May 15, 2017
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Sleep disturbances an important health concern that should be addressed in primary care

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If left untreated, sleep disturbances are known to have various long-term health consequences. Severe insomnia, one of the more common sleep disturbances, increases the risk for heart disease, hypertension, myocardial infarction, congestive heart failure and diabetes. For this reason, it is essential that primary care physicians monitor and treats sleep disturbances in their patients.

However, although sleep disturbances are often linked to various other diseases, they are not merely components of a larger condition, according to Larry Culpepper, MD, MPH professor in the department of family medicine at Boston University and a member of the Education Committee for the National Sleep Foundation.

Larry Culpepper
Larry Culpepper

“In the clinical setting, a misconception that’s still fairly frequent is that insomnia is just an almost to-be-expected part of medical and psychiatric conditions,” Culpepper told Healio Family Medicine. “That’s actually not the case. That was the major point that’s imbedded in the change from older diagnostic criteria and the new DSM-5 criteria for insomnia. In the past, we used to diagnose insomnia as either primary or secondary. Now, we’re recognizing that this is not helpful to patients. Insomnia is simply insomnia, and it stands on its own.”

Culpepper spoke with Healio Family Medicine about the causes of sleep disturbances, the types of treatments used and the ways PCPs can help improve a patient’s overall health by managing sleep disturbances.

Question: What are the most common types of sleep disturbance?

A: The most common is insomnia, followed by obstructive sleep apnea, restless leg syndrome and circadian rhythm problems. People aren’t necessarily up to date on the variances of insomnia, both in terms of the diagnostic considerations and the impact of insomnia on general health and medical morbidities.

Q: Can you discuss some of these impacts?

A: Insomnia can have a major impact on most chronic medical conditions. In chronic insomnia, which is characterized by shortened total sleep, patients often sleep fewer than 6 hours a night, chronically. Patients may just be persistently tired and fatigued, but may not recognize how impaired they actually are. So, when a patient says, “Oh, by the way, doctor, I’m not sleeping well,” as they’re exiting the exam room, we need to listen to that. We also need to recognize that insomnia has a major impact, both in terms of the emergence of comorbidities, but also to poor outcomes from these comorbidities. For example, a patient is two- to three-times more likely to develop hypertension and then coronary artery disease or stroke if they have chronic insomnia.

Insomnia also is a significant contributor to accidents. If we were to look at accidents that occur secondary to medical conditions, like chronic obstructive pulmonary disease, diabetes, osteoarthritis, GI reflux, sleep apnea, pain, congestive heart failure, hypertension, major depression, rheumatoid arthritis, and if we add up all the accidents that occur due to those conditions, they still don’t account for as many accidents as insomnia does.

A common misconception is that insomnia is a problem, but that it’s not consequential and it doesn’t amount to much — that it’s a nuisance diagnosis. That is not true at all. Understanding the impact is critical.

Q: How does a clinician make a diagnosis of insomnia?

A: This is an area where a lot of patients and clinicians are still kind of fuzzy. Say a patient has a chronic medical condition that has them getting up and going to the bathroom once or twice a night. That alone may not be problematic for many patients; they fall back asleep and it is not disruptive. However, insomnia is the diagnosis when someone gets up at 2 a.m., and they go back to bed, but can’t fall asleep. The insomnia part comes around the capacity to shift from a wake state to a sleep state normally. That’s critical to recognize. Patients who stay awake for a long time either at the beginning of the night or in the middle of the night, or who wake up to early, are patients we would diagnose with insomnia.

Q: What are some sleep hygiene best practices that patients should attempt to improve their night’s sleep?
A:
If insomnia is recognized, there are a couple of things to consider. One, sleep hygiene is an important component of advice for patients, but very frequently, it’s not enough. It’s a good base in terms of starting to get patients some help, but is often not sufficient alone.

Certainly, the keys to sleep hygiene are straightforward, but it can sometimes be difficult for patients to make the lifestyle changes required. You would need to look at the sleep environment. Is it cool? Is it dark? Are there shades so that the sun doesn’t wake the patient at 5:30 in the morning?

These are the basics. Then, we consider habits. A big meal right before bedtime or alcohol in the evening is going to tend to keep a patient up. Patients may use alcohol to try to help them get to sleep. While it often will have a soporific effect and will cause patients to fall asleep, as alcohol is metabolized, aldehydes emerge, often 3 or 4 hours later, which tends to disrupt sleep. So it may help initially, but it disrupts the second half of the night.
In addition, smoking right before bedtime is not helpful. Nicotine is a stimulant. That’s a bit of a Catch-22 for patients with a real nicotine addiction. I think exercise can also be quite helpful, particularly if it’s habitual. After a few weeks, regular exercise really kicks in, in terms of improving insomnia. In general, exercise is recommended 3 to 4 hours before bedtime, so that core body temperature is not elevated at bedtime.

Also, patients should not be working right up until the minute they go to bed. Some patients read in bed and that tends to put them to sleep; for others, reading is disruptive.

These factors are individualized, but certainly doing something that is highly stimulating right before attempting to sleep is not the best idea.

Q: What are some commonly held myths about sleep that do not help, and that may actually be a detriment to good sleep?

A: Again, treating insomnia as a secondary condition is not a good approach. In the past, if you had secondary insomnia, you treated the primary condition and waited to see if that improved the insomnia. We’ve recognized that that doesn’t work, and, in fact, it’s counterproductive. The current thinking is that you need to diagnose insomnia as a separate condition, and you need to treat it as such. Very often, patients do much better with all of their comorbidities if they’re treated at the same time.

An analogy would be a patient with diabetes and angina. You wouldn’t treat just one of those and try to get it stable before you’d consider treating the other. It’s the same with insomnia.

Q: Is there such thing as a sleep deficit, and how can this be resolved?

A: This leads into another misconception around sleep and insomnia: we think of insomnia as a sleep problem; we say, “I can’t get to sleep.” From a standpoint of understanding brain processes and behavior, it’s better to conceptualize it as a problem with wakefulness. Patients can’t turn off being awake, and in fact, people with insomnia really have too much drive to stay awake. That’s certainly reflected in brain processes, so that when we look at the control of sleep, a simple understanding of it is that we have two basic drives. The homeostatic drive builds up over time the longer we stay awake; it’s the drive to go to sleep. So, after you’ve been awake and active for 12 hours, it’s easier to go sleep than it is, say, after 3 or 4 hours. Once you’ve been awake for 24 hours, you drop off almost instantly. So, that’s the sleep drive.
The drive that counteracts that is the drive for wakefulness, which is a sort of counterbalancing drive in the brain. It’s part of our alerting mechanisms; it’s what keeps us alert and scanning the environment, aware of threats and so forth. For some individuals, those with chronic insomnia in particular, it’s really that drive, that alerting system, which is just set too high. The most effective strategy in terms of treating these patients is to really turn down the alerting mechanisms rather than trying to turn up the sleep drive.

Q: How is that achieved?

A: We’ve discussed sleep hygiene, and that’s certainly a good base. A second is cognitive behavioral therapy that’s focused on the insomnia. A number of studies have shown that a short-term, two-session cognitive behavioral therapy focused on insomnia can be very helpful. Cognitive behavioral therapy can interrupt processes and help patients reframe their thoughts about sleep. There are now online resources for cognitive behavioral therapy.

Q: When do you think patients should consider over-the-counter sleep aids?

A: My personal preference would be rarely, if ever. Most of the OTC sleep aids are diphenhydramine or antihistamine-based products. The problem is that their half-life is such that you take it in the night — or, very often, in the middle of the night — but they are quite impairing throughout the next day. Most patients find that these actually turn out to be counterproductive.

Q: What are some of the options in terms of prescription medications?

A: Going back to those mechanisms controlling sleep, we’ve got the sleep drive, and we have a number of neurotransmitters and neurochemicals that build up and contribute to that sleep drive. Certainly, GABA is involved in the sleep drive. GABA is a very widely used neurotransmitter, an inhibitory neurotransmitter. The problem with using GABA as the active agent is that, yes, you’re contributing to the sleep drive, but you’re basically shutting down the whole brain. It’s not focused so much on sleep as on being a total central nervous system depressant.

We now have the non-benzodiazepine GABA agents that are effective. For some patients with occasional insomnia, those can be reasonable, particularly for sleep onset or early part of the night insomnia.

If I have a patient with acute anxiety disorder who gets panic attacks, a regular benzodiazepine long-acting might be part of the therapy I’d use.
Sedating antidepressants are sometimes used, and some of these may be effective for certain patients. However, we don’t have much data on long-term effectiveness. It’s reasonable for some patients to attempt to use them, but we need to recognize that the patients need to be reassessed and that the drugs may lose efficacy.
That leaves us with the options that really approach the direct problem for most patients, which is the wakefulness drive. We find that wakefulness interrelates to circadian rhythm. Throughout the day, our brains stay activated through the circadian drive to stay awake. In the normal state, as night descends and it gets dark, the wakefulness drive decreases and allows the sleep drive to take over. It’s basically a 24-hour rhythm controlled in part by light and melatonin release through the hypothalamus. That’s a potential connection for how melatonin can be used, and in fact, some patients do find melatonin to be helpful. When we’re dealing with chronic insomnia with real circadian problems, the issue depends on how long it’s going to take the melatonin, neurochemically, to act on the centers of the hypothalamus that promote wakefulness. In a chronic insomnia state, we find that it is actually about 4 or 5 hours. So, for some patients, actually taking melatonin at 6 or 7 p.m. is the right thing to do, but in most patients using OTC melatonin, it can be taken an hour before bedtime.

Rozerem (ramelteon, Takeda) is a prescription drug that can be used. The issue with this medication is that it often takes 3 to 4 weeks for it to help, and often we find that patients have the expectation that a sleep drug needs to act like a benzodiazepine and sort of turn the lights off for them. When approaching treatment, we have to re-educate patients about what to expect. 
Given that expectation, it’s useful to think about other agents. The two main agents we have for inhibiting wakefulness are doxepin and Belsomra (suvorexant, Merck). 
Doxepin is classified as an antidepressant, and certainly, once you get to higher doses, like the 100-mg dose, it is an antidepressant. It works through serotonin pathways. At lower doses, though, such as 3 mg, 6 mg or maybe even 10 mg, it’s almost a pure antihistamine.
Histamine is a key neurotransmitter involved in stimulating the brain stem area called the reticular activating system, which basically serves to keep the brain awake. Blocking histamine with an antihistamine like doxepin can be an effective means of decreasing the wakefulness drive. Again, the issue with an antihistamine is that it has lots of other potential targets in the brain, so it’s not a highly specific medication for insomnia.

That leaves us with suvorexant, a prescription drug which very specifically targets orexins. Orexins are key neurotransmitters involved in promoting wakefulness, and suvorexant is an orexin antagonist. It can be used in patients who have difficulty falling asleep initially or falling back to sleep in the middle of the night.

Q: At what point would you consider a sleep disturbance to be a sign of a serious medical condition?

A: In cases where it is an older patient who has not had a sleep problem and suddenly develops one, I do think more about what might be going on. That’s certainly one red flag. Another is the patient who has a chronic medical illness, who has had diabetes, or cardiac problems or COPD, and now are suddenly finding sleep to be a real difficulty. That’s when we need to take a broad look at that patient and think through what might be different.

For more information:

Larry Culpepper, MD, can be reached at 771 Albany St., Boston, MA 02118; email: laculpep@bu.edu.

Disclosure: Culpepper reports advising or consulting for Alkermes, Lundbeck A/S Inc., Merck and Sunovian Pharmaceuticals; receiving royalties from UpTo-Date and Oxford University Press; receiving payment from Physicians Postgraduate Press for serving as editor in chief of the Primary Care Companion for CNS Diseases; and owning stock in M-3 Information, LLC.