Treating Insomnia With Dual Orexin Receptor Antagonists

Peter L. Salgo, MD: I don’t want to leave this list without the orexin antagonists. I’m going to try to pronounce this one, suvorexant. How’d I do on that one?

Sanford H. Auerbach, MD: Sounds good to me.

Peter L. Salgo, MD: Sounds good to me. Where is that?

Nicole Brandt, PharmD, MBA, BCPP, CGP, FASCP: I think what’s interesting about this agent, it’s a new mechanism of action.

Peter L. Salgo, MD: How so?

Nicole Brandt, PharmD, MBA, BCPP, CGP, FASCP: It inhibits that wake cycle in terms of using the orexin receptor agonist. There are 2 different types of orexin receptor agonist. By blocking them it improves that disruption of the sleep-wake cycle. I know I’m not a sleep physician, but I think I got that pretty close in terms of the pharmacologic implications of it.

Karl Doghramji, MD: As you know, orexin is more of an activating neurotransmitter, we think, along with many other arousing neurotransmitters. Orexin may also have a different role in stabilizing the relation between sleep and wakefulness. Nevertheless, by antagonizing the orexin activating system, these drugs purportedly seem to promote the onset of sleep.

Peter L. Salgo, MD: Now, that puts that one in a different class, right? The others are more global. Sleep is either a consequence of some adverse effect of the drug or it’s globally sedative. But the orexin inhibitors seem to be directed at arousal sensors or arousal receptor points, which is a different mechanism, yes? Am I wrong?

Sanford H. Auerbach, MD: It’s a different mechanism. The benzodiazepine class of medicines, the melatonin, the antihistamines, they all, even the antihistamines, target a specific neurotransmitter system in the brain that’s involved in wakefulness. Orexin is yet a different one and may have slightly different properties than all of the others.

Peter L. Salgo, MD: Are any of these drugs preferred for treating insomnia specifically in the elderly?

Nicole Brandt, PharmD, MBA, BCPP, CGP, FASCP: I think it gets back to what exactly are we treating and what are the comorbidities. I think as we look at some of the newer agents, the suvorexant, and how it’s being studied in maybe certain patient populations of older adults, there may be some safety signals. We’ll discuss that I think a little bit further in this program. I would be cautious in saying one is preferred. I think it’s really important to look at what’s going on with the patients and be very judicious in choosing one versus the other because of the comorbidities. And even within the guidelines, they show a discussion about what are the harms and benefits and the limited benefits with these medications. And they don’t come out and say one is preferred in older adults, but we do talk about how some coexisting comorbidities for an agent may be preferred because of the underlying pharmacologic activities and properties.

Karl Doghramji, MD: I think it’s too early to tell. The data with the benzodiazepines and the Z-drugs, which led to the cautions regarding usage with the elderly, in particular, were gathered along the course of many years and even decades. It’s really too early to tell whether these newer drugs with newer mechanisms may or may not have that same sort of baggage after many years of use.

Peter L. Salgo, MD: Have any of these drugs been specifically studied with the elderly in terms of their effect on sleep and improvement of insomnia? I see there’s someone smiling over there.

Sanford H. Auerbach, MD: I think the question is that in a systematic study of these things in a peer reviewed journal, randomized controlled trials and so forth, oftentimes the big problem is that you never see studies where they compare different drugs across different classes like this, at least none that I’m aware of. And so it’s very difficult to get. I think to Nicole’s point, you have to look at the various comorbidities of the patient, the positioning of the medication, in some cases even the cost of the medications, and balance that against what the needs are, what’s available.

Peter L. Salgo, MD: What am I missing here? I’ve heard earlier in this broadcast that insomnia affects perhaps 70% of people, and as you grow older it’s more common. If this were heart disease, cancer, infectious disease, there would be a raft of controlled, double-blinded studies in the elderly, in young people. Why isn’t there the same kind of literature for sleep medications?

Sanford H. Auerbach, MD: Because It’s considered a lifestyle problem.

Peter L. Salgo, MD: You’re pointing at Gary Johnson.

Sanford H. Auerbach, MD: Yes, he’s an insurance person.

Peter L. Salgo, MD: I’ve got to tell you, I don’t often wind up defending insurance companies, but this is a blunt attack.

Gary L. Johnson, MD, MS, MBA: I was going to say head-to-head comparisons are almost never done in the first place. The second place, most of the drugs that we’re talking about, except for some of the very newest ones, are essentially free, they’re cheap. And so nobody is going to invest in clinical trials. That’s kind of the reason why we don’t have the information. The endpoints are nebulous at best.

Peter L. Salgo, MD: OK. And they don’t need prior authorization mostly. But let me take this from the other perspective, from a payer’s perspective now. Someone comes to you and says, “I’m having trouble sleeping,” or the doctor calls you and says, “We want to prescribe A, B, or C,” and some of these are expensive or more expensive than others, which are, as you put it, relatively free. Are you going to insist on step therapy or are you going to say, you know what, this is a better drug, let’s just go with it?

Gary L. Johnson, MD, MS, MBA: It really depends on what the consumer has purchased in terms of their formulary. I deal almost exclusively with Medicare, and our company has 8 different Medicare formularies. They range from what we call lean to robust. These lean ones are very restrictive, with step therapy. The robust formularies pretty much get you what you ask for, and everything in between. So really there’s not a simple answer to your question because it really depends on what the consumer has purchased.

Peter L. Salgo, MD: What I’m looking for is—and I’m getting a bad feeling that I’m not going to get it—is if there is a rational, scientific hierarchy on all these plans to say, “Look, you got A, we’re going to start with drug A, and then go on to B, and then go on to C because I’ve got data and I’ve got research,” or is it, you pay more, you get more?

Gary L. Johnson, MD, MS, MBA: The simple answer is it’s the latter.

Peter L. Salgo, MD: Really?

Gary L. Johnson, MD, MS, MBA: Yes.

Peter L. Salgo, MD: That’s it. Does that make sense to you?

Sanford H. Auerbach, MD: Is it a description of what happens, or does it make sense?

Peter L. Salgo, MD: Pick your poison.

Gary L. Johnson, MD, MS, MBA: It’s 2 different questions.

Sanford H. Auerbach, MD: I think what happens has a lot to do with the perspectives of the individual clinician and how they approach insomnia, and how they deal with their patients and the complexities of their own individual patients. Although I would bet that we’ve never discussed it particularly, I bet Karl and I more or less put equal value on a lot of these medications. But we may choose 1 or 2 before the other. It all depends on the peculiarities of the patient. But I guess there is no algorithm. There’s no hard, fast algorithm.

Gary L. Johnson, MD, MS, MBA: And when you choose 1 or 2 rather than some of the others, is that because of hard clinical trial information or is it your personal experience?

Sanford H. Auerbach, MD: Oh, for me?

Peter L. Salgo, MD: Yes.

Sanford H. Auerbach, MD: Well, both. Part of it has to do with the data that are available. The problem is, you’ve already pointed out, when it gets down to the data. It’s interesting, when the American Academy of Sleep Medicine came out with their practice parameters about how to use the drugs that were available at the time, they looked at both the ones that are FDA approved and the ones that are not. And pretty much all the drugs that had FDA approval wound up in the column of recommended for use. All the ones that were commonly used, trazodone, even I think melatonin may have been on that list, were in the column of recommended to not use. But the fact that somebody paid enough money to get those studies done I think really dictated the difference between those 2 columns.