More on insomnia…

In Medication, Neuropsychology, Psychiatry on Thursday, 20 September 2012 at 06:30

Expert Interview – Emerging Concepts and Therapies in Insomnia: An Expert Interview With Daniel Buysse, MD

Daniel J. Buysse, MD, 2006


Editor’s Note:

Marni Kelman, MSc, Medscape Neurology & Neurosurgery Editorial Director, discussed emerging concepts and therapies in insomnia with Daniel Buysse, MD, Professor of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Insomnia in older adults, comorbid insomnia, new treatments on the horizon for insomnia, and new endpoints for therapeutic effectiveness of insomnia treatments were discussed.

Medscape: This issue of Current Perspectives in Insomnia includes a column on sleep disorders in older adults, with a focus on insomnia. What would you say is the impact of insomnia in older patients?

Dr. Buysse: The impact of insomnia in general is pretty wide-ranging, and some of those impairments are even greater in older people. Insomnia can have negative effects on a person’s mood the next day, on their concentration, on their energy level, or can cause fatigue or even sleepiness. Since older adults might experience these things for other reasons, insomnia tends to make them even worse.

Medscape: Are there any particular things that you take into consideration when you diagnose insomnia in an older patient?

Dr. Buysse: Because older adults will so commonly have medical or psychiatric comorbidity, it’s very important to look for those things. Older adults can have medical conditions that can cause pain, difficulty breathing, or impaired mobility, and all of those things can worsen insomnia. Older adults are also at risk for depression, which is the most common comorbid condition seen with insomnia. In addition, older adults are typically the ones who are taking the most medications, and because many medications can have effects on sleep, including insomnia, it’s very important to assess the effects of medications as well.

There are also a number of behavioral factors that can contribute to insomnia — things like going to bed early or spending too much time in bed — and those things, too, affect older adults disproportionately, since in older adults, limitations in daytime activities may leave them with fewer alternatives to going to bed. So, from both a medical perspective and a behavioral perspective, older adults are at risk.

There are a couple of sleep disorders that are more common in older adults that may be associated with insomnia symptoms, and those include restless legs syndrome and periodic limb movement disorder. There is almost certainly an increase in periodic limb movements with age, and again, this can lead to, or be associated with insomnia complaints. Older adults also have an increased incidence of sleep apnea, and compared to younger adults, sleep apnea may less commonly be associated with obesity, and less commonly associated with daytime sleepiness as the primary presenting complaint. The combination of sleep apnea with insomnia seems to be something that is disproportionately common in older adults.

The final sleep disorder that is common in older patients and that can cause insomnia is advanced sleep-phase syndrome. An individual with this syndrome feels very sleepy and goes to sleep early in the evening but then has insomnia characterized by early-morning awakening and an inability to return to sleep. This condition may be related to certain circadian changes that accompany aging.

Medscape: What special considerations do you take into account when you treat older patients with insomnia?

Dr. Buysse: With regard to medications, one needs to proceed a bit more cautiously for 2 reasons. First, older adults may have changes in drug-metabolizing enzymes, so they may metabolize drugs more slowly, or store drugs disproportionately longer because of an increase in the relative amount of body fat. This means that the same drug may have a longer than expected action in older adults. Second, older adults are typically on multiple medications, and some may have additive effects with some of the medications that we give for sleep.

With regard to behavioral treatments, I think the main thing to keep in mind is that older adults can and do benefit from those kinds of treatments as well. So the main message there is to not assume that older adults can’t learn these techniques; they can, and several studies have shown that they can be very effective.

Medscape: Are there particular types of medications that you use in the elderly and/or avoid?

Dr. Buysse: Generally, the approved hypnotic medications are appropriate for older adults, but you do need to be cautious, so it’s often wise to begin with a lower dose than you would use in younger and middle-aged adults. Because of the sensitivity that older people may have to the cognitive side effects of hypnotic drugs, in general, you would want to use a short-acting drug whenever possible to avoid the daytime cognitive and sedative consequences of hypnotic medications. The new hypnotic medication, ramelteon, may be particularly useful in older adults because it has very, very few — actually no — demonstrated cognitive side effects. So that may be a useful drug. The question there is whether it’s actually long enough acting to help with some of the sleep-maintenance problems that older adults might have.

Sedating antidepressants are pretty commonly used, as are antihistamines for the treatment of insomnia. Antihistaminic drugs should be approached with particular caution in the elderly because they often have anticholinergic effects that can worsen cognition and even lead to adverse consequences, such as delirium and urinary retention. One also needs to be careful when using sedating antidepressants in older adults.

Medscape: Another topic that we have discussed in this newsletter is insomnia associated with psychiatric and medical disorders. Are there particular considerations that you take into account when diagnosing those types of patients as well as treating them?

Dr. Buysse: The previous assumption was that if insomnia is associated with another condition, one would be best off just treating that other condition, and then the insomnia should get better. While there is clearly some evidence that treating comorbid conditions does lead to some improvement in insomnia, in many individuals insomnia may persist, even when the other disorder is adequately or optimally treated. In those cases, it may be useful to think of insomnia as a comorbid condition rather than as, strictly speaking, a symptom of that other disorder. If you think of insomnia as a comorbid condition, then in many cases it’s appropriate to direct treatment at the insomnia itself.

There is certainly emerging evidence that treating insomnia specifically does lead to improvement in sleep among patients with either medical conditions or psychiatric conditions. However, there is also a small, but growing, body of evidence that treating insomnia may actually lead to better outcomes of the comorbid medical or psychiatric condition itself.

Medscape: I would also like to ask for your feedback on emerging treatments for insomnia. Are there particular new therapeutic targets for therapy that you think are most promising?

Dr. Buysse: There are a lot of different therapeutic targets that are being examined, and I think the first general thing to say is that this is great because it’s unlikely that insomnia in all people results from the same problem. Therefore, having different ways to impact sleep just makes sense. The other point is that the regulation of sleep itself is very complex and involves multiple neurotransmitter systems. So again, having drugs that target different neurotransmitter systems just makes good sense.

Having said that, there are new agents under investigation that affect the GABA-benzodiazepine receptors and have modified-release preparations so that you can combine a reasonably long duration of action with a short half-life. That means that there is the possibility of providing adequate coverage of insomnia for the entire night, but rapid metabolism of the medication occurs toward the end of the night so that there are fewer daytime consequences.

That’s one strategy. Another strategy is to look at GABA reuptake or extrasynaptic GABA receptors. Other neurotransmitter systems are also being investigated, including serotonin 5HT2A receptors. Antagonists at that receptor have different effects on sleep, so that will be interesting to investigate. Different companies are looking into medications that interact with hypocretin or orexin receptors. That, too, promises, I think, to be a pretty exciting development.

Medscape: There has been some discussion about using new therapeutic endpoints for insomnia, for example, alertness, decreased depression, or decreased daytime napping. How do you feel about this, and what do you think are the most promising new endpoints that should be considered when looking at therapeutic effectiveness?

Dr. Buysse: I think that this is a very important area because patients with insomnia complain not only because their nighttime sleep is disturbed, but because that disturbance is associated with daytime consequences. Therefore, I think that the most interesting areas to look at are those that assess the daytime complaints presented by people with insomnia. One area is the routine assessment of mood symptoms and problems. We’ve been working on some data that show that it may be important not only to assess the person’s mood, but to evaluate how mood changes during the course of the day. So, looking at time-of-day effects may be very important. The second area to assess is fatigue, which is so commonly reported by people with insomnia and can be reliably measured with a number of rating scales. That should certainly be a focus of increased attention.

An area that has been somewhat perplexing, but very important, is the measurement of cognitive difficulties in people with insomnia. There have not been a lot of positive studies in this regard, so despite the fact that people complain of difficulty concentrating or problems with alertness, actually demonstrating impairments has generally not met with success. This may be due to the fact that the tools we have used have been of the wrong type or are not sensitive enough. So, I think trying to identify and develop tests that objectively measure daytime performance as related to the insomnia complaints would be very beneficial as well.

Medscape: What would you consider to be the biggest challenges in insomnia today?

Dr. Buysse: For behavioral and psychological treatments, the big challenge is making those treatments more widely available. We have several techniques that have demonstrated efficacy, but trying to really position them in the community so they have a wide impact is the challenge.

For medications, one of the biggest challenges is developing strategies for longer-term management of insomnia. We know that insomnia tends to be a chronic or recurring condition, and there is still uncertainty about the optimal way to manage chronic insomnia with medications.

The more general thing that I would say pertains to both behavioral and pharmacologic treatment: We really are in very substantial need of empirically supported treatment guidelines or treatment algorithms. We know that we have several efficacious treatments, but we don’t know how best to sequence them, how to target them to specific patients, and how to change from one to the other when the first treatment does not meet with success.


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