Risk Evaluation and Mitigation Strategies for Intranasal Esketamine in TRD

Steven Levine, MD: Could you talk a bit about some of the barriers that exist and how they can potentially be overcome?

Patricia Ares-Romero, MD, FASAM: One of the biggest challenges early on when the FDA approved intranasal esketamine was getting the prior authorization. It was getting authorized for treatment, so it took some time. Early on, there were some challenges with insurance companies not understanding what the treatment was, how it worked, that the medication had to be sent to the office—all those things. The biggest struggle was getting patients covered. That’s improved a lot for barriers of treatment. It was difficult to schedule the patient and make sure that they understand what the treatment consists of. Those are some of the challenges that we’re still seeing from the clinical perspective.

Martin Rosenzweig, MD: You bring up a good point, particularly with esketamine. There’s another piece that complicated this. When it got released, the manufacturer wasn’t prepared for the fact that there were REMS [Risk Evaluation and Mitigation Strategy] requirements. There was a scramble to understand what the certification was and how to build that network of physicians or practices if we’re able to deliver the drug in a safe way, including with the observation. The average psychiatrist doesn’t have space in their office for someone to sit around to be observed for 2 hours.

I share your pain, because as a payer, we struggle with that as well. We adhere to the FDA recommendations. We needed to validate that there was that certification. Most providers didn’t have it or were scrambling to figure out how to get it, so there was a period of 3 to 6 months in which we had to cobble this together pretty quickly that in hindsight probably caused a lot of pain. Patients could benefit from the treatment. Unfortunately, it’s 1 of those perfect storms. It was very difficult to put together a system that could do it safely.

Patricia Ares-Romero, MD, FASAM: We were lucky in our clinic because we were able to open and get the certification as soon as it got approved. There were a lot of gaps in communication with the insurer and provider, but those things have been ironed out, which is good to see.

Steven Levine, MD: While we’re on this subject, can we talk in a bit more detail about what REMS is and why it exists?

Patricia Ares-Romero, MD, FASAM: Sure. I can talk a little about that. It’s a strategy to manage potential risk with a medication such as esketamine, which is a controlled substance. The facility, clinic, or hospital—wherever it’s going to be administered—has to be REMS certified. It’s an easy procedure. You go online and get certified. We can talk about it later. Then the pharmacy that’s going to be dispensing the medication also has to be certified, as well as the patient.

The patient can be registered in only 1 facility at a time, which is great. It’s a wonderful thing, because it protects me as a provider, so we don’t have a patient jumping from clinic to clinic to divert medication. They can come to my clinic, and I have to discharge them if they were to go somewhere else. For instance, I have a patient who’s moving to Philadelphia, so I had to discharge him to go to Philadelphia and receive treatment there. It’s great. It’s to avoid diversion and to make sure we’re keeping the patient for the 2 hours to avoid any adverse effects, which are sedation and disassociation, which was what the FDA was most concerned about. It’s a simple way of getting registered with the REMS.

Steven Levine, MD: What’s involved in getting certified as a certified center for esketamine?

Patricia Ares-Romero, MD, FASAM: You go on the website. It’s as easy as that. You have to have a computer, go online, and have a designated provider. Then you put in their DEA [Drug Enforcement Administration] number. They have to have a DEA number and put in their NPI [National Provider Identifier] and the actual location where the treatment is going to be administered. It’s easy as long as you have all those things in order.

If you’re affiliated with a hospital, as I was before, we registered our pharmacy as well. We also did their DEA number, so we were able to get product through our pharmacy, which was very easy. It’s as simple as that. Now that I’m in an outpatient clinic, it’s the same thing. We went ahead and registered online, and then you’re able to have the REMS. You have to follow the REMS protocol, so you have to review it and make sure you understand what it entails.

Steven Levine, MD: Patricia, going back for a moment to the REMS that we were discussing before, you mentioned that included within are some considerations of safety. REMS is a longer-term way, postapproval, of gathering some safety data and the requirements under the REMS for where and how medicine is administered. It includes some period of monitoring after the patient self-administers the drug in the office. Can you talk about what that monitoring is and what that looks like in an office setting and who’s involved at the time?

Patricia Ares-Romero, MD, FASAM: Sure. In my clinical practice, we have an MA [medical assistant] in the office. We have to monitor blood pressure. That’s 1 REMS requirement for our patients, because it peaks after 40 minutes. Usually, when the patient comes in, we make sure they haven’t had anything to eat or drink for at least 1 to 2 hours to avoid things like nausea and vomiting. Then the patient self-administers. We take blood pressure before administration and then at 40 minutes postadministration. Then they stay in the office for the next 2 hours. I always get asked, “Do you have to be sitting there, staring at the patient?” No, you don’t. We invested in this technical thing that’s really expensive. It’s called a bell.

Steven Levine, MD: I’ve heard of those.

Patricia Ares-Romero, MD, FASAM: It’s amazing. We just give the patient a bell, and if they need to go to the restroom, one of my staff can help them. I usually make them go to the restroom before so they don’t have to walk around. I don’t want them walking by themselves. But they’re just by themselves in the room. They bring an iPad, listen to music, put their virtual things on, whatever it is that they want to feel comfortable.

In reality, you don’t have to hire additional staff. You don’t have to do anything different from what you already do. I have a recliner because it’s more comfortable for the patients, but I know other sites that just have regular chairs. That’s pretty much all it is. After 2 hours, we take their blood pressure again and make sure they’re OK to go home. Then we make sure they’re not driving, because they’re not supposed to drive until after a good night’s sleep.

Transcript Edited for Clarity