Factors in Selecting Pharmacologic Therapy for Insomnia


Practical considerations for selecting a particular agent or class when treating a patient with insomnia.


Michael J. Thorpy, MD: Nate, do you have a particular sort of algorithm that you use when you’re going to select a medication for a patient? How would you go through the process? We’ve talked about all these different types of medications. Which one are you going to pick first, and will you move to another one? And what about these newer agents, what place do they have in the treatment of insomnia?

Nathaniel Fletcher Watson, MD: When addressing patients with insomnia, and I think Karl mentioned this earlier, we’ve got to home in on what’s the complaint. Is it falling asleep, staying asleep, or early morning awakening, or a combination of those things? I’m going to take that into consideration and then think about which medications will address these specific issues. For instance, zolpidem is effective for sleep-onset insomnia. But if somebody had sleep-onset and sleep-maintenance insomnia, then zolpidem-CR [controlled release] might be a better option or zopiclone, or one of the dual orexin receptor antagonists [DORAs]. That’s an important point. I think we need to think about comorbidities and not prescribe medications that may make things worse. Karl mentioned narcolepsy, the dual orexin receptor antagonists are contraindicated in patients with narcolepsy. We don’t use benzodiazepines much anymore. But if a patient had obstructive sleep apnea, that would be contraindicated because it could make the sleep apnea worse. Thus, we have to make sure that they don’t have a comorbidity that’s problematic when we’re picking these medications.

Then there are these practical issues such as, how much do they cost? What’s the insurance policy around it in order to get patients access to these treatments? But in regard to the dual orexin receptor antagonist medications, I’m really excited about the prospect of these. There are 2 that are out now; daridorexant is another one that’s in the pipeline that actually has some data showing positive impact on daytime functioning in patients with insomnia. It reduced daytime sleepiness, improved mood, improvements in cognition, things like that, that we’ve alluded to earlier. And certainly, these DORAs, they’re kind of leveraging our increasing understanding of sleep and wakefulness. And really, instead of promoting sedation, which I think a lot of the medications that we have do, these basically block wakefulness. Thus, it’s kind of a different way of viewing it, and perhaps in many ways, a more effective way, at least as far as the way that they work, and the fact that patients don’t seem to have any kind of addictive properties, and they don’t seem to have a lot of next day adverse effects of these medications.

Michael J. Thorpy, MD: Right. With insomnia, we talk about this hyperarousal theory, where there’s increased alertness and arousal at night, whereas in the past, we’ve been trying to suppress and force sleep on people through the benzodiazepines and some of the older drugs. This new way of reducing that hyperarousal to allow normal sleep or natural sleep to occur is a different direction in insomnia. It is a new change. Now of course, for many patients who are on sleeping pills, and Erinn, I’m sure you see a lot of patients who come to you and they say, “Well, I’ve tried such and such a sleeping pill, it’s not working.” When do you decide whether you’re going to change them to a different medication? Do you try to keep them on the same one and do other things like behavioral things in conjunction with it? Or should you switch them to something different?

Erinn E. Beagin, MD:I think the No. 1 thing is going back to why are they even looking to treat the insomnia? It’s not just “Are you sleeping OK at night?” A lot of patients come back to me, especially with more of the hypnotic [medications], saying, “Well great, I slept OK at night, but I was even less functional the next day.” Thus, that’s where I think a lot of patients will come back. It’s the adverse effect profile, or how they are functioning the next day. I think, again, it’s looking at that daytime functioning, which the patient is sometimes more focused on, or sometimes the doctor’s more focused on, “How are you sleeping?” “Well, I slept OK, a little cranky going.” Or, “Well yes, except that I couldn’t get myself going in the morning, and I was drowsy for the first 5 hours of the day.” Thus, that didn’t work out so well. If they have adverse effects, if they’re not functioning well the next day, then I didn’t treat their insomnia, because by definition, daytime functioning is key in insomnia. That would be one thing.

If they are definitely using behavioral techniques, so if they said, “Yes, I’m taking this pill, but I’m still going to bed like you said at 8 pm and trying to get up at 8 am, and it’s not working.” OK, well, maybe I’m not going to change the medication, I really need to work more on behavior. Thus, asking them “What did you do in addition to taking this medication? Is it working for you?” Some people come back, and they say, “Listen,” and I may have missed the mark. And I think that’s the other thing as physicians is taking a step back and saying, “Did I get the right medications?” If I put you on zolpidem and I didn’t pay attention that, or you didn’t really realize, that you were still waking up throughout the night, well, then maybe I need to change to something, either a longer-acting zolpidem or a different medication. Hence, I think tweaking it, and a lot of times as an internist and a geriatrician, I do tend to start at a lower dose. Sometimes they’ll say, “I’m getting there, but I’m not quite there.” Then, increasing the dose if there is a lack of adverse effects allows that.

Transcript edited for clarity.

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