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The Use of Ketamine & Esketamine in the Treatment of Mental Health Disorders – Podcast

By Darkstar Digital on July 1, 2022


Ketamine and Esketamine are the first truly “new” medications to treat depression. Dr. Rachel Dalthorp discusses these revolutionary treatments, how they’re delivered and who can benefit. 

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Nicholette Leanza:

Welcome to, “Convos from the Couch,” from LifeStance Health, where each episode, you’ll hear engaging and informative conversations with leading mental health professionals that will help guide you on your journey to leading a healthier, more fulfilling life.

Nicholette Leanza:

Hello everyone, and welcome to, “Convos from the Couch” by LifeStance Health. I’m Nicky Leanza, and on today’s episode, I’ll be talking with Dr. Rachel Dalthorp on the use of ketamine and Esketamine in the treatment of mental health disorders. Welcome Dr. Dalthorp, really great to have you on.

Dr. Rachel Dalthorp:

Thank you so much for having me. It’s great to be here.

Nicholette Leanza:

I definitely see you as the authority on this topic, so I’m really looking forward to really digging in, and having you share your knowledge on this. As we begin, can you tell us a little bit about yourself?

Dr. Rachel Dalthorp:

Sure. I am a psychiatrist. I work for LifeStance Health in Oklahoma. I started a private practice in 2014, and I was focused, at that time, on women’s mental health. I developed a practice that treats women that have hormone-related mood disorders, like PMDD, peri and postpartum depression, and perimenopausal mood and anxiety disorder. A couple of years after I got started in that practice, I became very passionate about treatment resistant depression, and was looking for ways to treat patients that weren’t responding to traditional therapies, and came across research and data about these new medicines that work differently than traditional antidepressants. Ketamine and Esketamine are the medicines that I’m speaking of. I started to provide those in practice, and really, just changed the way that I practice, and how I view mental illness, and what’s happening in the brain, and really see these treatments as superior to what we have out there. I’m really passionate about increasing access to them.

Nicholette Leanza:

Great. Let’s begin. We’ll start with ketamine. Tell us what ketamine is.

Dr. Rachel Dalthorp:

Ketamine has been around for a very long time. It’s actually on the World Health Organization top 10 list of medications, because of it’s importance as an anesthetic. About 25 years ago, they started to realize that ketamine had antidepressant effects in patients. That kicked off some discovery, leading ultimately, to the FDA approval of Esketamine nasal spray, but along the way, helped us better understand the underlying pathophysiology involved in depression. Leading up to the development of these new medicines, we really had very limited mechanism of action for antidepressants.

Dr. Rachel Dalthorp:

Ketamine is generic. It is a racemic mixture of two enantiomers, Esketamine and Arketamine. Like I said, it’s been around a long time. Janssen Pharmaceuticals took the S enantiomer, which is the more potent part of that chemical, and created a new medication out of it, called Esketamine. It’s a nasal spray, it’s been on the market since 2019.

Nicholette Leanza:

That’s what the Esketamine is-

Dr. Rachel Dalthorp:

That’s what the Esketamine is.

Nicholette Leanza:

Nasal spray. Okay, that’s interesting. You mentioned earlier, as you were giving your introduction to yourself, of working with those who have treatment-resistant depression. I know that’s one of the uses, for sure, that we use ketamine and Esketamine. Tell us a little about what is treatment-resistant depression.

Dr. Rachel Dalthorp:

I mentioned that traditional antidepressants all worked the same. They were developed, going all the way back to the first ones, and looking at Fluoxetine, all the way through the newer medicines, they were developed on this theory that depression is caused by a deficiency in these monoamine neurotransmitters, dopamine, serotonin, neuroepinephrine. It’s true that, in many patients, a deficiency in those neurotransmitters causes depression. But, we realized that so many patients have different causes of their depression. It isn’t one disorder in the brain that causes everyone’s depression, so it’s insanity to think that you can treat a different type of depression with the same medicine. That’s what’s really special about these new medicines, they are differentiated. They work on a different neurotransmitter system in the brain, and they work rapidly, and they help people who haven’t been responsive, or haven’t tolerated traditional antidepressant therapies.

Nicholette Leanza:

As we’re looking at how it works in the brain, it’s definitely working on those neurotransmitters. Can you tell us a little bit more about that?

Dr. Rachel Dalthorp:

Yes. I’m sorry, I didn’t hear that.

Nicholette Leanza:

Give us a little bit more insight in how else ketamine and Esketamine works in the brain, to improve [inaudible 00:04:43]?

Dr. Rachel Dalthorp:

We mentioned the monoamine neurotransmitters, they are dysfunctional in patients who respond to ketamine and Esketamine, but the difference is the effect of stress in the brain. Esketamine and ketamine work rapidly to increase a hormone in the brain called brain derived neurotrophic factor. You can think about brain derived neurotrophic factor, BDNF for short, as fertilizer for your brain cells.

Nicholette Leanza:

Okay.

Dr. Rachel Dalthorp:

When someone is struggling with depression, stress often is part of that. The brain cells, the neurons, they start to not function well. They don’t have a lot of what we call dendritic spines, which enable them to talk to each other. They’re shriveled up, and they’re not healthy. If you increase brain derived neurotrophic factor, which these medicines do very rapidly, within four hours, it creates something called-

Nicholette Leanza:

Wow, that’s really quick.

Dr. Rachel Dalthorp:

It’s very fast, synaptic plasticity. That means that the brain cells that aren’t able to communicate well with each other are starting to grow, and sprout new connections.

Nicholette Leanza:

Wow.

Dr. Rachel Dalthorp:

When those neurons are able to connect to each other, they form connections called tracks of neurons, that then form circuits that connect different parts of the brain. We think that, in depression, patients don’t have the right balance of neurotransmitter function in different areas of the brain, and that leads to depressive illness.

Nicholette Leanza:

Wow, that’s really interesting. Two points here of, one, how quickly it seems to work, because I think when we’re looking at typical antidepressants, it could take weeks for people to feel the effect. It sounds like, with ketamine and Esketamine, you sound like you’re saying hours for people to start to feel a little better. Is that pretty typical, that it’s that short of a time?

Dr. Rachel Dalthorp:

I don’t ever tell a patient, “Tomorrow you’re going to feel great,” because I don’t want to set that expectation.

Nicholette Leanza:

Right.

Dr. Rachel Dalthorp:

Most of our patients are pretty hesitant to put too much hope into treatment, because they’ve experienced so many failures in the past. It’s not uncommon that someone will say, “I felt better by the next morning.” If it’s going to work, and it has a very high rate of response, maybe 70%, we’re going to know pretty quickly, within the first week or so, if this is a great option for patients.

Nicholette Leanza:

The next point is that it sounds like it actually grows and connects to neurons, truly, the neuroplasticity. That’s amazing. I don’t think that’s something, and I’m not sure about this, that traditional antidepressants do, or help nurture, like ketamine and Esketamine does.

Dr. Rachel Dalthorp:

Traditional antidepressants can increase brain derived neurotrophic factor, but it takes weeks, and traditional antidepressants come along with a host of side effects that many patients can’t tolerate.

Nicholette Leanza:

True.

Dr. Rachel Dalthorp:

If you have a patient with treatment-resistant depression, and you’re looking at medicines, by the time you get to option number three, you only have about a 14% chance of response in a patient. When I see a patient, and I start them on an antidepressant, I’m picking the one I think is going to have the best side effect profile, and it’s the best fit for their type of depression, and their symptoms they’re experiencing. By the time I get to number three, I’m probably on a medicine that’s going to have more side effects, maybe sexual dysfunction, weight gain, things that patients shouldn’t have to tolerate to have their depression in remission. If they fail a couple of medicines, I want to really think about these newer options and not spend more time doing more treatment with the same type of medicine.

Nicholette Leanza:

Right, of course. Can you give us a little bit of an idea of the treatment protocol, what this looks like?

Dr. Rachel Dalthorp:

Yep, very similar between ketamine and Esketamine. Esketamine is a nasal spray. They’re both in-office treatments. Ketamine is an IV infusion, the way that we provide it. We have what we call an induction phase. After a patient goes through the consultation process for treatment, we make sure that they’re a good candidate. They begin this induction phase. They have treatment twice a week, for three to four weeks. At that time, we start to taper off the treatment. We can go to once a week, and just see how far in between treatments they can go, and maintain the treatment response.

Nicholette Leanza:

Are there side effects? I know we mentioned about antidepressants having side effects, but are there side effects to ketamine and Esketamine?

Dr. Rachel Dalthorp:

There are, and for some that work in mental health, they’re not used to the type of side effects that these medicines have, because they’re truly different. They’re very transient. If you think about some of our traditional therapies that do cause problems with sexual dysfunction and obesity, those are problems that a patient is going to experience every day with that medicine. With these treatments, the side effects maybe feel a little bit more dramatic, but they’re sub transient. It’s while they’re here in the office, and we’re taking care of them and monitoring them. They can be things like increased blood pressure, something called dissociation, which is an altered level of consciousness, and we can talk more about that. Nausea and sedation, those are the most common side effects that we see. But again, very temporary, and they resolve before the patient leaves.

Nicholette Leanza:

That’s great. We talked about treatment-resistant depression, and how that’s often one of the number one things that ketamine and Esketamine will treat. Are there other mental health disorders that it might also be helpful with?

Dr. Rachel Dalthorp:

Esketamine, the nasal spray, does have FDA approval for two types of major depressive disorders. Treatment-resistant major depressive disorder, but also, depression in patients who also have suicidal ideation. Those are the two FDA approved indications for Esketamine. For ketamine, there’s a lot of research that’s ongoing, not just for depressive disorders, but other psychiatric disorders, including PTSD, personality disorders, bipolar depression, and even some substance abuse disorders.

Nicholette Leanza:

That’s great. Wow. Any other takeaways you’d like to share about ketamine or Esketamine?

Dr. Rachel Dalthorp:

I think the biggest takeaway for me is, we’re really in a mental health crisis. All the data, when you look at the incident rate of depression, is behind where we really are in practice. COVID has set us back, and the incident rate of depression is higher than it’s ever been. I have three sons that are college age. They’re more likely to die from suicide than any other cause at this time. We really are at a point where we’re at a crisis, and we have to act. If you or your family member was to get treatment for depression, you’d want the latest and greatest, and the medicine that’s most likely to put them into remission quickly, and without side effects, and that’s what these medicines can do. I hope that we can start to think of these medicines earlier when we’re treating patients, and I’m really working to increase access to them for everyone. That’s the takeaway, we really have a need.

Nicholette Leanza:

Yes, definitely there is, for sure. Thank you so much Dr. Dalthorp, for sharing this information, to really bring us into more people’s awareness. I don’t think people understand, really, what it is, if they have heard about it. You definitely did a great job expending your knowledge about it. I agree, it’s definitely cutting-edge, and we can all use some more cutting-edge treatment, especially within mental health, for sure. Thank you again.

Dr. Rachel Dalthorp:

Thank you for giving me the opportunity.

Nicholette Leanza:

You’re welcome.