Peter L. Salgo, MD: Let’s talk about some of the prescription drugs because they come in various flavors. There are the antidepressants, there are benzodiazepines, there’s something called the “Z-drugs”, which is zolpidem and eszopiclone.
Karl Doghramji, MD: Eszopiclones.
Peter L. Salgo, MD: I’ve never prescribed it, I can’t pronounce it. I’m glad you’re here. We’ve got melatonin receptor agonists, and we’ve got the orexin antagonists, right? Let’s go through them one at a time. How do they work? What’s going on with them?
Karl Doghramji, MD: Well, certainly, they’re the prescription drugs that are not indicated for insomnia, right, which many physicians use, the sedating antidepressants. Trazodone is a favorite. Low-dose mirtazapine is another one. So why do we use them? Well, we think that they’re safer. Maybe we think they’re not addictive so we like to use them, but also there’s a perception sometimes that if you add them in low doses, maybe they’ll also treat patients in a panacea way. You’re treating an underlying depression or anxiety disorder, although there are no data to show that that’s true. But we sort of believe that and sometimes use them. These drugs tend to work sometimes in patients, but generally there are no good studies showing that they do work predictably well. And to Nicole’s point, they may cause daytime sedation and other problems during the course of the day. So these are the prescription drugs not indicated for insomnia, that we tend to use for insomnia.
Sanford H. Auerbach, MD: But one of the reasons why I think that happened is because for many years, physicians thought that the best drug to use was zolpidem, or you had mentioned the Z-drugs. And the insurance companies made it too difficult to prescribe those.
Peter L. Salgo, MD: Why was that, they were expensive?
Sanford H. Auerbach, MD: They were expensive, right? I think that drives insurance companies.
Peter L. Salgo, MD: He’s kind of a Cheshire cat.
Sanford H. Auerbach, MD: And these other medications that Karl just mentioned, they’re cheaper and much more available, and nobody put any restriction on them. You didn’t have to get any prior authorizations. You could give them a full month’s supply, and nobody bothered you. And it is a problem that sometimes they create too much sedation. People would have a hangover effect and so forth.
Peter L. Salgo, MD: Why don’t we run these down a little bit, take them one at a time. The antidepressants.
Nicole Brandt, PharmD, MBA, BCPP, CGP, FASCP: To build on the antidepressants, there’s an older antidepressant too, doxepin, which I think is a unique medication because you’re using it at lower doses. To get back to the point that was brought up, oftentimes we’re using lower doses and not really depression or anxiety doses. But we’re using it for oftentimes the histamine blockade to help with that sedation and maybe that quick improvement in terms of the sleep quality, but over time, we may lose that benefit. I’d like to ask—and would love to hear the panel’s response—is the dose getting escalated? Where we started, it was originally for sleep, but now we might be bumping up the dose, and we’re not really addressing the sleep as well again, and the medication persists. I think we need to ask why we start it, do we really evaluate it? Because if we’re using that antihistamine effect at the beginning, the higher doses of mirtazapine, for instance, they don’t have that antihistamine effect as much. I think pharmacologically there are some unique properties.
And the same with doxepin. When we push up the doses of doxepin, you increase the anticholinergic effects, which we want to avoid in older adults. I think it’s really important when we think about the pharmacology, we think about the dose-related effects. And when we look at these medications, and we’ll talk about it, maybe lower doses might be safer, but depending on what we’re treating, they may not always be beneficial.
Karl Doghramji, MD: Good point. And as you know, low-dose doxepin, 3 mg and 6 mg, is indicated for insomnia.
Nicole Brandt, PharmD, MBA, BCPP, CGP, FASCP: Exactly.
Karl Doghramji, MD: It’s a pure antihistamine, whereas if one bumps up that dose to 50 mg, 150 mg, it becomes an antidepressant with significant anticholinergic and other effects.
Sanford H. Auerbach, MD: You hinted at something that I think is personally overlooked all the time, which is that they’re using these sedating antidepressants, which are not great antidepressants, and they’re going to sort of be a back-door approach to treating the anxiety and depression. And not enough attention is paid to the anxiety and depression in these patients.
Peter L. Salgo, MD: What about benzodiazepines? The number of folks who come in to see me, preoperatively, or I find out in the ICU [intensive care unit], say dad’s on Valium, Ativan, for sleep or something else, and it’s on all the time. It seems to me that there’s a lot of folks out there on benzodiazepines. Do they work? Are they safe? Are they useful? Who wants to jump in on this one?
Karl Doghramji, MD: Well, clearly they work, otherwise they would not be indicated for insomnia. There are a number of drugs that are benzodiazepine receptor agonists, or they promote GABA [gamma-aminobutyric acid] receptor activity, which in fact are indicated for insomnia. These are the longer-acting drugs, the Dalmanes and so on.
Peter L. Salgo, MD: Boy, there’s a name I haven’t heard in a long time.
Karl Doghramji, MD: Flurazepam, the first benzodiazepine hypnotic, yes.
Nicole Brandt, PharmD, MBA, BCPP, CGP, FASCP: Back in 1970.
Karl Doghramji, MD: 1970 by Hoffmann-La Roche.
Peter L. Salgo, MD: 1970?
Nicole Brandt, PharmD, MBA, BCPP, CGP, FASCP: 1970, yes.
Peter L. Salgo, MD: How old do you feel right now?
Karl Doghramji, MD: Going all the way up to triazolam or Halcion, which we don’t use much anymore, even though it’s a short-acting benzodiazepine, because of the potential for daytime sedation, amnesias. It was used in higher doses than it should have been, producing amnestic disturbances. The fact is they do work for sleep. The problem is they have baggage associated with daytime sedation. Also in the case of some of these, they do lead to tolerance and lack of activity after continued usage. So we’ve seen a movement away from these drugs toward what we consider as the Z-drugs, which tend to be safer, but not in every case.