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The Role of "Z-Drugs" in Treating Insomnia

Experts in the field of insomnia consider the efficacy of “Z-drugs” in treating insomnia, and the adverse effects of prescription medications.


Peter L. Salgo, MD: Again, some of those drugs that are tough to pronounce—we’ll call them the Z-drugs. What are these drugs?

Sanford H. Auerbach, MD: One of the problems, too, with these benzodiazepines is that most physicians, the physicians who prescribe Ativan and Xanax to your patients, is they have no clue how long those drugs hang around in those patients. They think of lorazepam as being a very short-acting drug, and it’s much more long-acting than they appreciate, probably 2 or 3 times longer.

Nicole Brandt, PharmD, MBA, BCPP, CGP, FASCP: Especially the Valium, the diazepam. It’s got an active metabolite that’s renally eliminated, so it’s going to stick around a lot longer.

Peter L. Salgo, MD: And in older folks sometimes their creatinine levels are up, and their renal excretion is down.

Nicole Brandt, PharmD, MBA, BCPP, CGP, FASCP: You’ve got it. Let me come back to the baggage that Karl brought up. It’s not just the daytime sedation the next day, we also find that the ability to adjust if you feel like you’re in a fog, the psychomotor retardation, becomes a concern with older adults. And so there are great falls data, which then leads to fracture risk increasing, and the discussion on the cognitive health. I’d love to hear your perspective, but we’ve seen short-term and especially long-term use of benzodiazepines. And then the psychological dependence, let alone the physical dependence on these medications. There’s a lot of baggage. We see their use and I always caution, especially as we’re training new providers, to really think twice before starting a benzodiazepine in an older adult for those baggage reasons.

Peter L. Salgo, MD: We see a lot of withdrawal from benzodiazepines postoperatively. It’s real.

Karl Doghramji, MD: Right.

Gary L. Johnson, MD, MS, MBA: How many automobile accidents are caused by some of this baggage? And there’s really no way to pinpoint that it’s caused by something that they’ve been taking.

Peter L. Salgo, MD: What about these Z-drugs, how do they differ?

Sanford H. Auerbach, MD: They’re very similar to the benzodiazepines in terms of how they actually work. I think that all of these benzodiazepines, Z-drugs, have a very similar point of action. They vary perhaps in potency. They vary a little bit on perhaps how quickly they’re taken up, and I think that one of the big things is they all vary on how long they hang around. And that’s oftentimes the culprit, particularly when you’re dealing with next day sedation and so forth, dealing with making sure there’s something. This Dalmane had a half-life of about 100 hours.

Karl Doghramji, MD: Metabolite.

Sanford H. Auerbach, MD: They would hang around forever, and then people were taking it every day and it would accumulate over time. I always think of them as one large class that varies among those different dimensions.

Nicole Brandt, PharmD, MBA, BCPP, CGP, FASCP: To Sandy’s point, we’ve seen that borne out of the literature in terms of post-marketing safety with both benzodiazepines and nonbenzodiazepine agonists, is that they have very similar effects in terms of the falls, the cognitive implications. I think we’ve got to treat them very cautiously. And then what’s also been interesting is some of the nighttime behaviors where people have done bizarre things, waking up in the middle of the night—some hazardous behaviors. There are warnings that have come out with these medications, as well, to monitor patients when they first start them.

Peter L. Salgo, MD: What about the melatonin receptor agonists, how do they differ? Are they better for older people?

Nicole Brandt, PharmD, MBA, BCPP, CGP, FASCP: I think they don’t have the same baggage, coming back to that baggage implication, in terms of the implications on falls and cognitive health. But I think in regard to the efficacy, they don’t work as quickly, is what I’ve seen in terms of when patients have been on a benzodiazepine, and if they were to go to one of the melatonin receptor agonists, such as ramelteon, it may not work as quickly. That’s been one of the things, education around how these medications differ.

Karl Doghramji, MD: Patients’ objective perception is also different with these drugs compared to the benzodiazepines. With the benzodiazepines, they are more effect cognitively. There’s an amnestic effect over the course of the night. They wake up not remembering what happened, and many insomniacs perceive that as a benefit, to sort of not have been aware of what was going on during their sleep. Whereas, with the melatonin receptor agonists, there’s a greater awareness of the experiences during sleep. So many patients tend to rate the melatonin receptor agonists as being less desirable when it comes to sleep for that reason.

Sanford H. Auerbach, MD: My question for you is how much more sleep do you think somebody with the Z-drugs gets per night?

Peter L. Salgo, MD: Based on what I’ve just heard, not a lot more. Am I right?

Nicole Brandt, PharmD, MBA, BCPP, CGP, FASCP: Yes.

Sanford H. Auerbach, MD: It’s just they feel better, maybe because they forget.

Peter L. Salgo, MD: They forget they feel bad?

Sanford H. Auerbach, MD: They forget they didn’t sleep well.

Peter L. Salgo, MD: If a tree sleeps in a forest but doesn’t remember, does that count?

Sanford H. Auerbach, MD: I guess it does.

Nicole Brandt, PharmD, MBA, BCPP, CGP, FASCP: I think to that point, the guidelines even speak to that, is looking at that risk-benefit, there’s a span of 8 minutes, or no minutes, of improvement, maybe up to 20 minutes to 30 minutes of improvement. But it is that subjectivity that started at the very beginning, but the next day, they’re more functional. I think that’s something to bring up as we look at the harms and benefits of these medications.

Sanford H. Auerbach, MD: I think it’s a trap for physicians that they get sucked into treating insomnia. Once they start down that pathway, they map it out according to how much sleep the patient thinks they’re getting, when in fact it’s really driven by how miserable they feel during the day. And the goal should be making them feel and function better during the day, which doesn’t necessarily equate 1-to-1 with their perception of how much they sleep.

Peter L. Salgo, MD: That’s sort of where my professors in medical school were going years ago than I would care to share with you. Remember that caveman story, let’s just stop right there. But the caution was always, once you start with sleeping pills, it’s a slippery slope, and you’ve got to be sure where you’re going and know what you’re looking for as opposed to just pushing the pills forward. Does that make sense?

Sanford H. Auerbach, MD: Exactly. To figure out your target, cleanly define it, be as wary as you can about the adverse effects, so you can monitor the patient appropriately.

 
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