expert roundtables

Balancing the Benefits of Improved Sleep Against the Side Effects of Treatment

by Ravi Allada, MD; Stephen M. Stahl, MD, PhD, DSc (Hon); and John W. Winkelman, MD, PhD

Overview

Patients with chronic insomnia often report feelings of fatigue, difficulty concentrating, and mood and anxiety effects, all of which may impact their level of function during the day. Currently available sleep medications are all linked to at least some next-day effects; however, treating the insomnia can improve the aforementioned functional deficits.

Q:

In the medical treatment of insomnia, how are the benefits of improved sleep balanced against the potential for side effects, such as morning sedation?

John W. Winkelman, MD, PhD

Professor of Psychiatry
Chief, Sleep Disorders Clinical Research Program
Department of Psychiatry
Massachusetts General Hospital
Harvard Medical School
Boston, MA

“We now have newer medications that seem to have lower risk profiles in the areas causing the most concern. Still, all currently available sleep medications are linked to at least some daytime side effects.”

John W. Winkelman, MD, PhD

The most prominent short-term consequences of insomnia include feelings of fatigue, difficulties with concentration, and mood and anxiety effects. However, when we perform actual cognitive testing on our patients with insomnia, it is difficult to document changes in cognitive function. It is possible that they will get through the test, but it simply may require more effort on their part. Improving sleep, whether it be through cognitive behavioral therapy for insomnia, medication, or both, can improve almost all of the deficits that have been documented by self-report in patients with insomnia, including fatigue, concentration, mood and anxiety effects, and potentially some of the longer-term sequelae (ie, mood disorders), in which the trajectory may change.

When we use medications for insomnia, we always try to balance the risks and benefits. Unfortunately, many clinicians feel that the risks of using sleep medications are not worth the benefits of treatment; however, I think that we need to recognize that insomnia has significant consequences for the individual. In some instances, the risks of sleep medication may be exaggerated. We now have newer medications that seem to have lower risk profiles in the areas causing the most concern. Still, all currently available sleep medications are linked to at least some daytime side effects, and the risks and benefits of any particular medication should be carefully considered.

Stephen M. Stahl, MD, PhD, DSc (Hon)

Professor of Psychiatry
University of California, Riverside
University of California, San Diego
Honorary Fellow, University of Cambridge
Senior Academic Advisor, California Department of State Hospitals
Sacramento, CA

“When trying to identify which scenario is worse—a poor night’s sleep or some degree of morning sedation—it is likely best to think in terms of the patient’s function.”

Stephen M. Stahl, MD, PhD, DSc (Hon)

There is still considerable debate regarding insomnia. Is it a comorbidity? Is it a symptom? Is it a disorder by itself? There are arguments to be made on all sides. It has long been recognized that a significant mismatch exists between the neurophysiology of sleep and the subjective reports of insomnia among patients. It is remarkable that many people with chronic insomnia can still function effectively during the day, whereas most individuals who lose 1 night of sleep (eg, due to an acute event or worry) are very tired the next day. And part of the backlash against insomnia medication, in my view, is a concern that, in the absence of functional problems, people are being overmedicated.

Therefore, when trying to identify which scenario is worse—a poor night’s sleep or some degree of morning sedation—it is likely best to think in terms of the patient’s function. The reality is that if you really do have a sleep abnormality, it can cause functional problems in cognition and daytime alertness. So, there is a need to assess not only the patient’s subjective experience but also the abnormal functional consequences that might be experienced by the patient during the day.

That is not to say that subjective reports can or should be discounted; for instance, many members of the military with posttraumatic stress disorder report the inability to get high-quality sleep. Many of us in psychiatry consider sleep a vital sign. Sleep is one of the barometers that can indicate whether an underlying psychiatric disorder is being treated effectively. However, the best approach to the treatment of the sleep disorder in this population is to treat the psychiatric disorder and have the sleep improve secondarily. Clinicians in psychiatry often use different medications and different doses of medications than are used to treat primary insomnia.

Ravi Allada, MD

Edward C. Stuntz Distinguished Professor of Neuroscience
Chair, Department of Neurobiology
Northwestern University
Evanston, IL

“The links between the basic neurophysiology of sleep/insomnia and functional consequences are still not fully understood, and so, the question of how to best approach the treatment of sleep disorders remains an open one.”

Ravi Allada, MD

Insomnia, particularly chronic insomnia, can have many adverse consequences due to inadequate or poor-quality sleep. These may include disrupted cognitive function, learning ability, and memory; in addition, chronic insomnia has been implicated in the risk of psychiatric and neurodegenerative disorders as well. Yet, as noted by both Dr Winkelman and Dr Stahl, a significant issue that impacts the treatment of insomnia is the potential mismatch between subjective and objective measurements of the disorder: How much of the basic neurophysiology of sleep and insomnia links to the functional consequences? These links are still not fully understood, and so, the question of how to best approach the treatment of sleep disorders remains an open one. The goal is to address the primary sleep issue, but it is also important to be cognizant of the fact that many of the sleep medications either have long half-lives or can vary in their metabolisms between individuals, leading to persistent effects on certain next-day functioning. Those are the major issues that need to be balanced, particularly for pharmacologic treatment.

References

Colvonen PJ, Ellison J, Haller M, Norman SB. Examining insomnia and PTSD over time in veterans in residential treatment for substance use disorders and PTSD. Behav Sleep Med. 2019;17(4):524-535. doi:10.1080/15402002.2018.1425869

Dinges DF, Basner M, Ecker AJ, Baskin P, Johnston SL. Effects of zolpidem and zaleplon on cognitive performance after emergent morning awakenings at Tmax: a randomized placebo-controlled trial. Sleep. 2019;42(3):zsy258. doi:10.1093/sleep/zsy258

Drake CL, Durrence H, Cheng P, et al. Arousability and fall risk during forced awakenings from nocturnal sleep among healthy males following administration of zolpidem 10 mg and doxepin 6 mg: a randomized, placebo-controlled, four-way crossover trial. Sleep. 2017;40(7). doi:10.1093/sleep/zsx086

Kärppä M, Yardley J, Pinner K, et al. Long-term efficacy and tolerability of lemborexant compared with placebo in adults with insomnia disorder: results from the phase 3 randomized clinical trial SUNRISE 2. Sleep2020;43(9):zsaa123. doi:10.1093/sleep/zsaa123

Kim H, Kim Y, Myung W, et al. Risks of suicide attempts after prescription of zolpidem in people with depression: a nationwide population study in South Korea. Sleep. 2020;43(3):zsz235. doi:10.1093/sleep/zsz235

McCall WV, Benca RM, Rosenquist PB, et al. Reducing suicidal ideation through insomnia treatment (REST-IT): a randomized clinical trial. Am J Psychiatry. 2019;176(11):957-965. doi:10.1176/appi.ajp.2019.19030267

Rezaie L, Fobian AD, McCall WV, Khazaie H. Paradoxical insomnia and subjective-objective sleep discrepancy: a review. Sleep Med Rev. 2018;40:196-202. doi:10.1016/j.smrv.2018.01.002

Trauer JM, Qian MY, Doyle JS, Rajaratnam SMW, Cunnington D. Cognitive behavioral therapy for chronic insomnia: a systematic review and meta-analysis. Ann Intern Med2015;163(3):191-204. doi:10.7326/M14-2841

Vermeeren A, Jongen S, Murphy P, et al. On-the-road driving performance the morning after bedtime administration of lemborexant in healthy adult and elderly volunteers. Sleep. 2019;42(4):zsy260. doi:10.1093/sleep/zsy260

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