basic ketamine in powder form that people squirt up their nose. There are no studies that really convincingly show that that’s a safe and effective way of doing this. And in fact, the American Psychiatric Association discourages people from using those off-label unapproved methods of ketamine administration. Spravato was very specifically designed and dosed to be just in that right-zone of having just the right amount delivered. And the nasal mucosa is one of the best methods of trying to bypass the liver metabolism that can happen if you take something orally. So anything you do besides that you’re really doing something that’s unproven and potentially dangerous.

Joe Clements 

So the idea with this Spravato, you get a controlled dose, gets absorbed into your mucous membrane, gets into your brain, how from there?

Dr. Grammer 

Well, you have what’s called a blood brain barrier. And so molecules will cross that blood brain barrier and get into the brain and with ketamine, what we’re you know, it’s interesting because ketamine binds to a receptor called the NMDA receptor. Okay, NMDA, November Mike Delta Alpha and…

Joe Clements 

What does that stand for?

Dr. Grammer 

It’s like a big long name.

Joe Clements 

Yeah, big long word.

Dr. Grammer 

N methyl something blah blah blah. And so that receptor is actually really complex. It’s got like multiple binding sites, like, you know, 50 binding sites, and all of them are somewhat allosteric, meaning the amount that it can either block or stimulate that receptor is variable. So you almost have an infinite number of combinations. But we know that there’s this downstream effect when you block that receptor, that then leads to an increase in a chemical in the brain called brain derived neurotrophic factor. And for the neuroscientists out there, there’s a middle step using a chemical called ANPA, I just want to throw that in there so people don’t say he didn’t talk about ANPA – not important. In the end, what happens is it enhances neuroplasticity and enhances the ability of the brain to kind of remodel, that seems to be some of the effect, but not all of it. Because there was an interesting study where they gave people essentially ketamine, and then they gave them an opioid blocker like Naltrexone and essentially eliminated the antidepressant response. So part of its antidepressant response may have to do with pain signaling as well. And for years, we’ve had this idea that some depression may be tied into our sort of pain modulation pathways within our body in our brain. But no one’s been able to kind of really tap into that yet to come up with a definitive molecule to help depression. So this may be kind of one of those first ones. The intoxication from ketamine, or from spravato is completely not related to its actual antidepressant effects. It’s just a side effect. So this is not one of those meds where people go on some spiritual journey and discover the meaning of life, they will get it have a brief period of intoxication that’s usually fairly mild. And that’s just a side effect of the drug. That’s not how it works. It works by that enhanced neuroplasticity and that kind of pain modulation effect we think.

Joe Clements 

So what would a patient doing a Spravato treatment experience? How often did they take it? How long did they take it to see results? Is it something to have to use forever? What’s that like for the patient?

Dr. Grammer 

Yeah, so all great questions. Spravato was approved by the Food and Drug Administration, but under a program called the risk evaluation and mitigation, approved through a process called the Risk Evaluation and Mitigation System, which is meant to give additional oversight into the safety of Spravato. So the reason that’s important is because the center has to be registered, the pharmacy that delivers the drug has to be registered, and the patient gets registered all in that REMS program. Okay, so everyone treated with nasal esketamine in the US

Joe Clements 

and to clarify their spravato is the brand name?

Dr. Grammer 

Yes.

Joe Clements 

Nasal esketamine is the generic term for it.

Dr. Grammer 

Correct.

Joe Clements 

So if you’re a patient, you might hear those words used interchangeably. And this is very common with a lot of treatments for depression, where there’s Zoloft, and then the generic version…

Dr. Grammer 

Sertraline.

Joe Clements 

Yeah. And you’ll you’ll see that all the time. And so you may hear words used interchangeably. It’s kind of the Kleenex versus tissue sort of deal for depression treatment. Yeah.

Dr. Grammer 

The one nice thing is at least right now, there’s only one approved compound that has this kind of technology, this nasal esketamine, so people won’t get confused. Yeah.

Joe Clements 

And so it’s still under, it’s still under patent going back to our patent discussion on Spravato, okay.

Dr. Grammer 

Yeah. Yeah. And what’s neat about it is the half of the molecule that they took out of ketamine, the belief was, it works better for depression and causes less intoxication. So I’ve had some patients come and see me that have been receiving IV ketamine, and they want to receive Spravato, because we can use their insurance, they don’t have to pay these ridiculous amounts out of pocket and everything. And they’re like, Oh, I’m not as intoxicated on this. Is it working as well? And the answer is, yeah, it actually may work better. The intoxication is not how it works. So it’s important people realize that because for a lot of people, they want that immediate kind of biofeedback, if you will, to say, oh, something’s happening. And in this case, you know, more may be happening with less of an immediate impact on their mental status. So you would have to get everyone registered, okay. And then, when everything’s done and you’re in the system, you would go to the center to receive the treatment, you sit in a reclining chair, typically, and you’re handed a nasal spray vial, you’ll typically kind of clear your nose a little bit, and then you the patient self administer the Spravato, one squirt in each nostril. each vial is 28 milligrams, so each dose is 14 in each nostril. And the two FDA approved doses are 56 milligrams and 84 milligrams, so you have to wait five minutes between each dosing. And then depending on whether you’re on 56, or 84, you take two or three, about 10 minutes after the second dose, most people will start to feel woozy. Now, it’s a little bit different than say, alcohol intoxication. Because ketamine is essentially a bit of a dissociative agent. So people and that’s a fancy way of saying like, it kind of changes your perception of reality. And some patients will describe feeling like a bit removed from themselves, I had one person say, you know, I feel like I was standing in the back of my head, watching myself talk. Other people feel like time can either expand or shrink. And thoughts may just get kind of clouded and confused. The other thing that can happen, and this is true of a lot of mind altering agents, is some people can get this false sense of epiphany. And it’s important that people realize this, because in the moment, people may be like, Oh, I think I’m beginning to understand like the meaning of the universe. And when they that’s just a phenomenon. When we have those kind of substances on board where we draw inappropriate causality between two different thoughts, we connect to thoughts that aren’t necessarily related. I had one person say, I think I understand it all. It’s all about clouds and love. And he was looking out the window. And then when he sobered up, he was like, I have no idea what I was talking about. There’s a lot of movies that kind of do that same thing, right?

Joe Clements 

Similar effect when people are coming to after surgery in the hospital.

Dr. Grammer 

Yeah.

Joe Clements 

Right? If you’ve ever sat with somebody as they’re coming, you know, back out of a…

Dr. Grammer 

That’s right. That’s right. So yeah, I tell people, like just pretend you’re on a carnival ride, don’t pay much attention. Just watch these things kind of go past. The intoxication, for most people will last about an hour, okay? The monitoring has to be no less than two hours. All right, to let people clear up enough to be able to leave the other thing with nasal esketamine, and ketamine IV is that it can raise blood pressure pretty substantially. So we have to monitor blood pressure at baseline 40 minutes in and at discharge at a minimum and then more if there’s a need for it. And we can’t treat people with uncontrolled hypertension, for example, or those that are at risk of bleeding if their blood pressure will elevate, such as those with a history of strokes or abnormal vascular malformations within their body, meaning where arteries and veins are inappropriately together. Something called an AVM. And so after two hours, we do one final check and we discharge the patient to another responsible adult who has to drive them home. And then they’re not allowed to do anything quote unquote hazardous for the rest of the days. So no operating like a wrecking ball or forklift or a motor vehicle. Then people go to bed, wake up in the morning, and then for the vast majority of people, they’re ready to resume their workday and so forth.

Joe Clements 

How many treatments does it take see an effect?

Dr. Grammer 

So really cool. This is one of the neat things about nasal esketamine was the effect began to differentiate from a placebo in as early as the first treatment, so it actually has a fairly rapid onset of action, which is unlike anything else we have in psychiatry, right, everything takes, you know, 4, 6, 8 weeks, this is one that can actually start working really, really quickly. The maximal effect is still weeks in. And it’s important that people get this, they understand there’s a bit of a phenomenon that occurs. And this is not well described in literature. But certainly anecdotally, a lot of people report this, what will happen is they’ll have brief elevations in mood early on, were like, Oh, I woke up the next day, and I felt pretty good.   Okay? And so I warn people, like, Hey, if you feel like you gum up and then crash, like, totally normal, don’t get worried about it, it means it’s working, you stick with it, and each of those times of improvement is going to expand further and further, you have to get treated twice a week for four weeks, once a week for four weeks. And then maintenance is once every one to two weeks thereafter. Now, a lot of people say, Well, how long do I have to stay on this? It’s a good question. And it kind of depends on the individual. Unfortunately, while ketamine works quickly, when you stop treatment for some people, it can lead to an early relapse as well, it can it can wear off quickly. So for some people in whom it works, well, it’s the only thing that works, they end up staying on that treatment once every one to two weeks indefinitely.

Joe Clements 

So that would lead to the follow up question on that, which is long term short term risks from being on something whether it’s for the eight week initial period, or whether it’s for years in the long term scenario.

Dr. Grammer 

Yeah. And I think acutely the biggest things actually, during the treatment administration, we worry about people getting overly anxious during the period of intoxication or getting agitated during intoxication. We also worry about uncontrolled elevations in blood pressure that can become potentially dangerous. But remember, I mentioned that REMS program before and actually I’ve reached out to the manufacturer of this medication and talked to their science folks, specifically about whether or not they’ve received any reports of people needing emergency medical care either for getting agitated during dosing or for blood pressure issues. And nowhere in the United States has anyone reported needing to do that yet? So though we monitor for it, though, we watch it, the reality is, it does not seem to be a prevalent issue if an issue at all, which is really, really good. Now, when I have had patients get anxious or upset during the intoxication, all of them have been able to be kind of talked back into a more relaxed state, just with verbal redirection. And I’m always very diligent about just making sure blood pressures are less than 140 over 90 before you start treatment and if anyone’s above that we don’t treat. We send them to get either their blood pressure managed, or I manage it or something. Longer term, there are some questions, right. So one would be addiction, can people… because people abuse this on the street, it’s like Special K, and actually using the drugs sometimes people call it K-holing. But the doses used on the street are about five times the amount that we use for depression. In addition, people on the street may use it at a frequency that is more often than what we do for depression with that kind of very regimented protocol that I mentioned, which is exactly what was done in the FDA trials. And so to date, again, there have been no reports of people developing new onset ketamine addiction from being placed on ketamine. What I have seen is people with past drug dependence, resonate with that sense of intoxication and crave their past drugs. So you have to be careful if you do have a history of significant addiction, that it doesn’t kind of trigger you into into kind of reactivating those old cravings, but it does look like the dependence potential with nasal esketamine seems to be, fortunately pretty low. Now, in street users of ketamine, there can be damage to the brain and damage to the bladder. Alright. And both of those can be very bad. Again, that wasn’t seen in any of the clinical trials and the nasal esketamine actually did a 52… a couple of 52 week trials where they follow people long term didn’t see any of that and the REMS program has never reported any of that. But we continue to monitor for it. Some people will have some some bladder urgency feelings with treatment, but it has not caused the… the bladder issues that we see on street users of ketamine, something called interstitial cystitis, which can be very problematic, so that has not happened. So I actually think with a drug like nasal esketamine, the REMS program is actually a really cool way of making sure we don’t ever end up in another like opioid crisis, right? Because it’s constantly under monitoring and vigilance. And if we start seeing any kind of signal of more common adverse effects, everyone’s gonna know about that right away.

Joe Clements 

So what types of patients or what sorts of depression scenarios tend to respond best to ketamine treatment, and are, you know, what would make somebody eligible for ketamine treatment? How would you know, if you’re depressed this is something you should look into?

Dr. Grammer 

Yeah, so I think in some ways the population is very similar to the transcranial magnetic stimulation population we talked about before. A lot of the who’s eligible unfortunately is dictated by insurance policy and not necessarily science. But right now that usually is non response to two medication trials, some require some history of psychotherapy. And one difference with nasal esketamine is it will only be approved for in the REMS program if you’re currently taking an antidepressant. Because in the clinical trial, everyone was on an antidepressant and then given ketamine on top of that, okay, so who else? Okay, so there are two FDA approved indications. One is for that kind of treatment resistant major depressive disorder. And then the other one is for symptoms of depression in patients with suicidal ideation. And that was an interesting study where they took people who were sort of on an inpatient unit with acute suicidal ideation that gave them the nasal esketamine, and they saw improvements in depressive symptoms. There’s other literature with IV ketamine suggesting perhaps an anti suicide effect. But the FDA language for nasal esketamine was a little bit more hedged and kind of talked about, well, it can help depression, but the suicide endpoint didn’t change in that study. But if you do have suicidal ideation, and you’re depressed, this seems to help alleviate the depressive symptoms, which hopefully, overall would improve your clinical condition.

Joe Clements 

So, patient has a… Well, so one of the things that, so they’d have to be on an antidepressant, but one of the qualifying things would seem to be that you have a medication failure. So almost by definition, you’re taking an antidepressant that isn’t producing a result for you.

Dr. Grammer 

Right, and, and the reason being, because when they did the clinical trial… The FDA is very regimented, and this is one of the reasons why a lot of doctors will do off-label treatments, because the FDA approves whatever you did in your study. And in their study, they’re like, you have to be on an antidepressant, we’re going to add nasal esketamine to it. And it can be a little weird for folks. But I will say, a lot of people I personally treated, what I’ll do, you know, we had that antidepressant talk several episodes ago. And I will often look at a medication regimen, and sometimes get genetic testing, and then look at their symptom complex and say, Ah, you’ve never been on X med. But I think this might be better for you than some of the other med trials you’ve had, because of these reasons. And I’ll go through that. And in some ways, I think it’s a nice opportunity to review whether or not they fully have maximized the logic exercise that goes into choosing a medication. And for most patients, there is room for potentially some improvement in another truly novel trial when you have to restart someone on a medication if they’re completely off meds when they show up.

Joe Clements 

And if you’re listening and you’re interested in more detail on that we covered antidepressants in the third episode. So if you went back and listen to that you would hear about the antidepressant prescribing tends to be overly simplified or heuristic, when there’s probably a lot more nuance to what patients, especially with major depressive disorder, should probably be exploring in many cases.

Dr. Grammer 

Yeah. And I think if someone goes and sees this provider provider, like, Hey, I have to start you on something, it’s a good opportunity to ask, why are you choosing this agent, right, and kind of review their overall treatment plan. So yeah, that honestly has not been a huge barrier, I also, the one thing I do do is, if someone’s been on a bunch of meds and have trouble with tolerance, I’ll often do a lower dose of the medication and for the REMS program, so far, at least, they’ve been less concerned with what the medication is dosed at, rather than sort of if they’re on a medication at all. So this is not one where you have to spend like three months escalating the dose to some therapeutic level, and they say, now we can start Spravato They just want to know that you’re on something. And then you can add the nasal esketamine to that.

Joe Clements 

So changing subjects a little bit, but a question I think we’ll ask in all of these emerging treatment options. If somebody is thinking, well, I could just self dose getting ketamine off the street, I don’t even need a doctor wouldn’t I get the same effect from that. What is the clinical response to that approach?

Dr. Grammer 

Yeah, so please, please don’t use street nasal or don’t use street ketamine of any form. Okay, for a couple of reasons. First off, like we mentioned, the doses people use on the street are often unpredictable, higher, the purity of the compound is going to be variable so you have no idea how many milligrams you’re actually getting. We know that street users do suffer consequences of their street use, including brain and bladder damage and you do not want that, right? A lot of the ketamine products sold on the street are also contaminated with other agents like fentanyl, and so forth. And that can be fatal. So you don’t want to do that. Also, if you use it on the street, you don’t have the medical monitoring that is a requirement for nasal esketamine administration. So I think it is extremely risky. I would not recommend people do that. This is a treatment that insurance covers, and you can get safely in a controlled supervised fashion.

Joe Clements 

So besides a major depressive disorder, are there any other types of mental health conditions where people could benefit from ketamine treatment?

Dr. Grammer 

It’s a good question. And right now the short answer is not really, right? So it’s approval is for depression. Now, ketamine has been used in the past to help control things like chronic pain. But that was not an endpoint that was necessarily studied as part of the nasal esketamine trial and the package insert very clearly states like don’t use this for chronic pain. Now, that being said, if I have someone that has depression, treatment resistant depression, and they also have something like chronic regional pain syndrome, or even fibromyalgia or an intractable migraines, that may weigh me towards thinking about nasal esketamine over other agents, because of that sort of off label idea of using it for chronic pain. We used to think dissociative disorders of which post traumatic stress disorder has a component of was a contraindication, to ketamine, but there was actually a recent trial that suggested that it actually may be somewhat beneficial. That was a smaller trial and so it’s hard to know how well we can extrapolate that. So I think what we’re going to see is other research going into, can we can we use this with comorbid conditions like anxiety disorders, and so forth? Can we use this with PTSD, and can we use this with pain conditions? But as of right now, the indication is depression.

Joe Clements 

Going back, you’ve used that term dissociative a number of times. So that would be the experience of not being like fully present. Right? Or how is that? How do you describe that? Just side note because you’ve used that term often.

Dr. Grammer 

Yeah. So there are a variety of sort of dissociative disorders, if you will. And then there’s the phenomenon of dissociation. And exactly dissociation is kind of losing a full awareness of the present, if you will. So if you’ve ever performed on stage, if you’ve ever been in a like played a musical instrument, if you’ve ever been in a sporting event, you probably had some level of dissociation. So if you’re playing, I’ll pick football. Again, that’s obviously I like football because I keep bringing it up, but you can’t focus on the crowd, you can’t focus on all the stuff going on around you, you need to be completely focused on just what’s happening on the field that requires you tune out certain environmental stimuli. And you have the singular focus on this one thing and some people kind of attribute dissociation as a little bit of that bringing your focus into one thing or the exclusion of others. Now, it can be problematic because sometimes that one thing is something you don’t want to focus on in the first place. Other people will have things called like depersonalization, derealization, that’s where you don’t really feel like you’re in your body or you don’t feel like the world is real around you. And for some people, that those can be sort of independent conditions that can be problematic. But when you receive Spravato, those same phenomena can sometimes occur but it’s usually just temp or not usually it’s temporary and it goes away once the med wears off.

Joe Clements 

Okay, anything else before we wrap up the ketamine episode that you think is important for somebody exploring ketamine for themselves or a loved one to know.

Dr. Grammer 

Yeah, so I, I think if you have treatment resistant depression, you need to ask your provider about other treatment options besides medications and therapy. And there’s a theme there. You know, one of the whole reasons we’re doing this podcast is so that people understand Psychiatry and Behavioral Health have moved on beyond just medicine therapy. And while meds and therapy are great for a lot of people, for whom it’s not effective, you need to know there’s other FDA scientifically studied well proven safe treatments and nasal esketamine would be one of those. I do think if nasal esketamine is not available in your area and you find a reliable provider who can do IV ketamine, that is not an unreasonable thing, but you’re doing it without that FDA approval, it’ll probably be out of pocket. And the protocol by which you do that infusion is a little less defined. Other methods of ketamine and I have seen it all intramuscular, oral, beneath the tongue, even suppositories, which is just bizarre. They do that to bypass the liver as well. But none of those are proven and quite the opposite. Actually, some studies have shown that because of the variability and bioavailability of the drug, meaning how much is actually in your bloodstream, those may not be effective, you need that very, very predictable, reliable absorption. And nasal and IV seemed to be the two ways to do that. And only the nasal form has this very circumscribed – this is what we studied, it worked, the FDA signed off on it, insurance will pay for it, so that’s what people should pursue. Anecdotely, what I have seen is there are some people who have not responded to meds therapy TMS and even ECT. And then they get Spravato and it is like curative. I mean, it’s to the transformation some people have is absolutely astonishing. So if you do have treatment resistant depression and you haven’t tried this, I would recommend trying to find a provider who offers it and giving yourself a trial, you’ll know pretty quickly if it works. So with that in mind, I think we’re out of time. Coming up, we’re going to talk about other controlled substances that are being used in psychiatry like psilocybin, which is hallucinogenic mushrooms. So please stay tuned for that. Joe, thank you once again very much for your questions. And joining me here today.

Joe Clements 

Thank you.

Dr. Grammer 

Take care, everyone.

Joe Clements 

Bye, everyone.

[Life to Live by Grace Mesa (Instrumental Version) begins]

Thank you for listening to Beyond Depressed! If you enjoyed this episode and you’d like to help support the podcast, please share it with others, post about it on social media or leave a rating and review. To catch all the latest from us, make sure to follow the podcast on your preferred podcast platform. The Beyond Depressed is shot and edited in the Trailways Studio at SDS in Tallahassee, Florida. Special thanks to Greenbrook TMS. See you next week!

This program is for educational purposes only and should not be considered or used as a substitute for medical advice, diagnosis or treatment. This program does not constitute the practice of any medical care or advice. None of the products or services discussed in this program suggest endorsement for your unique healthcare needs. The views expressed in this podcast are the views of the host speaker. Therefore, we advise listeners to always seek the advice of a physician or other qualified healthcare provider with any questions regarding personal health or medical conditions. If you have or suspect that you have a medical problem or condition, please contact a qualified health care professional immediately. If you’re in the United States and are experiencing a medical emergency, please call 911 or call for emergency medical help on the nearest telephone.

[Life to Live by Grace Mesa (Instrumental Version) ends]