Paul Doghramji, MD, FAAFP

: There are some challenges when we prescribe these newer agents, the DORAs because all 3 of them are branded products and they're relatively expensive. They don't have a generic counterpart compared to the older ones, the Z-drugs, which all come out in generic and are relatively expensive. And as a result, insurance companies will also have a say in it where they will want patients to try a generic, inexpensive medication like a Z-drug first before they will pay for one of the newer branded DORA products. The way to get around that sometimes if you want to prescribe a DORA and you think that's the right one and benzodiazepine or a benzodiazepine receptor agonist is not the right one is you can give samples out to patients. There are coupons, there are vouchers which you can use. Now, the newest one, the newest medication, which is daridorexant, they have a specific way where you can write the prescription out to a specific remote pharmacy where that remote pharmacy can contact the patient and have 30 days of the medication sent to the patient free of charge if they have commercial insurance. The patient can then try out that medication free of charge no matter what if they have commercial insurance and have a good trial of 30 days of that medication. Followed by after that, the medication can then either go through insurance or if it still doesn't, they can pay $25 a month for continuation of that medication. One company at least has tried to get the medication into a patient's hands in an easier way. And this is one of the things that makes daridorexant attractive to prescribe for our patients. Because again, if you can't get the medication into your patient's hands, of what use is it?

The one month that the daridorexant company is supplying a patient who has insomnia for free if they have commercial insurance is good. Now, obviously, I'd like to see it a little bit longer for me to be able to judge how well a patient is doing, maybe 6 or 7 weeks or so. But again, if they're doing well after one month, I'll want to then encourage the patient to go onto the second month so I can see by halfway through that second month where they are. Because that's probably going to be their peak benefit time. It is important for them to get the medication for a longer period than one month, but at least the one month is a very good start.

Insomnia is a risk factor for many psychiatric and medical conditions. People have a poorer quality of life and more negative outcomes because of poor sleep from insomnia. We in primary care, are best suited in identifying these patients and doing something about it. We need to be proactive. We see our patients very regularly over time. We are primary care providers. We're not emergency room physicians or emergency room providers where they come and go. These patients are coming to us all the time. We have many opportunities to ask about a patient's sleep. And if they're not doing very well, we need to be proficient at knowing which questions to ask to be able to get to the root of what's going on with their insomnia. We also need to know what the treatment options are, including cognitive behavioral therapy, including sleep hygiene, which is part of cognitive behavioral therapy, including the medications that are out there. We need to be proficient and know how to prescribe these medicines. We also need to talk to our patients about expectations that we want to get their sleep to be as good as possible so they're sleeping well through the night and feeling well throughout the day. And those should be our goals. And if we can't achieve that, then we can certainly get some help from our sleep experts. That's the main message that we need to impart to our primary care clinics about insomnia and their patients.

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An expert in sleep medicine highlights challenges in prescribing DORAs and importance of discussing insomnia with patients in the primary care setting.

Access and Treatment of Insomnia in Primary Care Clinics

: Most patients with insomnia don't want to take anything at all for their insomnia. But when they're forced to do so, you then must tell them how to take the medication properly. And for most patients, what we need to tell them is to take this medicine every single day. Because in fact, in some of the data that's come out with, let's say daridorexant, it seems like the medications benefit builds over time. With that in mind, I've been telling my patients, take this medicine every single day and try it out for a good month and a half, because the data with the daytime sleepiness and the total sleep time suggests that if you take the medicine over time, you may get increased improvement in benefit. In order to help them adhere to the medicine, giving them that information may be helpful. That, again, if you take this medicine on a nightly basis, you may get the best bang for your buck as opposed to trying to go to sleep, you don't fall asleep, then you take the medication, you're not sure whether you should take it or not. That isn’t a good way of doing it in general. But just looking at the clinical studies with these latest medications that I talked about, they were all nightly-used medication. And we should therefore recommend that patients that are taking these medications adhere to that which is nightly used. We think that's where they're going to get their best bang for their buck in treating their insomnia.

There are 2 to 3 instances where you want to switch medications. One of them is obviously when a patient is not getting the desired benefit. Maybe you've titrated the medication, you've given the medicine the best that you think that they can do and they're not doing well with it. That's one instance. The second one is obviously adverse effects. The patient doesn't like how they feel. Either during the night or during the day, they don't like how they feel. That's one. And the third thing, unfortunately, is also insurance or financial challenges. There are some instances where certain patients just can't afford the medicine, or their insurance won't pay for it. These are instances where you want to change the medication to something else.

If you're transitioning a patient from one medication to another, chances are if they're in the same mechanism of action medication. Like for example, if they're going from one Z-drug to another one, you can just go from one to the other and you're probably going to do well. But if you're transitioning to a different category of medication, let's say going from a Z-drug to a DORA, there's no clinical trials to guide us. But my recommendation would be 1 of 2 ways. One is to wean off the Z-drug completely and see where their sleep situation still lies. Do they still have just as much insomnia? Is it improved for whatever reason or is it worse? And depending on what happens, then you can go to the DORA. There are other instances, and I know some of my colleagues have done this, where they will put the both medications together while they wean off the Z-drug while they are also on the DORA. I tend not to do that. I tend to wean off the Z-drug and then go to the DORA. But I also want to tell the patient that the experience they're going to have with the DORA is probably not going to be the same experience that they had with the Z-drug. The Z-drugs tend to, for lack of a better way, knock you out, tranquilize you, whatever. Whereas the DORAs have more of a tendency to gradually put you to sleep and help you stay asleep. And that kind of an effect may improve over time. They're probably going to have a different experience. And I do counsel my patients that are on the DORAs specifically, daridorexant to take the medication for a good month and a half before they judge and see how well the medicine is working to help them get to sleep and stay asleep and how well they feel the next day.

Dr Paul Doghramji shares his approach to switching medications for the treatment of insomnia.

Treatment Adherence and Switching Treatments for Insomnia

: When the first dual orexin receptor antagonist came out, suvorexant, we started using it then. And it did come out of the 5, 10, 15, 20 mg. We had several different doses. We did prescribe the medication. It did seem to be effective in some patients to help them get to sleep and stay asleep. Lemborexant then came out again helping our patients get to sleep and stay asleep at the 5 and 10 mg dose. Now, daridorexant has come out at the 25 and 50 mg dose. And the interesting thing about daridorexant is at the 50 mg dose has had something unique with it as far as clinical studies showing that there is a decrease in sleepiness in some of the patients compared to placebo when they take that medication on a regular basis. And that's unique to that medication. But again, these dual orexin receptor antagonists by way of reducing one's wake drive, seem to be effective in helping patients get to sleep and stay asleep. And the 3 differ in their half-lives and their duration of action. That's the one. With daridorexant having the shortest duration of action.

In my experience with them has been varied in the sense that I've prescribed all 3 of them with good successes and all 3 of them with some patients doing better with one versus another. But they all are good medications that work quite well for patients who have insomnia. And as far as the adverse effect profile is concerned, all of them seem to have a relatively attractive adverse effect profile, which is relatively low. And the discontinuation rates due to adverse effects also seem to be low with all 3 of them. They are good medications. I have tried all 3. They seemed to fit a lot of patients that have insomnia where you don't necessarily want to use the traditional drugs that you've been using, whether it's the Z-drugs or the ones before. Patients seem to do quite well with these dual orexin receptor antagonists.

Paul Doghramji, MD, FAAFP, shares his personal experience with DORAs in clinical practice to manage insomnia and discusses treatment adherence with insomnia medications.

Using DORAs for the Treatment of Insomnia

: There have been a lot of medications that have come out that we use that are prescription for our patients who have insomnia. There are many that came out decades ago that were not indicated for insomnia, that were used for insomnia. There are many that have come out in the last couple of decades that are specifically indicated for insomnia. There are various categories of drugs. Some are off-label, some are on-label. The most common off-label medication that's used for insomnia is trazodone. It's interesting that it's the number one used sleep medication in this country, which again has no indication for insomnia. Let's talk about the medications that are indicated for insomnia because they're good medications and they're very helpful for our patients. Like I said, they are on-label. First are the benzodiazepines and some of them are still quite effective. One of them which is temazepam is probably the leading benzodiazepine to help our patients with insomnia. Then there are the benzodiazepine receptor agonists. They're non-benzodiazepines in their molecule, but they work similarly. They're called the Z-drugs, zaleplon, zolpidem, and eszopiclone. They have slightly different characteristics. Primarily the difference is their half-life and they can be used for our patients with insomnia. There's one targeting histamine and that's doxepin that's used to help patients only stay asleep better at the 10 mg dose. There's also a melatonin receptor agonist which is called ramelteon that's also been invented. There's only one in its class as well that's indicated only for sleep initiation. Also, in the last 10 years or there have been three medications that have come out in the most newest mechanism of action and that's the dual orexin receptor antagonists. The first one that came out is suvorexant. The second one that came out is lemborexant and the third newest one is daridorexant. These are dual orexin receptor antagonists that work by antagonizing orexin in the orexin nucleus, lowering the amount of wakefulness that's going on to help the patient get to sleep and stay asleep.

When the Z-drugs came out, zaleplon, zolpidem, and eszopiclone, they did help us fill a gap in our treatment. There are a lot of patients that were doing very poorly with the previous ones, whether they were anti-depressants, whether they were barbiturates, et cetera. They did well, but they had problems. Either they would have middle-of-the-night behaviors that patients would have where they would wake up and do bizarre things and not remember, they would have some falls in the beginning, in the night, they would have next day spillover effect, there was rebound insomnia, there was maybe some habituation that was going on. They had their problems. They helped, but they had their problems. We found something that did help some patients. Clearly, there was still a gap in treatment and that's why I think that we now have the dual orexin receptor antagonists that may fit some of the gaps in our treatment. But again, there have been challenges with the Z-drugs, but also, by the way, some of the challenges with the medicines that are used off-label. We’ve talked about trazodone. They can certainly have a lot of adverse effects to them. There's another one which is commonly used, quetiapine. That can have some issues with it as well. We all know about them. Gabapentin can also be used for sleep or is being used for sleeping off-label. There are a lot of medicines that have come out that have been used off-label in the past. There's plenty of challenges with them, and that's why maybe the introduction of a new type of medication is now seemingly attractive to clinicians when they're trying to treat their patients for their insomnia.

An expert in sleep medicine provides insight on the use of traditional insomnia medications in patients as well as DORAs, and common challenges experienced with these treatment options.

Paul Doghramji, MD, FAAFP

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