Michael J. Thorpy, MD

 We’re coming to a close. Let’s talk about what sort of advice you might give to physicians, treating physicians. For the physicians out there, are there particular pieces of information that you really feel they ought to know when it comes to the diagnosis and management of insomnia? Erinn?

 I think one of the biggest pieces of information is to ask, and for the general internist to not be afraid to ask about it, and not to be afraid to address it. I think that is a big thing in primary care. A lot of these medications are controlled, and so therefore, primary care physicians might be resistant to address it, and then have to start writing [prescriptions] for them. I think the biggest thing is to ask, and to realize that it is impacting the entire patient, their health, psychosocial aspects, everything. You may be missing the mark on a lot of your other goals of health care if you’re not addressing their insomnia and what’s going on. I think that would be one thing to do. The other thing would be to keep abreast of these newer agents that are coming up. Try to find a sleep medicine doctor in your area or at one of your local health care facilities or teaching hospitals who you can tap into. You may not be able to get all of your insomniacs to see a specialist like you are, but to be able to say, “OK, I tried this, this is what’s going on, what would my next step be?” I think the biggest thing that I would recommend to physicians is don’t be afraid of it. I think for many years, we’ve kind of been, “I don’t know, I don’t want to go there.” It isn’t something for which there are enough sleep doctors for us to refer everybody to.

 Karl, what do you find are the most important things that you want physicians to know about the diagnosis and management of insomnia? Are there certain take-home points that you would like them to hear about?

 I agree with Erinn, No. 1, don’t be afraid to ask. No. 2, once you do ask, develop a systematic approach to evaluate the problem, like you would with hypertension, with high blood sugar levels, step 1, step 2, step 3, do a differential diagnosis. What are the inventories you’d like to use? What are some of the tests? When would you refer? We already spoke about some of these, but you may want to develop a systematic method to address these in your office. And No. 3, how would you treat the problem, developing a strategy to do that? Which hypnotic for what disorder? And No. 4, when do you refer? I think as sleep specialists, we of course see a lot of referrals for insomnia. And I would say don’t be afraid to refer to the specialists. We have a lot we can do in terms of diagnostic approaches to be able to help your patients.

 I think it is very sound advice. Insomnia is such a common problem for all physicians, and they see it all the time. But there are a lot of things that they certainly can do. Taking a good history is most important for a start, working out what the associated factors are, whether comorbid conditions are worsening it. If there are underlying psychiatric conditions, which are really common, then treating those at the same time as treating the insomnia is essential. I think physicians tend to think, “Well, if the patient’s primary medical or psychiatric problem goes away, then the insomnia is going to go away as well.” But that’s not the case in most cases.

You do need to treat the insomnia. Consider the behavioral treatments we’ve talked about. I personally, as I mentioned, believe that controlling the timing of sleep within 24 hours is the most essential point. Thus, having the person go to bed at the same time, get up at the same time, and be in bed for an appropriate amount of time, which as I mentioned is no more than 8 hours, I think is essential for anyone with insomnia. Avoiding those daytime naps as well. And then, if you can have access, as you said, to cognitive behavioral therapists and be able to get them that specific treatment, that’s good. But most physicians are not going to have access to that. But there are things that they can do in the office, as we’ve talked about, concerning dealing with sleep restriction, about stimulus control, having them only go to bed when they’re sleepy, and then get up at the same time in the morning. Deal with some of those misunderstandings about sleep, for example, the patient who feels that the end of his life is really occurring because he’s got insomnia, but trying to tell the patient that there is help, that they can improve and that they don’t necessarily need to let this affect their life. And take a positive attitude, remove those negative sort of connotations with sleep, turn it into something more positive that they can do and that they’re going to make headway. Then consider, as we’ve mentioned, the newer medications, and it’s exciting that there are new drugs becoming available in the future. Particularly, that there are new mechanisms of action, I think that’s particularly exciting. Thus, there’s a lot that a physician can do.

I think we’ll bring this program to a close. I’d like to thank Karl, Erinn, Nathaniel, and Vikas, for their involvement with this discussion on insomnia. I think it has been very useful. I’ve certainly learned a lot from you all. I hope our audience has also picked up a lot of useful information. Once again, thank you very much for this very comprehensive and informative discussion.

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Closing their discussion on insomnia, panelists share final thoughts and advice for community physicians.

Managing Insomnia: Practical Advice for Community Physicians 

 Karl, there’s a drug that was mentioned by Nate called daridorexant. It’s a new drug. Can you tell us a little bit about this and what’s new and different about it?

 As Nate mentioned, it’s a dual orexin receptor antagonist [DORA], and it seems to have a shorter half-life than the other DORAs. And it may, for that reason, have different clinical effects. But one of the interesting things about the clinical development of this medication is that it’s also been looked at for daytime functioning disturbances with insomniacs. It has been shown to have some improvement in some areas of daytime functioning, which I think is very interesting, since we’ve been speaking about daytime functioning as being a critical area for insomniacs. I think we need more studies like this. It would be very helpful in the future if we could also develop more objective ways of quantifying daytime dysfunction with insomniacs and see if these medications could be helpful. This medication was also studied in, I believe, a 3-month trial where there was a rapid discontinuation. Of course, that’s a clinical issue with many of our patients who discontinue sleep medications, stop taking them. In this particular case, there was no rebound insomnia, which was very interesting to find out.

 Yes, this is interesting. You mentioned having effects on daytime functioning. When you survey patients, you find that daytime functioning is the biggest complaint, and I think you mentioned that at the beginning of the program. The fact that this medication has shown some benefit, not only at night, but also during the daytime, I think is a good direction. Hopefully, we will have other medications for insomnia that will address this as well and look at various daytime consequences of insomnia, not just look at how it’s improving the nighttime.

 Another medication, Michael, I want to mention in the pipeline is something called IMB-115; it does not have an official name yet. It is a medication being developed for not only insomnia, but also for insomnia associated with alcohol cessation. It actually acts at the receptors that are important for both pain as well as for mood and other issues and those susceptive receptors. And interestingly, it may have some effects on drug addiction as well. Thus, it has been developed as a way of possibly treating alcohol cessation insomnia as well as insomnia, period.

 Yes, I think this is particularly interesting because it’s a whole new different mechanism of action for a hypnotic [medication]. As you said, it’s affecting these pain receptors, it’s a pain receptor agonist. This medication is under investigation at the present time. What’s yet to be seen is whether it will eventually get FDA approved, of course. But it’s nice to think that there are new receptor types that could be affected by medications to help people sleep and not just the traditional ones.

Expert panelists share their excitement for novel agents that may impact the insomnia treatment landscape.

Improving Insomnia Management: Novel Agents in the Pipeline 

 We’ve talked a lot about insomnia, the symptoms, the diagnosis, and all the different treatment options. But looking to the future, what do we need to do? Vikas, what are the unmet needs for insomnia? What needs to be done to move the management of insomnia further ahead, do you think?

Vikas Jain, MD, FAASM, FAAFP, CCSH, CPE: 

I think we’ve discussed many of the limitations and the difficulties we all have in treating insomnia. The No. 1 guideline by the ACP [American College of Physicians] and American Academy of Sleep Medicine is to use cognitive behavioral therapy. However, access is limited. We don’t have as many trained behavioral sleep specialists that exist in our communities. That’s hopefully going to change in the future with more access, or even more online programs that can be beneficial. As Nate mentioned, many of these agents have traditionally just been measured by their ability to improve sleep onset or their ability to help a patient stay asleep at night, but not necessarily what influence they’re having on the day, or adverse effect profile. I also think access to medications can be an issue as well. As Karl had mentioned, with the American Geriatric Association, there are these medicines that they do not recommend using in the elderly population. But then sometimes many of the medicines that are recommended are cost-prohibitive for those patients as well. Thus, how do we continue to improve access to patients and have better medications hopefully available to use in the future to help treat this condition?

 Michael, as asleep physicians, we hardly ever think about the sleep environment. We never think about beds, or mattresses, or other things such as that. And I think that as we look to the future, we can see that our technological advancements are going to create sleeping environments that are going to be more conducive to sleep for the individual. It’s going to tailor a sleep environment to the individual. Thus, whether that’s the temperature in the bed or in the room, whether it’s the firmness of the mattress, depending on body position, because you might need a less firm mattress when you’re on your side than you do when you’re on your back. Whether it’s lifting the head of the bed, if snoring is present, to help address some sleep apnea-related issues; whether it’s generating a light when you step out of bed so that it reduces the risk of falls in patients who are at risk for that. I think that there are a lot of things that are going to happen out there that are going to improve the sleep environment for people, which hopefully will have a positive effect on insomnia.

A brief review of the unmet needs in insomnia management, particularly access to treatment and daytime functioning. 

Unmet Needs in the Management of Insomnia 

 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?

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.

 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?

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.

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

Michael J. Thorpy, MD

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