Sleep Medicine

HOUSTON — Narcolepsy is associated with a significantly increased risk for cardiovascular disease (CVD) and major adverse cardiac events (MACEs), independent of common comorbid conditions and medications commonly used to treat the chronic sleep disorder, according to two new studies.

A nationwide analysis revealed that people with narcolepsy had a 77% higher risk for CVD and an 82% higher risk for MACE than those without the disorder.

“These findings indicate that it is important for clinicians to regularly monitor patients for cardiovascular disease and take this into consideration when recommending specific treatments for narcolepsy,” study investigators Christopher Kaufmann, PhD; Munaza Riaz, PharmD, MPhil; and Rakesh Bhattacharjee, MD, told this news organization.

“Additionally, physicians should consider monitoring the presence of other health conditions as contributing factors to the risk of CVD,” they said. Dr. Kaufmann and Dr. Riaz are with the University of Florida, Gainesville, Florida, and Dr. Bhattacharjee is with the University of California, San Diego.

They presented their research at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies.
 

Independent Risk Factor

The National Institute of Neurological Disorders and Stroke reports an estimated 125,000 to 200,000 people in the United States live with narcolepsy. The condition often coexists with other common health conditions including obstructive sleep apnea (OSA), diabetes, and other comorbidities, which can all contribute to the risk for CVD.

This raises doubt as to whether narcolepsy itself directly leads to CVD or if it is the result of these comorbid health conditions. Additionally, some medications used to treat narcolepsy carry their own cardiovascular risks.

Using the IBM MarketScan Commercial and Medicare supplemental databases, the researchers identified 34,562 adults with a diagnosis of narcolepsy and a propensity-matched comparison cohort of 100,405 adults without narcolepsy. The patients had a mean age of 40 years, and 62% were women.

Compared with adults without narcolepsy, those with the chronic sleep disorder that causes overwhelming daytime drowsiness had a 77% increased risk for any CVD (hazard ratio [HR], 1.77) and an 82% increased risk for MACE (HR, 1.82).

They also had an increased risk for stroke (HR, 2.04), heart failure or myocardial infarction (MI; HR, 1.64), and atrial fibrillation (HR, 1.58).

The results were similar in a separate analysis of the same population that also controlled for baseline use of stimulants, oxybates, and wake-promoting agents — medications commonly used to treat excessive daytime sleepiness associated with narcolepsy.

In this analysis, narcolepsy was associated with an 89% higher risk for CVD (HR, 1.89) and a 95% increased risk for MACE (HR, 1.95). The risk for any stroke (HR, 2.06), heart failure (HR, 1.90), atrial fibrillation (HR, 1.66), and MI (HR, 1.93) was also higher in those with narcolepsy.

“Our study found that even after considering the presence of health conditions like obstructive sleep apnea, diabetes, hypertension, hyperlipidemia, and even depression, as well as medication use, there still appears to be an independent relationship between narcolepsy and CVD,” the investigators said.

They cautioned that the mechanisms explaining the link between CVD and narcolepsy are unclear and warrant further study.

“Sleep fragmentation is a hallmark of narcolepsy, and it is speculated that this fragmentation, which may trigger disturbances in autonomic function, predisposes individuals to CVD. In rodent models, a possible link has been observed between hypocretin — a central neurotransmitter that is reduced or deficient in patients with narcolepsy — and atherosclerosis.

“However, it remains uncertain whether this is the primary mechanism related to CVD,” they commented.
 

Compelling Evidence for Higher CVD

Commenting on the findings for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, Florida, called for narcolepsy to be recognized as a significant contributor to higher CVD risk.

“Given the compelling evidence linking narcolepsy to a higher incidence of cardiovascular disease, it is crucial that narcolepsy be included in clinical guidelines and risk assessment tools alongside other known risk factors,” said Dr. Lakhan, who was not involved in this research.

“Physicians and health care providers should proactively address the increased cardiovascular risk associated with narcolepsy by incorporating preventive strategies and interventions into the management of patients with this condition,” Dr. Lakhan suggested.

Regular CVD screening, a healthier lifestyle, and targeted therapies could all decrease cardiac risk, Dr. Lakhan added.

“Ultimately, novel disease-modifying therapies for narcolepsy should target the core mechanisms driving the increased cardiovascular risk associated with this condition. By elucidating the specific biological pathways and developing targeted therapies that address the unique challenges faced by narcolepsy patients, we can effectively mitigate the risk,” Dr. Lakhan said.

The studies were funded by the Sleep Research Society Foundation. The authors and Dr. Lakhan had no relevant disclosures.

A version of this article appeared on Medscape.com.

HOUSTON — Narcolepsy is associated with a significantly increased risk for cardiovascular disease (CVD) and major adverse cardiac events (MACEs), independent of common comorbid conditions and medications commonly used to treat the chronic sleep disorder, according to two new studies.

A nationwide analysis revealed that people with narcolepsy had a 77% higher risk for CVD and an 82% higher risk for MACE than those without the disorder.

“These findings indicate that it is important for clinicians to regularly monitor patients for cardiovascular disease and take this into consideration when recommending specific treatments for narcolepsy,” study investigators Christopher Kaufmann, PhD; Munaza Riaz, PharmD, MPhil; and Rakesh Bhattacharjee, MD, told this news organization.

“Additionally, physicians should consider monitoring the presence of other health conditions as contributing factors to the risk of CVD,” they said. Dr. Kaufmann and Dr. Riaz are with the University of Florida, Gainesville, Florida, and Dr. Bhattacharjee is with the University of California, San Diego.

They presented their research at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies.
 

Independent Risk Factor

The National Institute of Neurological Disorders and Stroke reports an estimated 125,000 to 200,000 people in the United States live with narcolepsy. The condition often coexists with other common health conditions including obstructive sleep apnea (OSA), diabetes, and other comorbidities, which can all contribute to the risk for CVD.

This raises doubt as to whether narcolepsy itself directly leads to CVD or if it is the result of these comorbid health conditions. Additionally, some medications used to treat narcolepsy carry their own cardiovascular risks.

Using the IBM MarketScan Commercial and Medicare supplemental databases, the researchers identified 34,562 adults with a diagnosis of narcolepsy and a propensity-matched comparison cohort of 100,405 adults without narcolepsy. The patients had a mean age of 40 years, and 62% were women.

Compared with adults without narcolepsy, those with the chronic sleep disorder that causes overwhelming daytime drowsiness had a 77% increased risk for any CVD (hazard ratio [HR], 1.77) and an 82% increased risk for MACE (HR, 1.82).

They also had an increased risk for stroke (HR, 2.04), heart failure or myocardial infarction (MI; HR, 1.64), and atrial fibrillation (HR, 1.58).

The results were similar in a separate analysis of the same population that also controlled for baseline use of stimulants, oxybates, and wake-promoting agents — medications commonly used to treat excessive daytime sleepiness associated with narcolepsy.

In this analysis, narcolepsy was associated with an 89% higher risk for CVD (HR, 1.89) and a 95% increased risk for MACE (HR, 1.95). The risk for any stroke (HR, 2.06), heart failure (HR, 1.90), atrial fibrillation (HR, 1.66), and MI (HR, 1.93) was also higher in those with narcolepsy.

“Our study found that even after considering the presence of health conditions like obstructive sleep apnea, diabetes, hypertension, hyperlipidemia, and even depression, as well as medication use, there still appears to be an independent relationship between narcolepsy and CVD,” the investigators said.

They cautioned that the mechanisms explaining the link between CVD and narcolepsy are unclear and warrant further study.

“Sleep fragmentation is a hallmark of narcolepsy, and it is speculated that this fragmentation, which may trigger disturbances in autonomic function, predisposes individuals to CVD. In rodent models, a possible link has been observed between hypocretin — a central neurotransmitter that is reduced or deficient in patients with narcolepsy — and atherosclerosis.

“However, it remains uncertain whether this is the primary mechanism related to CVD,” they commented.
 

Compelling Evidence for Higher CVD

Commenting on the findings for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, Florida, called for narcolepsy to be recognized as a significant contributor to higher CVD risk.

“Given the compelling evidence linking narcolepsy to a higher incidence of cardiovascular disease, it is crucial that narcolepsy be included in clinical guidelines and risk assessment tools alongside other known risk factors,” said Dr. Lakhan, who was not involved in this research.

“Physicians and health care providers should proactively address the increased cardiovascular risk associated with narcolepsy by incorporating preventive strategies and interventions into the management of patients with this condition,” Dr. Lakhan suggested.

Regular CVD screening, a healthier lifestyle, and targeted therapies could all decrease cardiac risk, Dr. Lakhan added.

“Ultimately, novel disease-modifying therapies for narcolepsy should target the core mechanisms driving the increased cardiovascular risk associated with this condition. By elucidating the specific biological pathways and developing targeted therapies that address the unique challenges faced by narcolepsy patients, we can effectively mitigate the risk,” Dr. Lakhan said.

The studies were funded by the Sleep Research Society Foundation. The authors and Dr. Lakhan had no relevant disclosures.

A version of this article appeared on Medscape.com.

HOUSTON — Narcolepsy is associated with a significantly increased risk for cardiovascular disease (CVD) and major adverse cardiac events (MACEs), independent of common comorbid conditions and medications commonly used to treat the chronic sleep disorder, according to two new studies.

A nationwide analysis revealed that people with narcolepsy had a 77% higher risk for CVD and an 82% higher risk for MACE than those without the disorder.

“These findings indicate that it is important for clinicians to regularly monitor patients for cardiovascular disease and take this into consideration when recommending specific treatments for narcolepsy,” study investigators Christopher Kaufmann, PhD; Munaza Riaz, PharmD, MPhil; and Rakesh Bhattacharjee, MD, told this news organization.

“Additionally, physicians should consider monitoring the presence of other health conditions as contributing factors to the risk of CVD,” they said. Dr. Kaufmann and Dr. Riaz are with the University of Florida, Gainesville, Florida, and Dr. Bhattacharjee is with the University of California, San Diego.

They presented their research at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies.
 

Independent Risk Factor

The National Institute of Neurological Disorders and Stroke reports an estimated 125,000 to 200,000 people in the United States live with narcolepsy. The condition often coexists with other common health conditions including obstructive sleep apnea (OSA), diabetes, and other comorbidities, which can all contribute to the risk for CVD.

This raises doubt as to whether narcolepsy itself directly leads to CVD or if it is the result of these comorbid health conditions. Additionally, some medications used to treat narcolepsy carry their own cardiovascular risks.

Using the IBM MarketScan Commercial and Medicare supplemental databases, the researchers identified 34,562 adults with a diagnosis of narcolepsy and a propensity-matched comparison cohort of 100,405 adults without narcolepsy. The patients had a mean age of 40 years, and 62% were women.

Compared with adults without narcolepsy, those with the chronic sleep disorder that causes overwhelming daytime drowsiness had a 77% increased risk for any CVD (hazard ratio [HR], 1.77) and an 82% increased risk for MACE (HR, 1.82).

They also had an increased risk for stroke (HR, 2.04), heart failure or myocardial infarction (MI; HR, 1.64), and atrial fibrillation (HR, 1.58).

The results were similar in a separate analysis of the same population that also controlled for baseline use of stimulants, oxybates, and wake-promoting agents — medications commonly used to treat excessive daytime sleepiness associated with narcolepsy.

In this analysis, narcolepsy was associated with an 89% higher risk for CVD (HR, 1.89) and a 95% increased risk for MACE (HR, 1.95). The risk for any stroke (HR, 2.06), heart failure (HR, 1.90), atrial fibrillation (HR, 1.66), and MI (HR, 1.93) was also higher in those with narcolepsy.

“Our study found that even after considering the presence of health conditions like obstructive sleep apnea, diabetes, hypertension, hyperlipidemia, and even depression, as well as medication use, there still appears to be an independent relationship between narcolepsy and CVD,” the investigators said.

They cautioned that the mechanisms explaining the link between CVD and narcolepsy are unclear and warrant further study.

“Sleep fragmentation is a hallmark of narcolepsy, and it is speculated that this fragmentation, which may trigger disturbances in autonomic function, predisposes individuals to CVD. In rodent models, a possible link has been observed between hypocretin — a central neurotransmitter that is reduced or deficient in patients with narcolepsy — and atherosclerosis.

“However, it remains uncertain whether this is the primary mechanism related to CVD,” they commented.
 

Compelling Evidence for Higher CVD

Commenting on the findings for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, Florida, called for narcolepsy to be recognized as a significant contributor to higher CVD risk.

“Given the compelling evidence linking narcolepsy to a higher incidence of cardiovascular disease, it is crucial that narcolepsy be included in clinical guidelines and risk assessment tools alongside other known risk factors,” said Dr. Lakhan, who was not involved in this research.

“Physicians and health care providers should proactively address the increased cardiovascular risk associated with narcolepsy by incorporating preventive strategies and interventions into the management of patients with this condition,” Dr. Lakhan suggested.

Regular CVD screening, a healthier lifestyle, and targeted therapies could all decrease cardiac risk, Dr. Lakhan added.

“Ultimately, novel disease-modifying therapies for narcolepsy should target the core mechanisms driving the increased cardiovascular risk associated with this condition. By elucidating the specific biological pathways and developing targeted therapies that address the unique challenges faced by narcolepsy patients, we can effectively mitigate the risk,” Dr. Lakhan said.

The studies were funded by the Sleep Research Society Foundation. The authors and Dr. Lakhan had no relevant disclosures.

A version of this article appeared on Medscape.com.

Do drugs work better if taken by the clock?

A new analysis published in The Lancet journal’s eClinicalMedicine suggests: Yes, they do — if you consider the patient’s individual body clock. The study is the first to find that timing blood pressure drugs to a person’s personal “chronotype” — that is, whether they are a night owl or an early bird — may reduce the risk for a heart attack.

The findings represent a significant advance in the field of circadian medicine or “chronotherapy” — timing drug administration to circadian rhythms. A growing stack of research suggests this approach could reduce side effects and improve the effectiveness of a wide range of therapies, including vaccines, cancer treatments, and drugs for depression, glaucoma, pain, seizures, and other conditions. Still, despite decades of research, time of day is rarely considered in writing prescriptions.

“We are really just at the beginning of an exciting new way of looking at patient care,” said Kenneth A. Dyar, PhD, whose lab at Helmholtz Zentrum München’s Institute for Diabetes and Cancer focuses on metabolic physiology. Dr. Dyar is co-lead author of the new blood pressure analysis.

“Chronotherapy is a rapidly growing field,” he said, “and I suspect we are soon going to see more and more studies focused on ‘personalized chronotherapy,’ not only in hypertension but also potentially in other clinical areas.”
 

The ‘Missing Piece’ in Chronotherapy Research

Blood pressure drugs have long been chronotherapy’s battleground. After all, blood pressure follows a circadian rhythm, peaking in the morning and dropping at night.

That healthy overnight dip can disappear in people with diabetes, kidney disease, and obstructive sleep apnea. Some physicians have suggested a bed-time dose to restore that dip. But studies have had mixed results, so “take at bedtime” has become a less common recommendation in recent years.

But the debate continued. After a large 2019 Spanish study found that bedtime doses had benefits so big that the results drew questions, an even larger, 2022 randomized, controlled trial from the University of Dundee in Dundee, Scotland — called the TIME study — aimed to settle the question.

Researchers assigned over 21,000 people to take morning or night hypertension drugs for several years and found no difference in cardiovascular outcomes.

“We did this study thinking nocturnal blood pressure tablets might be better,” said Thomas MacDonald, MD, professor emeritus of clinical pharmacology and pharmacoepidemiology at the University of Dundee and principal investigator for the TIME study and the recent chronotype analysis. “But there was no difference for heart attacks, strokes, or vascular death.”

So, the researchers then looked at participants’ chronotypes, sorting outcomes based on whether the participants were late-to-bed, late-to-rise “night owls” or early-to-bed, early-to-rise “morning larks.”

Their analysis of these 5358 TIME participants found the following results: Risk for hospitalization for a heart attack was at least 34% lower for “owls” who took their drugs at bedtime. By contrast, owls’ heart attack risk was at least 62% higher with morning doses. For “larks,” the opposite was true. Morning doses were associated with an 11% lower heart attack risk and night doses with an 11% higher risk, according to supplemental data.

The personalized approach could explain why some previous chronotherapy studies have failed to show a benefit. Those studies did not individualize drug timing as this one did. But personalization could be key to circadian medicine’s success.

“Our ‘internal personal time’ appears to be an important variable to consider when dosing antihypertensives,” said co-lead author Filippo Pigazzani, MD, PhD, clinical senior lecturer and honorary consultant cardiologist at the University of Dundee School of Medicine. “Chronotherapy research has been going on for decades. We knew there was something important with time of day. But researchers haven’t considered the internal time of individual people. I think that is the missing piece.”

The analysis has several important limitations, the researchers said. A total of 95% of participants were White. And it was an observational study, not a true randomized comparison. “We started it late in the original TIME study,” Dr. MacDonald said. “You could argue we were reporting on those who survived long enough to get into the analysis.” More research is needed, they concluded.
 

Looking Beyond Blood Pressure

What about the rest of the body? “Almost all the cells of our body contain ‘circadian clocks’ that are synchronized by daily environmental cues, including light-dark, activity-rest, and feeding-fasting cycles,” said Dr. Dyar.

An estimated 50% of prescription drugs hit targets in the body that have circadian patterns. So, experts suspect that syncing a drug with a person’s body clock might increase effectiveness of many drugs.

A handful of US Food and Drug Administration–approved drugs already have time-of-day recommendations on the label for effectiveness or to limit side effects, including bedtime or evening for the insomnia drug Ambien, the HIV antiviral Atripla, and cholesterol-lowering Zocor. Others are intended to be taken with or after your last meal of the day, such as the long-acting insulin Levemir and the cardiovascular drug Xarelto. A morning recommendation comes with the proton pump inhibitor Nexium and the attention-deficit/hyperactivity disorder drug Ritalin.

Interest is expanding. About one third of the papers published about chronotherapy in the past 25 years have come out in the past 5 years. The May 2024 meeting of the Society for Research on Biological Rhythms featured a day-long session aimed at bringing clinicians up to speed. An organization called the International Association of Circadian Health Clinics is trying to bring circadian medicine findings to clinicians and their patients and to support research.

Moreover, while recent research suggests minding the clock could have benefits for a wide range of treatments, ignoring it could cause problems.

In a Massachusetts Institute of Technology study published in April in Science Advances, researchers looked at engineered livers made from human donor cells and found more than 300 genes that operate on a circadian schedule, many with roles in drug metabolism. They also found that circadian patterns affected the toxicity of acetaminophen and atorvastatin. Identifying the time of day to take these drugs could maximize effectiveness and minimize adverse effects, the researchers said.
 

Timing and the Immune System

Circadian rhythms are also seen in immune processes. In a 2023 study in The Journal of Clinical Investigation of vaccine data from 1.5 million people in Israel, researchers found that children and older adults who got their second dose of the Pfizer mRNA COVID vaccine earlier in the day were about 36% less likely to be hospitalized with SARS-CoV-2 infection than those who got an evening shot.

“The sweet spot in our data was somewhere around late morning to late afternoon,” said lead researcher Jeffrey Haspel, MD, PhD, associate professor of medicine in the division of pulmonary and critical care medicine at Washington University School of Medicine in St. Louis.

In a multicenter, 2024 analysis of 13 studies of immunotherapy for advanced cancers in 1663 people, researchers found treatment earlier in the day was associated with longer survival time and longer survival without cancer progression.

“Patients with selected metastatic cancers seemed to largely benefit from early [time of day] infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking,” the researchers noted. But “retrospective randomized trials are needed to establish recommendations for optimal circadian timing.”

Other research suggests or is investigating possible chronotherapy benefits for depression, glaucoma, respiratory diseases, stroke treatment, epilepsy, and sedatives used in surgery. So why aren’t healthcare providers adding time of day to more prescriptions? “What’s missing is more reliable data,” Dr. Dyar said.
 

Should You Use Chronotherapy Now?

Experts emphasize that more research is needed before doctors use chronotherapy and before medical organizations include it in treatment recommendations. But for some patients, circadian dosing may be worth a try:

Night owls whose blood pressure isn’t well controlled. Dr. Dyar and Dr. Pigazzani said night-time blood pressure drugs may be helpful for people with a “late chronotype.” Of course, patients shouldn’t change their medication schedule on their own, they said. And doctors may want to consider other concerns, like more overnight bathroom visits with evening diuretics.

In their study, the researchers determined participants’ chronotype with a few questions from the Munich Chronotype Questionnaire about what time they fell asleep and woke up on workdays and days off and whether they considered themselves “morning types” or “evening types.” (The questions can be found in supplementary data for the study.)

If a physician thinks matching the timing of a dose with chronotype would help, they can consider it, Dr. Pigazzani said. “However, I must add that this was an observational study, so I would advise healthcare practitioners to wait for our data to be confirmed in new RCTs of personalized chronotherapy of hypertension.”

Children and older adults getting vaccines. Timing COVID shots and possibly other vaccines from late morning to mid-afternoon could have a small benefit for individuals and a bigger public-health benefit, Dr. Haspel said. But the most important thing is getting vaccinated. “If you can only get one in the evening, it’s still worthwhile. Timing may add oomph at a public-health level for more vulnerable groups.”
 

A version of this article appeared on Medscape.com.

Do drugs work better if taken by the clock?

A new analysis published in The Lancet journal’s eClinicalMedicine suggests: Yes, they do — if you consider the patient’s individual body clock. The study is the first to find that timing blood pressure drugs to a person’s personal “chronotype” — that is, whether they are a night owl or an early bird — may reduce the risk for a heart attack.

The findings represent a significant advance in the field of circadian medicine or “chronotherapy” — timing drug administration to circadian rhythms. A growing stack of research suggests this approach could reduce side effects and improve the effectiveness of a wide range of therapies, including vaccines, cancer treatments, and drugs for depression, glaucoma, pain, seizures, and other conditions. Still, despite decades of research, time of day is rarely considered in writing prescriptions.

“We are really just at the beginning of an exciting new way of looking at patient care,” said Kenneth A. Dyar, PhD, whose lab at Helmholtz Zentrum München’s Institute for Diabetes and Cancer focuses on metabolic physiology. Dr. Dyar is co-lead author of the new blood pressure analysis.

“Chronotherapy is a rapidly growing field,” he said, “and I suspect we are soon going to see more and more studies focused on ‘personalized chronotherapy,’ not only in hypertension but also potentially in other clinical areas.”
 

The ‘Missing Piece’ in Chronotherapy Research

Blood pressure drugs have long been chronotherapy’s battleground. After all, blood pressure follows a circadian rhythm, peaking in the morning and dropping at night.

That healthy overnight dip can disappear in people with diabetes, kidney disease, and obstructive sleep apnea. Some physicians have suggested a bed-time dose to restore that dip. But studies have had mixed results, so “take at bedtime” has become a less common recommendation in recent years.

But the debate continued. After a large 2019 Spanish study found that bedtime doses had benefits so big that the results drew questions, an even larger, 2022 randomized, controlled trial from the University of Dundee in Dundee, Scotland — called the TIME study — aimed to settle the question.

Researchers assigned over 21,000 people to take morning or night hypertension drugs for several years and found no difference in cardiovascular outcomes.

“We did this study thinking nocturnal blood pressure tablets might be better,” said Thomas MacDonald, MD, professor emeritus of clinical pharmacology and pharmacoepidemiology at the University of Dundee and principal investigator for the TIME study and the recent chronotype analysis. “But there was no difference for heart attacks, strokes, or vascular death.”

So, the researchers then looked at participants’ chronotypes, sorting outcomes based on whether the participants were late-to-bed, late-to-rise “night owls” or early-to-bed, early-to-rise “morning larks.”

Their analysis of these 5358 TIME participants found the following results: Risk for hospitalization for a heart attack was at least 34% lower for “owls” who took their drugs at bedtime. By contrast, owls’ heart attack risk was at least 62% higher with morning doses. For “larks,” the opposite was true. Morning doses were associated with an 11% lower heart attack risk and night doses with an 11% higher risk, according to supplemental data.

The personalized approach could explain why some previous chronotherapy studies have failed to show a benefit. Those studies did not individualize drug timing as this one did. But personalization could be key to circadian medicine’s success.

“Our ‘internal personal time’ appears to be an important variable to consider when dosing antihypertensives,” said co-lead author Filippo Pigazzani, MD, PhD, clinical senior lecturer and honorary consultant cardiologist at the University of Dundee School of Medicine. “Chronotherapy research has been going on for decades. We knew there was something important with time of day. But researchers haven’t considered the internal time of individual people. I think that is the missing piece.”

The analysis has several important limitations, the researchers said. A total of 95% of participants were White. And it was an observational study, not a true randomized comparison. “We started it late in the original TIME study,” Dr. MacDonald said. “You could argue we were reporting on those who survived long enough to get into the analysis.” More research is needed, they concluded.
 

Looking Beyond Blood Pressure

What about the rest of the body? “Almost all the cells of our body contain ‘circadian clocks’ that are synchronized by daily environmental cues, including light-dark, activity-rest, and feeding-fasting cycles,” said Dr. Dyar.

An estimated 50% of prescription drugs hit targets in the body that have circadian patterns. So, experts suspect that syncing a drug with a person’s body clock might increase effectiveness of many drugs.

A handful of US Food and Drug Administration–approved drugs already have time-of-day recommendations on the label for effectiveness or to limit side effects, including bedtime or evening for the insomnia drug Ambien, the HIV antiviral Atripla, and cholesterol-lowering Zocor. Others are intended to be taken with or after your last meal of the day, such as the long-acting insulin Levemir and the cardiovascular drug Xarelto. A morning recommendation comes with the proton pump inhibitor Nexium and the attention-deficit/hyperactivity disorder drug Ritalin.

Interest is expanding. About one third of the papers published about chronotherapy in the past 25 years have come out in the past 5 years. The May 2024 meeting of the Society for Research on Biological Rhythms featured a day-long session aimed at bringing clinicians up to speed. An organization called the International Association of Circadian Health Clinics is trying to bring circadian medicine findings to clinicians and their patients and to support research.

Moreover, while recent research suggests minding the clock could have benefits for a wide range of treatments, ignoring it could cause problems.

In a Massachusetts Institute of Technology study published in April in Science Advances, researchers looked at engineered livers made from human donor cells and found more than 300 genes that operate on a circadian schedule, many with roles in drug metabolism. They also found that circadian patterns affected the toxicity of acetaminophen and atorvastatin. Identifying the time of day to take these drugs could maximize effectiveness and minimize adverse effects, the researchers said.
 

Timing and the Immune System

Circadian rhythms are also seen in immune processes. In a 2023 study in The Journal of Clinical Investigation of vaccine data from 1.5 million people in Israel, researchers found that children and older adults who got their second dose of the Pfizer mRNA COVID vaccine earlier in the day were about 36% less likely to be hospitalized with SARS-CoV-2 infection than those who got an evening shot.

“The sweet spot in our data was somewhere around late morning to late afternoon,” said lead researcher Jeffrey Haspel, MD, PhD, associate professor of medicine in the division of pulmonary and critical care medicine at Washington University School of Medicine in St. Louis.

In a multicenter, 2024 analysis of 13 studies of immunotherapy for advanced cancers in 1663 people, researchers found treatment earlier in the day was associated with longer survival time and longer survival without cancer progression.

“Patients with selected metastatic cancers seemed to largely benefit from early [time of day] infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking,” the researchers noted. But “retrospective randomized trials are needed to establish recommendations for optimal circadian timing.”

Other research suggests or is investigating possible chronotherapy benefits for depression, glaucoma, respiratory diseases, stroke treatment, epilepsy, and sedatives used in surgery. So why aren’t healthcare providers adding time of day to more prescriptions? “What’s missing is more reliable data,” Dr. Dyar said.
 

Should You Use Chronotherapy Now?

Experts emphasize that more research is needed before doctors use chronotherapy and before medical organizations include it in treatment recommendations. But for some patients, circadian dosing may be worth a try:

Night owls whose blood pressure isn’t well controlled. Dr. Dyar and Dr. Pigazzani said night-time blood pressure drugs may be helpful for people with a “late chronotype.” Of course, patients shouldn’t change their medication schedule on their own, they said. And doctors may want to consider other concerns, like more overnight bathroom visits with evening diuretics.

In their study, the researchers determined participants’ chronotype with a few questions from the Munich Chronotype Questionnaire about what time they fell asleep and woke up on workdays and days off and whether they considered themselves “morning types” or “evening types.” (The questions can be found in supplementary data for the study.)

If a physician thinks matching the timing of a dose with chronotype would help, they can consider it, Dr. Pigazzani said. “However, I must add that this was an observational study, so I would advise healthcare practitioners to wait for our data to be confirmed in new RCTs of personalized chronotherapy of hypertension.”

Children and older adults getting vaccines. Timing COVID shots and possibly other vaccines from late morning to mid-afternoon could have a small benefit for individuals and a bigger public-health benefit, Dr. Haspel said. But the most important thing is getting vaccinated. “If you can only get one in the evening, it’s still worthwhile. Timing may add oomph at a public-health level for more vulnerable groups.”
 

A version of this article appeared on Medscape.com.

Do drugs work better if taken by the clock?

A new analysis published in The Lancet journal’s eClinicalMedicine suggests: Yes, they do — if you consider the patient’s individual body clock. The study is the first to find that timing blood pressure drugs to a person’s personal “chronotype” — that is, whether they are a night owl or an early bird — may reduce the risk for a heart attack.

The findings represent a significant advance in the field of circadian medicine or “chronotherapy” — timing drug administration to circadian rhythms. A growing stack of research suggests this approach could reduce side effects and improve the effectiveness of a wide range of therapies, including vaccines, cancer treatments, and drugs for depression, glaucoma, pain, seizures, and other conditions. Still, despite decades of research, time of day is rarely considered in writing prescriptions.

“We are really just at the beginning of an exciting new way of looking at patient care,” said Kenneth A. Dyar, PhD, whose lab at Helmholtz Zentrum München’s Institute for Diabetes and Cancer focuses on metabolic physiology. Dr. Dyar is co-lead author of the new blood pressure analysis.

“Chronotherapy is a rapidly growing field,” he said, “and I suspect we are soon going to see more and more studies focused on ‘personalized chronotherapy,’ not only in hypertension but also potentially in other clinical areas.”
 

The ‘Missing Piece’ in Chronotherapy Research

Blood pressure drugs have long been chronotherapy’s battleground. After all, blood pressure follows a circadian rhythm, peaking in the morning and dropping at night.

That healthy overnight dip can disappear in people with diabetes, kidney disease, and obstructive sleep apnea. Some physicians have suggested a bed-time dose to restore that dip. But studies have had mixed results, so “take at bedtime” has become a less common recommendation in recent years.

But the debate continued. After a large 2019 Spanish study found that bedtime doses had benefits so big that the results drew questions, an even larger, 2022 randomized, controlled trial from the University of Dundee in Dundee, Scotland — called the TIME study — aimed to settle the question.

Researchers assigned over 21,000 people to take morning or night hypertension drugs for several years and found no difference in cardiovascular outcomes.

“We did this study thinking nocturnal blood pressure tablets might be better,” said Thomas MacDonald, MD, professor emeritus of clinical pharmacology and pharmacoepidemiology at the University of Dundee and principal investigator for the TIME study and the recent chronotype analysis. “But there was no difference for heart attacks, strokes, or vascular death.”

So, the researchers then looked at participants’ chronotypes, sorting outcomes based on whether the participants were late-to-bed, late-to-rise “night owls” or early-to-bed, early-to-rise “morning larks.”

Their analysis of these 5358 TIME participants found the following results: Risk for hospitalization for a heart attack was at least 34% lower for “owls” who took their drugs at bedtime. By contrast, owls’ heart attack risk was at least 62% higher with morning doses. For “larks,” the opposite was true. Morning doses were associated with an 11% lower heart attack risk and night doses with an 11% higher risk, according to supplemental data.

The personalized approach could explain why some previous chronotherapy studies have failed to show a benefit. Those studies did not individualize drug timing as this one did. But personalization could be key to circadian medicine’s success.

“Our ‘internal personal time’ appears to be an important variable to consider when dosing antihypertensives,” said co-lead author Filippo Pigazzani, MD, PhD, clinical senior lecturer and honorary consultant cardiologist at the University of Dundee School of Medicine. “Chronotherapy research has been going on for decades. We knew there was something important with time of day. But researchers haven’t considered the internal time of individual people. I think that is the missing piece.”

The analysis has several important limitations, the researchers said. A total of 95% of participants were White. And it was an observational study, not a true randomized comparison. “We started it late in the original TIME study,” Dr. MacDonald said. “You could argue we were reporting on those who survived long enough to get into the analysis.” More research is needed, they concluded.
 

Looking Beyond Blood Pressure

What about the rest of the body? “Almost all the cells of our body contain ‘circadian clocks’ that are synchronized by daily environmental cues, including light-dark, activity-rest, and feeding-fasting cycles,” said Dr. Dyar.

An estimated 50% of prescription drugs hit targets in the body that have circadian patterns. So, experts suspect that syncing a drug with a person’s body clock might increase effectiveness of many drugs.

A handful of US Food and Drug Administration–approved drugs already have time-of-day recommendations on the label for effectiveness or to limit side effects, including bedtime or evening for the insomnia drug Ambien, the HIV antiviral Atripla, and cholesterol-lowering Zocor. Others are intended to be taken with or after your last meal of the day, such as the long-acting insulin Levemir and the cardiovascular drug Xarelto. A morning recommendation comes with the proton pump inhibitor Nexium and the attention-deficit/hyperactivity disorder drug Ritalin.

Interest is expanding. About one third of the papers published about chronotherapy in the past 25 years have come out in the past 5 years. The May 2024 meeting of the Society for Research on Biological Rhythms featured a day-long session aimed at bringing clinicians up to speed. An organization called the International Association of Circadian Health Clinics is trying to bring circadian medicine findings to clinicians and their patients and to support research.

Moreover, while recent research suggests minding the clock could have benefits for a wide range of treatments, ignoring it could cause problems.

In a Massachusetts Institute of Technology study published in April in Science Advances, researchers looked at engineered livers made from human donor cells and found more than 300 genes that operate on a circadian schedule, many with roles in drug metabolism. They also found that circadian patterns affected the toxicity of acetaminophen and atorvastatin. Identifying the time of day to take these drugs could maximize effectiveness and minimize adverse effects, the researchers said.
 

Timing and the Immune System

Circadian rhythms are also seen in immune processes. In a 2023 study in The Journal of Clinical Investigation of vaccine data from 1.5 million people in Israel, researchers found that children and older adults who got their second dose of the Pfizer mRNA COVID vaccine earlier in the day were about 36% less likely to be hospitalized with SARS-CoV-2 infection than those who got an evening shot.

“The sweet spot in our data was somewhere around late morning to late afternoon,” said lead researcher Jeffrey Haspel, MD, PhD, associate professor of medicine in the division of pulmonary and critical care medicine at Washington University School of Medicine in St. Louis.

In a multicenter, 2024 analysis of 13 studies of immunotherapy for advanced cancers in 1663 people, researchers found treatment earlier in the day was associated with longer survival time and longer survival without cancer progression.

“Patients with selected metastatic cancers seemed to largely benefit from early [time of day] infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking,” the researchers noted. But “retrospective randomized trials are needed to establish recommendations for optimal circadian timing.”

Other research suggests or is investigating possible chronotherapy benefits for depression, glaucoma, respiratory diseases, stroke treatment, epilepsy, and sedatives used in surgery. So why aren’t healthcare providers adding time of day to more prescriptions? “What’s missing is more reliable data,” Dr. Dyar said.
 

Should You Use Chronotherapy Now?

Experts emphasize that more research is needed before doctors use chronotherapy and before medical organizations include it in treatment recommendations. But for some patients, circadian dosing may be worth a try:

Night owls whose blood pressure isn’t well controlled. Dr. Dyar and Dr. Pigazzani said night-time blood pressure drugs may be helpful for people with a “late chronotype.” Of course, patients shouldn’t change their medication schedule on their own, they said. And doctors may want to consider other concerns, like more overnight bathroom visits with evening diuretics.

In their study, the researchers determined participants’ chronotype with a few questions from the Munich Chronotype Questionnaire about what time they fell asleep and woke up on workdays and days off and whether they considered themselves “morning types” or “evening types.” (The questions can be found in supplementary data for the study.)

If a physician thinks matching the timing of a dose with chronotype would help, they can consider it, Dr. Pigazzani said. “However, I must add that this was an observational study, so I would advise healthcare practitioners to wait for our data to be confirmed in new RCTs of personalized chronotherapy of hypertension.”

Children and older adults getting vaccines. Timing COVID shots and possibly other vaccines from late morning to mid-afternoon could have a small benefit for individuals and a bigger public-health benefit, Dr. Haspel said. But the most important thing is getting vaccinated. “If you can only get one in the evening, it’s still worthwhile. Timing may add oomph at a public-health level for more vulnerable groups.”
 

A version of this article appeared on Medscape.com.

Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

NASHVILLE, TENNESSEE — Fatigue and sleep problems are common among patients with multiple sclerosis (MS), but there are ways to help them manage these difficulties through personalized care.

Fatigue related to MS is complex, but it often follows a pattern. “Oftentimes when I meet with patients for the first time, they’re not always sure [what their own pattern is]. They know that the fatigue is present, and it’s limiting their activities. It’s important for us to break down and see that pattern for [the patient] specifically, and what are some ways that we can intervene to perhaps make that pattern something that improves quality of life and day-to-day living,” said Grace Tworek, PsyD, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

A cycle may start on a day that a patient has lots of energy. They are ambitious that day and get a lot done on their “to do” list while they have the energy. Unfortunately, they commonly overdo it, leading to fatigue the next day. Over ensuing days, the patient might feel unable to engage in everyday tasks and begin to feel they are falling behind. This in turn can affect mood, resulting in increased symptoms of depression and anxiety. That leads to days of inactivity and rest, which leads to recovery. Then comes a day with better mood and increased energy, where the cycle can begin again.

It’s an addressable problem. “What we really want to do is break this cycle, get out of those peaks and valleys of high energy days and very low energy days to try to create more sustainable patterns” said Dr. Tworek, who is a staff health psychologist at Cleveland Clinic’s Mellen Center for Multiple Sclerosis, Cleveland, Ohio.
 

Fatigue

When addressing fatigue in MS patients, Dr. Tworek and her colleagues begin with a fatigue diary that includes typical activities engaged in throughout the day. It also distinguishes between activities the patient feels are important and activities that give them satisfaction.

“If we can find ways to include these [satisfying] activities, and not focus only on those important activities. This is where that quality of life really comes into play. But I always say to folks, we are not striving for perfection at first. I want you to write down what’s actually happening so we can use this data to later inform how we are going to make changes,” said Dr. Tworek.

It’s also important to encourage patients to seek help. Activities that are neither important nor satisfying may not need doing at all, and they encourage patients to seek help in other tasks. As for tasks that are important in their day-to-day lives, “How can we break those down? We break those down by pacing activities,” said Dr. Tworek.

A simple way to pace yourself is to use “The rule of two.” It asks: How long can I do a task before I experience a two-point increase on a 1-10 fatigue scale. “At that time, is when we want to start inserting breaks. We want to find activities we can do that will reduce [fatigue] or get us back to baseline. Or if that’s not realistic, keep us where we are at rather than increasing fatigue,” said Dr. Tworek.

Another way to think about it is spoon theory, sometimes referred to as coin theory. The idea is that you wake up each morning with ten spoons. Each task on a given day will cost a certain number of spoons. “You might start your day, you go downstairs, you have breakfast, and you’re already down to seven points, the next day, you might still be at 10. So it’s really about monitoring where you’re at in terms of how many coins or spoons you’re spending so that we can then reflect on how many coins or spoons do I have left?” said Dr. Tworek.

The strategy can aid communication with partners or family members who may have difficulty understanding MS fatigue. “Sometimes putting a number to it can really open up the doors to having these difficult conversations with friends and family,” said Dr. Tworek.
 

Sleep

Fatigue and sleep are naturally intertwined, and sleep problems are also common in MS, with 30%-56% reporting problems, depending on the estimate.

One concept to think about is sleep drive. “From the moment we wake up, we are building sleep pressure, just like from the moment you stop eating, your body starts building pressure to eat again,” said Dr. Tworek.

Naps can interfere with that drive, much like a snack can rob you of a meal-time appetite. “A nap is going to curb that appetite for sleep, making it more difficult potentially to fall asleep,” said Dr. Tworek. If a nap is absolutely necessary, it’s better to do it earlier in the day to allow time to build sleep pressure again.

As with fatigue, Dr. Tworek has patients fill out a sleep diary that documents difficulty falling or staying asleep, timing and length of awakenings, quality of sleep, length and timing of any naps, and other factors. It sometimes reveals patterns, like difficulty falling asleep on specific days of the week. Such rhythms may be attributable to regular stressors, like anticipating some event the next morning. Then it might be possible to tie in other techniques like stress management to reduce accompanying anxiety.

Sleep hygiene is an important factor, employing strategies like staying off screens or social media while in bed. “About 1 hour before bedtime, we want to try to create some relaxation time,” said Dr. Tworek.

Her clinic also emphasizes consistent wake time. “If we are waking every day in about the same half hour period, we are able to build that sleep pressure consistently. [Then] your body is going to let you know when it is time for bed. You’re going to feel sleepiness,” said Dr. Tworek.

Dr. Tworek did not report any disclosures or conflicts of interest.

NASHVILLE, TENNESSEE — Fatigue and sleep problems are common among patients with multiple sclerosis (MS), but there are ways to help them manage these difficulties through personalized care.

Fatigue related to MS is complex, but it often follows a pattern. “Oftentimes when I meet with patients for the first time, they’re not always sure [what their own pattern is]. They know that the fatigue is present, and it’s limiting their activities. It’s important for us to break down and see that pattern for [the patient] specifically, and what are some ways that we can intervene to perhaps make that pattern something that improves quality of life and day-to-day living,” said Grace Tworek, PsyD, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

A cycle may start on a day that a patient has lots of energy. They are ambitious that day and get a lot done on their “to do” list while they have the energy. Unfortunately, they commonly overdo it, leading to fatigue the next day. Over ensuing days, the patient might feel unable to engage in everyday tasks and begin to feel they are falling behind. This in turn can affect mood, resulting in increased symptoms of depression and anxiety. That leads to days of inactivity and rest, which leads to recovery. Then comes a day with better mood and increased energy, where the cycle can begin again.

It’s an addressable problem. “What we really want to do is break this cycle, get out of those peaks and valleys of high energy days and very low energy days to try to create more sustainable patterns” said Dr. Tworek, who is a staff health psychologist at Cleveland Clinic’s Mellen Center for Multiple Sclerosis, Cleveland, Ohio.
 

Fatigue

When addressing fatigue in MS patients, Dr. Tworek and her colleagues begin with a fatigue diary that includes typical activities engaged in throughout the day. It also distinguishes between activities the patient feels are important and activities that give them satisfaction.

“If we can find ways to include these [satisfying] activities, and not focus only on those important activities. This is where that quality of life really comes into play. But I always say to folks, we are not striving for perfection at first. I want you to write down what’s actually happening so we can use this data to later inform how we are going to make changes,” said Dr. Tworek.

It’s also important to encourage patients to seek help. Activities that are neither important nor satisfying may not need doing at all, and they encourage patients to seek help in other tasks. As for tasks that are important in their day-to-day lives, “How can we break those down? We break those down by pacing activities,” said Dr. Tworek.

A simple way to pace yourself is to use “The rule of two.” It asks: How long can I do a task before I experience a two-point increase on a 1-10 fatigue scale. “At that time, is when we want to start inserting breaks. We want to find activities we can do that will reduce [fatigue] or get us back to baseline. Or if that’s not realistic, keep us where we are at rather than increasing fatigue,” said Dr. Tworek.

Another way to think about it is spoon theory, sometimes referred to as coin theory. The idea is that you wake up each morning with ten spoons. Each task on a given day will cost a certain number of spoons. “You might start your day, you go downstairs, you have breakfast, and you’re already down to seven points, the next day, you might still be at 10. So it’s really about monitoring where you’re at in terms of how many coins or spoons you’re spending so that we can then reflect on how many coins or spoons do I have left?” said Dr. Tworek.

The strategy can aid communication with partners or family members who may have difficulty understanding MS fatigue. “Sometimes putting a number to it can really open up the doors to having these difficult conversations with friends and family,” said Dr. Tworek.
 

Sleep

Fatigue and sleep are naturally intertwined, and sleep problems are also common in MS, with 30%-56% reporting problems, depending on the estimate.

One concept to think about is sleep drive. “From the moment we wake up, we are building sleep pressure, just like from the moment you stop eating, your body starts building pressure to eat again,” said Dr. Tworek.

Naps can interfere with that drive, much like a snack can rob you of a meal-time appetite. “A nap is going to curb that appetite for sleep, making it more difficult potentially to fall asleep,” said Dr. Tworek. If a nap is absolutely necessary, it’s better to do it earlier in the day to allow time to build sleep pressure again.

As with fatigue, Dr. Tworek has patients fill out a sleep diary that documents difficulty falling or staying asleep, timing and length of awakenings, quality of sleep, length and timing of any naps, and other factors. It sometimes reveals patterns, like difficulty falling asleep on specific days of the week. Such rhythms may be attributable to regular stressors, like anticipating some event the next morning. Then it might be possible to tie in other techniques like stress management to reduce accompanying anxiety.

Sleep hygiene is an important factor, employing strategies like staying off screens or social media while in bed. “About 1 hour before bedtime, we want to try to create some relaxation time,” said Dr. Tworek.

Her clinic also emphasizes consistent wake time. “If we are waking every day in about the same half hour period, we are able to build that sleep pressure consistently. [Then] your body is going to let you know when it is time for bed. You’re going to feel sleepiness,” said Dr. Tworek.

Dr. Tworek did not report any disclosures or conflicts of interest.

NASHVILLE, TENNESSEE — Fatigue and sleep problems are common among patients with multiple sclerosis (MS), but there are ways to help them manage these difficulties through personalized care.

Fatigue related to MS is complex, but it often follows a pattern. “Oftentimes when I meet with patients for the first time, they’re not always sure [what their own pattern is]. They know that the fatigue is present, and it’s limiting their activities. It’s important for us to break down and see that pattern for [the patient] specifically, and what are some ways that we can intervene to perhaps make that pattern something that improves quality of life and day-to-day living,” said Grace Tworek, PsyD, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

A cycle may start on a day that a patient has lots of energy. They are ambitious that day and get a lot done on their “to do” list while they have the energy. Unfortunately, they commonly overdo it, leading to fatigue the next day. Over ensuing days, the patient might feel unable to engage in everyday tasks and begin to feel they are falling behind. This in turn can affect mood, resulting in increased symptoms of depression and anxiety. That leads to days of inactivity and rest, which leads to recovery. Then comes a day with better mood and increased energy, where the cycle can begin again.

It’s an addressable problem. “What we really want to do is break this cycle, get out of those peaks and valleys of high energy days and very low energy days to try to create more sustainable patterns” said Dr. Tworek, who is a staff health psychologist at Cleveland Clinic’s Mellen Center for Multiple Sclerosis, Cleveland, Ohio.
 

Fatigue

When addressing fatigue in MS patients, Dr. Tworek and her colleagues begin with a fatigue diary that includes typical activities engaged in throughout the day. It also distinguishes between activities the patient feels are important and activities that give them satisfaction.

“If we can find ways to include these [satisfying] activities, and not focus only on those important activities. This is where that quality of life really comes into play. But I always say to folks, we are not striving for perfection at first. I want you to write down what’s actually happening so we can use this data to later inform how we are going to make changes,” said Dr. Tworek.

It’s also important to encourage patients to seek help. Activities that are neither important nor satisfying may not need doing at all, and they encourage patients to seek help in other tasks. As for tasks that are important in their day-to-day lives, “How can we break those down? We break those down by pacing activities,” said Dr. Tworek.

A simple way to pace yourself is to use “The rule of two.” It asks: How long can I do a task before I experience a two-point increase on a 1-10 fatigue scale. “At that time, is when we want to start inserting breaks. We want to find activities we can do that will reduce [fatigue] or get us back to baseline. Or if that’s not realistic, keep us where we are at rather than increasing fatigue,” said Dr. Tworek.

Another way to think about it is spoon theory, sometimes referred to as coin theory. The idea is that you wake up each morning with ten spoons. Each task on a given day will cost a certain number of spoons. “You might start your day, you go downstairs, you have breakfast, and you’re already down to seven points, the next day, you might still be at 10. So it’s really about monitoring where you’re at in terms of how many coins or spoons you’re spending so that we can then reflect on how many coins or spoons do I have left?” said Dr. Tworek.

The strategy can aid communication with partners or family members who may have difficulty understanding MS fatigue. “Sometimes putting a number to it can really open up the doors to having these difficult conversations with friends and family,” said Dr. Tworek.
 

Sleep

Fatigue and sleep are naturally intertwined, and sleep problems are also common in MS, with 30%-56% reporting problems, depending on the estimate.

One concept to think about is sleep drive. “From the moment we wake up, we are building sleep pressure, just like from the moment you stop eating, your body starts building pressure to eat again,” said Dr. Tworek.

Naps can interfere with that drive, much like a snack can rob you of a meal-time appetite. “A nap is going to curb that appetite for sleep, making it more difficult potentially to fall asleep,” said Dr. Tworek. If a nap is absolutely necessary, it’s better to do it earlier in the day to allow time to build sleep pressure again.

As with fatigue, Dr. Tworek has patients fill out a sleep diary that documents difficulty falling or staying asleep, timing and length of awakenings, quality of sleep, length and timing of any naps, and other factors. It sometimes reveals patterns, like difficulty falling asleep on specific days of the week. Such rhythms may be attributable to regular stressors, like anticipating some event the next morning. Then it might be possible to tie in other techniques like stress management to reduce accompanying anxiety.

Sleep hygiene is an important factor, employing strategies like staying off screens or social media while in bed. “About 1 hour before bedtime, we want to try to create some relaxation time,” said Dr. Tworek.

Her clinic also emphasizes consistent wake time. “If we are waking every day in about the same half hour period, we are able to build that sleep pressure consistently. [Then] your body is going to let you know when it is time for bed. You’re going to feel sleepiness,” said Dr. Tworek.

Dr. Tworek did not report any disclosures or conflicts of interest.

Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

A version of this article first appeared on Medscape.com.

Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

A version of this article first appeared on Medscape.com.

Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

A version of this article first appeared on Medscape.com.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

AIRWAYS DISORDERS NETWORK

Pediatric Chest Medicine Section

Children with severe lower respiratory tract infections (LRTIs) within the first 2 years of life had a 2.06-fold increased risk of developing pediatric OSA by age 5, according to a study comparing patients hospitalized with LRTI to controls without severe LRTI.¹ Prior studies linked LRTI and OSA, but the impact of LRTI severity was unknown.^2,3,4Using a case-control design, researchers analyzed data from 2,962 children enrolled in the Boston Birth Cohort (BBC): 235 children with severe LRTIs and 2,333 controls. They used Kaplan-Meier survival estimates and Cox proportional hazards models to evaluate the risk of OSA.

CHEST

Compared with patients with severe LRTIs, controls were more likely to have been full-term births, delivered vaginally, and breastfed. The OSA rate was significantly higher among children with severe LRTIs compared with controls (14.7% vs 6.8%). In the adjusted model controlling for relevant maternal and infant covariables, severe LRTI was significantly associated with increased OSA risk (HR, 2.06; 95% CI, 1.41-3.02; P < .001). Other factors such as prematurity (HR, 1.34; 95% CI, 1.01-1.77; P = .039) and maternal obesity (HR, 1.82; 95% CI, 1.32-2.52; P < .001) were also associated with increased OSA risk.

Maria Gutierrez, MD, of the Division of Pediatric Allergy, Immunology, and Rheumatology at Johns Hopkins University School of Medicine in Baltimore led the research. The study was published in Pediatric Pulmonology (2023 Dec 2. doi: 10.1002/ppul.26810). Study limitations included the use of electronic medical record data and potential lack of generalizability. The BBC is supported by the NIH.

– Agnes S. Montgomery, MD

Fellow-in-Training


References

1. Gayoso-Liviac MG, Nino G, Montgomery AS, Hong X, Wang X, Gutierrez MJ. Infants hospitalized with lower respiratory tract infections during the first two years of life have increased risk of pediatric obstructive sleep apnea. Pediatr Pulmonol. 2024;59:679-687.

2. Snow A, Dayyat E, Montgomery‐Downs HE, Kheirandish‐Gozal L, Gozal D. Pediatric obstructive sleep apnea: a potential late consequence of respiratory syncytial virus bronchiolitis. Pediatr Pulmonol. 2009;44(12):1186‐1191.

3. Chen VC‐H, Yang Y‐H, Kuo T‐Y, et al. Increased incidence of obstructive sleep apnea in hospitalized children after enterovirus infection: a nationwide population‐based cohort study. Pediatr Infect Dis J. 2018;37(9):872‐879.

4. Gutierrez MJ, Nino G, Landeo‐Gutierrez JS, et al. Lower respiratory tract infections in early life are associated with obstructive sleep apnea diagnosis during childhood in a large birth cohort. Sleep. 2021;44:12.
 

AIRWAYS DISORDERS NETWORK

Pediatric Chest Medicine Section

Children with severe lower respiratory tract infections (LRTIs) within the first 2 years of life had a 2.06-fold increased risk of developing pediatric OSA by age 5, according to a study comparing patients hospitalized with LRTI to controls without severe LRTI.¹ Prior studies linked LRTI and OSA, but the impact of LRTI severity was unknown.^2,3,4Using a case-control design, researchers analyzed data from 2,962 children enrolled in the Boston Birth Cohort (BBC): 235 children with severe LRTIs and 2,333 controls. They used Kaplan-Meier survival estimates and Cox proportional hazards models to evaluate the risk of OSA.

CHEST

Compared with patients with severe LRTIs, controls were more likely to have been full-term births, delivered vaginally, and breastfed. The OSA rate was significantly higher among children with severe LRTIs compared with controls (14.7% vs 6.8%). In the adjusted model controlling for relevant maternal and infant covariables, severe LRTI was significantly associated with increased OSA risk (HR, 2.06; 95% CI, 1.41-3.02; P < .001). Other factors such as prematurity (HR, 1.34; 95% CI, 1.01-1.77; P = .039) and maternal obesity (HR, 1.82; 95% CI, 1.32-2.52; P < .001) were also associated with increased OSA risk.

Maria Gutierrez, MD, of the Division of Pediatric Allergy, Immunology, and Rheumatology at Johns Hopkins University School of Medicine in Baltimore led the research. The study was published in Pediatric Pulmonology (2023 Dec 2. doi: 10.1002/ppul.26810). Study limitations included the use of electronic medical record data and potential lack of generalizability. The BBC is supported by the NIH.

– Agnes S. Montgomery, MD

Fellow-in-Training


References

1. Gayoso-Liviac MG, Nino G, Montgomery AS, Hong X, Wang X, Gutierrez MJ. Infants hospitalized with lower respiratory tract infections during the first two years of life have increased risk of pediatric obstructive sleep apnea. Pediatr Pulmonol. 2024;59:679-687.

2. Snow A, Dayyat E, Montgomery‐Downs HE, Kheirandish‐Gozal L, Gozal D. Pediatric obstructive sleep apnea: a potential late consequence of respiratory syncytial virus bronchiolitis. Pediatr Pulmonol. 2009;44(12):1186‐1191.

3. Chen VC‐H, Yang Y‐H, Kuo T‐Y, et al. Increased incidence of obstructive sleep apnea in hospitalized children after enterovirus infection: a nationwide population‐based cohort study. Pediatr Infect Dis J. 2018;37(9):872‐879.

4. Gutierrez MJ, Nino G, Landeo‐Gutierrez JS, et al. Lower respiratory tract infections in early life are associated with obstructive sleep apnea diagnosis during childhood in a large birth cohort. Sleep. 2021;44:12.
 

AIRWAYS DISORDERS NETWORK

Pediatric Chest Medicine Section

Children with severe lower respiratory tract infections (LRTIs) within the first 2 years of life had a 2.06-fold increased risk of developing pediatric OSA by age 5, according to a study comparing patients hospitalized with LRTI to controls without severe LRTI.¹ Prior studies linked LRTI and OSA, but the impact of LRTI severity was unknown.^2,3,4Using a case-control design, researchers analyzed data from 2,962 children enrolled in the Boston Birth Cohort (BBC): 235 children with severe LRTIs and 2,333 controls. They used Kaplan-Meier survival estimates and Cox proportional hazards models to evaluate the risk of OSA.

CHEST

Compared with patients with severe LRTIs, controls were more likely to have been full-term births, delivered vaginally, and breastfed. The OSA rate was significantly higher among children with severe LRTIs compared with controls (14.7% vs 6.8%). In the adjusted model controlling for relevant maternal and infant covariables, severe LRTI was significantly associated with increased OSA risk (HR, 2.06; 95% CI, 1.41-3.02; P < .001). Other factors such as prematurity (HR, 1.34; 95% CI, 1.01-1.77; P = .039) and maternal obesity (HR, 1.82; 95% CI, 1.32-2.52; P < .001) were also associated with increased OSA risk.

Maria Gutierrez, MD, of the Division of Pediatric Allergy, Immunology, and Rheumatology at Johns Hopkins University School of Medicine in Baltimore led the research. The study was published in Pediatric Pulmonology (2023 Dec 2. doi: 10.1002/ppul.26810). Study limitations included the use of electronic medical record data and potential lack of generalizability. The BBC is supported by the NIH.

– Agnes S. Montgomery, MD

Fellow-in-Training


References

1. Gayoso-Liviac MG, Nino G, Montgomery AS, Hong X, Wang X, Gutierrez MJ. Infants hospitalized with lower respiratory tract infections during the first two years of life have increased risk of pediatric obstructive sleep apnea. Pediatr Pulmonol. 2024;59:679-687.

2. Snow A, Dayyat E, Montgomery‐Downs HE, Kheirandish‐Gozal L, Gozal D. Pediatric obstructive sleep apnea: a potential late consequence of respiratory syncytial virus bronchiolitis. Pediatr Pulmonol. 2009;44(12):1186‐1191.

3. Chen VC‐H, Yang Y‐H, Kuo T‐Y, et al. Increased incidence of obstructive sleep apnea in hospitalized children after enterovirus infection: a nationwide population‐based cohort study. Pediatr Infect Dis J. 2018;37(9):872‐879.

4. Gutierrez MJ, Nino G, Landeo‐Gutierrez JS, et al. Lower respiratory tract infections in early life are associated with obstructive sleep apnea diagnosis during childhood in a large birth cohort. Sleep. 2021;44:12.
 

The National institutes of Health will soon start a clinical trial in an attempt to find potential treatments for symptoms of long COVID, focusing on sleep disturbances, problems with exercise, and post-exertional malaise. 

The trials will look to enroll more than 1,500 people across 50 study sites to tackle some of the most common symptoms of long COVID. 

“When people can’t get reliable sleep, can’t exert themselves and feel sick following tasks that used to be simple, the physical and mental anguish can lead to feelings of utter helplessness,” Walter J. Koroshetz, MD, director of the NIH’s National Institute of Neurological Disorders and Stroke, said in a statement. “We urgently need to come up with answers to help those struggling with long COVID feel whole again.”

The new trials will be part of the NIH’s Researching COVID to Enhance Recovery initiative, known as RECOVER. Since beginning enrollment in July 2023 for four trials, RECOVER now features eight trials across the country looking at all parts of long COVID. RECOVER is part of a $1.15 billion nationwide program that Congress approved in 2020 for the NIH to research and test treatments for long COVID. 

While focused on sleep disturbances, the trial will test two Food and Drug Administration–approved drugs currently used to treat people with hypersomnia. There will also be a trial to test if melatonin helps people with long COVID-related sleep problems. Light therapy will also be tested. 

The trials that deal with problems people have had with exercise will focus on personalized cardiopulmonary rehabilitation, where patients experiment with exercise training, strength and flexibility training, education, and social support. 

Another trial will look at structured pacing, which is designed to help people with exercise problems identify, control, and ease long COVID symptoms.

A version of this article appeared on WebMD.com.

The National institutes of Health will soon start a clinical trial in an attempt to find potential treatments for symptoms of long COVID, focusing on sleep disturbances, problems with exercise, and post-exertional malaise. 

The trials will look to enroll more than 1,500 people across 50 study sites to tackle some of the most common symptoms of long COVID. 

“When people can’t get reliable sleep, can’t exert themselves and feel sick following tasks that used to be simple, the physical and mental anguish can lead to feelings of utter helplessness,” Walter J. Koroshetz, MD, director of the NIH’s National Institute of Neurological Disorders and Stroke, said in a statement. “We urgently need to come up with answers to help those struggling with long COVID feel whole again.”

The new trials will be part of the NIH’s Researching COVID to Enhance Recovery initiative, known as RECOVER. Since beginning enrollment in July 2023 for four trials, RECOVER now features eight trials across the country looking at all parts of long COVID. RECOVER is part of a $1.15 billion nationwide program that Congress approved in 2020 for the NIH to research and test treatments for long COVID. 

While focused on sleep disturbances, the trial will test two Food and Drug Administration–approved drugs currently used to treat people with hypersomnia. There will also be a trial to test if melatonin helps people with long COVID-related sleep problems. Light therapy will also be tested. 

The trials that deal with problems people have had with exercise will focus on personalized cardiopulmonary rehabilitation, where patients experiment with exercise training, strength and flexibility training, education, and social support. 

Another trial will look at structured pacing, which is designed to help people with exercise problems identify, control, and ease long COVID symptoms.

A version of this article appeared on WebMD.com.

The National institutes of Health will soon start a clinical trial in an attempt to find potential treatments for symptoms of long COVID, focusing on sleep disturbances, problems with exercise, and post-exertional malaise. 

The trials will look to enroll more than 1,500 people across 50 study sites to tackle some of the most common symptoms of long COVID. 

“When people can’t get reliable sleep, can’t exert themselves and feel sick following tasks that used to be simple, the physical and mental anguish can lead to feelings of utter helplessness,” Walter J. Koroshetz, MD, director of the NIH’s National Institute of Neurological Disorders and Stroke, said in a statement. “We urgently need to come up with answers to help those struggling with long COVID feel whole again.”

The new trials will be part of the NIH’s Researching COVID to Enhance Recovery initiative, known as RECOVER. Since beginning enrollment in July 2023 for four trials, RECOVER now features eight trials across the country looking at all parts of long COVID. RECOVER is part of a $1.15 billion nationwide program that Congress approved in 2020 for the NIH to research and test treatments for long COVID. 

While focused on sleep disturbances, the trial will test two Food and Drug Administration–approved drugs currently used to treat people with hypersomnia. There will also be a trial to test if melatonin helps people with long COVID-related sleep problems. Light therapy will also be tested. 

The trials that deal with problems people have had with exercise will focus on personalized cardiopulmonary rehabilitation, where patients experiment with exercise training, strength and flexibility training, education, and social support. 

Another trial will look at structured pacing, which is designed to help people with exercise problems identify, control, and ease long COVID symptoms.

A version of this article appeared on WebMD.com.