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Optimizing Insomnia Management for the Elderly

  • Authors: Ruth Benca, MD, PhD; Richard Schwab, MD
  • CME / ABIM MOC / CE Released: 9/30/2022
  • Valid for credit through: 9/30/2023
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  • Credits Available

    Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.25 ABIM MOC points

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Target Audience and Goal Statement

This activity is intended for primary care physicians, psychiatrists, neurologists, nurses, and nurse practitioners.

The goal of this activity is that learners will be better able to individualize the treatment of insomnia in elderly patients.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Impact of aging on sleep
  • Have greater competence related to
    • Selecting an optimal treatment approach for elderly patients with insomnia


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  • Ruth Benca, MD, PhD

    Professor and Chair
    Department of Psychiatry and Behavioral Medicine
    Wake Forest School of Medicine
    Winston-Salem, North Carolina


    Ruth Benca, MD, PhD, has the following relevant financial relationships:
    Consultant or advisor for: Eisai; Genomind; Idorsia; Jazz Pharmaceuticals; Merck; Sage Therapeutics
    Research funding from: Eisai

  • Richard Schwab, MD

    Chief, Division of Sleep Medicine
    Professor of Medicine
    Perelman School of Medicine
    Philadelphia, Pennsylvania


    Richard Schwab, MD, has the following relevant financial relationships:
    Consultant or advisor for: eXciteOSA - Scientific Advisory Board; Eli Lilly - Research Consultant
    Research funding from: Cryosa; Inspire; ResMed


  • Kathy Merlo

    Medical Education Director, Medscape, LLC


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Compliance Reviewer/Nurse Planner

  • Lisa Simani, APRN, MS, ACNP

    Associate Director, Accreditation and Compliance, Medscape, LLC


    Lisa Simani, APRN, MS, ACNP, has no relevant financial relationships.

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Optimizing Insomnia Management for the Elderly

Authors: Ruth Benca, MD, PhD; Richard Schwab, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 9/30/2022

Valid for credit through: 9/30/2023


Activity Transcript

Ruth Benca, MD, PhD: Hello, I'm Dr Ruth Benca, Professor and Chair in the Department of Psychiatry and Behavioral Medicine at Wake Forest School of Medicine in Winston-Salem, North Carolina.

Dr Benca: Welcome to this program titled "Optimizing Insomnia Management in the Elderly." Joining me today is Dr Richard Schwab, who is Chief in the Division of Sleep Medicine at the Perelman School of Medicine in Philadelphia, Pennsylvania. Welcome Dr Schwab.

Richard Schwab, MD: Thanks. Welcome.

Dr Benca: To get started, I think it's important to kind of go over some of the statistics about sleep problems in older adults. It's really one of the most common problems that we encounter in clinical practice. And there are estimates that as many as half of older adults are going to complain about problems getting to sleep or staying asleep. Of course, we know the prevalence of insomnia is higher in older people than younger ones and particularly, those with multiple medical problems.

So the prevalence of insomnia symptoms in the elderly, depending on the study you read, could be from 30% to 50%. But the prevalence of insomnia disorder is a bit lower, although still pretty high, somewhere between 12% and 20%. And just to kind of review for everyone, insomnia as a disorder is defined as having complaints of difficulty falling asleep, difficulty staying asleep, and/or waking earlier than desired with dissatisfaction about the quality or quantity of sleep. And, in addition, the sleep problem must result in some impairment in daytime functioning, such as mood, concentration, getting along with other people, whatever. And that these symptoms have to occur at least 3 times a week for at least 3 months to be considered an insomnia disorder.

So Richard, why don't you tell us a little bit more about how sleep changes with age and how some of these changes in sleep that occur with aging may be contributing to the clinical problems that we see.

Dr Schwab: So with aging, we decrease our sleep. In particular, we lose delta sleep or slow wave of sleep, and also some rapid eye movement (REM) sleep. There's also increased nocturnal awakening. So that combination is not good for sleep. There is the SIESTA database, where they looked at healthy adults who didn't have any sleep problems between 20 and 90 years old. And in general, there was a reduction in sleep of about 8 minutes per decade for men and 10 minutes per decade for women. And then circadian rhythms also become abnormal and less robust with aging. There's typically an advance in circadian timing. There's a decrease in the circadian amplitude. And in general, just more difficulty adjusting to changes in circadian rhythms, such as if you fly to Europe, it just becomes more challenging. There is a progressive decline in the function of the suprachiasmatic nucleus. And then there's also some hormonal changes, so we reduce nocturnal melatonin, thyroid stimulating hormone, and there's increased cortisol.

Dr Benca: So, it sounds like there are a lot of other factors that contribute to sleep problems in older adults, differently from some of the insomnia causes that we see in younger people. So along those lines, how does menopause affect sleep? Because we know women, particularly during the menopausal transition, have a lot of sleep issues.

Dr Schwab: That's correct. So, women have a lot of trouble with menopause. And there's more nocturnal awakenings as they go through menopause, these can be pretty bothersome symptoms. Anywhere from 40% to 60% of menopausal women complain of difficulty sleeping. There are changes during the menopause transition and postmenopausal - the estradiol levels decrease, FSH levels increase, there are changes in reproductive hormones, increased complaints of difficulty falling asleep and staying asleep. And maybe the most problematic issue is hot flushes and sweating. And these are consistently associated with poor self-reported sleep quality and chronic insomnia. So, women through menopause, whether it's pre, peri or post, have difficulty sleeping. Ruth, can you discuss how sleep disturbances and disorders are related to age-related cognitive decline and dementia?

Dr Benca: Oh, that's another big concern these days because we're starting to recognize the relationship between various sleep problems and sleep disorders and an increased risk for dementia. So we know that people who have dementia, whether it's Alzheimer's disease or vascular dementia or other forms of dementia, have a lot of sleep problems. What we're also now starting to recognize is that insomnia is a risk factor for Alzheimer's disease and is fairly specific for an increased risk of Alzheimer's vs other types of dementia. And obviously you've already told us about the sleep changes that occur with normal aging, but those changes are even worse in people who have mild cognitive impairment or dementia, their sleep is even more disturbed. Their circadian rhythms are more disrupted than the non-demented elderly. So, the evidence really suggests that sleep dysfunction is probably contributing to the severity and progression of neurodegeneration. And we're also starting to understand a bit about why that is, which is that sleep, particularly that deep, slow wave sleep, is known to be important for clearing amyloid and tau, which are substances involved in the pathogenesis of Alzheimer's disease.

Dr Schwab: Ruth, could you go through the health risks associated with insomnia? And there's a bunch of them.

Dr Benca: First and foremost is that people who have insomnia, particularly older adults with insomnia, are at increased risk of falling. So we always worry about giving patients sleeping pills that might make them fall. But insomnia itself is a risk factor for falling. As in younger people, in elderly patients, insomnia is a risk factor for new or recurrence of depression. It is a risk factor for anxiety and it is a risk factor for suicide. So people who have insomnia have increased suicidal ideation, increased suicidal behaviors, and increases in completed suicides, which is really important right now to keep in mind because we have a suicide epidemic right now in this country. And finally, chronic insomnia in adults, in general, has been shown to be a risk factor for hypertension, stroke, heart disease, and diabetes. And in older adults, insomnia is an increased risk factor for earlier death. So it is really a potentially serious issue.

So Richard, given how problematic insomnia is in older adults and some of the really significant health risks associated with it. How should we approach insomnia treatment in our elderly patients?

Dr Schwab: So the American College of Physicians recommends nonpharmacologic treatment as the first line for chronic insomnia. So not pharmacotherapy, but cognitive behavioral therapy or brief therapy. And you can do this through the internet, you can see a provider. But the primary treatment should be cognitive behavioral therapy. And if that doesn't work, then you can think about pharmacotherapy. And you have to pay attention to a lot of factors. I mean there's drug-related factors, so the mechanism of action, the half-life, residual effects, adverse events, they're all relevant here. So those are sort of drug-related factors. But then there's patient-related factors. So how old is the patient or do they have comorbidity? Do they have renal failure, what medications they are on, do they interact? And then there's the insomnia-related factors. Is it sleep-onset insomnia, is it sleep maintenance insomnia, how long is their insomnia, the timing of the medication? So these are all important factors.

Dr Benca: Yeah, I think those are great points. A couple of things. Again, cognitive behavioral therapy is not sleep hygiene. And I think a lot of people make the mistake of thinking that just giving patient sleep hygiene instructions is going to fix their insomnia. While it's really an important starting point, cognitive behavioral therapy really goes well beyond that. And now thinking about pharmacotherapy, tell us what our options are for older adults? Taking into account recommendations of the American Geriatric Society Beers Criteria related to hypnotics.

Dr Schwab: Yeah, there's a lot of issues related to hypnotics. Benzodiazepines in the elderly, there's increased sensitivity, decreased metabolism, so they're not great. I think most of the people who are listening to this already know that benzodiazepines increase your risk of cognitive impairment, delirium, fall risk, fractures, motor vehicle accidents. So benzodiazepine's not a great choice. Non-benzodiazepines also have similar issues related to benzodiazepines. Again, delirium, falls, fractures, increased emergency room visits, hospitalizations, motor vehicle accidents. So there's a lot of issues related to using those type of medications in the elderly for insomnia. And then there's the box warning with some of the medications, which include sleep walking, sleep driving, sleep texting, sleep cooking, things that are just odd that happen.

Dr Benca: And those aren't just in elderly people?

Dr Schwab: That's in everybody, yes, and many of those are patients who are on multiple medications. So typically, patients on just the hypnotic, you're not probably going to see that. But in patients who have underlying medical conditions or on multiple medications, you have to really worry about these complex sleep behaviors. And you need to ask about it. And then in terms of over the counter, which is really a concern because they're easy to get, there's no control. And typically, it's antihistamines and these are highly anticholinergic. There's reduced clearance with advanced age, there's tolerance, constipation, dry mouth. So we don't recommend that either. And the other issue, we don't like alcohol. Alcohol also disturbs sleep. It is a bad choice as well.

Dr Benca: Given all these problems with many of the popular over-the-counter and prescription agents, what treatments should we be considering in older adults?

Dr Schwab: Yeah, I think that's a great question. And I don't think we really have a great answer. But there are some that we can talk about. The first is melatonin receptor agonist, ramelteon. It addresses primarily sleep-onset insomnia. The typical dose is 8 mg 30 minutes before bedtime. It's a relatively safe medication. There's been a randomized, double-blind placebo-controlled trial in men and women over the age of 65. There was a relatively large number, 829 individuals with chronic insomnia. And it was placebo vs ramelteon, at 4 mg of ramelteon and 8 mg. And it was taken nightly for 5 weeks. The primary outcomes were sleep latency at week 1 and then a sustained efficacy examined at weeks 3 and 5. And so what did it show? Well, both doses of ramelteon produced statistically significant reductions in sleep latency vs placebo. There was a reduced sleep latency at week three with ramelteon at eight mg. And at week five with ramelteon at 4 and 8 mg. And there really weren't a lot of adverse events and they were pretty mild to moderate.

Dr Benca: So, a fairly safe drug, but really only for sleep-onset issues. So, what other options do we have?

Dr Schwab: Right. So, that was a safe drug and it is for sleep onset. So you can use doxepin, which is a histamine wake-promoting neurotransmitter. This is more used, this is used for sleep maintenance. Typically, a 3- to 6-mg dose is approved for insomnia. You have to be worried at higher doses for anticholinergic effects. Again, there was a randomized, double-blind, placebo-controlled trial. And patients were randomized at 12 weeks of either nightly treatment with anticholinergic at 1 mg or 3 mg or placebo. And the anticholinergic at 3 mg showed improvements compared to placebo in wake after sleep onset for N1 as the primary endpoint, total sleep time, overall sleep efficiency, sleep efficiency in the last quarter of the night, and sleep efficiency at hour 8. So it worked pretty well. The rates of discontinuation were low. Safety profiles were comparable across all 3 groups. And there weren't a lot of next day effects, which is really important.

Dr Benca: So doxepin, of course, is an antidepressant, but this is a teeny tiny dose and it's probably not going to do much for anybody's depression.

Dr Schwab: Correct. It's not going to affect your depression. It's a small dose. You shouldn't think about it as an antidepressant, but as a medication for insomnia.Ruth, can you discuss how the inhibition of orexin impacts sleep and the use of dual orexin receptor antagonists (DORAs) in older adults?

Dr Benca: Okay. Well, this is the newest class of drugs that have been approved for treating insomnia. And DORA stands for dual orexin receptor antagonist. Orexin is a neuropeptide that is actually important for maintaining wakefulness. And the disorder narcolepsy, in which patients are unable to remain awake, is caused by a deficiency of orexin. So orexin is what lets you stay awake. There's no clear evidence that orexin levels are higher in patients with insomnia. Although there are some reports that maybe it might be increased a bit in the brains of people with Alzheimer's disease. More data are still needed. But there is evidence that people who have insomnia are hyper-aroused. In other words, their wake systems don't get turned off, which interferes with their ability to sleep. So, we know that to fall asleep normally suppression of the wake-promoting system is really necessary for sleep onset and maintenance to occur. So the point of the DORA is, let's see if we can turn off the wake system and will that allow you to sleep?

Currently, there are 3 DORAs that have been approved in the US for treating insomnia. And those are suvorexant, Lemborexant, and the most recent is daridorexant. As you can see, they have a fairly longer half-life, which is why they're effective both for onset and maintenance of sleep.

So, Richard, can you tell us a little bit about some of the data from studies of suvorexant and lemborexant, particularly in older adults or those who have cognitive impairment?

Dr Schwab: So, they had been used in patients with cognitive impairment and older adults. And the first study was on suvorexant. And it was a subgroup analysis of a pooled 3 months of data from 2 randomized, double-blind, placebo-controlled, parallel-group studies. And the participants were elderly and they used suvorexant at 30 mg or 15 mg compared to placebo. And the findings were that the 30-mg dose of suvorexant improved sleep onset and maintenance and total sleep time throughout 3 months per self-report. And on the PSG at least in terms of stage 1 sleep. The 15-mg dosage improved sleep maintenance and total sleep time throughout the 3 months. And the sleep-onset effect was not significant after week 1. So, were there any adverse effects? Well, they weren't different between placebo in terms of next day somnolence at the 30-mg dose. There were some rare episodes of sleep paralysis, hypnotic hallucinations, which are findings in narcotic-like narcoleptics on the 30-mg dose, but not on the lower dose. And there was no report of cataplexy.

Dr Benca: And that's just a reminder that these are drugs that should not be used in people with narcolepsy.

Dr Schwab: Correct.

Dr Benca: Even though they may have sleep problems.

Dr Schwab: So, lemborexant, in terms of that data, there was a double-blind, placebo-controlled study of over 1,000 patients over the age of 55 years. And they either got 5 or 10 mg of lemborexant compared to placebo. And they also compared it to zolpidem at 6.25 mg. And so the patients with insomnia were characterized by sleep maintenance problems, confirmed by history, sleep diary, and PSG. And both lemborexant doses, compared to zolpidem, significantly reduced sleep latency and improved sleep efficiency at 1 month compared to sleep diary and PSG data. And there was a reduction in wake after sleep onset during the second half of the night. And that was better, it was greater, that reduction was greater for both doses of lemborexant compared to zolpidem.

They also looked at 5 to 10 mg in terms of postural stability. And so this is important because there are issues about falling. And we've talked about that. And so not only about cognitive performance, but also postural stability. And what they looked at 4 hours post dose, is body sway, which is synonymous for potential fall risk, and it was much lower with lemborexant than it was with zolpidem. And also, there was improvement in memory and attention compared to placebo in the morning for any of the treatments.

So, daridorexant was recently approved, as you're aware. Can you tell us how that can be used in the elderly?

Dr Benca: Yeah. So this is the newest entry. So a post-hoc analysis in an older adult subpopulation, in a phase 3 study of almost 400 patients that had a mean age of 70 years and were over 65 years, looked at the effects of 25 mg and 50 mg of daridorexant vs placebo. With the primary endpoints being the minutes awake after sleep onset and latency to persistent sleep. And a secondary endpoint was subjective total sleep time. The other thing that was done in this study, which I think is very important, is that they used a validated questionnaire to assess daytime function. So it's not just how much better did people sleep at night, but how were they functioning during the daytime as a result of the treatment. So this was the insomnia daytime symptoms and impacts questionnaire (IDSIQ). And what they found first of all, was that both doses of daridorexant improved or decreased the number of minutes awake after sleep onset, decreased the latency to persistent sleep, and increased subjective total sleep time in a dose-dependent manner. So better with 50 mg than with 25 mg. And they also improved daytime functioning.

The treatment-emergent side effects or adverse effects were pretty comparable across the treatment groups. The adverse events of special interest, there were 2 participants that reported probably a side effect that was directly due to daridorexant. One was somnolence, but that was mild, and another patient with mild sleep paralysis. Again, that can be a side effect of a DORA. What was very interesting though, was that falls were less frequent in the daridorexant groups than in the placebo group. Again, getting at that issue is that the insomnia or the sleeping medication that causes the fall. And not surprisingly, fatigue was a bit more frequent in the treatment groups than the placebo group.

They also did a run out study of patients who completed a 12-week double-blind treatment and carried them out for a year. And found that improvements in sleep and daytime functioning observed at 3 months were maintained for total sleep time. And the IDSIQ domain scores through month 12. And again, with a low incidence of serious treatment-emergent adverse effects and no evidence of withdrawal symptoms or rebound when treatment was discontinued.

So to conclude, I think what we've tried to get across today is how important it is to assess sleep issues in older adults, as sleep disturbance is a risk factor for poor health outcomes and treatment can at least improve quality of life of patients and potentially, their caregivers. How should we be treating these patients, Richard, in a nutshell, what are our clinical pearls today?

Dr Schwab: Yeah, I think as we discussed, you want to start with cognitive behavioral therapy as a first choice. And if that doesn't work, I think the 3 other choices would be ramelteon, doxepin, or a DORA.

Dr Benca: Richard, thank you for this great discussion.

Dr Schwab: Thanks Ruth.

Dr Benca: And thank you for participating in this activity. Please continue on to answer the questions that follow and complete the evaluation.

This transcript has been edited for style and clarity.

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