On March 5, 2019, the Food and Drug Administration (FDA) approved the first new medication for major depression in decades.1 The drug, esketamine, a nasal spray made from the anesthetic ketamine was found to have an antidepressant effect.

Although most commonly used for depression, it can also be utilized for post-traumatic stress disorder, obsessive-compulsive disorder, bipolar depression, and anxiety. 2

Ketamine is thought to affect the brain directly through modification of glutamatergic neurotransmission, although it has also been shown to mediate its effects through modulation of dopaminergic neurotransmission and serotonergic neurotransmission.3


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A nasal spray isn’t the only delivery option when it comes to ketamine. Patients can choose to have ketamine administered intramuscularly in an in-office clinic or can take a tab or troche of esketamine in their home while being monitored online.

We first look at the administration of ketamine via nasal spray and intramuscular administration. Next week we examine in-home administration. In this article we interviewed Tyson Lippe, MD, Psychiatrist, Heading Health, Austin, Texas. Heading Health provides in-clinic treatment.

Heading Health uses intramuscular ketamine and the SPRAVATO® nasal spray. Is there a difference between the 2 therapies based on methods of delivery?

Tyson Lippe, MD

Dr Lippe:  Whenever you receive an injection of ketamine it’s usually what we call racemic ketamine.  Meaning it’s a mixture of esketamine and arketamine.  Whereas SPRAVATO is purely esketamine. In the research that I have seen they haven’t really shown that arketamine or esketamine is necessarily superior to the other, but the human trials for arketamine are just beginning. There is what’s called a non-inferiority study, comparing intravenous esketamine to intravenous racemic ketamine, and esketamine was deemed non-inferior to racemic ketamine.

How does in-clinic administration of ketamine work?

Dr Lippe: I do an assessment each time I meet with a patient just to get an update on how they’re doing. I see if we need to adjust the dosage, and assess them in general. After that, they’ll get their treatment whether it’s the SPRAVATO or the intramuscular ketamine. And then we’ll come in and check on them at least 3 times to check vital signs and see how they’re doing. 

We do intermittent check-ins and each patient has a call bell. We also have cameras in each of the rooms, and the patients are aware of that. By having a camera in each room we can keep an eye on them from the nursing station.

We know that just from side effects, people can have some pretty intense experiences. It can increase blood pressure, and pulse, so you need to be able to monitor them and intervene in case anything might happen while they’re undergoing treatment. It’s incredibly rare and an incredibly low risk, but it is something that needs to be monitored.

The FDA has said that patients need to be monitored by a health care provider for at least 2 hours after receiving their dosage of Spravato. Is that the usual treatment at Heading Health?

Dr Lippe: Yes, that’s what we do for SPRAVATO. And we monitor folks in the office for about the same time for intramuscular ketamine as well. This medication requires some degree of monitoring because of its side effects. The FDA follows out monitoring through REMS (Risk Evaluation Mitigation Strategy). Each patient has to be enrolled in this program. You have to submit monitoring forms to this entity showing that you’ve monitored vital signs, reported any side effects, and show how long they were monitored in-clinic.

What are some of the side effects of medically administered ketamine?

Dr Lippe: Side effects, in general, tend to be fairly mild and tolerable. Most folks will describe their treatment sessions as neutral or positive. Rarely do they describe it as distressing. But you can have dissociation or nausea. Both are pretty common. Feeling tired or sedated, kind of groggy, or like you have a brain fog, and altered perceptions are also not uncommon.

Then there is the possibility of visual disturbances or change in your sensory input. I had a patient who said that they felt like they could taste color. It wasn’t distressing, but that’s just what they experienced and a lot of the times people will say that they can’t even verbalize their experience. So, for example, I’ve heard a lot of people say that they have a lot of thoughts where they get a new perspective on something. But they can’t really explain details. 

What happens if someone has an adverse reaction to SPRAVATO or intramuscular ketamine?

Dr Lippe: We have not, at least at this point, had to do any major interventions such as sending anyone to the ER or intubating them. But it is helpful, if they’re having a very distressful experience to sit down with them, face-to-face, talk them through things, kind of be that calming presence. 

Do you have a patient that you can tell us about in which the administration of ketamine really turned this particular patient around? 

Dr Lippe: The patient who comes specifically to mind is related to SPRAVATO. This individual suffered from depression for more than 40 years. When we had elicited feedback from them they had said, “I had given up hope that anything was going to work.” They had been through multiple forms of therapy, multiple oral medications, and TMS [Transcranial Magnetic Stimulation].

So, in their mind, SPRAVATO was a last-ditch effort and they have responded really well to it. It’s improved daily life, getting out of bed, interacting with their spouse, their interests are back, they’re writing again. Even just talking to this person during the initial appointment, they were very despondent, depressed, and seemed pretty hopeless.

Fast-forward to today and they were talking about their life, in my mind, you would not think that this is someone who struggles with depression daily anymore. And so, it’s been really nice to see those kinds of outcomes with patients with ketamine products.

Tyson Lippe, MD, Psychiatrist, Heading Health, Austin, TX.

References

1. Chen J. How ketamine drug helps with depression. Yale Medicine. Published March 21, 2019. Updated March 9, 2022. Assessed April 11, 2022. https://www.yalemedicine.org/news/ketamine-depression

2. Walsh Z. Mollaahmetoglu OM, Rootman J, et al. Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review. BJPsych Open. Published December 23, 2021. Assessed April 11, 2022. doi:10.1192/bjo.2021.1061

3. Pribish A, Wood N, Kalava A. A review of nonanesthetic uses of ketamine. Anesthesiol Res Pract. 2020; 2020: 5798285. doi:10.1155/2020/5798285