Sleep Medicine

People who frequently alter the amount of sleep and time they go to bed each night are twofold more likely to develop cardiovascular disease, independent of traditional CVD risk factors, new research suggests.

Prior studies have focused on shift workers because night shift work will influence circadian rhythm and increase CVD risk. But it is increasingly recognized that circadian disruption may occur outside of shift work and accumulate over time, particularly given modern lifestyle factors such as increased use of mobile devices and television at night, said study coauthor Tianyi Huang, ScD, MSc, of Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts.

“Even if they tend to go to sleep at certain times, by following that lifestyle or behavior, it can interfere with their planned sleep timing,” he said.

“One thing that surprised me in this sample is that about one third of participants have irregular sleep patterns that can put them at increased risk of cardiovascular disease. So I think the prevalence is higher than expected,” Huang added.

As reported today in the Journal of the American College of Cardiology, the investigators used data from 7-day wrist actigraphy, 1 night of at-home polysomnography, and sleep questionnaires to assess sleep duration and sleep-onset timing among 1,992 Multi-Ethnic Study of Atherosclerosis () participants, aged 45 to 84 years, who were free of CVD and prospectively followed for a me MESA dian of 4.9 years.

A total of 786 patients (39.5%) had sleep duration standard deviation (SD) > 90 minutes and 510 (25.6%) had sleep-onset timing SD > 90 minutes.

During follow-up, there were 111 incident CVD events, including myocardial infarction, coronary heart disease death, stroke, and other coronary events.

Compared with people who had less than 1 hour of variation in sleep duration, the risk for incident CVD was 9% higher for people whose sleep duration varied 61 to 90 minutes (hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.62 - 1.92), even after controlling for a variety of cardiovascular and sleep-related risk factors such as body mass index, systolic blood pressure, smoking status, total cholesterol, average sleep duration, insomnia symptoms, and sleep apnea.

Moreover, the adjusted CVD risk was substantially increased with 91 to 120 minutes of variation (HR, 1.59; 95% CI, 0.91 - 2.76) and more than 120 minutes of variation in sleep duration (HR, 2.14; 95% CI, 1.24 - 3.68).

Every 1-hour increase in sleep duration SD was associated with 36% higher CVD risk (95% CI; 1.07 - 1.73).

Compared with people with no more than a half hour of variation in nightly bedtimes, the adjusted hazard ratios for CVD were 1.16 (95% CI, 0.64 - 2.13), 1.52 (95% CI, 0.81 - 2.88), and 2.11 (95% CI, 1.13 - 3.91) when bedtimes varied by 31 to 60 minutes, 61 to 90 minutes, and more than 90 minutes.

For every 1-hour increase in sleep-onset timing SD, the risk of CVD was 18% higher (95% CI; 1.06 - 1.31).

“The results are similar for the regularity of sleep timing and the regularity of sleep duration, which means that both can contribute to circadian disruption and then lead to development of cardiovascular disease,” Huang said.

This is an important article and signals how sleep is an important marker and possibly a mediator of cardiovascular risk, said Harlan Krumholz, MD, of Yale School of Medicine in New Haven, Connecticut, who was not involved with the study.

“What I like about this is it’s a nice longitudinal, epidemiologic study with not just self-report, but sensor-detected sleep, that has been correlated with well-curated and adjudicated outcomes to give us a strong sense of this association,” he told theheart.org/Medscape Cardiology. “And also, that it goes beyond just the duration — they combine the duration and timing in order to give a fuller picture of sleep.”

Nevertheless, Krumholz said researchers are only at the beginning of being able to quantify the various dimensions of sleep and the degree to which sleep is a reflection of underlying physiologic issues, or whether patients are having erratic sleep patterns that are having a toxic effect on their overall health.

Questions also remain about the mechanism behind the association, whether the increased risk is universal or more harmful for some people, and the best way to measure factors during sleep that can most comprehensively and precisely predict risk.

“As we get more information flowing in from sensors, I think we will begin to develop more sophisticated approaches toward understanding risk, and it will be accompanied by other studies that will help us understand whether, again, this is a reflection of other processes that we should be paying attention to or whether it is a cause of disease and risk,” Krumholz said.

Subgroup analyses suggested positive associations between irregular sleep and CVD in African Americans, Hispanics, and Chinese Americans but not in whites. This could be because sleep irregularity, both timing and duration, was substantially higher in minorities, especially African Americans, but may also be as a result of chance because the study sample is relatively small, Huang explained.

The authors note that the overall findings are biologically plausible because of their previous work linking sleep irregularity with metabolic risk factors that predispose to atherosclerosis, such as obesity, diabetes, and hypertension. Participants with irregular sleep tended to have worse baseline cardiometabolic profiles, but this only explained a small portion of the associations between sleep irregularity and CVD, they note.

Other possible explanations include circadian clock genes, such as clock, per2 and bmal1, which have been shown experimentally to control a broad range of cardiovascular functions, from blood pressure and endothelial functions to vascular thrombosis and cardiac remodeling.

Irregular sleep may also influence the rhythms of the autonomic nervous system, and behavioral rhythms with regard to timing and/or amount of eating or exercise.

Further research is needed to understand the mechanisms driving the associations, the impact of sleep irregularity on individual CVD outcomes, and to determine whether a 7-day SD of more than 90 minutes for either sleep duration or sleep-onset timing can be used clinically as a threshold target for promoting cardiometabolically healthy sleep, Huang said.

“When providers communicate with their patients regarding strategies for CVD prevention, usually they focus on healthy diet and physical activity; and even when they talk about sleep, they talk about whether they have good sleep quality or sufficient sleep,” he said. “But one thing they should provide is advice regarding sleep regularity and [they should] recommend their patients follow a regular sleep pattern for the purpose of cardiovascular prevention.”

In a related editorial, Olaf Oldenburg, MD, Luderus-Kliniken Münster, Clemenshospital, Münster, Germany, and Jens Spiesshoefer, MD, Institute of Life Sciences, Scuola Superiore Sant’Anna, Pisa, Italy, write that the observed independent association between sleep irregularity and CVD “is a particularly striking finding given that impaired circadian rhythm is likely to be much more prevalent than the extreme example of shift work.”

They call on researchers to utilize big data to facilitate understanding of the association and say it is essential to test whether experimental data support the hypothesis that altered circadian rhythms would translate into unfavorable changes in 24-hour sympathovagal and neurohormonal balance, and ultimately CVD.

The present study “will, and should, stimulate much needed additional research on the association between sleep and CVD that may offer novel approaches to help improve the prognosis and daily symptom burden of patients with CVD, and might make sleep itself a therapeutic target in CVD,” the editorialists conclude.

This research was supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI), and by grants from the National Center for Advancing Translational Sciences. The MESA Sleep Study was supported by an NHLBI grant. Huang was supported by a career development grant from the National Institutes of Health.

Krumholz and Oldenburg have disclosed no relevant financial relationships. Spiesshoefer is supported by grants from the Else-Kröner-Fresenius Stiftung, the Innovative Medical Research program at the University of Münster, and Deutsche Herzstiftung; and by young investigator research support from Scuola Superiore Sant’Anna Pisa. He also has received travel grants and lecture honoraria from Boehringer Ingelheim and Chiesi.
 

Source: J Am Coll Cardiol. 2020 Mar 2. doi: 10.1016/j.jacc.2019.12.054.

This article first appeared on Medscape.com.

People who frequently alter the amount of sleep and time they go to bed each night are twofold more likely to develop cardiovascular disease, independent of traditional CVD risk factors, new research suggests.

Prior studies have focused on shift workers because night shift work will influence circadian rhythm and increase CVD risk. But it is increasingly recognized that circadian disruption may occur outside of shift work and accumulate over time, particularly given modern lifestyle factors such as increased use of mobile devices and television at night, said study coauthor Tianyi Huang, ScD, MSc, of Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts.

“Even if they tend to go to sleep at certain times, by following that lifestyle or behavior, it can interfere with their planned sleep timing,” he said.

“One thing that surprised me in this sample is that about one third of participants have irregular sleep patterns that can put them at increased risk of cardiovascular disease. So I think the prevalence is higher than expected,” Huang added.

As reported today in the Journal of the American College of Cardiology, the investigators used data from 7-day wrist actigraphy, 1 night of at-home polysomnography, and sleep questionnaires to assess sleep duration and sleep-onset timing among 1,992 Multi-Ethnic Study of Atherosclerosis () participants, aged 45 to 84 years, who were free of CVD and prospectively followed for a me MESA dian of 4.9 years.

A total of 786 patients (39.5%) had sleep duration standard deviation (SD) > 90 minutes and 510 (25.6%) had sleep-onset timing SD > 90 minutes.

During follow-up, there were 111 incident CVD events, including myocardial infarction, coronary heart disease death, stroke, and other coronary events.

Compared with people who had less than 1 hour of variation in sleep duration, the risk for incident CVD was 9% higher for people whose sleep duration varied 61 to 90 minutes (hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.62 - 1.92), even after controlling for a variety of cardiovascular and sleep-related risk factors such as body mass index, systolic blood pressure, smoking status, total cholesterol, average sleep duration, insomnia symptoms, and sleep apnea.

Moreover, the adjusted CVD risk was substantially increased with 91 to 120 minutes of variation (HR, 1.59; 95% CI, 0.91 - 2.76) and more than 120 minutes of variation in sleep duration (HR, 2.14; 95% CI, 1.24 - 3.68).

Every 1-hour increase in sleep duration SD was associated with 36% higher CVD risk (95% CI; 1.07 - 1.73).

Compared with people with no more than a half hour of variation in nightly bedtimes, the adjusted hazard ratios for CVD were 1.16 (95% CI, 0.64 - 2.13), 1.52 (95% CI, 0.81 - 2.88), and 2.11 (95% CI, 1.13 - 3.91) when bedtimes varied by 31 to 60 minutes, 61 to 90 minutes, and more than 90 minutes.

For every 1-hour increase in sleep-onset timing SD, the risk of CVD was 18% higher (95% CI; 1.06 - 1.31).

“The results are similar for the regularity of sleep timing and the regularity of sleep duration, which means that both can contribute to circadian disruption and then lead to development of cardiovascular disease,” Huang said.

This is an important article and signals how sleep is an important marker and possibly a mediator of cardiovascular risk, said Harlan Krumholz, MD, of Yale School of Medicine in New Haven, Connecticut, who was not involved with the study.

“What I like about this is it’s a nice longitudinal, epidemiologic study with not just self-report, but sensor-detected sleep, that has been correlated with well-curated and adjudicated outcomes to give us a strong sense of this association,” he told theheart.org/Medscape Cardiology. “And also, that it goes beyond just the duration — they combine the duration and timing in order to give a fuller picture of sleep.”

Nevertheless, Krumholz said researchers are only at the beginning of being able to quantify the various dimensions of sleep and the degree to which sleep is a reflection of underlying physiologic issues, or whether patients are having erratic sleep patterns that are having a toxic effect on their overall health.

Questions also remain about the mechanism behind the association, whether the increased risk is universal or more harmful for some people, and the best way to measure factors during sleep that can most comprehensively and precisely predict risk.

“As we get more information flowing in from sensors, I think we will begin to develop more sophisticated approaches toward understanding risk, and it will be accompanied by other studies that will help us understand whether, again, this is a reflection of other processes that we should be paying attention to or whether it is a cause of disease and risk,” Krumholz said.

Subgroup analyses suggested positive associations between irregular sleep and CVD in African Americans, Hispanics, and Chinese Americans but not in whites. This could be because sleep irregularity, both timing and duration, was substantially higher in minorities, especially African Americans, but may also be as a result of chance because the study sample is relatively small, Huang explained.

The authors note that the overall findings are biologically plausible because of their previous work linking sleep irregularity with metabolic risk factors that predispose to atherosclerosis, such as obesity, diabetes, and hypertension. Participants with irregular sleep tended to have worse baseline cardiometabolic profiles, but this only explained a small portion of the associations between sleep irregularity and CVD, they note.

Other possible explanations include circadian clock genes, such as clock, per2 and bmal1, which have been shown experimentally to control a broad range of cardiovascular functions, from blood pressure and endothelial functions to vascular thrombosis and cardiac remodeling.

Irregular sleep may also influence the rhythms of the autonomic nervous system, and behavioral rhythms with regard to timing and/or amount of eating or exercise.

Further research is needed to understand the mechanisms driving the associations, the impact of sleep irregularity on individual CVD outcomes, and to determine whether a 7-day SD of more than 90 minutes for either sleep duration or sleep-onset timing can be used clinically as a threshold target for promoting cardiometabolically healthy sleep, Huang said.

“When providers communicate with their patients regarding strategies for CVD prevention, usually they focus on healthy diet and physical activity; and even when they talk about sleep, they talk about whether they have good sleep quality or sufficient sleep,” he said. “But one thing they should provide is advice regarding sleep regularity and [they should] recommend their patients follow a regular sleep pattern for the purpose of cardiovascular prevention.”

In a related editorial, Olaf Oldenburg, MD, Luderus-Kliniken Münster, Clemenshospital, Münster, Germany, and Jens Spiesshoefer, MD, Institute of Life Sciences, Scuola Superiore Sant’Anna, Pisa, Italy, write that the observed independent association between sleep irregularity and CVD “is a particularly striking finding given that impaired circadian rhythm is likely to be much more prevalent than the extreme example of shift work.”

They call on researchers to utilize big data to facilitate understanding of the association and say it is essential to test whether experimental data support the hypothesis that altered circadian rhythms would translate into unfavorable changes in 24-hour sympathovagal and neurohormonal balance, and ultimately CVD.

The present study “will, and should, stimulate much needed additional research on the association between sleep and CVD that may offer novel approaches to help improve the prognosis and daily symptom burden of patients with CVD, and might make sleep itself a therapeutic target in CVD,” the editorialists conclude.

This research was supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI), and by grants from the National Center for Advancing Translational Sciences. The MESA Sleep Study was supported by an NHLBI grant. Huang was supported by a career development grant from the National Institutes of Health.

Krumholz and Oldenburg have disclosed no relevant financial relationships. Spiesshoefer is supported by grants from the Else-Kröner-Fresenius Stiftung, the Innovative Medical Research program at the University of Münster, and Deutsche Herzstiftung; and by young investigator research support from Scuola Superiore Sant’Anna Pisa. He also has received travel grants and lecture honoraria from Boehringer Ingelheim and Chiesi.
 

Source: J Am Coll Cardiol. 2020 Mar 2. doi: 10.1016/j.jacc.2019.12.054.

This article first appeared on Medscape.com.

People who frequently alter the amount of sleep and time they go to bed each night are twofold more likely to develop cardiovascular disease, independent of traditional CVD risk factors, new research suggests.

Prior studies have focused on shift workers because night shift work will influence circadian rhythm and increase CVD risk. But it is increasingly recognized that circadian disruption may occur outside of shift work and accumulate over time, particularly given modern lifestyle factors such as increased use of mobile devices and television at night, said study coauthor Tianyi Huang, ScD, MSc, of Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts.

“Even if they tend to go to sleep at certain times, by following that lifestyle or behavior, it can interfere with their planned sleep timing,” he said.

“One thing that surprised me in this sample is that about one third of participants have irregular sleep patterns that can put them at increased risk of cardiovascular disease. So I think the prevalence is higher than expected,” Huang added.

As reported today in the Journal of the American College of Cardiology, the investigators used data from 7-day wrist actigraphy, 1 night of at-home polysomnography, and sleep questionnaires to assess sleep duration and sleep-onset timing among 1,992 Multi-Ethnic Study of Atherosclerosis () participants, aged 45 to 84 years, who were free of CVD and prospectively followed for a me MESA dian of 4.9 years.

A total of 786 patients (39.5%) had sleep duration standard deviation (SD) > 90 minutes and 510 (25.6%) had sleep-onset timing SD > 90 minutes.

During follow-up, there were 111 incident CVD events, including myocardial infarction, coronary heart disease death, stroke, and other coronary events.

Compared with people who had less than 1 hour of variation in sleep duration, the risk for incident CVD was 9% higher for people whose sleep duration varied 61 to 90 minutes (hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.62 - 1.92), even after controlling for a variety of cardiovascular and sleep-related risk factors such as body mass index, systolic blood pressure, smoking status, total cholesterol, average sleep duration, insomnia symptoms, and sleep apnea.

Moreover, the adjusted CVD risk was substantially increased with 91 to 120 minutes of variation (HR, 1.59; 95% CI, 0.91 - 2.76) and more than 120 minutes of variation in sleep duration (HR, 2.14; 95% CI, 1.24 - 3.68).

Every 1-hour increase in sleep duration SD was associated with 36% higher CVD risk (95% CI; 1.07 - 1.73).

Compared with people with no more than a half hour of variation in nightly bedtimes, the adjusted hazard ratios for CVD were 1.16 (95% CI, 0.64 - 2.13), 1.52 (95% CI, 0.81 - 2.88), and 2.11 (95% CI, 1.13 - 3.91) when bedtimes varied by 31 to 60 minutes, 61 to 90 minutes, and more than 90 minutes.

For every 1-hour increase in sleep-onset timing SD, the risk of CVD was 18% higher (95% CI; 1.06 - 1.31).

“The results are similar for the regularity of sleep timing and the regularity of sleep duration, which means that both can contribute to circadian disruption and then lead to development of cardiovascular disease,” Huang said.

This is an important article and signals how sleep is an important marker and possibly a mediator of cardiovascular risk, said Harlan Krumholz, MD, of Yale School of Medicine in New Haven, Connecticut, who was not involved with the study.

“What I like about this is it’s a nice longitudinal, epidemiologic study with not just self-report, but sensor-detected sleep, that has been correlated with well-curated and adjudicated outcomes to give us a strong sense of this association,” he told theheart.org/Medscape Cardiology. “And also, that it goes beyond just the duration — they combine the duration and timing in order to give a fuller picture of sleep.”

Nevertheless, Krumholz said researchers are only at the beginning of being able to quantify the various dimensions of sleep and the degree to which sleep is a reflection of underlying physiologic issues, or whether patients are having erratic sleep patterns that are having a toxic effect on their overall health.

Questions also remain about the mechanism behind the association, whether the increased risk is universal or more harmful for some people, and the best way to measure factors during sleep that can most comprehensively and precisely predict risk.

“As we get more information flowing in from sensors, I think we will begin to develop more sophisticated approaches toward understanding risk, and it will be accompanied by other studies that will help us understand whether, again, this is a reflection of other processes that we should be paying attention to or whether it is a cause of disease and risk,” Krumholz said.

Subgroup analyses suggested positive associations between irregular sleep and CVD in African Americans, Hispanics, and Chinese Americans but not in whites. This could be because sleep irregularity, both timing and duration, was substantially higher in minorities, especially African Americans, but may also be as a result of chance because the study sample is relatively small, Huang explained.

The authors note that the overall findings are biologically plausible because of their previous work linking sleep irregularity with metabolic risk factors that predispose to atherosclerosis, such as obesity, diabetes, and hypertension. Participants with irregular sleep tended to have worse baseline cardiometabolic profiles, but this only explained a small portion of the associations between sleep irregularity and CVD, they note.

Other possible explanations include circadian clock genes, such as clock, per2 and bmal1, which have been shown experimentally to control a broad range of cardiovascular functions, from blood pressure and endothelial functions to vascular thrombosis and cardiac remodeling.

Irregular sleep may also influence the rhythms of the autonomic nervous system, and behavioral rhythms with regard to timing and/or amount of eating or exercise.

Further research is needed to understand the mechanisms driving the associations, the impact of sleep irregularity on individual CVD outcomes, and to determine whether a 7-day SD of more than 90 minutes for either sleep duration or sleep-onset timing can be used clinically as a threshold target for promoting cardiometabolically healthy sleep, Huang said.

“When providers communicate with their patients regarding strategies for CVD prevention, usually they focus on healthy diet and physical activity; and even when they talk about sleep, they talk about whether they have good sleep quality or sufficient sleep,” he said. “But one thing they should provide is advice regarding sleep regularity and [they should] recommend their patients follow a regular sleep pattern for the purpose of cardiovascular prevention.”

In a related editorial, Olaf Oldenburg, MD, Luderus-Kliniken Münster, Clemenshospital, Münster, Germany, and Jens Spiesshoefer, MD, Institute of Life Sciences, Scuola Superiore Sant’Anna, Pisa, Italy, write that the observed independent association between sleep irregularity and CVD “is a particularly striking finding given that impaired circadian rhythm is likely to be much more prevalent than the extreme example of shift work.”

They call on researchers to utilize big data to facilitate understanding of the association and say it is essential to test whether experimental data support the hypothesis that altered circadian rhythms would translate into unfavorable changes in 24-hour sympathovagal and neurohormonal balance, and ultimately CVD.

The present study “will, and should, stimulate much needed additional research on the association between sleep and CVD that may offer novel approaches to help improve the prognosis and daily symptom burden of patients with CVD, and might make sleep itself a therapeutic target in CVD,” the editorialists conclude.

This research was supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI), and by grants from the National Center for Advancing Translational Sciences. The MESA Sleep Study was supported by an NHLBI grant. Huang was supported by a career development grant from the National Institutes of Health.

Krumholz and Oldenburg have disclosed no relevant financial relationships. Spiesshoefer is supported by grants from the Else-Kröner-Fresenius Stiftung, the Innovative Medical Research program at the University of Münster, and Deutsche Herzstiftung; and by young investigator research support from Scuola Superiore Sant’Anna Pisa. He also has received travel grants and lecture honoraria from Boehringer Ingelheim and Chiesi.
 

Source: J Am Coll Cardiol. 2020 Mar 2. doi: 10.1016/j.jacc.2019.12.054.

This article first appeared on Medscape.com.

LAS VEGAS – Clinicians should spend 1 hour with patients who present with a chief complaint of insomnia, rather than rushing to a treatment after a 10- to 15-minute office visit, according to John W. Winkelman, MD, PhD.

Doug Brunk/MDedge News

“Why? Because sleep problems are usually multifactorial, involving psychiatric illness, sleep disorders, medical illness, medication, and poor sleep hygiene/stress,” he said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “There are usually many contributing problems, and sleep quality is only as strong as the weakest link. Maybe you don’t have an hour [to meet with new patients], but you need to give adequate time, otherwise you’re not going to do justice to the problem.”

During that first visit, Dr. Winkelman recommends establishing and prioritizing goals with the patient. “Ask, ‘what is it that bothers you most about your insomnia? Is it the time awake at night, your total sleep time, or how you feel during the day?’ Because we’re going to use different approaches based on that chief complaint of the insomnia,” said Dr. Winkelman, chief of the Massachusetts General Sleep Disorders Clinical Research Program in the department of psychiatry at Harvard Medical School, Boston. “Cognitive-behavioral therapy for insomnia [CBT-I], for instance, is very good at reducing time awake at night. It won’t increase total sleep time, but it reduces time awake at night dramatically.”

According to the DSM-5, insomnia disorder is marked by dissatisfaction with sleep quality or quantity associated with at least one of the following: difficulty initiating sleep, difficulty maintaining sleep, and early morning awakening. “Just getting up to pee five times a night is not insomnia,” he said. “Just taking an hour and a half to fall asleep at the beginning of the night is not insomnia. There has to be distress or dysfunction related to the sleep disturbance, for a minimum of three times per week for 3 months.”

Most sleep problems are transient, but 25%-30% last more than 1 year. The differential diagnosis for chronic insomnia includes primary psychiatric disorders, medications, substances, restless legs syndrome, sleep schedule disorders, and obstructive sleep apnea.

“In general, we do not order sleep studies in people with insomnia unless we suspect sleep apnea; it’s just a waste of time,” said Dr. Winkelman, who is also a professor of psychiatry at Harvard Medical School. Indications for polysomnography include loud snoring plus one of the following: daytime sleepiness, witnessed apneas, or refractory hypertension. Other indications include abnormal behaviors or movements during sleep, unexplained excessive daytime sleepiness, and refractory sleep complaints, especially repetitive brief awakenings.

Many common cognitive and behavioral issues can produce or worsen insomnia, including inconsistent bedtimes and wake times. “That irregular schedule wreaks havoc with sleep,” he said. “It messes up the circadian rhythm. Also, homeostatic drive needs to build up: We need to be awake 16 or more hours in order to be sleepy. If people are sleeping until noon on Sundays and then trying to go to bed at their usual time, 10 or 11 at night, they’ve only been awake 10 or 11 hours. That’s why they’re going to have problems falling asleep. Also, a lot of people doze off after dinner in front of the TV. That doesn’t help.”

Spending excessive time in bed can also trigger or worsen insomnia. Dr. Winkelman recommends that people restrict their access to bed to the number of hours it is reasonable to sleep. “I see a lot of people in their 70s and 80s spending 10 hours in bed,” he said. “It doesn’t sound that crazy, but there is no way they’re going to get 10 hours of sleep. It’s physically impossible, so they spend 2 or 3 hours awake at night.” Clock-watching is another no-no. “In the middle of the night you wake up, look at the clock, and say to yourself: ‘Oh my god, I’ve been awake for 3 hours. I have 4 hours left. I need 7 hours. That means I need to go to sleep now!’ ”

An estimated 30%-40% of people with chronic insomnia have a psychiatric disorder. That means “you have to be thorough in your evaluation and act as if you’re doing a structured interview,” Dr. Winkelman said. “Ask about obsessive-compulsive disorder, generalized anxiety disorder, PTSD, et cetera, so that you understand the complete myriad of psychiatric illnesses, because psychiatric illnesses run in gangs. Comorbidity is generally the rule.”

The first-line treatment for chronic insomnia disorder is CBT-I, a multicomponent approach that includes time-in-bed restriction, stimulus control, cognitive therapy, relaxation therapy, and sleep hygiene. According to Dr. Winkelman, the cornerstone of CBT-I is time-in-bed restriction. “Many people with insomnia are spending 8.5 hours in bed to get 6.5 hours of sleep,” he said. “What you do is restrict access to bed to 6.5 hours; you initially sleep deprive them. Over the first few weeks, they hate you. After a few weeks when they start sleeping well, you start gradually increasing time in bed, but they rarely get back to the 8.5 hours in bed they were spending beforehand.”

Online CBT-I programs such as Sleepio can also be effective for improving sleep latency and wake after sleep onset, but not for total sleep time (JAMA Psychiatry. 2017;74[1]:68-75). “Not everybody responds to CBT; 50% don’t respond at a couple of months,” he said. “These are the people you need to think about medication for.”

Medications commonly used for chronic insomnia include benzodiazepine receptor agonists (BzRAs) – temazepam, eszopiclone, triazolam, zolpidem, and zaleplon are Food and Drug Administration approved – melatonin agonists, orexin antagonists, sedating antidepressants, anticonvulsants, and dopaminergic antagonists. “Each of the agents in these categories has somewhat similar mechanisms of action, and similar efficacy and contraindications,” Dr. Winkelman said. “The best way to divide the benzodiazepine receptor agonists is based on half-life. How long do you want drug on receptor in somebody with insomnia? Probably not much longer than 8 hours. Nevertheless, some psychiatrists love clonazepam, which has a 40-hour half-life. The circumstances under which clonazepam should be used for insomnia are small, such as in people with a daytime anxiety disorder.”

Consider trying triazolam, zolpidem, and zaleplon for patients who have problems falling asleep, he said, while oxazepam and eszopiclone are sensible options for people who have difficulty falling and staying asleep. Clinical response to BzRAs is common, yet only about half of people who have insomnia remit with one of these agents.

Dr. Winkelman said that patients and physicians often ask him whether BzRAs and other agents used as sleep aids are addictive. Abuse is identified when recurrent use causes clinically and functionally significant impairment, such as health problems; disability; and failure to meet major responsibilities at work, home, or school. “These are concerns with BzRAs. Misuse and abuse generally occur in younger people. Once you get to 35 years old, misuse rates get very low. In older people, rates of side effects go up.

“Tolerance, physiological and psychological dependence, and nonmedical diversion are also of concern,” he said. However, for the majority of people, BzRA hypnotics are effective and safe.

As for other agents, meta-analyses have demonstrated that melatonin 1-3 mg can help people fall asleep when it’s not being endogenously released. “That’s during the day,” he said. “That might be most relevant for jet lag and for people doing shift work.” Two orexin antagonists on the market for insomnia include suvorexant and lemborexant 10-20 mg. Advantages of these include little abuse liability and few side effects. “In one head-to-head polysomnography study in the elderly, lemborexant was superior to zolpidem 6.25 mg CR on both objective and subjective ability to fall asleep and stay asleep,” Dr. Winkelman said. (JAMA Netw Open. 2019;2[12]:e1918254).

Antidepressants are another treatment option, including mirtazapine 15-30 mg, trazodone 25-100 mg, and amitriptyline and doxepin (10-50 mg). Advantages include little abuse liability, while potential drawbacks include daytime sedation, weight gain, and anticholinergic side effects. Meanwhile, atypical antipsychotics such as quetiapine 25-100 mg have long been known to be helpful for sleep. “Advantages are that they’re anxiolytic, they’re mood stabilizing, and there is little abuse liability,” Dr. Winkelman said. “Drawbacks are that they’re probably less effective than BzRAs, they cause daytime sedation, weight gain, risks of extrapyramidal symptoms and glucose and lipid abnormalities.”

Dr. Winkelman said that he uses “a fair amount” of the anticonvulsant gabapentin as a second- or third-line hypnotic agent. “I usually start with 300 mg [at bedtime],” he added. “Drawbacks are that it’s probably less effective than BzRAs; it affects cognition; and can cause daytime sedation, dizziness, and weight gain. There are also concerns about abuse.”

Dr. Winkelman reported that he has received grant/research support from Merck, the RLS Foundation, and Luitpold Pharmaceuticals. He is also a consultant for Advance Medical, Avadel Pharmaceuticals, and UpToDate and is a member of the speakers’ bureau for Luitpold.

[email protected]

LAS VEGAS – Clinicians should spend 1 hour with patients who present with a chief complaint of insomnia, rather than rushing to a treatment after a 10- to 15-minute office visit, according to John W. Winkelman, MD, PhD.

Doug Brunk/MDedge News

“Why? Because sleep problems are usually multifactorial, involving psychiatric illness, sleep disorders, medical illness, medication, and poor sleep hygiene/stress,” he said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “There are usually many contributing problems, and sleep quality is only as strong as the weakest link. Maybe you don’t have an hour [to meet with new patients], but you need to give adequate time, otherwise you’re not going to do justice to the problem.”

During that first visit, Dr. Winkelman recommends establishing and prioritizing goals with the patient. “Ask, ‘what is it that bothers you most about your insomnia? Is it the time awake at night, your total sleep time, or how you feel during the day?’ Because we’re going to use different approaches based on that chief complaint of the insomnia,” said Dr. Winkelman, chief of the Massachusetts General Sleep Disorders Clinical Research Program in the department of psychiatry at Harvard Medical School, Boston. “Cognitive-behavioral therapy for insomnia [CBT-I], for instance, is very good at reducing time awake at night. It won’t increase total sleep time, but it reduces time awake at night dramatically.”

According to the DSM-5, insomnia disorder is marked by dissatisfaction with sleep quality or quantity associated with at least one of the following: difficulty initiating sleep, difficulty maintaining sleep, and early morning awakening. “Just getting up to pee five times a night is not insomnia,” he said. “Just taking an hour and a half to fall asleep at the beginning of the night is not insomnia. There has to be distress or dysfunction related to the sleep disturbance, for a minimum of three times per week for 3 months.”

Most sleep problems are transient, but 25%-30% last more than 1 year. The differential diagnosis for chronic insomnia includes primary psychiatric disorders, medications, substances, restless legs syndrome, sleep schedule disorders, and obstructive sleep apnea.

“In general, we do not order sleep studies in people with insomnia unless we suspect sleep apnea; it’s just a waste of time,” said Dr. Winkelman, who is also a professor of psychiatry at Harvard Medical School. Indications for polysomnography include loud snoring plus one of the following: daytime sleepiness, witnessed apneas, or refractory hypertension. Other indications include abnormal behaviors or movements during sleep, unexplained excessive daytime sleepiness, and refractory sleep complaints, especially repetitive brief awakenings.

Many common cognitive and behavioral issues can produce or worsen insomnia, including inconsistent bedtimes and wake times. “That irregular schedule wreaks havoc with sleep,” he said. “It messes up the circadian rhythm. Also, homeostatic drive needs to build up: We need to be awake 16 or more hours in order to be sleepy. If people are sleeping until noon on Sundays and then trying to go to bed at their usual time, 10 or 11 at night, they’ve only been awake 10 or 11 hours. That’s why they’re going to have problems falling asleep. Also, a lot of people doze off after dinner in front of the TV. That doesn’t help.”

Spending excessive time in bed can also trigger or worsen insomnia. Dr. Winkelman recommends that people restrict their access to bed to the number of hours it is reasonable to sleep. “I see a lot of people in their 70s and 80s spending 10 hours in bed,” he said. “It doesn’t sound that crazy, but there is no way they’re going to get 10 hours of sleep. It’s physically impossible, so they spend 2 or 3 hours awake at night.” Clock-watching is another no-no. “In the middle of the night you wake up, look at the clock, and say to yourself: ‘Oh my god, I’ve been awake for 3 hours. I have 4 hours left. I need 7 hours. That means I need to go to sleep now!’ ”

An estimated 30%-40% of people with chronic insomnia have a psychiatric disorder. That means “you have to be thorough in your evaluation and act as if you’re doing a structured interview,” Dr. Winkelman said. “Ask about obsessive-compulsive disorder, generalized anxiety disorder, PTSD, et cetera, so that you understand the complete myriad of psychiatric illnesses, because psychiatric illnesses run in gangs. Comorbidity is generally the rule.”

The first-line treatment for chronic insomnia disorder is CBT-I, a multicomponent approach that includes time-in-bed restriction, stimulus control, cognitive therapy, relaxation therapy, and sleep hygiene. According to Dr. Winkelman, the cornerstone of CBT-I is time-in-bed restriction. “Many people with insomnia are spending 8.5 hours in bed to get 6.5 hours of sleep,” he said. “What you do is restrict access to bed to 6.5 hours; you initially sleep deprive them. Over the first few weeks, they hate you. After a few weeks when they start sleeping well, you start gradually increasing time in bed, but they rarely get back to the 8.5 hours in bed they were spending beforehand.”

Online CBT-I programs such as Sleepio can also be effective for improving sleep latency and wake after sleep onset, but not for total sleep time (JAMA Psychiatry. 2017;74[1]:68-75). “Not everybody responds to CBT; 50% don’t respond at a couple of months,” he said. “These are the people you need to think about medication for.”

Medications commonly used for chronic insomnia include benzodiazepine receptor agonists (BzRAs) – temazepam, eszopiclone, triazolam, zolpidem, and zaleplon are Food and Drug Administration approved – melatonin agonists, orexin antagonists, sedating antidepressants, anticonvulsants, and dopaminergic antagonists. “Each of the agents in these categories has somewhat similar mechanisms of action, and similar efficacy and contraindications,” Dr. Winkelman said. “The best way to divide the benzodiazepine receptor agonists is based on half-life. How long do you want drug on receptor in somebody with insomnia? Probably not much longer than 8 hours. Nevertheless, some psychiatrists love clonazepam, which has a 40-hour half-life. The circumstances under which clonazepam should be used for insomnia are small, such as in people with a daytime anxiety disorder.”

Consider trying triazolam, zolpidem, and zaleplon for patients who have problems falling asleep, he said, while oxazepam and eszopiclone are sensible options for people who have difficulty falling and staying asleep. Clinical response to BzRAs is common, yet only about half of people who have insomnia remit with one of these agents.

Dr. Winkelman said that patients and physicians often ask him whether BzRAs and other agents used as sleep aids are addictive. Abuse is identified when recurrent use causes clinically and functionally significant impairment, such as health problems; disability; and failure to meet major responsibilities at work, home, or school. “These are concerns with BzRAs. Misuse and abuse generally occur in younger people. Once you get to 35 years old, misuse rates get very low. In older people, rates of side effects go up.

“Tolerance, physiological and psychological dependence, and nonmedical diversion are also of concern,” he said. However, for the majority of people, BzRA hypnotics are effective and safe.

As for other agents, meta-analyses have demonstrated that melatonin 1-3 mg can help people fall asleep when it’s not being endogenously released. “That’s during the day,” he said. “That might be most relevant for jet lag and for people doing shift work.” Two orexin antagonists on the market for insomnia include suvorexant and lemborexant 10-20 mg. Advantages of these include little abuse liability and few side effects. “In one head-to-head polysomnography study in the elderly, lemborexant was superior to zolpidem 6.25 mg CR on both objective and subjective ability to fall asleep and stay asleep,” Dr. Winkelman said. (JAMA Netw Open. 2019;2[12]:e1918254).

Antidepressants are another treatment option, including mirtazapine 15-30 mg, trazodone 25-100 mg, and amitriptyline and doxepin (10-50 mg). Advantages include little abuse liability, while potential drawbacks include daytime sedation, weight gain, and anticholinergic side effects. Meanwhile, atypical antipsychotics such as quetiapine 25-100 mg have long been known to be helpful for sleep. “Advantages are that they’re anxiolytic, they’re mood stabilizing, and there is little abuse liability,” Dr. Winkelman said. “Drawbacks are that they’re probably less effective than BzRAs, they cause daytime sedation, weight gain, risks of extrapyramidal symptoms and glucose and lipid abnormalities.”

Dr. Winkelman said that he uses “a fair amount” of the anticonvulsant gabapentin as a second- or third-line hypnotic agent. “I usually start with 300 mg [at bedtime],” he added. “Drawbacks are that it’s probably less effective than BzRAs; it affects cognition; and can cause daytime sedation, dizziness, and weight gain. There are also concerns about abuse.”

Dr. Winkelman reported that he has received grant/research support from Merck, the RLS Foundation, and Luitpold Pharmaceuticals. He is also a consultant for Advance Medical, Avadel Pharmaceuticals, and UpToDate and is a member of the speakers’ bureau for Luitpold.

[email protected]

LAS VEGAS – Clinicians should spend 1 hour with patients who present with a chief complaint of insomnia, rather than rushing to a treatment after a 10- to 15-minute office visit, according to John W. Winkelman, MD, PhD.

Doug Brunk/MDedge News

“Why? Because sleep problems are usually multifactorial, involving psychiatric illness, sleep disorders, medical illness, medication, and poor sleep hygiene/stress,” he said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “There are usually many contributing problems, and sleep quality is only as strong as the weakest link. Maybe you don’t have an hour [to meet with new patients], but you need to give adequate time, otherwise you’re not going to do justice to the problem.”

During that first visit, Dr. Winkelman recommends establishing and prioritizing goals with the patient. “Ask, ‘what is it that bothers you most about your insomnia? Is it the time awake at night, your total sleep time, or how you feel during the day?’ Because we’re going to use different approaches based on that chief complaint of the insomnia,” said Dr. Winkelman, chief of the Massachusetts General Sleep Disorders Clinical Research Program in the department of psychiatry at Harvard Medical School, Boston. “Cognitive-behavioral therapy for insomnia [CBT-I], for instance, is very good at reducing time awake at night. It won’t increase total sleep time, but it reduces time awake at night dramatically.”

According to the DSM-5, insomnia disorder is marked by dissatisfaction with sleep quality or quantity associated with at least one of the following: difficulty initiating sleep, difficulty maintaining sleep, and early morning awakening. “Just getting up to pee five times a night is not insomnia,” he said. “Just taking an hour and a half to fall asleep at the beginning of the night is not insomnia. There has to be distress or dysfunction related to the sleep disturbance, for a minimum of three times per week for 3 months.”

Most sleep problems are transient, but 25%-30% last more than 1 year. The differential diagnosis for chronic insomnia includes primary psychiatric disorders, medications, substances, restless legs syndrome, sleep schedule disorders, and obstructive sleep apnea.

“In general, we do not order sleep studies in people with insomnia unless we suspect sleep apnea; it’s just a waste of time,” said Dr. Winkelman, who is also a professor of psychiatry at Harvard Medical School. Indications for polysomnography include loud snoring plus one of the following: daytime sleepiness, witnessed apneas, or refractory hypertension. Other indications include abnormal behaviors or movements during sleep, unexplained excessive daytime sleepiness, and refractory sleep complaints, especially repetitive brief awakenings.

Many common cognitive and behavioral issues can produce or worsen insomnia, including inconsistent bedtimes and wake times. “That irregular schedule wreaks havoc with sleep,” he said. “It messes up the circadian rhythm. Also, homeostatic drive needs to build up: We need to be awake 16 or more hours in order to be sleepy. If people are sleeping until noon on Sundays and then trying to go to bed at their usual time, 10 or 11 at night, they’ve only been awake 10 or 11 hours. That’s why they’re going to have problems falling asleep. Also, a lot of people doze off after dinner in front of the TV. That doesn’t help.”

Spending excessive time in bed can also trigger or worsen insomnia. Dr. Winkelman recommends that people restrict their access to bed to the number of hours it is reasonable to sleep. “I see a lot of people in their 70s and 80s spending 10 hours in bed,” he said. “It doesn’t sound that crazy, but there is no way they’re going to get 10 hours of sleep. It’s physically impossible, so they spend 2 or 3 hours awake at night.” Clock-watching is another no-no. “In the middle of the night you wake up, look at the clock, and say to yourself: ‘Oh my god, I’ve been awake for 3 hours. I have 4 hours left. I need 7 hours. That means I need to go to sleep now!’ ”

An estimated 30%-40% of people with chronic insomnia have a psychiatric disorder. That means “you have to be thorough in your evaluation and act as if you’re doing a structured interview,” Dr. Winkelman said. “Ask about obsessive-compulsive disorder, generalized anxiety disorder, PTSD, et cetera, so that you understand the complete myriad of psychiatric illnesses, because psychiatric illnesses run in gangs. Comorbidity is generally the rule.”

The first-line treatment for chronic insomnia disorder is CBT-I, a multicomponent approach that includes time-in-bed restriction, stimulus control, cognitive therapy, relaxation therapy, and sleep hygiene. According to Dr. Winkelman, the cornerstone of CBT-I is time-in-bed restriction. “Many people with insomnia are spending 8.5 hours in bed to get 6.5 hours of sleep,” he said. “What you do is restrict access to bed to 6.5 hours; you initially sleep deprive them. Over the first few weeks, they hate you. After a few weeks when they start sleeping well, you start gradually increasing time in bed, but they rarely get back to the 8.5 hours in bed they were spending beforehand.”

Online CBT-I programs such as Sleepio can also be effective for improving sleep latency and wake after sleep onset, but not for total sleep time (JAMA Psychiatry. 2017;74[1]:68-75). “Not everybody responds to CBT; 50% don’t respond at a couple of months,” he said. “These are the people you need to think about medication for.”

Medications commonly used for chronic insomnia include benzodiazepine receptor agonists (BzRAs) – temazepam, eszopiclone, triazolam, zolpidem, and zaleplon are Food and Drug Administration approved – melatonin agonists, orexin antagonists, sedating antidepressants, anticonvulsants, and dopaminergic antagonists. “Each of the agents in these categories has somewhat similar mechanisms of action, and similar efficacy and contraindications,” Dr. Winkelman said. “The best way to divide the benzodiazepine receptor agonists is based on half-life. How long do you want drug on receptor in somebody with insomnia? Probably not much longer than 8 hours. Nevertheless, some psychiatrists love clonazepam, which has a 40-hour half-life. The circumstances under which clonazepam should be used for insomnia are small, such as in people with a daytime anxiety disorder.”

Consider trying triazolam, zolpidem, and zaleplon for patients who have problems falling asleep, he said, while oxazepam and eszopiclone are sensible options for people who have difficulty falling and staying asleep. Clinical response to BzRAs is common, yet only about half of people who have insomnia remit with one of these agents.

Dr. Winkelman said that patients and physicians often ask him whether BzRAs and other agents used as sleep aids are addictive. Abuse is identified when recurrent use causes clinically and functionally significant impairment, such as health problems; disability; and failure to meet major responsibilities at work, home, or school. “These are concerns with BzRAs. Misuse and abuse generally occur in younger people. Once you get to 35 years old, misuse rates get very low. In older people, rates of side effects go up.

“Tolerance, physiological and psychological dependence, and nonmedical diversion are also of concern,” he said. However, for the majority of people, BzRA hypnotics are effective and safe.

As for other agents, meta-analyses have demonstrated that melatonin 1-3 mg can help people fall asleep when it’s not being endogenously released. “That’s during the day,” he said. “That might be most relevant for jet lag and for people doing shift work.” Two orexin antagonists on the market for insomnia include suvorexant and lemborexant 10-20 mg. Advantages of these include little abuse liability and few side effects. “In one head-to-head polysomnography study in the elderly, lemborexant was superior to zolpidem 6.25 mg CR on both objective and subjective ability to fall asleep and stay asleep,” Dr. Winkelman said. (JAMA Netw Open. 2019;2[12]:e1918254).

Antidepressants are another treatment option, including mirtazapine 15-30 mg, trazodone 25-100 mg, and amitriptyline and doxepin (10-50 mg). Advantages include little abuse liability, while potential drawbacks include daytime sedation, weight gain, and anticholinergic side effects. Meanwhile, atypical antipsychotics such as quetiapine 25-100 mg have long been known to be helpful for sleep. “Advantages are that they’re anxiolytic, they’re mood stabilizing, and there is little abuse liability,” Dr. Winkelman said. “Drawbacks are that they’re probably less effective than BzRAs, they cause daytime sedation, weight gain, risks of extrapyramidal symptoms and glucose and lipid abnormalities.”

Dr. Winkelman said that he uses “a fair amount” of the anticonvulsant gabapentin as a second- or third-line hypnotic agent. “I usually start with 300 mg [at bedtime],” he added. “Drawbacks are that it’s probably less effective than BzRAs; it affects cognition; and can cause daytime sedation, dizziness, and weight gain. There are also concerns about abuse.”

Dr. Winkelman reported that he has received grant/research support from Merck, the RLS Foundation, and Luitpold Pharmaceuticals. He is also a consultant for Advance Medical, Avadel Pharmaceuticals, and UpToDate and is a member of the speakers’ bureau for Luitpold.

[email protected]

Underlying cardiac disease, airway anomalies, and younger age each independently boosted the risk of severe perioperative respiratory adverse events (PRAE) in children undergoing adenotonsillectomy to treat obstructive sleep apnea, in a review of 374 patients treated at a single Canadian tertiary-referral center.

In contrast, the analysis failed to show independent, significant effects from any assessed polysomnography or oximetry parameters on the rate of postoperative respiratory complications. The utility of preoperative polysomnography or oximetry for risk stratification is questionable for pediatric patients scheduled to adenotonsillectomy to treat obstructive sleep apnea, wrote Sherri L. Katz, MD, of the University of Ottawa, and associates in a recent report published in the Journal of Clinical Sleep Medicine, although they also added that making these assessments may be “unavoidable” because of their need for diagnosing obstructive sleep apnea and determining the need for surgery.

Despite this caveat, “overall our study results highlight the need to better define the complex interaction between comorbidities, age, nocturnal respiratory events, and gas exchange abnormalities in predicting risk for PRAE” after adenotonsillectomy, the researchers wrote. These findings “are consistent with existing clinical care guidelines,” and “cardiac and craniofacial conditions have been associated with risk of postoperative complications in other studies.”

The analysis used data collected from all children aged 0-18 years who underwent polysomnography assessment followed by adenotonsillectomy at one Canadian tertiary-referral center, Children’s Hospital of Eastern Ontario in Ottawa, during 2010-2016. Their median age was just over 6 years, and 39 patients (10%) were younger than 3 years at the time of their surgery. More than three-quarters of the patients, 286, had at least one identified comorbidity, and nearly half had at least two comorbidities. Polysomnography identified sleep-disordered breathing in 344 of the children (92%), and diagnosed obstructive sleep apnea in 256 (68%), including 148 (43% of the full cohort) with a severe apnea-hypopnea index.

Sixty-six of the children (18%) had at least one severe PRAE that required intervention. Specifically these were either oxygen desaturations requiring intervention or need for airway or ventilatory support with interventions such as jaw thrust, oral or nasal airway placement, bag and mask ventilation, or endotracheal intubation.

A multivariate regression analysis of the measured comorbidity, polysomnography, and oximetry parameters, as well as age, identified three factors that independently linked with a statistically significant increase in the rate of severe PRAE: airway anomaly, underlying cardiac disease, and young age. Patients with an airway anomaly had a 219% increased rate of PRAE, compared with those with no anomaly; patients with underlying cardiac disease had a 109% increased rate, compared with those without cardiac disease; and patients aged younger than 3 years had a 310% higher rate of PRAE, compared with the children aged 6 years or older, while children aged 3-5 years had a 121% higher rate of PRAE, compared with older children.

The study received no commercial funding. Dr. Katz has received honoraria for speaking from Biogen that had no relevance to the study.

[email protected]

SOURCE: Katz SL et al. J Clin Sleep Med. 2020 Jan 15;16(1):41-8.

Underlying cardiac disease, airway anomalies, and younger age each independently boosted the risk of severe perioperative respiratory adverse events (PRAE) in children undergoing adenotonsillectomy to treat obstructive sleep apnea, in a review of 374 patients treated at a single Canadian tertiary-referral center.

In contrast, the analysis failed to show independent, significant effects from any assessed polysomnography or oximetry parameters on the rate of postoperative respiratory complications. The utility of preoperative polysomnography or oximetry for risk stratification is questionable for pediatric patients scheduled to adenotonsillectomy to treat obstructive sleep apnea, wrote Sherri L. Katz, MD, of the University of Ottawa, and associates in a recent report published in the Journal of Clinical Sleep Medicine, although they also added that making these assessments may be “unavoidable” because of their need for diagnosing obstructive sleep apnea and determining the need for surgery.

Despite this caveat, “overall our study results highlight the need to better define the complex interaction between comorbidities, age, nocturnal respiratory events, and gas exchange abnormalities in predicting risk for PRAE” after adenotonsillectomy, the researchers wrote. These findings “are consistent with existing clinical care guidelines,” and “cardiac and craniofacial conditions have been associated with risk of postoperative complications in other studies.”

The analysis used data collected from all children aged 0-18 years who underwent polysomnography assessment followed by adenotonsillectomy at one Canadian tertiary-referral center, Children’s Hospital of Eastern Ontario in Ottawa, during 2010-2016. Their median age was just over 6 years, and 39 patients (10%) were younger than 3 years at the time of their surgery. More than three-quarters of the patients, 286, had at least one identified comorbidity, and nearly half had at least two comorbidities. Polysomnography identified sleep-disordered breathing in 344 of the children (92%), and diagnosed obstructive sleep apnea in 256 (68%), including 148 (43% of the full cohort) with a severe apnea-hypopnea index.

Sixty-six of the children (18%) had at least one severe PRAE that required intervention. Specifically these were either oxygen desaturations requiring intervention or need for airway or ventilatory support with interventions such as jaw thrust, oral or nasal airway placement, bag and mask ventilation, or endotracheal intubation.

A multivariate regression analysis of the measured comorbidity, polysomnography, and oximetry parameters, as well as age, identified three factors that independently linked with a statistically significant increase in the rate of severe PRAE: airway anomaly, underlying cardiac disease, and young age. Patients with an airway anomaly had a 219% increased rate of PRAE, compared with those with no anomaly; patients with underlying cardiac disease had a 109% increased rate, compared with those without cardiac disease; and patients aged younger than 3 years had a 310% higher rate of PRAE, compared with the children aged 6 years or older, while children aged 3-5 years had a 121% higher rate of PRAE, compared with older children.

The study received no commercial funding. Dr. Katz has received honoraria for speaking from Biogen that had no relevance to the study.

[email protected]

SOURCE: Katz SL et al. J Clin Sleep Med. 2020 Jan 15;16(1):41-8.

Underlying cardiac disease, airway anomalies, and younger age each independently boosted the risk of severe perioperative respiratory adverse events (PRAE) in children undergoing adenotonsillectomy to treat obstructive sleep apnea, in a review of 374 patients treated at a single Canadian tertiary-referral center.

In contrast, the analysis failed to show independent, significant effects from any assessed polysomnography or oximetry parameters on the rate of postoperative respiratory complications. The utility of preoperative polysomnography or oximetry for risk stratification is questionable for pediatric patients scheduled to adenotonsillectomy to treat obstructive sleep apnea, wrote Sherri L. Katz, MD, of the University of Ottawa, and associates in a recent report published in the Journal of Clinical Sleep Medicine, although they also added that making these assessments may be “unavoidable” because of their need for diagnosing obstructive sleep apnea and determining the need for surgery.

Despite this caveat, “overall our study results highlight the need to better define the complex interaction between comorbidities, age, nocturnal respiratory events, and gas exchange abnormalities in predicting risk for PRAE” after adenotonsillectomy, the researchers wrote. These findings “are consistent with existing clinical care guidelines,” and “cardiac and craniofacial conditions have been associated with risk of postoperative complications in other studies.”

The analysis used data collected from all children aged 0-18 years who underwent polysomnography assessment followed by adenotonsillectomy at one Canadian tertiary-referral center, Children’s Hospital of Eastern Ontario in Ottawa, during 2010-2016. Their median age was just over 6 years, and 39 patients (10%) were younger than 3 years at the time of their surgery. More than three-quarters of the patients, 286, had at least one identified comorbidity, and nearly half had at least two comorbidities. Polysomnography identified sleep-disordered breathing in 344 of the children (92%), and diagnosed obstructive sleep apnea in 256 (68%), including 148 (43% of the full cohort) with a severe apnea-hypopnea index.

Sixty-six of the children (18%) had at least one severe PRAE that required intervention. Specifically these were either oxygen desaturations requiring intervention or need for airway or ventilatory support with interventions such as jaw thrust, oral or nasal airway placement, bag and mask ventilation, or endotracheal intubation.

A multivariate regression analysis of the measured comorbidity, polysomnography, and oximetry parameters, as well as age, identified three factors that independently linked with a statistically significant increase in the rate of severe PRAE: airway anomaly, underlying cardiac disease, and young age. Patients with an airway anomaly had a 219% increased rate of PRAE, compared with those with no anomaly; patients with underlying cardiac disease had a 109% increased rate, compared with those without cardiac disease; and patients aged younger than 3 years had a 310% higher rate of PRAE, compared with the children aged 6 years or older, while children aged 3-5 years had a 121% higher rate of PRAE, compared with older children.

The study received no commercial funding. Dr. Katz has received honoraria for speaking from Biogen that had no relevance to the study.

[email protected]

SOURCE: Katz SL et al. J Clin Sleep Med. 2020 Jan 15;16(1):41-8.

Clinical significance

Continuous positive airway pressure remains the gold standard and first-line treatment for moderate to severe OSA. When CPAP and other medical therapies fail or are poorly adopted, surgical solutions - either standalone or in unison - can be directed to target precision therapy.

The newest of these techniques is neuromodulation of the lingual musculature, particularly by way of selective stimulation of the hypoglossal nerve, which first demonstrated success in human clinical trials in 1996.¹ Upper airway stimulation (UAS) was formally FDA-approved in 2014 (Inspire Medical Systems, Inc). UAS is designed to eliminate clinically significant OSA through stimulation of the anteriorly directed branches of the hypoglossal nerve, increasing the posterior airway space in a multilevel fashion.² Since this time, over 7,500 patients have been treated with Inspire in nine countries (United States, Germany, The Netherlands, Switzerland, Belgium, Spain, France, Italy, and Finland). Prospective, international multicenter trials have demonstrated 68% to 96% clinical efficacy in well selected individuals. This is defined as a ≥ 50% reduction in the apnea hypopnea index (AHI) to an overall AHI of ≤ 20/hour.^3,4 Additionally, post-UAS analysis demonstrates subjective reduction in daytime sleepiness as reported by Epworth sleepiness scores, with improvements in sleep-related quality of life. Further, UAS reduces socially disruptive snoring with 85% of bedpartners reporting soft to no snoring at 48-month follow-up.⁵ The procedure has also demonstrated long-term cost benefit in the US health-care system.⁶
 

Background and pathophysiology

Oliven and colleagues⁷ first observed the critical finding that selective intra-muscular stimulation of the genioglossus muscle lowered airway critical closing pressure (PCrit), thereby stabilizing the pharyngeal airway. Conversely, activation of the “retrusor” musculature, namely the hyoglossus and styloglossus muscles, increased Pcrit, increasing collapsibility of the pharyngeal airway.

Therapeutic implantation requires three incisions directed to the neck, chest, and right rib space (between the 4th to 6th intercostal spaces), with an operative time of 90 minutes or less in experienced hands. The majority of patients are discharged on the day of the procedure. Morbidity remains low with minimal pain reported during recovery. The most common complication is that of temporary tongue weakness, which typically resolves within 2 to 3 weeks. While very infrequent, patients should be counseled on the risk of postoperative hematoma, which can precipitate infection and subsequent explant of the device. Average recovery time spans between 3 and 7 days with activation of the device 4 weeks after surgical implantation to allow for appropriate tissue healing and reduce the risk of dislodgement of the implanted components. In contrast to other surgical treatment options, UAS is also reversible with no underlying alteration to existing pharyngeal anatomy apart from external incisions created during the procedure.
 

Stimulation to titration

As the need for a multidisciplinary approach to salvage of patients failing first-line therapy for OSA continues to grow, UAS with its multilevel impact continues to be of key interest. In similar fashion to established medical therapies such as PAP and oral appliance therapy (OAT), close observation between sleep medicine specialists and the implanting surgeon during the adaptation period with attention paid to titration parameters such as stimulation duration, pulse width, amplitude, and polarity, allow optimization of response outcome.

The stimulation electrode, which is designed in the form of a cuff to envelope the anterior (protrusor) branches of the hypoglossal nerve receives electrical stimulation from the implanted pulse generator, implanted above the pectoralis muscle of the chest wall. This design allows for collaborative awake and overnight titration of the device as directed by a sleep medicine physician. Attention is paid not only to the voltage “strength” administered with each pulse but also the degree of synchronization between respiration and stimulation, as well as pattern of pulse administration. Our experience remains that true success and adaptation to therapy requires not just meticulous surgical technique but a diligent approach to postoperative therapeutic titration to achieve a comfortable, yet effective, voltage for maintaining airway patency. Thus, akin to initiation of CPAP, UAS requires regular follow-up and device fine-tuning with patient comfort taken into consideration to achieve optimal results, and patient expectation should be aligned with this process.
 

Current indications

Success in UAS relies heavily on appropriate presurgical evaluation and clinical phenotyping. The following surgical indications have been demonstrated in the Stimulation Therapy for Apnea Reduction (STAR) trial and subsequent 3-year clinical follow-up: AHI between 15 and 80 events/hour (with ≤ 25% central apneas) and a BMI ≤ 32.⁸

As OSA often results from multi-level airway collapse, UAS targets an increase not only in the diameter of the retropalatal/oropharyngeal airway space but also the antero-posterior hypopharyngeal airway. Original criteria for implantation excluded patients with a pattern of complete circumferential collapse (CCC) noted on dynamic airway evaluation during pre-implant drug-induced sleep endoscopy (DISE). DISE aims to precisely target dynamic airway collapse patterns during simulated (propofol or midazolom induced) sleep.
 

Future directions

The effects of UAS are dependent on upper-airway cross-sectional area, particularly diameter. In patients who demonstrate CCC, the anteroposterior direction of activation derived from the UAS stimulus is unable to overcome CCC. In a recent prospective study, our group demonstrated that CCC can be converted to an airway collapse pattern compatible with UAS implantation, using a modified palatopharyngoplasty prior to UAS implantation. By stabilizing the lateral walls of the oropharyngeal airway with pre-implant palatal surgery, UAS is able to successfully direct widening of the airway cross-sectional area in an antero-posterior fashion. This exciting finding potentially allows for expansion of current indications, thus opening treatment to a wider patient population.⁹ Still, UAS remains highly studied in a relatively uniform patient population with data in more diverse subsets requiring further directed attention to expand and better define optimal patient populations for treatment.

From the perspective of improving patient adaptation and tolerance in UAS, a well-established concept in the CPAP literature can be applied, as explained by the Starling resistor model. The starling resistor is comprised of two rigid tubes connected by a collapsible segment in between. In parallel, the pharynx is a collapsible muscular tube connected on either end by the nose/nasal cavity and the trachea – both of which are bony/cartilaginous, noncollapsible structures. As has been shown in the use of CPAP, the same pressure required to maintain stability of the collapsible muscular pharynx via nasal breathing may lead to pharyngeal collapse when applied orally.¹⁰ This concept has also been directed towards UAS with our clinical experience demonstrating that oro or oronasal breathers tend to require a higher amplitude to maintain airway patency versus nasal breathers. This is an important area for future-directed study as medically/surgically improving nasal breathing in UAS subjects may subsequently lower amplitude requirements and improve patient tolerance.

Future direction to allow for improvement in the technology for application in a broader populational segment, external or alternative device powering mechanisms, along with MRI Compatibility and reducing the number of required external incisions will continue to broaden the patient selection criteria. As we move from a “stimulation” to a precision-tailored “stimulation and titration” approach, the mid to long term data supporting UAS remains very promising with 5-year follow up demonstrating sustained polysomnographic and subjective reported outcomes in well selected patients.
 

Dr. Awad is Assistant Professor – Department of Otolaryngology/Head & Neck Surgery, and Chief – Division of Sleep Surgery; Northwestern University, Chicago, Illinois. Dr. Capasso is Associate Professor – Department of Otolaryngology/Head & Neck Surgery, and Chief – Division of Sleep Surgery; Stanford Hospital and Clinics, Stanford, California.

References

1. Schwartz AR et al. Electrical stimulation of the lingual musculature in obstructive sleep apnea. J Appl Physiol. 1996;81(2):643-52. doi: 10.1152/jappl.1996.81.2.643.

2. Ong AA et al. Efficacy of upper airway stimulation on collapse patterns observed during drug-induced sedation endoscopy. Otolaryngol Head Neck Surg. 2016;154(5):970-7. doi: 10.1177/0194599816636835.

3. Woodson BT et al. Three-year outcomes of cranial nerve stimulation for obstructive sleep apnea: The STAR trial. Otolaryngol Head Neck Surg. 2016;154(1):181-8. doi: 10.1177/0194599815616618.

4. Heiser C et al. Outcomes of upper airway stimulation for obstructive sleep apnea in a multicenter german postmarket study. Otolaryngol Head Neck Surg. 2017;156(2):378-84. doi: 10.1177/0194599816683378.

5. Gillespie MB et al. Upper airway stimulation for obstructive sleep apnea: Patient-reported outcomes after 48 months of follow-up. Otolaryngol Head Neck Surg. 2017;156(4):765-71. doi: 10.1177/0194599817691491.

6. Pietzsch JB et al. Long-term cost-effectiveness of upper airway stimulation for the treatment of obstructive sleep apnea: A model-based projection based on the star trial. Sleep. 2015;38(5):735-44. doi: 10.5665/sleep.4666.

7. Oliven A et al. Improved upper airway patency elicited by electrical stimulation of the hypoglossus nerves. Respiration. 1996;63(4):213-16. doi: 10.1159/000196547.

8. Strollo PJ et al. Upper-airway stimulation for obstructive sleep apnea. N Engl J Med. 2014;370(2):139-49. doi: 10.1056/NEJMoa1308659.

9. Liu YC et al. Palatopharyngoplasty resolves concentric collapse in patients ineligible for upper airway stimulation. Laryngoscope. Forthcoming.

10. De Andrade RGS et al. Impact of the type of mask on the effectiveness of and adherence to continuous positive airway pressure treatment for obstructive sleep apnea. J Bras Pneumol. 2014;40(6):658-68. doi: 10.1590/S1806-37132014000600010

Clinical significance

Continuous positive airway pressure remains the gold standard and first-line treatment for moderate to severe OSA. When CPAP and other medical therapies fail or are poorly adopted, surgical solutions - either standalone or in unison - can be directed to target precision therapy.

The newest of these techniques is neuromodulation of the lingual musculature, particularly by way of selective stimulation of the hypoglossal nerve, which first demonstrated success in human clinical trials in 1996.¹ Upper airway stimulation (UAS) was formally FDA-approved in 2014 (Inspire Medical Systems, Inc). UAS is designed to eliminate clinically significant OSA through stimulation of the anteriorly directed branches of the hypoglossal nerve, increasing the posterior airway space in a multilevel fashion.² Since this time, over 7,500 patients have been treated with Inspire in nine countries (United States, Germany, The Netherlands, Switzerland, Belgium, Spain, France, Italy, and Finland). Prospective, international multicenter trials have demonstrated 68% to 96% clinical efficacy in well selected individuals. This is defined as a ≥ 50% reduction in the apnea hypopnea index (AHI) to an overall AHI of ≤ 20/hour.^3,4 Additionally, post-UAS analysis demonstrates subjective reduction in daytime sleepiness as reported by Epworth sleepiness scores, with improvements in sleep-related quality of life. Further, UAS reduces socially disruptive snoring with 85% of bedpartners reporting soft to no snoring at 48-month follow-up.⁵ The procedure has also demonstrated long-term cost benefit in the US health-care system.⁶
 

Background and pathophysiology

Oliven and colleagues⁷ first observed the critical finding that selective intra-muscular stimulation of the genioglossus muscle lowered airway critical closing pressure (PCrit), thereby stabilizing the pharyngeal airway. Conversely, activation of the “retrusor” musculature, namely the hyoglossus and styloglossus muscles, increased Pcrit, increasing collapsibility of the pharyngeal airway.

Therapeutic implantation requires three incisions directed to the neck, chest, and right rib space (between the 4th to 6th intercostal spaces), with an operative time of 90 minutes or less in experienced hands. The majority of patients are discharged on the day of the procedure. Morbidity remains low with minimal pain reported during recovery. The most common complication is that of temporary tongue weakness, which typically resolves within 2 to 3 weeks. While very infrequent, patients should be counseled on the risk of postoperative hematoma, which can precipitate infection and subsequent explant of the device. Average recovery time spans between 3 and 7 days with activation of the device 4 weeks after surgical implantation to allow for appropriate tissue healing and reduce the risk of dislodgement of the implanted components. In contrast to other surgical treatment options, UAS is also reversible with no underlying alteration to existing pharyngeal anatomy apart from external incisions created during the procedure.
 

Stimulation to titration

As the need for a multidisciplinary approach to salvage of patients failing first-line therapy for OSA continues to grow, UAS with its multilevel impact continues to be of key interest. In similar fashion to established medical therapies such as PAP and oral appliance therapy (OAT), close observation between sleep medicine specialists and the implanting surgeon during the adaptation period with attention paid to titration parameters such as stimulation duration, pulse width, amplitude, and polarity, allow optimization of response outcome.

The stimulation electrode, which is designed in the form of a cuff to envelope the anterior (protrusor) branches of the hypoglossal nerve receives electrical stimulation from the implanted pulse generator, implanted above the pectoralis muscle of the chest wall. This design allows for collaborative awake and overnight titration of the device as directed by a sleep medicine physician. Attention is paid not only to the voltage “strength” administered with each pulse but also the degree of synchronization between respiration and stimulation, as well as pattern of pulse administration. Our experience remains that true success and adaptation to therapy requires not just meticulous surgical technique but a diligent approach to postoperative therapeutic titration to achieve a comfortable, yet effective, voltage for maintaining airway patency. Thus, akin to initiation of CPAP, UAS requires regular follow-up and device fine-tuning with patient comfort taken into consideration to achieve optimal results, and patient expectation should be aligned with this process.
 

Current indications

Success in UAS relies heavily on appropriate presurgical evaluation and clinical phenotyping. The following surgical indications have been demonstrated in the Stimulation Therapy for Apnea Reduction (STAR) trial and subsequent 3-year clinical follow-up: AHI between 15 and 80 events/hour (with ≤ 25% central apneas) and a BMI ≤ 32.⁸

As OSA often results from multi-level airway collapse, UAS targets an increase not only in the diameter of the retropalatal/oropharyngeal airway space but also the antero-posterior hypopharyngeal airway. Original criteria for implantation excluded patients with a pattern of complete circumferential collapse (CCC) noted on dynamic airway evaluation during pre-implant drug-induced sleep endoscopy (DISE). DISE aims to precisely target dynamic airway collapse patterns during simulated (propofol or midazolom induced) sleep.
 

Future directions

The effects of UAS are dependent on upper-airway cross-sectional area, particularly diameter. In patients who demonstrate CCC, the anteroposterior direction of activation derived from the UAS stimulus is unable to overcome CCC. In a recent prospective study, our group demonstrated that CCC can be converted to an airway collapse pattern compatible with UAS implantation, using a modified palatopharyngoplasty prior to UAS implantation. By stabilizing the lateral walls of the oropharyngeal airway with pre-implant palatal surgery, UAS is able to successfully direct widening of the airway cross-sectional area in an antero-posterior fashion. This exciting finding potentially allows for expansion of current indications, thus opening treatment to a wider patient population.⁹ Still, UAS remains highly studied in a relatively uniform patient population with data in more diverse subsets requiring further directed attention to expand and better define optimal patient populations for treatment.

From the perspective of improving patient adaptation and tolerance in UAS, a well-established concept in the CPAP literature can be applied, as explained by the Starling resistor model. The starling resistor is comprised of two rigid tubes connected by a collapsible segment in between. In parallel, the pharynx is a collapsible muscular tube connected on either end by the nose/nasal cavity and the trachea – both of which are bony/cartilaginous, noncollapsible structures. As has been shown in the use of CPAP, the same pressure required to maintain stability of the collapsible muscular pharynx via nasal breathing may lead to pharyngeal collapse when applied orally.¹⁰ This concept has also been directed towards UAS with our clinical experience demonstrating that oro or oronasal breathers tend to require a higher amplitude to maintain airway patency versus nasal breathers. This is an important area for future-directed study as medically/surgically improving nasal breathing in UAS subjects may subsequently lower amplitude requirements and improve patient tolerance.

Future direction to allow for improvement in the technology for application in a broader populational segment, external or alternative device powering mechanisms, along with MRI Compatibility and reducing the number of required external incisions will continue to broaden the patient selection criteria. As we move from a “stimulation” to a precision-tailored “stimulation and titration” approach, the mid to long term data supporting UAS remains very promising with 5-year follow up demonstrating sustained polysomnographic and subjective reported outcomes in well selected patients.
 

Dr. Awad is Assistant Professor – Department of Otolaryngology/Head & Neck Surgery, and Chief – Division of Sleep Surgery; Northwestern University, Chicago, Illinois. Dr. Capasso is Associate Professor – Department of Otolaryngology/Head & Neck Surgery, and Chief – Division of Sleep Surgery; Stanford Hospital and Clinics, Stanford, California.

References

1. Schwartz AR et al. Electrical stimulation of the lingual musculature in obstructive sleep apnea. J Appl Physiol. 1996;81(2):643-52. doi: 10.1152/jappl.1996.81.2.643.

2. Ong AA et al. Efficacy of upper airway stimulation on collapse patterns observed during drug-induced sedation endoscopy. Otolaryngol Head Neck Surg. 2016;154(5):970-7. doi: 10.1177/0194599816636835.

3. Woodson BT et al. Three-year outcomes of cranial nerve stimulation for obstructive sleep apnea: The STAR trial. Otolaryngol Head Neck Surg. 2016;154(1):181-8. doi: 10.1177/0194599815616618.

4. Heiser C et al. Outcomes of upper airway stimulation for obstructive sleep apnea in a multicenter german postmarket study. Otolaryngol Head Neck Surg. 2017;156(2):378-84. doi: 10.1177/0194599816683378.

5. Gillespie MB et al. Upper airway stimulation for obstructive sleep apnea: Patient-reported outcomes after 48 months of follow-up. Otolaryngol Head Neck Surg. 2017;156(4):765-71. doi: 10.1177/0194599817691491.

6. Pietzsch JB et al. Long-term cost-effectiveness of upper airway stimulation for the treatment of obstructive sleep apnea: A model-based projection based on the star trial. Sleep. 2015;38(5):735-44. doi: 10.5665/sleep.4666.

7. Oliven A et al. Improved upper airway patency elicited by electrical stimulation of the hypoglossus nerves. Respiration. 1996;63(4):213-16. doi: 10.1159/000196547.

8. Strollo PJ et al. Upper-airway stimulation for obstructive sleep apnea. N Engl J Med. 2014;370(2):139-49. doi: 10.1056/NEJMoa1308659.

9. Liu YC et al. Palatopharyngoplasty resolves concentric collapse in patients ineligible for upper airway stimulation. Laryngoscope. Forthcoming.

10. De Andrade RGS et al. Impact of the type of mask on the effectiveness of and adherence to continuous positive airway pressure treatment for obstructive sleep apnea. J Bras Pneumol. 2014;40(6):658-68. doi: 10.1590/S1806-37132014000600010

Clinical significance

Continuous positive airway pressure remains the gold standard and first-line treatment for moderate to severe OSA. When CPAP and other medical therapies fail or are poorly adopted, surgical solutions - either standalone or in unison - can be directed to target precision therapy.

The newest of these techniques is neuromodulation of the lingual musculature, particularly by way of selective stimulation of the hypoglossal nerve, which first demonstrated success in human clinical trials in 1996.¹ Upper airway stimulation (UAS) was formally FDA-approved in 2014 (Inspire Medical Systems, Inc). UAS is designed to eliminate clinically significant OSA through stimulation of the anteriorly directed branches of the hypoglossal nerve, increasing the posterior airway space in a multilevel fashion.² Since this time, over 7,500 patients have been treated with Inspire in nine countries (United States, Germany, The Netherlands, Switzerland, Belgium, Spain, France, Italy, and Finland). Prospective, international multicenter trials have demonstrated 68% to 96% clinical efficacy in well selected individuals. This is defined as a ≥ 50% reduction in the apnea hypopnea index (AHI) to an overall AHI of ≤ 20/hour.^3,4 Additionally, post-UAS analysis demonstrates subjective reduction in daytime sleepiness as reported by Epworth sleepiness scores, with improvements in sleep-related quality of life. Further, UAS reduces socially disruptive snoring with 85% of bedpartners reporting soft to no snoring at 48-month follow-up.⁵ The procedure has also demonstrated long-term cost benefit in the US health-care system.⁶
 

Background and pathophysiology

Oliven and colleagues⁷ first observed the critical finding that selective intra-muscular stimulation of the genioglossus muscle lowered airway critical closing pressure (PCrit), thereby stabilizing the pharyngeal airway. Conversely, activation of the “retrusor” musculature, namely the hyoglossus and styloglossus muscles, increased Pcrit, increasing collapsibility of the pharyngeal airway.

Therapeutic implantation requires three incisions directed to the neck, chest, and right rib space (between the 4th to 6th intercostal spaces), with an operative time of 90 minutes or less in experienced hands. The majority of patients are discharged on the day of the procedure. Morbidity remains low with minimal pain reported during recovery. The most common complication is that of temporary tongue weakness, which typically resolves within 2 to 3 weeks. While very infrequent, patients should be counseled on the risk of postoperative hematoma, which can precipitate infection and subsequent explant of the device. Average recovery time spans between 3 and 7 days with activation of the device 4 weeks after surgical implantation to allow for appropriate tissue healing and reduce the risk of dislodgement of the implanted components. In contrast to other surgical treatment options, UAS is also reversible with no underlying alteration to existing pharyngeal anatomy apart from external incisions created during the procedure.
 

Stimulation to titration

As the need for a multidisciplinary approach to salvage of patients failing first-line therapy for OSA continues to grow, UAS with its multilevel impact continues to be of key interest. In similar fashion to established medical therapies such as PAP and oral appliance therapy (OAT), close observation between sleep medicine specialists and the implanting surgeon during the adaptation period with attention paid to titration parameters such as stimulation duration, pulse width, amplitude, and polarity, allow optimization of response outcome.

The stimulation electrode, which is designed in the form of a cuff to envelope the anterior (protrusor) branches of the hypoglossal nerve receives electrical stimulation from the implanted pulse generator, implanted above the pectoralis muscle of the chest wall. This design allows for collaborative awake and overnight titration of the device as directed by a sleep medicine physician. Attention is paid not only to the voltage “strength” administered with each pulse but also the degree of synchronization between respiration and stimulation, as well as pattern of pulse administration. Our experience remains that true success and adaptation to therapy requires not just meticulous surgical technique but a diligent approach to postoperative therapeutic titration to achieve a comfortable, yet effective, voltage for maintaining airway patency. Thus, akin to initiation of CPAP, UAS requires regular follow-up and device fine-tuning with patient comfort taken into consideration to achieve optimal results, and patient expectation should be aligned with this process.
 

Current indications

Success in UAS relies heavily on appropriate presurgical evaluation and clinical phenotyping. The following surgical indications have been demonstrated in the Stimulation Therapy for Apnea Reduction (STAR) trial and subsequent 3-year clinical follow-up: AHI between 15 and 80 events/hour (with ≤ 25% central apneas) and a BMI ≤ 32.⁸

As OSA often results from multi-level airway collapse, UAS targets an increase not only in the diameter of the retropalatal/oropharyngeal airway space but also the antero-posterior hypopharyngeal airway. Original criteria for implantation excluded patients with a pattern of complete circumferential collapse (CCC) noted on dynamic airway evaluation during pre-implant drug-induced sleep endoscopy (DISE). DISE aims to precisely target dynamic airway collapse patterns during simulated (propofol or midazolom induced) sleep.
 

Future directions

The effects of UAS are dependent on upper-airway cross-sectional area, particularly diameter. In patients who demonstrate CCC, the anteroposterior direction of activation derived from the UAS stimulus is unable to overcome CCC. In a recent prospective study, our group demonstrated that CCC can be converted to an airway collapse pattern compatible with UAS implantation, using a modified palatopharyngoplasty prior to UAS implantation. By stabilizing the lateral walls of the oropharyngeal airway with pre-implant palatal surgery, UAS is able to successfully direct widening of the airway cross-sectional area in an antero-posterior fashion. This exciting finding potentially allows for expansion of current indications, thus opening treatment to a wider patient population.⁹ Still, UAS remains highly studied in a relatively uniform patient population with data in more diverse subsets requiring further directed attention to expand and better define optimal patient populations for treatment.

From the perspective of improving patient adaptation and tolerance in UAS, a well-established concept in the CPAP literature can be applied, as explained by the Starling resistor model. The starling resistor is comprised of two rigid tubes connected by a collapsible segment in between. In parallel, the pharynx is a collapsible muscular tube connected on either end by the nose/nasal cavity and the trachea – both of which are bony/cartilaginous, noncollapsible structures. As has been shown in the use of CPAP, the same pressure required to maintain stability of the collapsible muscular pharynx via nasal breathing may lead to pharyngeal collapse when applied orally.¹⁰ This concept has also been directed towards UAS with our clinical experience demonstrating that oro or oronasal breathers tend to require a higher amplitude to maintain airway patency versus nasal breathers. This is an important area for future-directed study as medically/surgically improving nasal breathing in UAS subjects may subsequently lower amplitude requirements and improve patient tolerance.

Future direction to allow for improvement in the technology for application in a broader populational segment, external or alternative device powering mechanisms, along with MRI Compatibility and reducing the number of required external incisions will continue to broaden the patient selection criteria. As we move from a “stimulation” to a precision-tailored “stimulation and titration” approach, the mid to long term data supporting UAS remains very promising with 5-year follow up demonstrating sustained polysomnographic and subjective reported outcomes in well selected patients.
 

Dr. Awad is Assistant Professor – Department of Otolaryngology/Head & Neck Surgery, and Chief – Division of Sleep Surgery; Northwestern University, Chicago, Illinois. Dr. Capasso is Associate Professor – Department of Otolaryngology/Head & Neck Surgery, and Chief – Division of Sleep Surgery; Stanford Hospital and Clinics, Stanford, California.

References

1. Schwartz AR et al. Electrical stimulation of the lingual musculature in obstructive sleep apnea. J Appl Physiol. 1996;81(2):643-52. doi: 10.1152/jappl.1996.81.2.643.

2. Ong AA et al. Efficacy of upper airway stimulation on collapse patterns observed during drug-induced sedation endoscopy. Otolaryngol Head Neck Surg. 2016;154(5):970-7. doi: 10.1177/0194599816636835.

3. Woodson BT et al. Three-year outcomes of cranial nerve stimulation for obstructive sleep apnea: The STAR trial. Otolaryngol Head Neck Surg. 2016;154(1):181-8. doi: 10.1177/0194599815616618.

4. Heiser C et al. Outcomes of upper airway stimulation for obstructive sleep apnea in a multicenter german postmarket study. Otolaryngol Head Neck Surg. 2017;156(2):378-84. doi: 10.1177/0194599816683378.

5. Gillespie MB et al. Upper airway stimulation for obstructive sleep apnea: Patient-reported outcomes after 48 months of follow-up. Otolaryngol Head Neck Surg. 2017;156(4):765-71. doi: 10.1177/0194599817691491.

6. Pietzsch JB et al. Long-term cost-effectiveness of upper airway stimulation for the treatment of obstructive sleep apnea: A model-based projection based on the star trial. Sleep. 2015;38(5):735-44. doi: 10.5665/sleep.4666.

7. Oliven A et al. Improved upper airway patency elicited by electrical stimulation of the hypoglossus nerves. Respiration. 1996;63(4):213-16. doi: 10.1159/000196547.

8. Strollo PJ et al. Upper-airway stimulation for obstructive sleep apnea. N Engl J Med. 2014;370(2):139-49. doi: 10.1056/NEJMoa1308659.

9. Liu YC et al. Palatopharyngoplasty resolves concentric collapse in patients ineligible for upper airway stimulation. Laryngoscope. Forthcoming.

10. De Andrade RGS et al. Impact of the type of mask on the effectiveness of and adherence to continuous positive airway pressure treatment for obstructive sleep apnea. J Bras Pneumol. 2014;40(6):658-68. doi: 10.1590/S1806-37132014000600010

The American Academy of Neurology (AAN) has issued a new guideline for the treatment of sleep problems in children and teenagers with autism spectrum disorders (ASD). The guideline was published online ahead of print Feb. 12 in Neurology.

“While up to 40% of children and teens in the general population will have sleep problems at some point during their childhood, such problems usually lessen with age,” lead author Ashura Williams Buckley, MD, director of the Sleep and Neurodevelopment Service at the National Institute of Mental Health in Bethesda, Md., said in a press release. “For children and teens with autism, sleep problems are more common and more likely to persist, resulting in poor health and poor quality of life. Some sleep problems may be directly related to autism, but others are not. Regardless, autism symptoms may make sleep problems worse.”
 

Few evidence-based treatments are available

Dr. Williams Buckley and colleagues developed the current guideline to evaluate which pharmacologic, behavioral, and complementary and alternative medicine (CAM) interventions improve bedtime resistance, sleep onset latency, sleep continuity, total sleep time, and daytime behavior in children and adolescents with ASD. The panel evaluated 900 abstracts of articles that had been included in systematic reviews, as well as 1,087 additional abstracts. One hundred thirty-nine articles were potentially relevant, 12 met criteria for data extraction, and eight were rated class III or higher and were included in the panel’s review.

The authors observed what they called a dearth of evidence-based treatments for sleep dysregulation in ASD. Evidence indicates that melatonin, with or without cognitive–behavioral therapy (CBT), improves several sleep outcomes, compared with placebo. “Evidence for other interventions is largely lacking,” wrote Dr. Williams Buckley and colleagues. They observed a lack of long-term safety data for melatonin in children, which they considered concerning, because melatonin affects the hypothalamic–gonadal axis and can potentially influence pubertal development.
 

Screening for comorbid conditions and concomitant medications

The guideline recommends that clinicians assess children with ASD and sleep disturbances for coexisting conditions and concomitant medications that could be contributing to these sleep disturbances. They should ensure that children receive appropriate treatment for coexisting conditions and adjust or discontinue potentially problematic medications appropriately, according to the guideline.

Furthermore, clinicians should counsel parents or guardians about behavioral strategies as a first-line treatment for improving sleep function. These strategies could be administered alone or with pharmacologic or neutraceutical approaches as needed, according to the authors. Suggested behavioral approaches include unmodified extinction (i.e., imposing a bedtime and ignoring a child’s protests), graduated extinction (i.e., ignoring protests for a specified period before responding), positive routines (i.e., establishing pre-bedtime calming rituals), and bedtime fading (i.e., putting a child to bed close to the time he or she begins to fall asleep).

If a child’s contributing coexisting conditions and medications have been addressed and behavioral strategies have not been helpful, clinicians should offer melatonin, according to the guideline. Because over-the-counter formulations contain variable concentrations of melatonin, clinicians should write a prescription for it or recommend high-purity pharmaceutical grade melatonin. The initial dose should be 1-3 mg/day at 60-30 minutes before bedtime. The dose can be titrated to 10 mg/day. Clinicians also should counsel children and their parents about potential adverse events of melatonin and the lack of long-term safety data, according to the guideline.

In addition, clinicians should advise children and parents that no evidence supports the routine use of weighted blankets or specialized mattress technology for improving sleep. Parents who ask about weighted blankets should be told that the reviewed trial reported no serious adverse events with this intervention, and that blankets could be a reasonable nonpharmacologic approach for some patients, according to the guideline.
 

Optimal outcome measures are undefined

Dr. Williams Buckley and colleagues also suggested areas for future research. Investigators have not yet defined optimal outcome measures (e.g., questionnaires, polysomnography, and actigraphy) that balance tolerability and accuracy, they wrote. Clinically important differences for most measures also have yet to be determined. Researchers should investigate whether long-term adverse events are associated with chronic melatonin use and study patients with ASD and comorbid mood disorders, wrote the authors. “Research tying the underlying neurobiology in early-life sleep disruption to behavior might help clinicians and researchers understand which treatments might work for which people with ASD,” they concluded.

The AAN supported the development of the guideline. Dr. Williams Buckley had no conflicts of interest. Six authors had conflicts of interest that the AAN deemed not significant enough to prevent their participation in the development of the guideline.

[email protected]

SOURCE: Williams Buckley A et al. Neurology. 2020;94:393-405. doi: 10.1212/WNL0000000000009033.

The American Academy of Neurology (AAN) has issued a new guideline for the treatment of sleep problems in children and teenagers with autism spectrum disorders (ASD). The guideline was published online ahead of print Feb. 12 in Neurology.

“While up to 40% of children and teens in the general population will have sleep problems at some point during their childhood, such problems usually lessen with age,” lead author Ashura Williams Buckley, MD, director of the Sleep and Neurodevelopment Service at the National Institute of Mental Health in Bethesda, Md., said in a press release. “For children and teens with autism, sleep problems are more common and more likely to persist, resulting in poor health and poor quality of life. Some sleep problems may be directly related to autism, but others are not. Regardless, autism symptoms may make sleep problems worse.”
 

Few evidence-based treatments are available

Dr. Williams Buckley and colleagues developed the current guideline to evaluate which pharmacologic, behavioral, and complementary and alternative medicine (CAM) interventions improve bedtime resistance, sleep onset latency, sleep continuity, total sleep time, and daytime behavior in children and adolescents with ASD. The panel evaluated 900 abstracts of articles that had been included in systematic reviews, as well as 1,087 additional abstracts. One hundred thirty-nine articles were potentially relevant, 12 met criteria for data extraction, and eight were rated class III or higher and were included in the panel’s review.

The authors observed what they called a dearth of evidence-based treatments for sleep dysregulation in ASD. Evidence indicates that melatonin, with or without cognitive–behavioral therapy (CBT), improves several sleep outcomes, compared with placebo. “Evidence for other interventions is largely lacking,” wrote Dr. Williams Buckley and colleagues. They observed a lack of long-term safety data for melatonin in children, which they considered concerning, because melatonin affects the hypothalamic–gonadal axis and can potentially influence pubertal development.
 

Screening for comorbid conditions and concomitant medications

The guideline recommends that clinicians assess children with ASD and sleep disturbances for coexisting conditions and concomitant medications that could be contributing to these sleep disturbances. They should ensure that children receive appropriate treatment for coexisting conditions and adjust or discontinue potentially problematic medications appropriately, according to the guideline.

Furthermore, clinicians should counsel parents or guardians about behavioral strategies as a first-line treatment for improving sleep function. These strategies could be administered alone or with pharmacologic or neutraceutical approaches as needed, according to the authors. Suggested behavioral approaches include unmodified extinction (i.e., imposing a bedtime and ignoring a child’s protests), graduated extinction (i.e., ignoring protests for a specified period before responding), positive routines (i.e., establishing pre-bedtime calming rituals), and bedtime fading (i.e., putting a child to bed close to the time he or she begins to fall asleep).

If a child’s contributing coexisting conditions and medications have been addressed and behavioral strategies have not been helpful, clinicians should offer melatonin, according to the guideline. Because over-the-counter formulations contain variable concentrations of melatonin, clinicians should write a prescription for it or recommend high-purity pharmaceutical grade melatonin. The initial dose should be 1-3 mg/day at 60-30 minutes before bedtime. The dose can be titrated to 10 mg/day. Clinicians also should counsel children and their parents about potential adverse events of melatonin and the lack of long-term safety data, according to the guideline.

In addition, clinicians should advise children and parents that no evidence supports the routine use of weighted blankets or specialized mattress technology for improving sleep. Parents who ask about weighted blankets should be told that the reviewed trial reported no serious adverse events with this intervention, and that blankets could be a reasonable nonpharmacologic approach for some patients, according to the guideline.
 

Optimal outcome measures are undefined

Dr. Williams Buckley and colleagues also suggested areas for future research. Investigators have not yet defined optimal outcome measures (e.g., questionnaires, polysomnography, and actigraphy) that balance tolerability and accuracy, they wrote. Clinically important differences for most measures also have yet to be determined. Researchers should investigate whether long-term adverse events are associated with chronic melatonin use and study patients with ASD and comorbid mood disorders, wrote the authors. “Research tying the underlying neurobiology in early-life sleep disruption to behavior might help clinicians and researchers understand which treatments might work for which people with ASD,” they concluded.

The AAN supported the development of the guideline. Dr. Williams Buckley had no conflicts of interest. Six authors had conflicts of interest that the AAN deemed not significant enough to prevent their participation in the development of the guideline.

[email protected]

SOURCE: Williams Buckley A et al. Neurology. 2020;94:393-405. doi: 10.1212/WNL0000000000009033.

The American Academy of Neurology (AAN) has issued a new guideline for the treatment of sleep problems in children and teenagers with autism spectrum disorders (ASD). The guideline was published online ahead of print Feb. 12 in Neurology.

“While up to 40% of children and teens in the general population will have sleep problems at some point during their childhood, such problems usually lessen with age,” lead author Ashura Williams Buckley, MD, director of the Sleep and Neurodevelopment Service at the National Institute of Mental Health in Bethesda, Md., said in a press release. “For children and teens with autism, sleep problems are more common and more likely to persist, resulting in poor health and poor quality of life. Some sleep problems may be directly related to autism, but others are not. Regardless, autism symptoms may make sleep problems worse.”
 

Few evidence-based treatments are available

Dr. Williams Buckley and colleagues developed the current guideline to evaluate which pharmacologic, behavioral, and complementary and alternative medicine (CAM) interventions improve bedtime resistance, sleep onset latency, sleep continuity, total sleep time, and daytime behavior in children and adolescents with ASD. The panel evaluated 900 abstracts of articles that had been included in systematic reviews, as well as 1,087 additional abstracts. One hundred thirty-nine articles were potentially relevant, 12 met criteria for data extraction, and eight were rated class III or higher and were included in the panel’s review.

The authors observed what they called a dearth of evidence-based treatments for sleep dysregulation in ASD. Evidence indicates that melatonin, with or without cognitive–behavioral therapy (CBT), improves several sleep outcomes, compared with placebo. “Evidence for other interventions is largely lacking,” wrote Dr. Williams Buckley and colleagues. They observed a lack of long-term safety data for melatonin in children, which they considered concerning, because melatonin affects the hypothalamic–gonadal axis and can potentially influence pubertal development.
 

Screening for comorbid conditions and concomitant medications

The guideline recommends that clinicians assess children with ASD and sleep disturbances for coexisting conditions and concomitant medications that could be contributing to these sleep disturbances. They should ensure that children receive appropriate treatment for coexisting conditions and adjust or discontinue potentially problematic medications appropriately, according to the guideline.

Furthermore, clinicians should counsel parents or guardians about behavioral strategies as a first-line treatment for improving sleep function. These strategies could be administered alone or with pharmacologic or neutraceutical approaches as needed, according to the authors. Suggested behavioral approaches include unmodified extinction (i.e., imposing a bedtime and ignoring a child’s protests), graduated extinction (i.e., ignoring protests for a specified period before responding), positive routines (i.e., establishing pre-bedtime calming rituals), and bedtime fading (i.e., putting a child to bed close to the time he or she begins to fall asleep).

If a child’s contributing coexisting conditions and medications have been addressed and behavioral strategies have not been helpful, clinicians should offer melatonin, according to the guideline. Because over-the-counter formulations contain variable concentrations of melatonin, clinicians should write a prescription for it or recommend high-purity pharmaceutical grade melatonin. The initial dose should be 1-3 mg/day at 60-30 minutes before bedtime. The dose can be titrated to 10 mg/day. Clinicians also should counsel children and their parents about potential adverse events of melatonin and the lack of long-term safety data, according to the guideline.

In addition, clinicians should advise children and parents that no evidence supports the routine use of weighted blankets or specialized mattress technology for improving sleep. Parents who ask about weighted blankets should be told that the reviewed trial reported no serious adverse events with this intervention, and that blankets could be a reasonable nonpharmacologic approach for some patients, according to the guideline.
 

Optimal outcome measures are undefined

Dr. Williams Buckley and colleagues also suggested areas for future research. Investigators have not yet defined optimal outcome measures (e.g., questionnaires, polysomnography, and actigraphy) that balance tolerability and accuracy, they wrote. Clinically important differences for most measures also have yet to be determined. Researchers should investigate whether long-term adverse events are associated with chronic melatonin use and study patients with ASD and comorbid mood disorders, wrote the authors. “Research tying the underlying neurobiology in early-life sleep disruption to behavior might help clinicians and researchers understand which treatments might work for which people with ASD,” they concluded.

The AAN supported the development of the guideline. Dr. Williams Buckley had no conflicts of interest. Six authors had conflicts of interest that the AAN deemed not significant enough to prevent their participation in the development of the guideline.

[email protected]

SOURCE: Williams Buckley A et al. Neurology. 2020;94:393-405. doi: 10.1212/WNL0000000000009033.

Modafinil exposure during pregnancy was associated with an approximately tripled risk of congenital malformations in a large Danish registry-based study.

Modafinil (Provigil) is commonly prescribed to address daytime sleepiness in narcolepsy and multiple sclerosis. An interim postmarketing safety analysis showed increased rates of major malformation in modafinil-exposed pregnancies, so the manufacturer issued an alert advising health care professionals of this safety signal in June 2019, wrote Per Damkier, MD, PhD, corresponding author of a JAMA research letter reporting the Danish study results. The postmarketing study had shown a major malformation rate of about 15% in modafinil-exposed pregnancies, much higher than the 3% background rate.

Dr. Damkier and Anne Broe, MD, PhD, both of the department of clinical biochemistry and pharmacology at Odense (Denmark) University Hospital, compared outcomes for pregnant women who were prescribed modafinil at any point during the first trimester of pregnancy with those who were prescribed an active comparator, methylphenidate, as well as with those who had neither exposure. Methylphenidate is not associated with congenital malformations and is used for indications similar to modafinil.

Looking at all pregnancies for whom complete records existed in Danish health registries between 2004 and 2017, the investigators found 49 modafinil-exposed pregnancies, 963 methylphenidate-exposed pregnancies, and 828,644 pregnancies with neither exposure.

Six major congenital malformations occurred in the modafinil-exposed group for an absolute risk of 12%. Major malformations occurred in 43 (4.5%) of the methylphenidate-exposed group and 32,466 (3.9%) of the unexposed group.

Using the extensive data available in public registries, the authors were able to perform logistic regression to adjust for concomitant use of other psychotropic medication; comorbidities such as diabetes and hypertension; and demographic and anthropometric measures such as maternal age, smoking status, and body mass index.

After this statistical adjustment, the researchers found that modafinil exposure during the first trimester of pregnancy was associated with an odds ratio of 3.4 (95% confidence interval, 1.2-9.7) for major congenital malformation, compared with first-trimester methylphenidate exposure. Compared with the unexposed cohort, modafinil-exposed pregnancies had an adjusted odds ratio of 2.7 (95% CI, 1.1-6.9) for major congenital malformation.

A total of 13 (27%) women who took modafinil had multiple sclerosis, but the authors excluded women who’d received a prescription for the multiple sclerosis drug teriflunomide (Aubagio), a known teratogen. Sleep disorders were reported for 39% of modafinil users, compared with 4.5% of methylphenidate users. Rates of psychoactive drug use were 41% for the modafinil group and 30% for the methylphenidate group.

The authors acknowledged the possibility of residual confounders affecting their results, and of the statistical problems with the very small sample size of modafinil-exposed pregnancies. Also, actual medication use – rather than prescription redemption – wasn’t captured in the study.

The study was partially funded by the Novo Nordisk Foundation. The authors reported no conflicts of interest.

[email protected]

SOURCE: Damkier P, Broe A. JAMA. 2020;323(4):374-6.

Modafinil exposure during pregnancy was associated with an approximately tripled risk of congenital malformations in a large Danish registry-based study.

Modafinil (Provigil) is commonly prescribed to address daytime sleepiness in narcolepsy and multiple sclerosis. An interim postmarketing safety analysis showed increased rates of major malformation in modafinil-exposed pregnancies, so the manufacturer issued an alert advising health care professionals of this safety signal in June 2019, wrote Per Damkier, MD, PhD, corresponding author of a JAMA research letter reporting the Danish study results. The postmarketing study had shown a major malformation rate of about 15% in modafinil-exposed pregnancies, much higher than the 3% background rate.

Dr. Damkier and Anne Broe, MD, PhD, both of the department of clinical biochemistry and pharmacology at Odense (Denmark) University Hospital, compared outcomes for pregnant women who were prescribed modafinil at any point during the first trimester of pregnancy with those who were prescribed an active comparator, methylphenidate, as well as with those who had neither exposure. Methylphenidate is not associated with congenital malformations and is used for indications similar to modafinil.

Looking at all pregnancies for whom complete records existed in Danish health registries between 2004 and 2017, the investigators found 49 modafinil-exposed pregnancies, 963 methylphenidate-exposed pregnancies, and 828,644 pregnancies with neither exposure.

Six major congenital malformations occurred in the modafinil-exposed group for an absolute risk of 12%. Major malformations occurred in 43 (4.5%) of the methylphenidate-exposed group and 32,466 (3.9%) of the unexposed group.

Using the extensive data available in public registries, the authors were able to perform logistic regression to adjust for concomitant use of other psychotropic medication; comorbidities such as diabetes and hypertension; and demographic and anthropometric measures such as maternal age, smoking status, and body mass index.

After this statistical adjustment, the researchers found that modafinil exposure during the first trimester of pregnancy was associated with an odds ratio of 3.4 (95% confidence interval, 1.2-9.7) for major congenital malformation, compared with first-trimester methylphenidate exposure. Compared with the unexposed cohort, modafinil-exposed pregnancies had an adjusted odds ratio of 2.7 (95% CI, 1.1-6.9) for major congenital malformation.

A total of 13 (27%) women who took modafinil had multiple sclerosis, but the authors excluded women who’d received a prescription for the multiple sclerosis drug teriflunomide (Aubagio), a known teratogen. Sleep disorders were reported for 39% of modafinil users, compared with 4.5% of methylphenidate users. Rates of psychoactive drug use were 41% for the modafinil group and 30% for the methylphenidate group.

The authors acknowledged the possibility of residual confounders affecting their results, and of the statistical problems with the very small sample size of modafinil-exposed pregnancies. Also, actual medication use – rather than prescription redemption – wasn’t captured in the study.

The study was partially funded by the Novo Nordisk Foundation. The authors reported no conflicts of interest.

[email protected]

SOURCE: Damkier P, Broe A. JAMA. 2020;323(4):374-6.

Modafinil exposure during pregnancy was associated with an approximately tripled risk of congenital malformations in a large Danish registry-based study.

Modafinil (Provigil) is commonly prescribed to address daytime sleepiness in narcolepsy and multiple sclerosis. An interim postmarketing safety analysis showed increased rates of major malformation in modafinil-exposed pregnancies, so the manufacturer issued an alert advising health care professionals of this safety signal in June 2019, wrote Per Damkier, MD, PhD, corresponding author of a JAMA research letter reporting the Danish study results. The postmarketing study had shown a major malformation rate of about 15% in modafinil-exposed pregnancies, much higher than the 3% background rate.

Dr. Damkier and Anne Broe, MD, PhD, both of the department of clinical biochemistry and pharmacology at Odense (Denmark) University Hospital, compared outcomes for pregnant women who were prescribed modafinil at any point during the first trimester of pregnancy with those who were prescribed an active comparator, methylphenidate, as well as with those who had neither exposure. Methylphenidate is not associated with congenital malformations and is used for indications similar to modafinil.

Looking at all pregnancies for whom complete records existed in Danish health registries between 2004 and 2017, the investigators found 49 modafinil-exposed pregnancies, 963 methylphenidate-exposed pregnancies, and 828,644 pregnancies with neither exposure.

Six major congenital malformations occurred in the modafinil-exposed group for an absolute risk of 12%. Major malformations occurred in 43 (4.5%) of the methylphenidate-exposed group and 32,466 (3.9%) of the unexposed group.

Using the extensive data available in public registries, the authors were able to perform logistic regression to adjust for concomitant use of other psychotropic medication; comorbidities such as diabetes and hypertension; and demographic and anthropometric measures such as maternal age, smoking status, and body mass index.

After this statistical adjustment, the researchers found that modafinil exposure during the first trimester of pregnancy was associated with an odds ratio of 3.4 (95% confidence interval, 1.2-9.7) for major congenital malformation, compared with first-trimester methylphenidate exposure. Compared with the unexposed cohort, modafinil-exposed pregnancies had an adjusted odds ratio of 2.7 (95% CI, 1.1-6.9) for major congenital malformation.

A total of 13 (27%) women who took modafinil had multiple sclerosis, but the authors excluded women who’d received a prescription for the multiple sclerosis drug teriflunomide (Aubagio), a known teratogen. Sleep disorders were reported for 39% of modafinil users, compared with 4.5% of methylphenidate users. Rates of psychoactive drug use were 41% for the modafinil group and 30% for the methylphenidate group.

The authors acknowledged the possibility of residual confounders affecting their results, and of the statistical problems with the very small sample size of modafinil-exposed pregnancies. Also, actual medication use – rather than prescription redemption – wasn’t captured in the study.

The study was partially funded by the Novo Nordisk Foundation. The authors reported no conflicts of interest.

[email protected]

SOURCE: Damkier P, Broe A. JAMA. 2020;323(4):374-6.

Patients suffering from chronic pain who take medicinal cannabis to initiate and maintain sleep appear to experience short-term benefit, but long-term use may ultimately disrupt slumber, new research shows.

Investigators found whole-plant medical cannabis use was associated with fewer problems with respect to waking up at night, but they also found that frequent medical cannabis use was associated with more problems initiating and maintaining sleep.

LPETTET/Getty Images

A common problem

Estimates suggest chronic pain affects up to 37% of adults in the developed world. Individuals who suffer chronic pain often experience comorbid insomnia, which includes difficulty initiating sleep, sleep disruption, and early morning wakening.

For its part, medical cannabis to treat chronic pain symptoms and manage sleep problems has been widely reported as a prime motivation for medical cannabis use. Indeed, previous studies have concluded that the endocannabinoid system plays a role in sleep regulation, including sleep promotion and maintenance.

In recent years, investigators have reported the beneficial effects of medical cannabis for sleep. Nevertheless, some preclinical research has also concluded that chronic administration of tetrahydrocannabinol may result in tolerance to the sleep-enhancing effects of cannabis.

With that in mind, the researchers set out to examine the potential impact of whole-plant medicinal cannabis on sleep problems experienced by middle-aged patients suffering from chronic pain.

“People are self-reporting that they’re using cannabis for sleep and that it helps, but as we know, just because people are reporting that it works doesn’t mean that it will hold up in research,” Dr. Sznitman said.

The study included 128 individuals (mean age, 61±6 years; 51% females) with chronic neuropathic pain: 66 were medical cannabis users and 62 were not.

Three indicators of insomnia were measured using the 7-point Likert scale to assess issues with sleep initiation and maintenance.

In addition, investigators collected sociodemographic information, as well as data on daily consumption of tobacco, frequency of alcohol use, and pain severity. Finally, they collected patient data on the use of sleep-aid medications during the past month as well as tricyclic antidepressant use.
 

Frequent use, more sleep problems?

On average, medical cannabis users were 3 years younger than their nonusing counterparts (mean age, 60±6 vs. 63±6 years, respectively, P = .003) and more likely to be male (58% vs 40%, respectively, P = .038). Otherwise, the two groups were comparable.

Medical cannabis users reported taking the drug for an average of 4 years, at an average quantity of 31 g per month. The primary mode of administration was smoking (68.6%), followed by oil extracts (21.4%) and vaporization (20%).

Results showed that, of the total sample, 24.1% reported always waking up early and not falling back to sleep, 20.2% reported always having difficulty falling asleep, and 27.2% reported always waking up during the night.

After adjusting for patient age, sex, pain level, and use of sleep medications and antidepressants, medical cannabis use was associated with fewer problems with waking up at night, compared with nonmedical cannabis use. No differences were found between groups with respect to problems falling asleep or waking up early without being able to fall back to sleep, Dr. Sznitman and associates reported.

The final analysis of a subsample of patients that only included medical cannabis users showed frequency of medical cannabis use was associated with sleep problems, they said.

Specifically, more frequent cannabis use was associated with more problems related to waking up at night, as well as problems falling asleep.

Sleep problems associated with frequent medical cannabis use may signal the development of tolerance to the agent. However, frequent users of medical cannabis also maybsuffer pain or other comorbidities, which, in turn, may be linked to more sleep problems.

Either way, Dr. Sznitman said the study might open the door to another treatment option for patients suffering from chronic pain who struggle with sleep.

“If future research shows that the effect of medical cannabis on sleep is a consistent one, then we may be adding a new therapy for sleep problems, which are huge in society and especially in chronic pain patients,” she said.
 

Early days

Commenting on the findings in an interview, Ryan G. Vandrey, PhD, who was not involved in the study, said the findings are in line with previous research.

“I think the results make sense with respect to the data I’ve collected and from what I’ve seen,” said Dr. Vandrey, associate professor of psychiatry and behavioral sciences at Johns Hopkins Medicine in Baltimore.

“We typically only want to use sleep medications for short periods of time,” he continued. “When you think about recommended prescribing practices for any hypnotic medication, it’s usually short term, 2 weeks or less. Longer-term use often leads to tolerance, dependence, and withdrawal symptoms when the medication is stopped, which leads to an exacerbation of disordered sleep,” Dr. Vandrey said.

Nevertheless, he urged caution when interpreting the results.

“I think the study warrants caution about long-term daily use of cannabinoids with respect to sleep,” he said. “But we need more detailed evaluations, as the trial wasn’t testing a defined product, specific dose, or dose regimen.

“In addition, this was all done in the context of people with chronic pain and not treating disordered sleep or insomnia, but the study highlights the importance of recognizing that long-term chronic use of cannabis is not likely to fully resolve sleep problems.”

Dr. Sznitman agreed that the research is still in its very early stages.

“We’re still far from saying we have the evidence to support the use of medical cannabis for sleep,” she said. “For in the end it was just a cross-sectional, observational study, so we cannot say anything about cause and effect. But if these results pan out, they could be far-reaching and exciting.”

The study was funded by the University of Haifa and Rambam Hospital in Israel, and by the Evelyn Lipper Foundation. Dr. Sznitman and Dr. Vandrey have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.
 

Patients suffering from chronic pain who take medicinal cannabis to initiate and maintain sleep appear to experience short-term benefit, but long-term use may ultimately disrupt slumber, new research shows.

Investigators found whole-plant medical cannabis use was associated with fewer problems with respect to waking up at night, but they also found that frequent medical cannabis use was associated with more problems initiating and maintaining sleep.

LPETTET/Getty Images

A common problem

Estimates suggest chronic pain affects up to 37% of adults in the developed world. Individuals who suffer chronic pain often experience comorbid insomnia, which includes difficulty initiating sleep, sleep disruption, and early morning wakening.

For its part, medical cannabis to treat chronic pain symptoms and manage sleep problems has been widely reported as a prime motivation for medical cannabis use. Indeed, previous studies have concluded that the endocannabinoid system plays a role in sleep regulation, including sleep promotion and maintenance.

In recent years, investigators have reported the beneficial effects of medical cannabis for sleep. Nevertheless, some preclinical research has also concluded that chronic administration of tetrahydrocannabinol may result in tolerance to the sleep-enhancing effects of cannabis.

With that in mind, the researchers set out to examine the potential impact of whole-plant medicinal cannabis on sleep problems experienced by middle-aged patients suffering from chronic pain.

“People are self-reporting that they’re using cannabis for sleep and that it helps, but as we know, just because people are reporting that it works doesn’t mean that it will hold up in research,” Dr. Sznitman said.

The study included 128 individuals (mean age, 61±6 years; 51% females) with chronic neuropathic pain: 66 were medical cannabis users and 62 were not.

Three indicators of insomnia were measured using the 7-point Likert scale to assess issues with sleep initiation and maintenance.

In addition, investigators collected sociodemographic information, as well as data on daily consumption of tobacco, frequency of alcohol use, and pain severity. Finally, they collected patient data on the use of sleep-aid medications during the past month as well as tricyclic antidepressant use.
 

Frequent use, more sleep problems?

On average, medical cannabis users were 3 years younger than their nonusing counterparts (mean age, 60±6 vs. 63±6 years, respectively, P = .003) and more likely to be male (58% vs 40%, respectively, P = .038). Otherwise, the two groups were comparable.

Medical cannabis users reported taking the drug for an average of 4 years, at an average quantity of 31 g per month. The primary mode of administration was smoking (68.6%), followed by oil extracts (21.4%) and vaporization (20%).

Results showed that, of the total sample, 24.1% reported always waking up early and not falling back to sleep, 20.2% reported always having difficulty falling asleep, and 27.2% reported always waking up during the night.

After adjusting for patient age, sex, pain level, and use of sleep medications and antidepressants, medical cannabis use was associated with fewer problems with waking up at night, compared with nonmedical cannabis use. No differences were found between groups with respect to problems falling asleep or waking up early without being able to fall back to sleep, Dr. Sznitman and associates reported.

The final analysis of a subsample of patients that only included medical cannabis users showed frequency of medical cannabis use was associated with sleep problems, they said.

Specifically, more frequent cannabis use was associated with more problems related to waking up at night, as well as problems falling asleep.

Sleep problems associated with frequent medical cannabis use may signal the development of tolerance to the agent. However, frequent users of medical cannabis also maybsuffer pain or other comorbidities, which, in turn, may be linked to more sleep problems.

Either way, Dr. Sznitman said the study might open the door to another treatment option for patients suffering from chronic pain who struggle with sleep.

“If future research shows that the effect of medical cannabis on sleep is a consistent one, then we may be adding a new therapy for sleep problems, which are huge in society and especially in chronic pain patients,” she said.
 

Early days

Commenting on the findings in an interview, Ryan G. Vandrey, PhD, who was not involved in the study, said the findings are in line with previous research.

“I think the results make sense with respect to the data I’ve collected and from what I’ve seen,” said Dr. Vandrey, associate professor of psychiatry and behavioral sciences at Johns Hopkins Medicine in Baltimore.

“We typically only want to use sleep medications for short periods of time,” he continued. “When you think about recommended prescribing practices for any hypnotic medication, it’s usually short term, 2 weeks or less. Longer-term use often leads to tolerance, dependence, and withdrawal symptoms when the medication is stopped, which leads to an exacerbation of disordered sleep,” Dr. Vandrey said.

Nevertheless, he urged caution when interpreting the results.

“I think the study warrants caution about long-term daily use of cannabinoids with respect to sleep,” he said. “But we need more detailed evaluations, as the trial wasn’t testing a defined product, specific dose, or dose regimen.

“In addition, this was all done in the context of people with chronic pain and not treating disordered sleep or insomnia, but the study highlights the importance of recognizing that long-term chronic use of cannabis is not likely to fully resolve sleep problems.”

Dr. Sznitman agreed that the research is still in its very early stages.

“We’re still far from saying we have the evidence to support the use of medical cannabis for sleep,” she said. “For in the end it was just a cross-sectional, observational study, so we cannot say anything about cause and effect. But if these results pan out, they could be far-reaching and exciting.”

The study was funded by the University of Haifa and Rambam Hospital in Israel, and by the Evelyn Lipper Foundation. Dr. Sznitman and Dr. Vandrey have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.
 

Patients suffering from chronic pain who take medicinal cannabis to initiate and maintain sleep appear to experience short-term benefit, but long-term use may ultimately disrupt slumber, new research shows.

Investigators found whole-plant medical cannabis use was associated with fewer problems with respect to waking up at night, but they also found that frequent medical cannabis use was associated with more problems initiating and maintaining sleep.

LPETTET/Getty Images

A common problem

Estimates suggest chronic pain affects up to 37% of adults in the developed world. Individuals who suffer chronic pain often experience comorbid insomnia, which includes difficulty initiating sleep, sleep disruption, and early morning wakening.

For its part, medical cannabis to treat chronic pain symptoms and manage sleep problems has been widely reported as a prime motivation for medical cannabis use. Indeed, previous studies have concluded that the endocannabinoid system plays a role in sleep regulation, including sleep promotion and maintenance.

In recent years, investigators have reported the beneficial effects of medical cannabis for sleep. Nevertheless, some preclinical research has also concluded that chronic administration of tetrahydrocannabinol may result in tolerance to the sleep-enhancing effects of cannabis.

With that in mind, the researchers set out to examine the potential impact of whole-plant medicinal cannabis on sleep problems experienced by middle-aged patients suffering from chronic pain.

“People are self-reporting that they’re using cannabis for sleep and that it helps, but as we know, just because people are reporting that it works doesn’t mean that it will hold up in research,” Dr. Sznitman said.

The study included 128 individuals (mean age, 61±6 years; 51% females) with chronic neuropathic pain: 66 were medical cannabis users and 62 were not.

Three indicators of insomnia were measured using the 7-point Likert scale to assess issues with sleep initiation and maintenance.

In addition, investigators collected sociodemographic information, as well as data on daily consumption of tobacco, frequency of alcohol use, and pain severity. Finally, they collected patient data on the use of sleep-aid medications during the past month as well as tricyclic antidepressant use.
 

Frequent use, more sleep problems?

On average, medical cannabis users were 3 years younger than their nonusing counterparts (mean age, 60±6 vs. 63±6 years, respectively, P = .003) and more likely to be male (58% vs 40%, respectively, P = .038). Otherwise, the two groups were comparable.

Medical cannabis users reported taking the drug for an average of 4 years, at an average quantity of 31 g per month. The primary mode of administration was smoking (68.6%), followed by oil extracts (21.4%) and vaporization (20%).

Results showed that, of the total sample, 24.1% reported always waking up early and not falling back to sleep, 20.2% reported always having difficulty falling asleep, and 27.2% reported always waking up during the night.

After adjusting for patient age, sex, pain level, and use of sleep medications and antidepressants, medical cannabis use was associated with fewer problems with waking up at night, compared with nonmedical cannabis use. No differences were found between groups with respect to problems falling asleep or waking up early without being able to fall back to sleep, Dr. Sznitman and associates reported.

The final analysis of a subsample of patients that only included medical cannabis users showed frequency of medical cannabis use was associated with sleep problems, they said.

Specifically, more frequent cannabis use was associated with more problems related to waking up at night, as well as problems falling asleep.

Sleep problems associated with frequent medical cannabis use may signal the development of tolerance to the agent. However, frequent users of medical cannabis also maybsuffer pain or other comorbidities, which, in turn, may be linked to more sleep problems.

Either way, Dr. Sznitman said the study might open the door to another treatment option for patients suffering from chronic pain who struggle with sleep.

“If future research shows that the effect of medical cannabis on sleep is a consistent one, then we may be adding a new therapy for sleep problems, which are huge in society and especially in chronic pain patients,” she said.
 

Early days

Commenting on the findings in an interview, Ryan G. Vandrey, PhD, who was not involved in the study, said the findings are in line with previous research.

“I think the results make sense with respect to the data I’ve collected and from what I’ve seen,” said Dr. Vandrey, associate professor of psychiatry and behavioral sciences at Johns Hopkins Medicine in Baltimore.

“We typically only want to use sleep medications for short periods of time,” he continued. “When you think about recommended prescribing practices for any hypnotic medication, it’s usually short term, 2 weeks or less. Longer-term use often leads to tolerance, dependence, and withdrawal symptoms when the medication is stopped, which leads to an exacerbation of disordered sleep,” Dr. Vandrey said.

Nevertheless, he urged caution when interpreting the results.

“I think the study warrants caution about long-term daily use of cannabinoids with respect to sleep,” he said. “But we need more detailed evaluations, as the trial wasn’t testing a defined product, specific dose, or dose regimen.

“In addition, this was all done in the context of people with chronic pain and not treating disordered sleep or insomnia, but the study highlights the importance of recognizing that long-term chronic use of cannabis is not likely to fully resolve sleep problems.”

Dr. Sznitman agreed that the research is still in its very early stages.

“We’re still far from saying we have the evidence to support the use of medical cannabis for sleep,” she said. “For in the end it was just a cross-sectional, observational study, so we cannot say anything about cause and effect. But if these results pan out, they could be far-reaching and exciting.”

The study was funded by the University of Haifa and Rambam Hospital in Israel, and by the Evelyn Lipper Foundation. Dr. Sznitman and Dr. Vandrey have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.
 

Insomnia is a common problem for veterans with PTSD, and the frequency of sleep problems is associated with increasing severity of PTSD, according to a study published in of the Journal of Traumatic Stress.

Raymond C. Rosen, PhD, of the New England Research Institutes, Watertown, Mass., and coauthors wrote that exploration of the relationship between PTSD and insomnia is complicated by the fact that it can be difficult to separate out disturbed sleep from other elements of PTSD, and because of the presence of other comorbidities in veterans, such as depression and traumatic brain injury.

The cohort study involved 1,643 veterans – roughly equal numbers of women and men – of Iraq and Afghanistan. Around two-thirds of the cohort had a diagnosis of PTSD. The participants completed a self-administered survey online or by mail, and were also assessed in a telephone interview, then followed up within 2-4 years.

While the prevalence of sleep problems was high across the cohort, the study found that 74% of participants with PTSD at baseline said they had experienced sleep difficulties for at least half of the previous 30 days, and one-third had been prescribed for a sedative-hypnotic drug in the past year.

In comparison, veterans without PTSD had fewer sleep problems and were prescribed significantly fewer sedative-hypnotic drugs.

The prevalence of sleep problems was similar in men and women with PTSD, although women had significantly higher rates of sedative-hypnotic prescriptions than men (40.4% vs. 35%, P = .006). A similar gender difference in prescription rates was seen in individuals without PTSD.

The study found that, although there was only a weak association between the severity of PTSD symptoms at baseline and the frequency of sleep problems at follow-up, there was a stronger association in reverse. Veterans with a higher frequency of sleep problems at baseline showed a significant increase in PTSD symptoms at follow-up.

The authors commented that this was in line with previous studies finding a similar effect of sleep disturbance on PTSD severity, both in military personnel and civilians.

“From a neurobiological perspective, it has been proposed that chronic sleep loss can lead to emotional dysregulation or heightened autonomic arousal, which in turn may be a risk factor for PTSD in trauma-exposed individuals,” they wrote. “It has also been proposed that prior sleep disturbance may attenuate the effects of extinction learning, leading to more enduring or severe symptoms in trauma-exposed individuals with concomitant sleep disorders.”

Given this association, the authors called for more attention to be given to identifying, diagnosing, and treating sleep disorders in veterans with and without PTSD.

The authors noted that they did not have access to polysomnographic data for participants, and were also unable to assess the prevalence, frequency, or intensity of nightmares in the cohort.

The study was supported by the Department of Defense. Conflict of interest disclosures were unavailable.

SOURCE: Rosen RC et al. J Trauma Stress. 2020;32:936-45.

Insomnia is a common problem for veterans with PTSD, and the frequency of sleep problems is associated with increasing severity of PTSD, according to a study published in of the Journal of Traumatic Stress.

Raymond C. Rosen, PhD, of the New England Research Institutes, Watertown, Mass., and coauthors wrote that exploration of the relationship between PTSD and insomnia is complicated by the fact that it can be difficult to separate out disturbed sleep from other elements of PTSD, and because of the presence of other comorbidities in veterans, such as depression and traumatic brain injury.

The cohort study involved 1,643 veterans – roughly equal numbers of women and men – of Iraq and Afghanistan. Around two-thirds of the cohort had a diagnosis of PTSD. The participants completed a self-administered survey online or by mail, and were also assessed in a telephone interview, then followed up within 2-4 years.

While the prevalence of sleep problems was high across the cohort, the study found that 74% of participants with PTSD at baseline said they had experienced sleep difficulties for at least half of the previous 30 days, and one-third had been prescribed for a sedative-hypnotic drug in the past year.

In comparison, veterans without PTSD had fewer sleep problems and were prescribed significantly fewer sedative-hypnotic drugs.

The prevalence of sleep problems was similar in men and women with PTSD, although women had significantly higher rates of sedative-hypnotic prescriptions than men (40.4% vs. 35%, P = .006). A similar gender difference in prescription rates was seen in individuals without PTSD.

The study found that, although there was only a weak association between the severity of PTSD symptoms at baseline and the frequency of sleep problems at follow-up, there was a stronger association in reverse. Veterans with a higher frequency of sleep problems at baseline showed a significant increase in PTSD symptoms at follow-up.

The authors commented that this was in line with previous studies finding a similar effect of sleep disturbance on PTSD severity, both in military personnel and civilians.

“From a neurobiological perspective, it has been proposed that chronic sleep loss can lead to emotional dysregulation or heightened autonomic arousal, which in turn may be a risk factor for PTSD in trauma-exposed individuals,” they wrote. “It has also been proposed that prior sleep disturbance may attenuate the effects of extinction learning, leading to more enduring or severe symptoms in trauma-exposed individuals with concomitant sleep disorders.”

Given this association, the authors called for more attention to be given to identifying, diagnosing, and treating sleep disorders in veterans with and without PTSD.

The authors noted that they did not have access to polysomnographic data for participants, and were also unable to assess the prevalence, frequency, or intensity of nightmares in the cohort.

The study was supported by the Department of Defense. Conflict of interest disclosures were unavailable.

SOURCE: Rosen RC et al. J Trauma Stress. 2020;32:936-45.

Insomnia is a common problem for veterans with PTSD, and the frequency of sleep problems is associated with increasing severity of PTSD, according to a study published in of the Journal of Traumatic Stress.

Raymond C. Rosen, PhD, of the New England Research Institutes, Watertown, Mass., and coauthors wrote that exploration of the relationship between PTSD and insomnia is complicated by the fact that it can be difficult to separate out disturbed sleep from other elements of PTSD, and because of the presence of other comorbidities in veterans, such as depression and traumatic brain injury.

The cohort study involved 1,643 veterans – roughly equal numbers of women and men – of Iraq and Afghanistan. Around two-thirds of the cohort had a diagnosis of PTSD. The participants completed a self-administered survey online or by mail, and were also assessed in a telephone interview, then followed up within 2-4 years.

While the prevalence of sleep problems was high across the cohort, the study found that 74% of participants with PTSD at baseline said they had experienced sleep difficulties for at least half of the previous 30 days, and one-third had been prescribed for a sedative-hypnotic drug in the past year.

In comparison, veterans without PTSD had fewer sleep problems and were prescribed significantly fewer sedative-hypnotic drugs.

The prevalence of sleep problems was similar in men and women with PTSD, although women had significantly higher rates of sedative-hypnotic prescriptions than men (40.4% vs. 35%, P = .006). A similar gender difference in prescription rates was seen in individuals without PTSD.

The study found that, although there was only a weak association between the severity of PTSD symptoms at baseline and the frequency of sleep problems at follow-up, there was a stronger association in reverse. Veterans with a higher frequency of sleep problems at baseline showed a significant increase in PTSD symptoms at follow-up.

The authors commented that this was in line with previous studies finding a similar effect of sleep disturbance on PTSD severity, both in military personnel and civilians.

“From a neurobiological perspective, it has been proposed that chronic sleep loss can lead to emotional dysregulation or heightened autonomic arousal, which in turn may be a risk factor for PTSD in trauma-exposed individuals,” they wrote. “It has also been proposed that prior sleep disturbance may attenuate the effects of extinction learning, leading to more enduring or severe symptoms in trauma-exposed individuals with concomitant sleep disorders.”

Given this association, the authors called for more attention to be given to identifying, diagnosing, and treating sleep disorders in veterans with and without PTSD.

The authors noted that they did not have access to polysomnographic data for participants, and were also unable to assess the prevalence, frequency, or intensity of nightmares in the cohort.

The study was supported by the Department of Defense. Conflict of interest disclosures were unavailable.

SOURCE: Rosen RC et al. J Trauma Stress. 2020;32:936-45.

Adenotonsillectomy does not improve cognitive function in preschoolers with mild obstructive sleep apnea, according to a prospective study.

The study showed no significant difference in global IQ at 12 months between children who underwent adenotonsillectomy and those who did not. However, as expected, the adenotonsillectomy group did experience improvements in sleep.

deyangeorgiev/thinkstockphotos.com

[email protected]

SOURCE: Waters KA et al. Pediatrics. 2020;145(2):e20191450; Francis DO and Lam DJ. Pediatrics. 2020;145(2):e20192479.

Adenotonsillectomy does not improve cognitive function in preschoolers with mild obstructive sleep apnea, according to a prospective study.

The study showed no significant difference in global IQ at 12 months between children who underwent adenotonsillectomy and those who did not. However, as expected, the adenotonsillectomy group did experience improvements in sleep.

deyangeorgiev/thinkstockphotos.com

[email protected]

SOURCE: Waters KA et al. Pediatrics. 2020;145(2):e20191450; Francis DO and Lam DJ. Pediatrics. 2020;145(2):e20192479.

Adenotonsillectomy does not improve cognitive function in preschoolers with mild obstructive sleep apnea, according to a prospective study.

The study showed no significant difference in global IQ at 12 months between children who underwent adenotonsillectomy and those who did not. However, as expected, the adenotonsillectomy group did experience improvements in sleep.

deyangeorgiev/thinkstockphotos.com

[email protected]

SOURCE: Waters KA et al. Pediatrics. 2020;145(2):e20191450; Francis DO and Lam DJ. Pediatrics. 2020;145(2):e20192479.

Insomnia, restless legs syndrome (RLS), and frequent snoring were significantly associated with subsequent ADHD symptoms in a large longitudinal study of adolescents in China.

Investigators twice assessed 7,072 middle and high school students participating in the larger longitudinal Shandong Adolescent Behavior & Health Cohort – in 2015 and 1 year later in 2016 – for sleep, mental health, psychosocial factors (using the self-administered Adolescent Health Questionnaire, or AHQ), and for ADHD symptoms (using the Youth Self-Report, or YSR, of the Achenbach Child Behavior Checklist).

At baseline, ADHD symptoms were reported by 7.6% of adolescents and were significantly correlated, after adjusting for adolescent and family covariates, with all the sleep variables studied: sleep duration of 7 hours or less per night, insomnia symptoms, poor sleep quality, RLS symptoms, frequent snorting, and hypnotic use, reported Xianchen Liu, MD, PhD, of Shandong (China) University, and coinvestigators. They noted a dose-response relationship between sleep duration and the odds of having ADHD symptoms.

At 1-year follow-up, 4.5% of the 6,531 participants who did not have ADHD symptoms at baseline now reported them. After adjustments for covariates, any insomnia (odds ratio, 1.48), difficulty initiating sleep (one of the insomnia symptoms) (OR, 2.09), RLS (OR, 1.47), and frequent snoring (OR, 2.30) at baseline were each significantly associated with development of incident ADHD symptoms and with ADHD severity at 1 year, they reported in Sleep.

“Given the fact that sleep disorders in adolescents are often underdiagnosed and untreated primarily in the primary care setting, our findings highlight that clinicians should assess and manage short sleep duration and sleep problems for effective treatment of ADHD in adolescents,” as well as for prevention, they wrote.

The AHQ includes questions that assess nocturnal sleep duration and sleep problems during the past month. The adolescent and family variables that were selected as covariates and controlled for include cigarette smoking, alcohol drinking, use of mental health services, chronic physical diseases, and parental education and occupation. Depression was also a covariate but was assessed through a different scale.

The YSR measures eight ADHD symptoms during the past 6 months on a 3-point scale (not true, somewhat or sometimes true, and very true or often true). The adolescent participants of this study were in grades 7, 8, and 10 at baseline. Their mean age at baseline was 15 years; half were male. They were part of the larger Shandong Adolescent and Behavioral Cohort, a longitudinal study of almost 12,000 adolescents.

Growing evidence has demonstrated a bidirectional relationship between sleep problems and ADHD symptoms in pediatric populations, the investigators wrote, and further research is needed to examine the “mediators, moderators, and biological mechanisms of the sleep-ADHD link [in adolescents].”

While there are multiple potential pathways for this link, sleep problems may sometimes result in a cluster of behavioral and cognitive symptoms that are not true ADHD but that mimic the disorder, they noted.

The investigators also noted that approximately 67% of adolescents who had clinically relevant ADHD symptoms at baseline no longer had these symptoms at 1-year follow-up – a finding that “supports the [idea]” that ADHD symptoms with onset in adolescence may be transient or episodic rather than persistent.

The study was funded in part by the National Natural Science Foundation of China. The authors reported that they have no conflicts of interest.

SOURCE: Liu X et al. Sleep. 2019 Dec 2. doi: 10.1093/sleep/zsz294.

Insomnia, restless legs syndrome (RLS), and frequent snoring were significantly associated with subsequent ADHD symptoms in a large longitudinal study of adolescents in China.

Investigators twice assessed 7,072 middle and high school students participating in the larger longitudinal Shandong Adolescent Behavior & Health Cohort – in 2015 and 1 year later in 2016 – for sleep, mental health, psychosocial factors (using the self-administered Adolescent Health Questionnaire, or AHQ), and for ADHD symptoms (using the Youth Self-Report, or YSR, of the Achenbach Child Behavior Checklist).

At baseline, ADHD symptoms were reported by 7.6% of adolescents and were significantly correlated, after adjusting for adolescent and family covariates, with all the sleep variables studied: sleep duration of 7 hours or less per night, insomnia symptoms, poor sleep quality, RLS symptoms, frequent snorting, and hypnotic use, reported Xianchen Liu, MD, PhD, of Shandong (China) University, and coinvestigators. They noted a dose-response relationship between sleep duration and the odds of having ADHD symptoms.

At 1-year follow-up, 4.5% of the 6,531 participants who did not have ADHD symptoms at baseline now reported them. After adjustments for covariates, any insomnia (odds ratio, 1.48), difficulty initiating sleep (one of the insomnia symptoms) (OR, 2.09), RLS (OR, 1.47), and frequent snoring (OR, 2.30) at baseline were each significantly associated with development of incident ADHD symptoms and with ADHD severity at 1 year, they reported in Sleep.

“Given the fact that sleep disorders in adolescents are often underdiagnosed and untreated primarily in the primary care setting, our findings highlight that clinicians should assess and manage short sleep duration and sleep problems for effective treatment of ADHD in adolescents,” as well as for prevention, they wrote.

The AHQ includes questions that assess nocturnal sleep duration and sleep problems during the past month. The adolescent and family variables that were selected as covariates and controlled for include cigarette smoking, alcohol drinking, use of mental health services, chronic physical diseases, and parental education and occupation. Depression was also a covariate but was assessed through a different scale.

The YSR measures eight ADHD symptoms during the past 6 months on a 3-point scale (not true, somewhat or sometimes true, and very true or often true). The adolescent participants of this study were in grades 7, 8, and 10 at baseline. Their mean age at baseline was 15 years; half were male. They were part of the larger Shandong Adolescent and Behavioral Cohort, a longitudinal study of almost 12,000 adolescents.

Growing evidence has demonstrated a bidirectional relationship between sleep problems and ADHD symptoms in pediatric populations, the investigators wrote, and further research is needed to examine the “mediators, moderators, and biological mechanisms of the sleep-ADHD link [in adolescents].”

While there are multiple potential pathways for this link, sleep problems may sometimes result in a cluster of behavioral and cognitive symptoms that are not true ADHD but that mimic the disorder, they noted.

The investigators also noted that approximately 67% of adolescents who had clinically relevant ADHD symptoms at baseline no longer had these symptoms at 1-year follow-up – a finding that “supports the [idea]” that ADHD symptoms with onset in adolescence may be transient or episodic rather than persistent.

The study was funded in part by the National Natural Science Foundation of China. The authors reported that they have no conflicts of interest.

SOURCE: Liu X et al. Sleep. 2019 Dec 2. doi: 10.1093/sleep/zsz294.

Insomnia, restless legs syndrome (RLS), and frequent snoring were significantly associated with subsequent ADHD symptoms in a large longitudinal study of adolescents in China.

Investigators twice assessed 7,072 middle and high school students participating in the larger longitudinal Shandong Adolescent Behavior & Health Cohort – in 2015 and 1 year later in 2016 – for sleep, mental health, psychosocial factors (using the self-administered Adolescent Health Questionnaire, or AHQ), and for ADHD symptoms (using the Youth Self-Report, or YSR, of the Achenbach Child Behavior Checklist).

At baseline, ADHD symptoms were reported by 7.6% of adolescents and were significantly correlated, after adjusting for adolescent and family covariates, with all the sleep variables studied: sleep duration of 7 hours or less per night, insomnia symptoms, poor sleep quality, RLS symptoms, frequent snorting, and hypnotic use, reported Xianchen Liu, MD, PhD, of Shandong (China) University, and coinvestigators. They noted a dose-response relationship between sleep duration and the odds of having ADHD symptoms.

At 1-year follow-up, 4.5% of the 6,531 participants who did not have ADHD symptoms at baseline now reported them. After adjustments for covariates, any insomnia (odds ratio, 1.48), difficulty initiating sleep (one of the insomnia symptoms) (OR, 2.09), RLS (OR, 1.47), and frequent snoring (OR, 2.30) at baseline were each significantly associated with development of incident ADHD symptoms and with ADHD severity at 1 year, they reported in Sleep.

“Given the fact that sleep disorders in adolescents are often underdiagnosed and untreated primarily in the primary care setting, our findings highlight that clinicians should assess and manage short sleep duration and sleep problems for effective treatment of ADHD in adolescents,” as well as for prevention, they wrote.

The AHQ includes questions that assess nocturnal sleep duration and sleep problems during the past month. The adolescent and family variables that were selected as covariates and controlled for include cigarette smoking, alcohol drinking, use of mental health services, chronic physical diseases, and parental education and occupation. Depression was also a covariate but was assessed through a different scale.

The YSR measures eight ADHD symptoms during the past 6 months on a 3-point scale (not true, somewhat or sometimes true, and very true or often true). The adolescent participants of this study were in grades 7, 8, and 10 at baseline. Their mean age at baseline was 15 years; half were male. They were part of the larger Shandong Adolescent and Behavioral Cohort, a longitudinal study of almost 12,000 adolescents.

Growing evidence has demonstrated a bidirectional relationship between sleep problems and ADHD symptoms in pediatric populations, the investigators wrote, and further research is needed to examine the “mediators, moderators, and biological mechanisms of the sleep-ADHD link [in adolescents].”

While there are multiple potential pathways for this link, sleep problems may sometimes result in a cluster of behavioral and cognitive symptoms that are not true ADHD but that mimic the disorder, they noted.

The investigators also noted that approximately 67% of adolescents who had clinically relevant ADHD symptoms at baseline no longer had these symptoms at 1-year follow-up – a finding that “supports the [idea]” that ADHD symptoms with onset in adolescence may be transient or episodic rather than persistent.

The study was funded in part by the National Natural Science Foundation of China. The authors reported that they have no conflicts of interest.

SOURCE: Liu X et al. Sleep. 2019 Dec 2. doi: 10.1093/sleep/zsz294.