Risk Assessment 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 might be overcome?

Patricia Ares-Romero, MD, FASAM: One of the biggest challenges early on when the FDA approved intranasal esketamine was getting preclearance. He was being cleared for treatment, so it took a while. In the beginning, there were difficulties with the insurance companies not understanding what the treatment was, how it worked, that the drugs had to be sent to the office—all those things. The biggest difficulty was to cover the patients. It improved a lot for treatment barriers. It was difficult to program the patient and make sure he understood what the treatment was about. These are some of the challenges we still face from a clinical perspective.

Martin Rosenzweig, MD: You raise a good point, particularly with esketamine. There is another element that has complicated this. When released, the manufacturer was not prepared for the fact that there were REMS [Risk Evaluation and Mitigation Strategy] terms. There was a scramble to figure out what certification was and how to build that network of doctors or practices if we’re able to deliver the drug in a safe way, including with observation. The average psychiatrist doesn’t have space in their office for someone to sit and be observed for 2 hours.

I share your pain, because as payers we are also fighting against this. We adhere to FDA recommendations. We had to validate that there was this certification. Most vendors either didn’t have it or were scrambling to figure out how to get it, so there was a 3-6 month period where we had to cobble this together pretty quickly, which in hindsight, probably caused a lot of pain. Patients could benefit from the treatment. Unfortunately, it’s one of those perfect storms. It was very difficult to put together a system that could do this safely.

Patricia Ares-Romero, MD, FASAM: We were lucky in our clinic because we were able to open and get certified as soon as it was 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 topic, can we talk a bit more about what REMS is and why it exists?

Patricia Ares-Romero, MD, FASAM: Sure. I can talk a bit about that. It’s a strategy to manage the potential risk with a drug like esketamine, which is a controlled substance. The facility, clinic or hospital, regardless of where it will be administered, must be REMS certified. It is an easy procedure. You go online and get certified. We can talk about that later. Then, the pharmacy that will dispense the medicine must also be certified, as well as the patient.

The patient can only be enrolled in one facility at a time, which is fine. It’s a wonderful thing, because it protects me as a provider, so that a patient doesn’t jump from clinic to clinic to divert drugs. They can come to my clinic, and I have to fire them if they go anywhere else. For example, I have a patient who is moving to Philadelphia, so I had to send him back to Philadelphia for treatment. It’s good. It’s to avoid diversion and to make sure that we keep the patient on for the 2 hours to avoid any adverse effects, which is sedation and dissociation, which the FDA was most concerned about. This is an easy way to register for REMS.

Steven Levine, MD: What is involved in obtaining certification as a certified center for esketamine?

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

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

Steven Levine, MD: Patricia, coming back for a moment to the REMS that we were talking about before, you mentioned that there were some safety considerations. REMS is a longer-term, post-approval way of collecting safety data and REMS requirements for where and how drugs are administered. It includes a period of monitoring after the patient has self-administered the drug in the office. Can you explain to us what this surveillance consists of and what it looks like in an office and who is involved at that time?

Patricia Ares-Romero, MD, FASAM: Sure. In my clinical practice, we have a master’s degree [medical assistant] in the office. We need to monitor blood pressure. This is 1 REMS requirement for our patients as it peaks after 40 minutes. Usually when the patient arrives we make sure they have not eaten or drunk anything for at least 1-2 hours to avoid things like nausea and vomiting. Then the patient self-administers. We take blood pressure before administration and then 40 minutes after administration. Then they stay in the office for the next 2 hours. I always get asked, “Do you have to be sitting there watching the patient?” No, you don’t. We have invested in this technical thing which is very expensive. It’s called a bell.

Steven Levine, MD: I heard about it.

Patricia Ares-Romero, MD, FASAM: It’s incredible. We just give the patient a bell, and if he needs to go to the toilet, a member of my staff can help him. I usually make them go to the bathroom first so they don’t have to walk around. I don’t want them walking alone. But they are alone in the room. They bring an iPad, listen to music, put on their virtual objects, whatever they want to make comfortable.

In reality, you don’t need to hire additional staff. You don’t have to do anything different from what you are already doing. I have a recliner because it’s more comfortable for patients, but I know of other sites that only have regular chairs. That is just about everything. After 2 hours we take their blood pressure again and make sure they are okay to go home. Then we make sure they don’t drive, because they’re only supposed to drive after a good night’s sleep.

Transcripts edited for clarity.

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