Dual Orexin Receptor Antagonist (DORA) for Treatment of Insomnia

Wendy L. Wright, DNP, ANP-BC, FNP-BC, FAANP, FAAN, FNAP: We talked a bit about the different products that are out there, but I want us to now focus on the DORAs [dual orexin receptor antagonists]. I think that so many of our colleagues haven’t heard of orexin before because, for me, I didn’t know what orexin was because I came out of graduate school long before orexin was even identified. We can start by talking about the different dual orexin receptor antagonists; the first one that came out was suvorexant. Do you remember that launch? It was at least 10 years ago.

Debra Davis, CRNP: I do.

Wendy L. Wright, DNP, ANP-BC, FNP-BC, FAANP, FAAN, FNAP: I was really excited to use it. I often tell people if I could design a sleep algorithm, I would do CBT-I [cognitive behavioral therapy for insomnia], sleep hygiene as our first-line therapy. But when I have to go to a drug, I would go to a DORA first because I think of everything you and I have talked about long before I ever tried any of those other agents. When suvorexant first came out, people tried it, but a lot of people said it didn’t work for them, and I think a lot of our colleagues lost momentum. In order to get the drug approved, we had to have failed 2 other things, and here we are selling this to our patients and saying this is a good agent, and they didn’t feel like it worked. The dose that the FDA approved it at was actually a suboptimal dose, based on everything I’ve read, and probably 20 mg really needed to be the dose for efficacy. What’s your thought on suvorexant?

Debra Davis, CRNP: Suvorexant, when it first came out, it’s like you said, the dose was just too small. You can have the best drug in the world, but if your patients don’t like it and it doesn’t work for them, you just can’t make that happen. The other thing about the DORAs that is disappointing to me is that they are controlled substances. I do not think they deserve to be controlled substances. I don’t think this one deserves to be a controlled substance, and I don’t think the other two deserve to be controlled substances. A lot of times I think that stops, especially nurse practitioners who don’t have a DEA [Drug Enforcement Administration] registration number to even try a drug like this. They’re like, “Well trazodone, it might not be preferred, it might not be the best, but I can write a prescription for it.” So, they don’t even try these.

I think this started the DORAs on the wrong foot, and after that, it made the next two a very hard sell because doctors are like, “I’m sorry, patients don’t like DORAs. Come back when you have something else.” As we’ve seen, these have definitely improved over time. I think the third one, the daridorexant, is definitely my favorite, and the thing is the half-life. The half-life of suvorexant is 12 hours. The half-life of the other ones are 17 to 19 hours. But the half-life of daridorexant is 8 hours, and it makes all the difference in the world in me being comfortable in prescribing it.

Wendy L. Wright, DNP, ANP-BC, FNP-BC, FAANP, FAAN, FNAP: After suvorexant came out, it was a bunch of years later that lemborexant came out. Both of these as well as daridorexant are all CYP3A4 substrates. So, our colleagues, if you are going to prescribe this class, any of them, it’s important for you to recognize that there could be drug-to-drug interactions. You want to try to avoid those strong CYP3A4 inhibitors.

Transcript edited for clarity