Waking Up to the Dangers of Insomnia

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Announcement: 0:00

Welcome to MedEvidence, where we help you navigate the truth behind medical research with unbiased, evidence-proven facts Hosted by cardiologist and top medical researcher, Dr Michael Koren.

Dr. Michael Koren: 0:11

Hello, I'm Dr Michael Koren, the executive editor of MedEvidence, and I'm here with my colleague, Dr. Mitchell Rothstein. Mitch, thanks for joining us again on MedEvidence! Always a pleasure. And, mitch, I'm going to pick your brain today for our audience. In fact, I'm going to call this our Medical Wisdom series.

Dr. Mitchell Rothstein: 0:30

Nice, okay, who you can have as a guest? Yeah.

Dr. Michael Koren: 0:34

And you are a master clinician. You have a background in pulmonary medicine and sleep medicine and critical care medicine, and I want to talk about a very common problem and I want to break it down for our audience so that everybody can view this and have a really good idea on how to approach it for themselves or for a family member. And that problem is insomnia

Dr. Mitchell Rothstein: 1:00

Common problem.

Dr. Michael Koren: 1:01

You're familiar with that?

Dr. Mitchell Rothstein: 1:02

Very.

Dr. Michael Koren: 1:03

So it's something that a lot of people talk about. You go to cocktail parties and people talk about it, but I rarely hear anybody approach it systematically or approach it from the way old school clinicians used to approach problems. So you and I are kind of old school clinicians I hate to admit that, but I guess we are and so let's help people understand that. Break it down for people.

Dr. Michael Koren: 1:28

All right, All right. So insomnia you said it's a common problem. How common is it?

Dr. Mitchell Rothstein: 1:33

The current estimate is that about 30% of the adult population suffers from insomnia Now, that's not all chronic insomnia. Of that, 30% about 10% suffer from chronic insomnia. And we define chronic insomnia as having poor sleep on at least three nights a week for at least three months. And when we talk about poor sleep, remember this is primarily a perceptual issue. So poor sleep is defined as the perception of inadequate, insufficient or fragmented sleep associated with a daytime consequence, which is something that initially, when we were treating patients with insomnia, we didn't have included in the definition. And that's given an adequate opportunity to sleep Okay.

Dr. Michael Koren: 2:19

So when a person identifies the fact that they're having sleep problems, should they assume that that's insomnia in of itself, or are there specific things that they should know to understand that this is maybe a medical issue that needs to be looked at? So help break that down. First of all, every night that you don't sleep well doesn't mean that you have insomnia.

Dr. Mitchell Rothstein: 2:44

Correct. So there are common cases of transient insomnia and I think every human experiences those over time. For example, when there's trauma, death in a family, people have difficulty sleeping for a period of time that may go on for a week or two, but once it extends beyond, that is a point where you have to start considering other alternatives, especially when those daytime consequences start to appear. So, for example, in the United States right now, we think that there's probably about 100 million adults that have chronic insomnia. And that costs, in terms of productivity, about $100 billion in domestic product loss because of their presentism at work, because they're drowsy, because they're making mistakes. It has huge social impacts, it has impacts on your health and well-being and we know that it's associated with a number of medical problems. So my kind of rule for people in general when they were coming to see me for insomnia as patients was, if it got to the point where it was interfering with your life and it was going on for more than a month, that was the time that you should seek medical attention.

Dr. Michael Koren: 3:56

Okay, so let's just break that down a little bit more for people.

Dr. Michael Koren: 3:59

So let's have you having a bad week. You're not sleeping right, you're out of sink, maybe you are traveling and you haven't gotten back into your rhythm. Is that when you call a physician, or is there some things you can do to sort of address it before you get medical advice?

Dr. Mitchell Rothstein: 4:17

There's plenty you can do to address it before you get medical advice, and the most obvious issue in our current society is sleep deprivation. More people suffer from sleep deprivation than any other medical condition out there and you know that's thanks to electricity, it's thanks to being on the computer and watching TV and we're going to see a bump in this as our COVID generation kind of moves into adulthood, because they've grown up in a very poor sleep hygiene environment. You know they were spending a lot of time in their rooms, on their beds, on their computers, and we like people sleep specialists, like people to associate seeing the bed with sleep, not seeing the bed with being on the computer or watching TV or being on your phone talking to friends, and that association is lost. You know, as things go on and we become more technically associated.

Dr. Michael Koren: 5:12

When your bed becomes your office, you have a problem.

Dr. Mitchell Rothstein: 5:15

You can have a problem.

Dr. Mitchell Rothstein: 5:16

Now there's people that don't have any problem at all. You know they can be doing whatever they can be watching you know fights on TV, shut off the lights and go right to sleep. There's other people where, if they hear you know a drip from the faucet in the house next door, it keeps them awake all night because they're worried about it. So there's a number of issues that kind of complicate not really complicate this, that kind of determine what happens to people and we kind of, in broad phrases, we kind of separate those into predisposing factors, precipitating factors and then perpetuating factors. So, just like everything else, you know people that are that have high blood pressure or are predisposed to high blood pressure. If they stay away from salt, their blood pressure is fine. If they eat salt, their blood pressure goes up.

Dr. Mitchell Rothstein: 5:59

When people have the same issues with insomnia, some are predisposed to this hyper arousal state that they can't shut their brain off. And if a precipitating factor happens, there's an accident, they end up in the hospital, something changes in their environment that triggers them over the line and they have insomnia and then, depending on how they cope with that, determines whether the insomnia is going to be transient and goes away after that trauma is over or is going to continue if they develop bad coping mechanisms. So kind of to answer your question. The first thing somebody should do is look at their own sleep hygiene. You know what are their sleep patterns.

Dr. Mitchell Rothstein: 6:36

When did they get up, when did they go to bed? Do they have an adequate sleep period? Is the sleep environment cool and quiet? Is it conducive to good sleep or not? And so, once you start looking at that, if there's a correctable easy issue there, if you know that the light's on in the hallway and it bothers you, make sure the light's out. If you stop using caffeine and alcohol six to 10 hours before bedtime, if you shut off the TV you know two hours before bedtime.

Dr. Mitchell Rothstein: 7:05

If you avoid even dim light illumination an hour before bedtime, all those things can help you fall asleep. And if those things aren't working, after about a month and you're recognizing daytime consequences, you're not as sharp as you used to, you have daytime fatigue, you're irritable. That's the point where you need to see a physician.

Dr. Michael Koren: 7:27

Okay Now before we get to the physician part, are there any home remedies that you would recommend? People talk about melatonin or things that are- antihistamines that can help just help the audience understand what is a reasonable over-the-counter approach to that.

Dr. Mitchell Rothstein: 7:43

Yeah, so there's no over-the-counter approach that's actually been shown to be effective in any clinical FDA-approved trial.

Dr. Mitchell Rothstein: 7:53

That's why they're over-the-counter. So the issues with melatonin initially we thought melatonin was going to be a great drug because melatonin drives the S phase of sleep and our circadian rhythms, but as it turns out it seems to have a very limited application and it might be helpful for people with jet lag, maybe in the elderly at low dose to help sleep onset, but doesn't really seem to have any real clinical effectiveness. Antihistamines work by our major alerting neurotransmitter in our brain is histamine. So when you take an antihistamine you're dulling our major alerting process and the problem with antihistamines is there's hangover and there's very rapid habituation, so people become tolerant to it and then there are side effects. I mean it's largely an elderly population that has glaucoma or large prostates and you get into a lot of problems with that. Magnesium has been touted as a sleep aid and for people who are magnesium deficient it might work, but in general large trials it doesn't seem to really have any proven effectiveness with either sleep onset or sleep maintenance.

Dr. Michael Koren: 9:08

Okay. So just to get a little granular, if you're having a bad week, you're not sleeping well. Do you pop three milligrams of melatonin? Do you pop 10 milligrams? Do you pop 25 mg of Benadryl? Just help people with those dose ranges and what would be reasonable before you get medical attention.

Dr. Mitchell Rothstein: 9:24

Well, I would say that in general, if you're going to use melatonin, most of the data suggests that for somebody under the age of 50, they need a dose of at least 5 milligrams. And if you're going to use an antihistamine, usually 25 milligrams is the recommended dose. But I don't really want to recommend either of those to people. There is a placebo effect that may help them fall asleep and from that aspect, maybe they'll be effective. If you're going to use an antihistamine, I wouldn't use it for more than a week.

Dr. Michael Koren: 9:56

Okay, and magnesium you mentioned, is there a dose that you recommend?

Dr. Mitchell Rothstein: 10:00

Not really, so there's-

Dr. Michael Koren: 10:02

Magnesium oxide 400 before you go to sleep can't hurt.

Dr. Mitchell Rothstein: 10:06

It can. I think that's the right answer. It CAN hurt so now and the same thing. There's also things that are available over the counter without prescriptions that can definitely help, and that's cognitive behavioral therapy, and there's actually online programs for free where, if you Google cognitive behavioral therapy for insomnia, they'll hook you up with a program and you can go through the steps of the program for behavioral training, which has definitely proven to help people with insomnia.

Dr. Michael Koren: 10:35

Okay, and how about devices putting a pillow over your head? Yeah, tell me about those type of approaches.

Dr. Mitchell Rothstein: 10:43

Well, I think most of these kind of external issues really are forms of relaxation therapy and to some degree some of the medications are a form of relaxation therapy. If you believe that an antihistamine, you know Tylenol pm, is going to help you sleep, it has a better chance of working than if you don't believe that it's going to help you. And the same goes true with like noise generating devices and other sound generating devices. Those can help people transition from an activated, aroused state to a more relaxed state that's conducive to sleep onset.

Dr. Michael Koren: 11:21

What about a shot of Jack Daniels before you go to sleep? Does that work?

Dr. Mitchell Rothstein: 11:24

Well, it will help you fall asleep, but as alcohol is metabolized, its byproducts will actually wake you up. So people don't sleep through the night and then they take another shot of alcohol. They'll sleep through the rest of the night.

Dr. Michael Koren: 11:35

Okay. So you're past that one week mark and you're still struggling. It's been a month and you're just having trouble. You're not sleeping well. You either wake up early spontaneously or you have difficulty getting to sleep in the first place. So what are your next steps? Should you go to your primary physician, go to a sleep specialist? Google something? What's the next step? And help people understand the difference between difficulty falling asleep and people who wake up spontaneously?

Dr. Mitchell Rothstein: 12:06

So the next step is a good question. I think it's largely insurance dependent right.

Dr. Mitchell Rothstein: 12:11

So if you have insurance that requires you to see your primary care physician. That would be your next step and in the ideal world you would see a sleep specialist. And as a sleep specialist, the first job of the sleep specialist is to figure out if what you're dealing with is insomnia or insufficient sleep. So the first thing we do is look at a sleep log and we have the patients fill out a sleep log of when they go to bed, when they get up, their awakenings during the night and their estimate as to how much sleep they're getting per night. For about two weeks and when the patients come back, we know that if the patient truly has insomnia, the most common underlying issue is a mood disorder. We know that 50% of patients with insomnia either suffer from anxiety and or depression and we'll usually do a depression scale or an anxiety scale and if that's the case, we'll treat that underlying mood disorder.

Dr. Mitchell Rothstein: 13:06

If that's not the case, then we want to rule out other things that can interfere with sleep. So in an aging population, the most common, prevalent underlying condition that interferes with sleep is pain. So people have arthritic pains that will wake them up. We evaluate them for that. We evaluate them for bladder issues that might wake them up, for bowel issues that might wake them up at night. We want to make sure that their environment is like we talked about before, is adequate and in all those cases, regardless of what the underlying etiology is for insomnia, the first step is always cognitive behavioral therapy, which includes teaching people how to relax, teaching people that the stimulus, that their sleep environment can't act as an arousal stimulus, and teaching people what to do if they're waking up during the night.

Dr. Mitchell Rothstein: 13:59

So, for example, if your issue is a sleep onset issue, if you go to bed and you're doing the right things to help your brain relax and you're not entering sleep after minutes, we have you get out of bed, go in another room.

Dr. Mitchell Rothstein: 14:13

You can't do something stimulating, you know you can't turn the tv on. You can listen to music, you can read in a dim light and then we have you retry bed, but we don't let you then extend your morning awakening past its usual time. So the biggest problem that people have with inadequate sleep hygiene is they don't have a regular wake-up time and that's important, not because that's when you wake up, but it's important because that's associated with your first exposure to bright natural light. So one of the things people can do that suffer from insomnia is pick a regular wake-up time is pick a regular wake-up time, usually before 9 am. Get outside in natural sunlight, because that natural sunlight hits your retina. The retina is connected to your hypothalamus and in your hypothalamus is this organ called the suprachiasmatic nucleus which is the pacemaker for your entire body.

Dr. Mitchell Rothstein: 15:07

It tells your body that after my first bright light exposure, which usually has to be about 20, 000 lux, which transfers to being outside in natural light, you don't have to sunbathe, you can sit in the shade, just be around natural light, no sunglasses, and you can't be hot, be behind uv protective glass, because that eliminates that 400 wave blue green light that you need. And your brain knows that about 12 hours after that first bright light exposure is when I'm going to start secreting melatonin, because that means that my day is over and I'll be going to sleep. So if you sleep in, or if you get up at 8 in the morning but you don't go outside till noon, your brain thinks noon is 7 o'clock in the morning and then you're up at 8 in the morning but you don't go outside till noon, your brain thinks noon is 7 o'clock in the morning and then you're up till 5 in the morning.

Dr. Michael Koren: 15:54

So you have to reset those circadian rhythms. So interesting, so you do recommend that you use natural light to help you wake up in the morning.

Dr. Mitchell Rothstein: 16:01

Yeah, and actually we call it natural light, and you'll like this because I know you like language is a zeitgeber. So zeit- is time and -geber is giver or gatekeeper, and so the most powerful zeitgeber we have is exposure to natural bright light. But there's other zeitgebers that occur all during the day. In fact, in the early 1970s they did a study where they took eight men and they put them in a cave and they had this cave because the cave had a standard temperature that didn't fluctuate during the day. And they had them cave because the cave had a standard temperature that didn't fluctuate during the day. And they had them in a room with dim light, 24 7, and they had them served by attendants that came in that were always freshly shaven.

Dr. Mitchell Rothstein: 16:40

They didn't serve them breakfast, lunch and dinner. They served them lunch, lunch and dinner. So the participants didn't know what time it was to see what our the natural was. And it turns out that our normal natural cycle is about 24.2 hours. And what these zeitgebers do light meals, exercise, change in temperature is it shortens that natural cycle from 24.2 hours to 24 hours. If you don't do that, every day gets a little later and a little later and a little later, and then you have insomnia from that perspective as well.

Dr. Michael Koren: 17:14

So interesting, so, so interesting. So, getting back to that initial diagnosis, you said it should take about 20 minutes to fall asleep. If it's more than 30 minutes, then you may have a problem. And you're saying that you should change your environment after 20 to 30 minutes to see if you can find some other way to get to sleep.

Dr. Mitchell Rothstein: 17:36

But just to interrupt, there's some other things that you can do. Also, if your sleep environment is activating your brain, what an average person wants to be able to do is they want to open the door to their bedroom, see their bed, and they want their brain to say to them oh, thank God, I get to go to sleep. Now, if you're opening the door and your brain is saying to you, oh no, I'm not going to sleep again, I'm going to be up on blah, blah, blah, you want to change that environment. So we have had people, you know, change their sheets, paint their room a different color, change the position of their bed, and that's called, you know, stimulus control therapy. You want to have that stimulus not there anymore, that stimulus that was causing the arousal and the anxiety and the difficulty falling asleep, and change it. So it doesn't do that. In fact, a lot of people that suffer from insomnia find that they have insomnia every night when they're home. They go away to a conference or in a hotel room one night they sleep like a baby.

Dr. Mitchell Rothstein: 18:38

They come back home and they're having that problem again, and that's all due to that kind of association with the bedroom not being a place of relaxation and sleep.

Dr. Michael Koren: 18:41

Interesting, so interesting. So you mentioned about sleep logs. Is something you do as a sleep specialist. I would imagine that's a little bit challenging, because how do you record how long it takes you to go to sleep, if you're sleeping? So do you recommend devices nowadays?

Dr. Mitchell Rothstein: 18:55

That's an excellent point. And sleep is a perceptual issue. So we have people in the sleep labs. So if you came into our sleep lab and you went to bed at nine and then you woke up at 11, for 15 minutes, you went back to bed. You woke up at two, you were up for 15 minutes, went back to bed and fell asleep and then you woke up at four and were up for 15 minutes, fell back to sleep and then at seven o'clock I came in and woke you up and I said Mike, how'd you sleep last night? And you go, you son of a bitch. I was up all night Because, like you said, all you really remember is the time you're awake.

Dr. Mitchell Rothstein: 19:27

You don't remember the time you're asleep. So, since it's a perceptual issue, when we start doing sleep logs, we also do something called actigraphy, which is on everybody's watch now, and it actually will record motion which is fairly well associated with sleep, and we can see how consistent people are with what they think their sleep was like, with what the actigraph and that's called sleep stage misperception. So you don't remember the time you're asleep, you only remember the time you're awake. And that separates out people that have actual sleep deprivation associated insomnia from people who have the sleep stage misperception. Both of them can be associated with daytime consequences, but they're treated a little differently.

Dr. Michael Koren: 20:11

Understood. So the devices that are generally available to the public. They're usually pretty good at making the diagnosis, would you say.

Dr. Mitchell Rothstein: 20:18

Well, they're pretty good at recording the difference between sleep and wake, not recording, obviously, differences in sleep staging or arousal activity. And it's really the arousal activity, the breaking up of sleep into these 10 to 15 seconds, issues- periods that are not really recognized the following morning but are associated with generalized fatigue. So all of us, during our course of normal sleep, have arousals. So during the course of an hour of sleep, an average adult might have arousals, which are defined on an EEG as showing awake activity for 15 seconds or less, but not awakening you so that you have memory of it, and an average adult might have 15 to 20 of these an hour. People with insomnia have twice that or three times that, and they might sleep through the night, where some of them might actually awaken them to full consciousness. But regardless of that, that sleep fragmentation is associated with the daytime consequences of fatigue and lack of concentration and the things that people start complaining about.

Dr. Michael Koren: 21:27

So before we get into some of the medications in old-time movies people used to wear those eye shades to help them go to sleep. Obviously, they would not be subject to natural light to wake them up in the morning. If they're wearing them, is there still a role for something like that?

Dr. Mitchell Rothstein: 21:42

Sure, and it's not natural light that wakes you up in the morning. What wakes you up in the morning is your own circadian pacemaker. So we have these two kind of opposing processes that help us sleep during the night. One is our circadian drive and one is our homeostatic drive. So the homeostatic drive is driven by the accumulation in our brains of adenosine, that's what caffeine kind of counteracts and helps us stay awake. So during the course of the day your homeostatic drive continues to go up and up, and up and up, until it reaches a point that kind of tips you over and you go from wakefulness to sleep. And that's a compounded with a circadian drive. So in the morning, when you first wake up before you've seen sunlight, your circadian drive is at its lowest. And then during the day your circadian drive kind of reaches a peak in mid-afternoon, siesta time.

Dr. Michael Koren: 22:35

Right.

Dr. Mitchell Rothstein: 22:35

And then, interestingly, whether you take a siesta or not, your circadian drive goes away and you're feel okay again. So even if you don't sleep, you don't feel tired anymore, and that kind of peaks at the same time that your homeostatic drive and that adenosine is building up during the night and then it kind of tips you over into sleep, let's say at 11 PM, and then during the course of the night your adenosine level is being metabolized. So that's going away, so you're sleeping off your sleep drive, but the circadian clock is what's keeping you asleep and continuing kind of to pelt your brain with GABA to keep you sleeping till morning, at which point you wake up and that's when your temperature starts to rise and your cortisol starts to rise, and that's what wakes you up in the morning.

Dr. Mitchell Rothstein: 23:18

Not the bright light isn't what wakes you up. The bright light is actually what tells you when to go to sleep.

Dr. Michael Koren: 23:22

Got it Okay. Now you mentioned napping. I'm a personal big fan of napping. Do you recommend that when you're treating insomnia? So give us some advice about that.

Dr. Mitchell Rothstein: 23:34

So the napping data that's out there and there were plenty of studies done over the last couple of decades on napping. Napping is good for you but there are some kind of boundaries on it. So number one is that if you have difficulty falling asleep you don't want to reduce your sleep drives, that adenosine buildup, and napping is going to reduce your adenosine levels. So for people that have trouble falling asleep at night we don't recommend napping and we don't recommend napping in close proximity to your regular bedtime because again'll reduce your sleep drive.

Dr. Mitchell Rothstein: 24:05

But for average people napping is refreshing. We limit naps to about 20 minutes and we want to time them around that kind of siesta circadian bump, which is usually about 12, 12 noon to about 2 pm, and we limit them to 20 minutes because that prevents your brain from cycling into deep sleep. So I'm sure you've had that experience. I've had it where you wake up at a deep sleep and you don't know where you are, you have no idea what time it is, where you are, and that's called sleep drunkenness and that is because your brain has cycled into deeper sleep, which is a synchronized, non-awake version of sleep and it's difficult to kind of get reorganized from that. And when people enter that, the nap becomes unrefreshing, whereas if they're in lighter stages, of sleep for 20 minutes, the nap is refreshing, interesting.

Dr. Michael Koren: 24:56

Well, it's about noon right now. Can we take a break for about 20 minutes?

Dr. Mitchell Rothstein: 24:59

Absolutely.

Dr. Michael Koren: 25:02

Anyway. So, getting back to other ways of approaching insomnia, one of the things that comes up all the time is what medicines do you use under what circumstances? And there are different categories. We have, of course, the sedatives, benzodiazepines being most common. We talked about antihistamines. We talked about melatonin and other quote supplements, and then now cannabis is being recommended as something that can help a lot of people. So what's right for people? How do you figure that out? Do you combine modalities?

Dr. Mitchell Rothstein: 25:37

Yeah, we definitely combine modalities. We always combine behavioral therapy with pharmaceutical therapy For people that have resistant insomnia, that have been following all the rules the cognitive behavioral therapy, the stimulus control, relaxation, training and they're still having unrefreshing sleep. That's associated with daytime consequences. We generally start with a short course of hypnotic and, as you pointed out, the hypnotics are in different classes and some of them have benefits over others. The most recent class of hypnotics out are these orexin antagonists. So these are fascinating drugs and the whole development of this class and associated with our understanding of how sleep works and the sleep wake kind of toggles, which was kind of pertinent to their discovery. So, if you think about in general, there's no advantage to being a drowsy person walking around, just like you know, if you're a drowsy zebra on the african veldt, you're not going to last very long and as a person, you don't want to be drowsy.

Dr. Mitchell Rothstein: 26:45

You either want to be completely asleep or completely awake, and these orexin antagonists. Orexin antagonists inhibit orexin, which appears to be the flip switch in our brain, from switching from wakefulness to sleep, so it keeps you either asleep when you're asleep or awake when you're awake, and it does that by stimulating different parts of our brain that act on the wake centers and the sleep centers. Now, if you antagonize that, the major thing that orexin does is enhance arousal. So if you shut off arousal, you then will have a more propensity to go into sleep. And it seems to work quite well. It appears to be non-addictive. They're all expensive and in general, whether we're using that group or benzodiazepines or the Z classes of medications, we want to limit our initial use of hypnotic to about one to two weeks and during that period of time, reinforcing the behavioral activities and hopefully at that time the patients can stop using the hypnotics and rely on the behavioral techniques to keep them asleep. If that fails, then there's a point where you make determinations about whether or not if you're treating the underlying issues that are inhibiting sleep mood disorders. Treating the underlying issues that are inhibiting sleep mood disorders, pain, prostate issues, whatever the issue is, thyroid disease, hyperadrenalism and all those issues seem to be a baseline.

Dr. Mitchell Rothstein: 28:15

There are people who have we call it primary insomnia, where their brains are just hyperactive and they're just not good sleepers. In fact, there's a family, there's a condition called fatal familial insomnia, where it's mostly in the Mediterranean group. It's an autosomal, dominant disease and people start having trouble with insomnia in their teenage years and it's uniformly fatal. People die from chronic sleep loss. And the problem with insomnia is and this was just discovered in the last decade is that your brain clears all these bad proteins and neurotransmitters during sleep through something called the glymphatic system.

Dr. Michael Koren: 28:50

Glymphatic?

Dr. Mitchell Rothstein: 28:51

Glymphatic, which is connected to your lymphatics. But during sleep the glymphatics, through this extravascular penetration and concentration differences, take out all these prion proteins, adenosine and everything out and filter it out and clear out your brain so that during daytime you can be awake and alert again.

Dr. Michael Koren: 29:11

Interesting. So breaking it down a little bit more in terms of those medication classes and how you start. You mentioned that there's a newer class that is expensive, but is that what you start with? Or do you start with benzodiazepine?

Dr. Michael Koren: 29:27

And you can mention some names, so people know what categories you're talking about.

Dr. Mitchell Rothstein: 29:30

-And this is obviously patient-dependent, cost-dependent. The traditional old benzodiazepines like triazolam, flurazepam, temazepam are effective and good.

Dr. Michael Koren: 29:43

Use some of the trade names so people know Halcyon.

Dr. Mitchell Rothstein: 29:44

Right.

Dr. Mitchell Rothstein: 29:46

Halcyon and Tamezapam is Restoril. Those medications and these are classic benzodiazepines, all that group are effective as hypnotics.

Dr. Michael Koren: 30:00

They're short-acting drugs in the Valium class of drugs but they're shorter-acting yeah.

Dr. Mitchell Rothstein: 30:04

Absolutely. And the problem with that class is they can be addictive and they can have other consequences. So that whole class is associated with not only hypnosis but anxiolysis, anti-convulsant activity and myorelaxation and they can have cross-effects with other medications that people are on. There's another class called the Z medications, which is like Ambien and Lunesta and those are benzodiazepine-like. They hit the same receptor but they don't have the anxiolysis and the muscle relaxant activity and they seem to have less of the potential for drug-drug interactions but also addictive less of the potential for drug-drug interactions, but also, addictive. These orexin antagonists don't appear to have addictive activity because they don't actively put you to sleep. They're not depressing, they're stopping a lot of that arousal activity from coming in.

Dr. Michael Koren: 30:57

And examples of those?

Dr. Mitchell Rothstein: 30:59

Are things like daridorexant, suvorexant, lemborexant. In fact, one of the first studies I did with the Jacksonville Center for Clinical Research was about using the orexin antagonist yeah, suvorexant.

Dr. Michael Koren: 31:12

And a trade name for those.

Dr. Mitchell Rothstein: 31:14

Belsomra, Quivivic are the two most common that are out there that I can recall [also Dayvigo]. There's also ramelteon, which is pharmaceutical melatonin, so that appears to again have a place for maybe sleep onset in some patients and for jet lag, for circadian rhythm disorders and as a hypnotic. Overall it's still in that category but doesn't seem to be as powerful as the other medications.

Dr. Michael Koren: 31:42

So interesting.

Dr. Michael Koren: 31:43

And how about cannabis? That's become something that a lot of people are talking about as a treatment for insomnia.

Dr. Mitchell Rothstein: 31:49

Cannabis? I didn't know, but there are cannabinoid receptors in our brain and they have effects on muscle tone as well as electrical activity. They appear to have their primary hypnotic effect through anxiolysis, so people that are anxious appear to benefit from them. There aren't a lot of long-term studies on whether cannabis is a good long-term medication for insomnia, but certainly can be used in the short term and intermittently.

Dr. Michael Koren: 32:23

Any advice for people You're having trouble sleeping for a week Should you go to your local dispensary and get a joint? What should you be doing?

Dr. Mitchell Rothstein: 32:32

Well, as a still practicing physician, I have to offer conservative recommendations, not ones that I would necessarily follow, but ones that everybody else should.

Dr. Michael Koren: 32:43

Sure.

Dr. Mitchell Rothstein: 32:44

And so I would say in general that the initial approach to insomnia if it's transient insomnia, if you know what's causing it, if you know that you were upset by something or you just had surgery and you're having trouble sleeping for a short period of time, a short course of a hypnotic may be beneficial. If you have insomnia and you don't know what's causing it, that's where you want to think about seeking medical attention, because that's an investigation along the lines we just talked about that should be undertaken to help you. It's a devastating illness. It affects people's social activities, it affects their whole life, and when your whole life is about not sleeping well, that's not the kind of life most of us want to live.

Dr. Michael Koren: 33:34

Well, that was a brilliant, brilliant summary. Mitch, thank you very much for sharing that information with the MedEvidence audience. And fortunately, I don't have the sleep problem, but I know people in my life that do and I feel that I am now better prepared to help them. So, thank you so much.

Dr. Mitchell Rothstein: 33:51

Thank you.

Announcement: 33:52

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