Amanda Wilde (Host): Ketamine is a drug that has a long established use as an anesthetic. But more recently, ketamine has been found to be effective for treating depression and as an antidote to suicidal thoughts. Psychiatrist Dr. Lou Ann Eads shares the details as we talk about the application and effects of ketamine for mental health conditions.

Welcome to UAMS Health Talk, a podcast from University of Arkansas for Medical Sciences. I'm Amanda Wilde. And welcome, Dr. Eads. Really looking forward to learning about just exactly what ketamine does in terms of mental health, because as we know, it's been effective as an anesthetic, but when was it introduced into Psychiatry?

Dr Lou Ann Eads: It's an anesthetic that's been around for several decades. And around the 1990s, some researchers up at Yale University began to notice that a subtherapeutic dose, a lower dose than you usually use for anesthesia was helpful with decreasing depression symptoms and suicidality and did more and more research and established a protocol initially for IV ketamine. And that's how I got started.

Host: Well, how does ketamine help with depression?

Dr Lou Ann Eads: Ketamine targets a novel or different neurotransmitter than any of our other antidepressants. It targets the glutamate NMDA receptors, which stimulates release of various proteins such as BDNF and mTOR, which ultimately leads to repairing damaged neurons and helping to regrow neurons that are lost during a depressive episode. So, it's called neuroplasticity.

Host: When do you decide that that is the right therapy?

Dr Lou Ann Eads: Ketamine is generally considered an option for treatment-resistant depression, which is usually described as failure to respond to at least two antidepressants of adequate length and duration.

Host: And is ketamine prescribed only after those other drugs because it's stronger? it sounds more like a last resort than a first resort.

Dr Lou Ann Eads: Well, it's targeting a different neurotransmitter system. So, that is helpful. It can potentially be addictive. It does have some risk with use. So, you want to make sure that individual doesn't have a lot of cardiovascular disease or poorly controlled blood pressure, those kinds of issues, because it can cause some significant side effects such as heart attacks, strokes, death, those kind of issues.

Host: So, ketamine is dependent on the mental health condition you're actually treating and looking at a history of maybe being resistant to more traditional therapies.

Dr Lou Ann Eads: Yes. I mean, once you go through a couple of antidepressants, your chances of responding to a third, a fourth, a fifth are less and less each time around. So, once you've filled at least a couple of them, it's reasonable to think about what are the other options, with ketamine being one of those other options.

Host: And how do you assess risk level? You mentioned there are some risks, and you'll have to look at a person's overall health. How often do you run into complications?

Dr Lou Ann Eads: The FDA approved version of ketamine is nasal ketamine or esketamine, and it falls under an FDA REMS program, which is a Risk Evaluation Mitigation Program. They specifically recommend a baseline blood pressure 140 over 90 or less, because you have the potential of raising the systolic blood pressure 40 points after you've administered the drug. So, you don't want the blood pressure to get so high that it's going to precipitate a heart attack or a stroke. We monitor for drug screens. Females that are pregnant or breastfeeding should not be using ketamine.

Host: So, there's a very careful assessment process. And you mentioned it's nasal ketamine. So, how is the drug administered?

Dr Lou Ann Eads: It falls under the FDA REMS program. So, the drug is delivered directly to us. And once the individual comes in, then we hand it to them. We watch them use it and we dispose of the canister. Then, they stay with us for a minimum of two hours for safety, and their blood pressure and pulse rate sedation level are monitored throughout those two hours.

Afterwards, assuming that they're looking good, then they get discharge with an individual who takes them home. They should not be driving the rest of the day. They should not be making really important detailed decisions. A lot of them will go home and take a nap and sleep a little bit.

Host: So, you described kind of what happens for the patient during the therapy in terms of administering it, but what are the effects?

Dr Lou Ann Eads: The effects kind of vary from person to person and from treatment to treatment. Usually, there's some degree of disassociation, out-of-body experiences, changes in colors or shapes, tingling. A lot of times, the individual goes to a calm or happy place. There is a rare risk of having a negative or an unusual trip and having some anxiety from that, but that resolves itself pretty quickly.

Host: You mentioned people who have drug-resistant depression often will respond to ketamine therapy. Are there any other groups of people that are likely to benefit from ketamine therapy?

Dr Lou Ann Eads: Besides the FDA indication for treatment-resistant depression, there's also an indication for acute suicidality. So, ketamine is unique among all of our other agents in that its response happens pretty quickly after its use. And with IV ketamine, it's usually a few hours that you can start seeing a response. With the nasal ketamine, usually a few days or a few weeks, you can start seeing a response.

The way the FDA protocol for the nasal ketamine is set up, get treated two days a week for four weeks, then you get treated weekly for four weeks. And then if you show enough improvement, 50% or more, from where you started out, then there's your option of going into a maintenance phase where you can come in every one to two weeks for treatment. The downside of ketamine is, even though we know we get this response, we lose it pretty rapidly compared with other antidepressants. If you were to treat with IV ketamine three weeks later, you probably lost most of your benefits. So, it's not a long sustaining response, which is why you need the maintenance phase.

Host: But that dovetails into my next question, what have you seen in terms of long--term outcomes with ketamine therapy?

Dr Lou Ann Eads: It is, again, variable. Probably about a third of the patients do extremely well and, after a period of maintenance, are able to go to PRN or as needed use and respond well. About a third of patients have significant benefits, not as much as they would hope, and about a third of patients don't seem to get much benefit.

Host: Speaking of benefits, for those who are curious about ketamine, will insurance cover ketamine therapy?

Dr Lou Ann Eads: It is FDA approved, it is covered by insurance, If it's part of the insurance company's formulary. There are some insurances that do not have it on their formulary.

Host: Anything else you would like to add about your work with ketamine?

Dr Lou Ann Eads: For some of our patients that have really struggled with treatment-resistant depression the depression has had a really adverse effect on their overall life and functioning, then it has the potential of making a significant difference and giving them a response that has made their lives much better.

Host: Well, Dr. Eads, thank you for the facts on ketamine.

Dr Lou Ann Eads: You're welcome.

Host: That was Dr. Lou Ann Eads, psychiatrist at University of Arkansas for Medical Sciences. You can get more information on ketamine treatment at uamshealth.com/treatment/ketamine or call 501-526-8200. And if you found this podcast helpful, please share it on your social channels and check out the full podcast library for additional topics of interest. This is UAMS Health Talk from the University of Arkansas for Medical Sciences.