Examining Treatment Options for Insomnia: From Orexin to GABA

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Dr. Trice: 
Good afternoon, I'm Dr. Kevin Trice. I'm the Medical Director of Adult Sleep Medicine at Norton Healthcare in Louisville, Kentucky. And I want to talk to you about examining treatment options for insomnia from orexin to GABA.

Insomnia is a disorder that we're all very familiar with. I'm sure you've heard a lot about it, and you see it all the time as well. And the sleep disturbance can be characterized by patients having difficulty falling asleep, difficulty staying asleep, or early morning wakening. Of course, there's also mild, moderate, and severe, intermittent, temporary, and long-term or chronic insomnia. It can also manifest as having difficulty with activities during the day. It can have a huge impact on overall health, and of course, mood and symptom dysregulation for other things as well.

So the WHO puts the prevalence of insomnia about 30% of the population. Of course women can have a little bit more than men. It doesn't mean that men don't have it. And of course, age plays a role as well. We know that as we age, patients tend to have more insomnia as well. They can have difficulty falling asleep, but particularly difficulty maintaining sleep and early morning wakening. So in those older patients, it’s important asked about insomnia-like symptoms, and not just blame it on their age. Other factors like stress, anxiety, depression, changing work schedules, or changing care schedules for other people in the home, can lead to insomnia as well. And then, of course, we always talk about the modern lifestyle, things with our cell phones and tablets and social media, and 24-hour cable news, all these things can really have a major impact on insomnia as well.

We know that cognitive behavioral therapy for insomnia is the gold standard, and of course, where you're looking at sleep hygiene, and the two big factors of sleep restriction and stimulus control that can have positive effects over a dedicated 8- to 12-week period. Whether that is done in person with a psychotherapist or provider, or whether an online portal, it's been shown to be beneficial, and is always recommended. But we know the hurdles it takes to get patients not only signed up, but to complete a program of CBTI, whether that's cost, just access and wait times, ability to stick with the program, and the lack of kind of instant or almost instant response. So because of that, I think although we all recommend it, we have to think about medications.

And when you look at particular neurotransmitters like orexin, also known as hypocretin, which is a neuropeptide, it plays an important role in the regulation of sleep and wake. And so the drugs that act on the orexin or the orexin receptor antagonists is a class that has been shown to decrease the effective activity of orexin and provide you with longer sleep and deeper sleep, which is what our patients are looking for.

So this class of dual orexin receptor antagonists, we know common drugs like lemborexant and suvorexant, and there are minor differences between the 2 drugs. As providers, it's very important that we know the little nuances between these drugs so that we don't feel uncomfortable prescribing them and can predict the outcome that we want our patients to have when starting on those medications.

So for instance, lemborexant, the generic name, we know it is a dual orexin receptor antagonist, slightly different than some of the other ones, it takes effect in about 30 minutes, so in a normal sleep latency time, and it can last for about 7 hours. Compared to some of the other drugs, it may have a little bit less fall risk than suvorexant, and of course, benzodiazepines which are still commonly prescribed and have their own associated risks associated with them.

When you compare that to suvorexant, which is an orexin receptor antagonist, similar onset of action about 30 minutes, but a little bit longer half-life of 7 to 10 hours possibly, but it can have different side effects that are more common. It doesn't prevent you from using it, but you may look out for things like headache, somnolence, or even some sleep paralysis, which of course is usually very temporary.

When we think about the GABAergic system in insomnia, similar to orexin, and we're looking at another neurotransmitter that can be inhibitory. And a lot of the GABA drugs or Z drugs that we use out there, you're familiar with temazepam, triazolams, they have more of a global effect and can have varying half-life's, anywhere from 2.5 hours up to about 6 hours. And there's only 5 FDA drugs that are actually approved for insomnia, although there's a lot of other Z drugs in that category that aren't really approved. Of course, they carry a risk of dependence and falls, and can be habit forming, which is why we try to stay away from them, maybe looking at these other drugs as an option.

When we think about the new things coming down the pipeline, of course, there’s melatonin receptor antagonists, light therapy, fixing circadian rhythm, herbal supplements over the counter, lifestyle, exercise, these things are not to be underestimated. But again, you want to think about the things that you can really control. And always keep your eye on new future research that’s coming out. There's a lot of things out there that hopefully will be helping with insomnia in the future. And our job is to know when they're coming so that we can adequately tell our patients about them and inform them early on so they can do adequate research and follow-up as well.

I hope this really helps and gets rid of a little fear you have in terms of starting these medications, and thanks for attending.

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