Karl Doghramji, MDKarl Doghramji, MD
The luxury of a good night’s sleep waxes and wanes throughout life, but for over 40% of elderly adults, a restful and fulfilling sleep is far from reality.1 Complicated by comorbidities and polypharmacy, diagnosing and treating sleep problems in this population is particularly difficult.

In an effort to better educate the health care community about these concerns, Karl Doghramji, MD, medical director of the Jefferson Sleep Disorders Center at Jefferson University Hospitals in Philadelphia, Pennsylvania, sat down with NeurologyLive® for an in-depth interview on the optimal management of sleep disorders, particularly insomnia, in elderly adults.

How do sleep patterns change in the elderly and what are the consequences of those changes?

We know that the prevalence of insomnia increases as we age, and there are a number of reasons for that. One of the major and most important reasons is that sleep seems to naturally fragment as we age. We sleep less during the course of the night, and older individuals become sleepier during the course of the day and nap more. In addition, they seem to have a shortened amount of slow- wave sleep or some of the deeper stages of sleep, and an increased amount of shallow sleep or stage I sleep.

The question has always been, are these changes a result of the natural process of aging, or are these caused by medical and psychiatric and other conditions, which also increase in prevalence as we age? The data seem to suggest that not all these changes are due to comorbid conditions, and that there seems to be a natural degradation in sleep as we age.

Insomnia, and poor sleep in general, seems to be related to a number of consequences that are still being worked on and defined both in older and younger individuals. From a neurocognitive standpoint, we know that poor sleep is related to memory decline, especially working memory and episodic memory, and memory about one’s own recent life. Poor sleep seems to augment that memory decrement in older individuals. Interestingly, many studies have shown that in older individuals, one of the strongest predictors of falls, which we worry about a great deal, is poor sleep and short sleep time, independent of hypnotic medications or sleep medica- tions. The impairment in motor behavior in older people could be related to the way they’ve slept the night before.

In the context of the hospital setting, poor sleep is also associated with the risk of delirium, and [results of ] some studies have shown that by treating poor sleep after admission to a hospital, we can actually diminish the risk of delirium after admission to a hospital. From a systemic standpoint, we know that individuals who sleep more poorly over the course of time have a higher likelihood of developing hyper- tension and metabolic abnormalities or becoming glucose intolerant, which is very interesting, and that really suggests that insomnia may have significant systemic effects as well as neurocognitive effects.

What are some of the nonpharmacologic options available to manage insomnia in this population, and what are the advantages or disadvantages versus pharmacotherapy?

Because behavioral abnormalities in older individuals are so common, the initial approach to the management of an older individual’s insomnia should really rest on behavioral modification, sleep hygiene, and other cognitive behavioral methods. This has been the recommendation of a number of societies, including the American College of Physicians and the American Academy of Family Physicians.

Things such as ensuring a regularity in terms of both bedtime and waking time in the morning on a regular basis, systematically waking an older individual up at the same time every morning and preventing napping as much as possible during the course of the day, and avoiding napping as much as possible may be very helpful.

Maximizing exposure to light in the morning by taking older individuals to settings where there are bright-lit rooms, for example, could be very helpful, as well as maximizing daytime exercise. It has been shown time and time again that aerobic exercise on a regular basis enhances sleep in individuals and enhances the quantity and the perceived quality of sleep and diminishes daytime sleepiness.

There are a number of therapies that can also modify the quality of sleep, one of which is called sleep restriction therapy. Older individuals have a propensity to wake up a great deal during sleep, making their sleep inefficient and less productive. So limiting the amount of time they spend in bed over the course of weeks and months could actually produce more sleep depth and continuity over the course of time.

Cognitive behavioral therapy (CBT) has a number of advantages. Obviously, it does not introduce the metabolic and adverse-effect burden of medications, and it tends to have a long-acting, or longer-acting effect. Many months and even years after the discontinuation of CBT, we see evidence of continued efficacy with insomnia. It still works up to 1 or 2 years after therapy has been completed. This is not something we see with hypnotic medications or sleeping pills, as they stop working very quickly after discontinuing the medication. CBT is also much more appropriate in individuals who have multiple medical conditions and who have multiple drugs on board. The data clearly show that these [individuals] are better treated and the treatments are more effective when CBT is the choice over pharmacotherapy. In addition, CBT, especially in older individuals, does not introduce many of the cost risks associated with medications, and cost factors are significant in older individuals.

On the other side of the equation, the disadvantages of CBT are that the number of therapists who are available and trained well to do the therapy are few and far between, unfortunately, and some of them don’t have adequate insurance coverage. The other disad- vantage of CBT is that it tends to not work quite as quickly as pharmacotherapy. If there are individuals who need rapid treatment, that may be the less appropriate approach.

When is it appropriate to use pharmacotherapy in these patients, and how do you select the optimal therapy?

I think the use of these agents is appropriate in older individuals if treatment of the comorbid conditions have really not been successful in eliminating insomnia or if direct treatment of the insomnia with cognitive behavioral techniques has not been effective. The agents that are used fall into 2 general classes: those that are indicated specifically for insomnia and those that are not indi- cated for insomnia but used off-label.

The question of which drug to use for which patient rests on a number of parameters, one of which is, what’s the nature of the sleep complaint? If the complaint is one of sleep initiation—not being able to fall asleep quickly enough—then there are certain agents that are appropriate for that. If it’s one of sleep maintenance, which is waking up a lot during the night, then there are other sets of agents. And if there’s a combination, then there are other agents as well. In general, if it’s a sleep initiation problem only, something like ramelteon, zolpidem, or zaleplon may be appropriate. If it’s a sleep maintenance problem, low-dose doxepin, 3 mg or 6 mg, may be appropriate. If it’s a problem involving both sleep initiation and maintenance, zolpidem extended release, S-zopiclone, as well as suvorexant, may be appropriate.

A second consideration is whether the patient has some comor- bidities and safety issues, including respiratory compromise, sleep apnea, or COPD [chronic obstructive pulmonary disease], which are common in the elderly. If those are present, it favors the use
of agents that have been tested in these disorders. Agents such as suvorexant and ramelteon seem to be safe in mild and moderate sleep apnea and COPD. Finally, if the patient has a history of drug addiction, we use agents that don’t have GABA [gamma-amino-butyric acid]-ergic potential that are not scheduled. For example, ramelteon and doxepin low-dose may be appropriate.

If the drugs are used for an appropriate length of time at the right dosage and they’re simply not working, if their benefit is minimal compared to what we’d like to see, or if they have significant adverse effects, I think at that point stop the drug and go to something else. We don’t have any good data on whether we should stay with the same mechanism of drug or switch mechanisms, but many physicians recommend switching to another mechanism drug just on the basis of a theoretical potential advantage.

The American Geriatrics Society developed a new set of Beers Criteria for the inappropriate use of medications in the elderly. In terms of the recommendations that apply specifically to sleep drugs, short-, intermediate-, and long-acting benzodiazepines not be utilized in the elderly because of the possibility of developing neurocognitive difficulties, delirium, and falls and hip fractures. They also recommend that the “Z” drugs, such as zaleplon, zolpidem, and zopiclone not be utilized, again because of similar concerns about falls and potential hip fractures. Third, they’ve recommended that the antihistamines not be utilized—things like diphenhydramine and doxylamine—for insomnia, because of the potential for anticholinergic adverse effects with these drugs, potentially producing delirium and also dry mouth, urinary retention, and gastrointestinal difficulties. And finally, they’ve cautioned against using antipsychotics for insomnia in the elderly specifically because similar concerns as above.

Are there any drugs currently in development that you feel are promising treatment options in this population?

Lemborexant is an investigational orexin receptor antagonist, and by antagonizing orexin receptors it promotes sleep, both maintenance as well as sleep onset. Lemborexant has been studied in more than 2000 patients in 2 pivotal clinical trials, one lasting approximately 1 month and the other lasting 6 months. The first trial involved actual sleep laboratory data, and the second trial was mainly subjective in nature.

The orexin neurotransmission system in the central nervous system is thought to promote wakefulness along with many other neurotransmitters such as dopamine, norepinephrine, serotonin, and acetylcholine. However, the orexin system seems to also be important in terms of maintaining good balance between sleep and wakefulness.

A few other drugs are also being explored. For example, cannabinoid agents. The cannabinoid receptors are helpful potentially not only for sleep but also for anxiety. Antihistaminic agents, of which some are already available, are also being explored further, as well as additional orexin receptor antagonists.

Some nonpharmacologic agents are also being looked at, including a head cooling device which can actually cool the brain. We think by doing so, it can actually produce better sleep. Many of the apps we have are being developed further, not only to monitor sleep but also to be able to help us fall asleep and stay asleep through some of the interventions that they provide in terms of recommendations on how to sleep better, maybe even anxiety-reducing techniques. Overall, there’s a lot happening in the field of sleep, and we’ll see much more about this in the next few years.
REFERENCE
Stepnowsky CJ, Ancoli-israel S. Sleep and its disorders in seniors. Sleep Med Clin. 2008;3(2):281-293. doi: 10.1016/j.jsmc.2008.01.011.