Sleep Medicine

Residual excessive daytime sleepiness (REDS) is defined as the urge to sleep during the day despite an intention to remain alert after optimal treatment of obstructive sleep apnea (OSA). This is a distressing outcome with an estimated prevalence of 9% to 22% among patients with OSA (Pépin JL, et al. Eur Respir J. 2009;33[5]:1062). The pathophysiology of the condition is complex, and experimental studies conducted on animal models have demonstrated that chronic sleep fragmentation and chronic intermittent hypoxia can result in detrimental effects on wake-­promoting neurons. Additionally, there is evidence of heightened oxidative stress and alterations in melatonin secretion, with the severity and duration of the disease playing a significant role in the manifestation of these effects (Javaheri S, et al. Chest. 2020;158[2]:776). It is considered a diagnosis of exclusion, with the assessment being mostly subjective. Prior to diagnosing REDS, it is crucial to optimize positive airway pressure (PAP) therapy and nocturnal ventilation, ensure sufficient adherence to sleep hygiene practices, and exclude the presence of other sleep disorders. The Epworth Sleepiness Scale (ESS) score is widely utilized as a primary clinical tool in the assessment of sleepiness. To enhance the precision of this score, it is advantageous to take input from both family members and friends. Additional objective assessments that could be considered include the utilization of the Multiple Sleep Latency Test (MSLT) or the Maintenance of Wakefulness Test (MWT).

Due to the socioeconomic and public health considerations of REDS, pharmacological therapy is crucial to its management after exhausting conservative measures. Off-label use of traditional central nervous system stimulants, like amphetamine or methylphenidate, in these patients is almost extinct. The potential for abuse and negative consequences outweighs the potential benefits. FDA-approved medications for treatment of REDS in OSA include modafinil, armodafinil, and solriamfetol in the United States.

Historically, modafinil and armodafinil are the first-line and most commonly used wake-promoting agents. Both agents bind to the dopamine transporter and inhibit dopamine reuptake. They have demonstrated efficacy in reducing EDS and improving wakefulness in patients with OSA treated with CPAP. A meta-analysis of 10 randomized, placebo-controlled trials of modafinil and armodafinil found that they were better than placebo by 2.2 points on the ESS score and 3 minutes on the MWT (Maintenance of Wakefulness Test) (Chapman JL, et al. Eur Respir J. 2016;47[5]:1420). Both drugs have common adverse effects of headache, nausea, nervousness, insomnia, dizziness, rhinitis, and diarrhea. Drug interaction with CYP3A4/5 substrates and oral contraceptives is a concern with these medications. In 2010, the European Medicines Agency restricted the use of modafinil only to patients with narcolepsy, considering its cardiovascular and neuropsychiatric risks (European Medicines Agency website; press release, July 22, 2010).

Solriamfetol is the newest medication being utilized for EDS in OSA and is approved in both the United States and Europe for this indication. It is a dopamine and norepinephrine reuptake inhibitor with a simultaneous effect on both transporters. It has been effective in improving wakefulness and reducing sleepiness in patients with residual OSA. In the landmark trial TONES 3, dose-dependent (37.5, 75, 150, and 300 mg/day) effects were observed, with improvements in ESS scores of –1.9 to –4.7 points and sleep latency in MWT by 4.5 to 12.8 minutes (Schweitzer PK, et al. Am J Respir Crit Care Med. 2019;199[11]:1421). The current recommended dosing for REDS in OSA is to start with the lowest dose of 37.5 mg/day and increase to the maximum dose of 150 mg/day by titrating up every 3 days if needed. A recent meta-analysis showed an indirect treatment comparison between efficacy and safety among the medications solriamfetol, modafinil, and armodafinil (Ronnebaum S, et al. J Clin Sleep Med. 2021;17[12]:2543). Six parallel-arm, placebo-controlled, randomized, controlled trials were looked at. The ESS score, MWT20 sleep latency, and CGI-C (Clinical Global Impression of Change) all got better in comparison to the placebo. Relative to the comparators and placebo at 12 weeks, solriamfetol at 150 mg and 300 mg had the highest degree of improvement in all the outcomes studied. Common adverse effects of solriamfetol include headache, nausea, decreased appetite, insomnia, dry mouth, anxiety, and minimal increase in blood pressure and heart rate. The adverse effects in terms of blood pressure and heart rate change have a dose-dependent relationship, and serial vitals monitoring is recommended for patients every 6 months to a year. This medication is contraindicated in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days following discontinuation of an MAOI because of the risk of hypertensive reactions. Solriamfetol is renally excreted, so dose adjustment is needed in patients with moderate to severe renal impairment. It is not recommended for use in end-stage renal disease (eGFR <15 mL/min/1.73 m²) (SUNOSI. Full prescribing information. Axsome; revised 06/2023. https://www.sunosihcp.com/assets/files/sunosi.en.uspi.pdf. Accessed: Sept 24, 2023). Solriamfetol demonstrates a comparatively shorter half-life when compared with traditional pharmaceuticals like modafinil and armodafinil, implying the possibility of a decreased duration of its effects. The effect in question may exhibit interpersonal diversity in its impact on quality of life when applied in a therapeutic setting.

Pitolisant is another potential medication to treat REDS in patients with OSA. While only approved for treating EDS and cataplexy in adult US patients with narcolepsy, it is currently approved for REDS in OSA in Europe (Ozawade. European Medicines Agency. Last updated 12/05/2022. https://www.ema.europa.eu/en/medicines/human/EPAR/ozawade#product-information-­section. Accessed: Oct 2, 2023). It is a selective histamine H3 receptor antagonist and an inverse agonist of the presynaptic H3 receptor. The fact that this medication is not scheduled and has a negligible or nonexistent risk of abuse is one of its advantages. It is dosed once daily, and the most frequent adverse effects include headaches and insomnia. A prolonged QT interval was observed in a few patients; caution is needed with concomitant use of other medications with known similar effects. Dosage modification is recommended in patients with moderate hepatic impairment and moderate to severe renal impairment. Drug interactions are also observed with the concomitant use of CYP2D6 inhibitors and CYP3A4 inducers. Pitolisant may reduce the efficacy of hormonal contraception, including up to 21 days after its discontinuation (WAKIX. Full prescribing information. Harmony biosciences; revised 12/2022.https://wakixhcp.com/pdf/wakix-­tablets-pi.pdf. Accessed: Sept 24, 2023).
 

Dr. Mechineni is Sleep Attending Physician, Ascension Illinois, Alexian Brothers Medical Center, Chicago. Dr. Sahni is Assistant Professor of Clinical Medicine, Associate Program Director, Sleep Medicine Fellowship; Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago.

Residual excessive daytime sleepiness (REDS) is defined as the urge to sleep during the day despite an intention to remain alert after optimal treatment of obstructive sleep apnea (OSA). This is a distressing outcome with an estimated prevalence of 9% to 22% among patients with OSA (Pépin JL, et al. Eur Respir J. 2009;33[5]:1062). The pathophysiology of the condition is complex, and experimental studies conducted on animal models have demonstrated that chronic sleep fragmentation and chronic intermittent hypoxia can result in detrimental effects on wake-­promoting neurons. Additionally, there is evidence of heightened oxidative stress and alterations in melatonin secretion, with the severity and duration of the disease playing a significant role in the manifestation of these effects (Javaheri S, et al. Chest. 2020;158[2]:776). It is considered a diagnosis of exclusion, with the assessment being mostly subjective. Prior to diagnosing REDS, it is crucial to optimize positive airway pressure (PAP) therapy and nocturnal ventilation, ensure sufficient adherence to sleep hygiene practices, and exclude the presence of other sleep disorders. The Epworth Sleepiness Scale (ESS) score is widely utilized as a primary clinical tool in the assessment of sleepiness. To enhance the precision of this score, it is advantageous to take input from both family members and friends. Additional objective assessments that could be considered include the utilization of the Multiple Sleep Latency Test (MSLT) or the Maintenance of Wakefulness Test (MWT).

Due to the socioeconomic and public health considerations of REDS, pharmacological therapy is crucial to its management after exhausting conservative measures. Off-label use of traditional central nervous system stimulants, like amphetamine or methylphenidate, in these patients is almost extinct. The potential for abuse and negative consequences outweighs the potential benefits. FDA-approved medications for treatment of REDS in OSA include modafinil, armodafinil, and solriamfetol in the United States.

Historically, modafinil and armodafinil are the first-line and most commonly used wake-promoting agents. Both agents bind to the dopamine transporter and inhibit dopamine reuptake. They have demonstrated efficacy in reducing EDS and improving wakefulness in patients with OSA treated with CPAP. A meta-analysis of 10 randomized, placebo-controlled trials of modafinil and armodafinil found that they were better than placebo by 2.2 points on the ESS score and 3 minutes on the MWT (Maintenance of Wakefulness Test) (Chapman JL, et al. Eur Respir J. 2016;47[5]:1420). Both drugs have common adverse effects of headache, nausea, nervousness, insomnia, dizziness, rhinitis, and diarrhea. Drug interaction with CYP3A4/5 substrates and oral contraceptives is a concern with these medications. In 2010, the European Medicines Agency restricted the use of modafinil only to patients with narcolepsy, considering its cardiovascular and neuropsychiatric risks (European Medicines Agency website; press release, July 22, 2010).

Solriamfetol is the newest medication being utilized for EDS in OSA and is approved in both the United States and Europe for this indication. It is a dopamine and norepinephrine reuptake inhibitor with a simultaneous effect on both transporters. It has been effective in improving wakefulness and reducing sleepiness in patients with residual OSA. In the landmark trial TONES 3, dose-dependent (37.5, 75, 150, and 300 mg/day) effects were observed, with improvements in ESS scores of –1.9 to –4.7 points and sleep latency in MWT by 4.5 to 12.8 minutes (Schweitzer PK, et al. Am J Respir Crit Care Med. 2019;199[11]:1421). The current recommended dosing for REDS in OSA is to start with the lowest dose of 37.5 mg/day and increase to the maximum dose of 150 mg/day by titrating up every 3 days if needed. A recent meta-analysis showed an indirect treatment comparison between efficacy and safety among the medications solriamfetol, modafinil, and armodafinil (Ronnebaum S, et al. J Clin Sleep Med. 2021;17[12]:2543). Six parallel-arm, placebo-controlled, randomized, controlled trials were looked at. The ESS score, MWT20 sleep latency, and CGI-C (Clinical Global Impression of Change) all got better in comparison to the placebo. Relative to the comparators and placebo at 12 weeks, solriamfetol at 150 mg and 300 mg had the highest degree of improvement in all the outcomes studied. Common adverse effects of solriamfetol include headache, nausea, decreased appetite, insomnia, dry mouth, anxiety, and minimal increase in blood pressure and heart rate. The adverse effects in terms of blood pressure and heart rate change have a dose-dependent relationship, and serial vitals monitoring is recommended for patients every 6 months to a year. This medication is contraindicated in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days following discontinuation of an MAOI because of the risk of hypertensive reactions. Solriamfetol is renally excreted, so dose adjustment is needed in patients with moderate to severe renal impairment. It is not recommended for use in end-stage renal disease (eGFR <15 mL/min/1.73 m²) (SUNOSI. Full prescribing information. Axsome; revised 06/2023. https://www.sunosihcp.com/assets/files/sunosi.en.uspi.pdf. Accessed: Sept 24, 2023). Solriamfetol demonstrates a comparatively shorter half-life when compared with traditional pharmaceuticals like modafinil and armodafinil, implying the possibility of a decreased duration of its effects. The effect in question may exhibit interpersonal diversity in its impact on quality of life when applied in a therapeutic setting.

Pitolisant is another potential medication to treat REDS in patients with OSA. While only approved for treating EDS and cataplexy in adult US patients with narcolepsy, it is currently approved for REDS in OSA in Europe (Ozawade. European Medicines Agency. Last updated 12/05/2022. https://www.ema.europa.eu/en/medicines/human/EPAR/ozawade#product-information-­section. Accessed: Oct 2, 2023). It is a selective histamine H3 receptor antagonist and an inverse agonist of the presynaptic H3 receptor. The fact that this medication is not scheduled and has a negligible or nonexistent risk of abuse is one of its advantages. It is dosed once daily, and the most frequent adverse effects include headaches and insomnia. A prolonged QT interval was observed in a few patients; caution is needed with concomitant use of other medications with known similar effects. Dosage modification is recommended in patients with moderate hepatic impairment and moderate to severe renal impairment. Drug interactions are also observed with the concomitant use of CYP2D6 inhibitors and CYP3A4 inducers. Pitolisant may reduce the efficacy of hormonal contraception, including up to 21 days after its discontinuation (WAKIX. Full prescribing information. Harmony biosciences; revised 12/2022.https://wakixhcp.com/pdf/wakix-­tablets-pi.pdf. Accessed: Sept 24, 2023).
 

Dr. Mechineni is Sleep Attending Physician, Ascension Illinois, Alexian Brothers Medical Center, Chicago. Dr. Sahni is Assistant Professor of Clinical Medicine, Associate Program Director, Sleep Medicine Fellowship; Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago.

Residual excessive daytime sleepiness (REDS) is defined as the urge to sleep during the day despite an intention to remain alert after optimal treatment of obstructive sleep apnea (OSA). This is a distressing outcome with an estimated prevalence of 9% to 22% among patients with OSA (Pépin JL, et al. Eur Respir J. 2009;33[5]:1062). The pathophysiology of the condition is complex, and experimental studies conducted on animal models have demonstrated that chronic sleep fragmentation and chronic intermittent hypoxia can result in detrimental effects on wake-­promoting neurons. Additionally, there is evidence of heightened oxidative stress and alterations in melatonin secretion, with the severity and duration of the disease playing a significant role in the manifestation of these effects (Javaheri S, et al. Chest. 2020;158[2]:776). It is considered a diagnosis of exclusion, with the assessment being mostly subjective. Prior to diagnosing REDS, it is crucial to optimize positive airway pressure (PAP) therapy and nocturnal ventilation, ensure sufficient adherence to sleep hygiene practices, and exclude the presence of other sleep disorders. The Epworth Sleepiness Scale (ESS) score is widely utilized as a primary clinical tool in the assessment of sleepiness. To enhance the precision of this score, it is advantageous to take input from both family members and friends. Additional objective assessments that could be considered include the utilization of the Multiple Sleep Latency Test (MSLT) or the Maintenance of Wakefulness Test (MWT).

Due to the socioeconomic and public health considerations of REDS, pharmacological therapy is crucial to its management after exhausting conservative measures. Off-label use of traditional central nervous system stimulants, like amphetamine or methylphenidate, in these patients is almost extinct. The potential for abuse and negative consequences outweighs the potential benefits. FDA-approved medications for treatment of REDS in OSA include modafinil, armodafinil, and solriamfetol in the United States.

Historically, modafinil and armodafinil are the first-line and most commonly used wake-promoting agents. Both agents bind to the dopamine transporter and inhibit dopamine reuptake. They have demonstrated efficacy in reducing EDS and improving wakefulness in patients with OSA treated with CPAP. A meta-analysis of 10 randomized, placebo-controlled trials of modafinil and armodafinil found that they were better than placebo by 2.2 points on the ESS score and 3 minutes on the MWT (Maintenance of Wakefulness Test) (Chapman JL, et al. Eur Respir J. 2016;47[5]:1420). Both drugs have common adverse effects of headache, nausea, nervousness, insomnia, dizziness, rhinitis, and diarrhea. Drug interaction with CYP3A4/5 substrates and oral contraceptives is a concern with these medications. In 2010, the European Medicines Agency restricted the use of modafinil only to patients with narcolepsy, considering its cardiovascular and neuropsychiatric risks (European Medicines Agency website; press release, July 22, 2010).

Solriamfetol is the newest medication being utilized for EDS in OSA and is approved in both the United States and Europe for this indication. It is a dopamine and norepinephrine reuptake inhibitor with a simultaneous effect on both transporters. It has been effective in improving wakefulness and reducing sleepiness in patients with residual OSA. In the landmark trial TONES 3, dose-dependent (37.5, 75, 150, and 300 mg/day) effects were observed, with improvements in ESS scores of –1.9 to –4.7 points and sleep latency in MWT by 4.5 to 12.8 minutes (Schweitzer PK, et al. Am J Respir Crit Care Med. 2019;199[11]:1421). The current recommended dosing for REDS in OSA is to start with the lowest dose of 37.5 mg/day and increase to the maximum dose of 150 mg/day by titrating up every 3 days if needed. A recent meta-analysis showed an indirect treatment comparison between efficacy and safety among the medications solriamfetol, modafinil, and armodafinil (Ronnebaum S, et al. J Clin Sleep Med. 2021;17[12]:2543). Six parallel-arm, placebo-controlled, randomized, controlled trials were looked at. The ESS score, MWT20 sleep latency, and CGI-C (Clinical Global Impression of Change) all got better in comparison to the placebo. Relative to the comparators and placebo at 12 weeks, solriamfetol at 150 mg and 300 mg had the highest degree of improvement in all the outcomes studied. Common adverse effects of solriamfetol include headache, nausea, decreased appetite, insomnia, dry mouth, anxiety, and minimal increase in blood pressure and heart rate. The adverse effects in terms of blood pressure and heart rate change have a dose-dependent relationship, and serial vitals monitoring is recommended for patients every 6 months to a year. This medication is contraindicated in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days following discontinuation of an MAOI because of the risk of hypertensive reactions. Solriamfetol is renally excreted, so dose adjustment is needed in patients with moderate to severe renal impairment. It is not recommended for use in end-stage renal disease (eGFR <15 mL/min/1.73 m²) (SUNOSI. Full prescribing information. Axsome; revised 06/2023. https://www.sunosihcp.com/assets/files/sunosi.en.uspi.pdf. Accessed: Sept 24, 2023). Solriamfetol demonstrates a comparatively shorter half-life when compared with traditional pharmaceuticals like modafinil and armodafinil, implying the possibility of a decreased duration of its effects. The effect in question may exhibit interpersonal diversity in its impact on quality of life when applied in a therapeutic setting.

Pitolisant is another potential medication to treat REDS in patients with OSA. While only approved for treating EDS and cataplexy in adult US patients with narcolepsy, it is currently approved for REDS in OSA in Europe (Ozawade. European Medicines Agency. Last updated 12/05/2022. https://www.ema.europa.eu/en/medicines/human/EPAR/ozawade#product-information-­section. Accessed: Oct 2, 2023). It is a selective histamine H3 receptor antagonist and an inverse agonist of the presynaptic H3 receptor. The fact that this medication is not scheduled and has a negligible or nonexistent risk of abuse is one of its advantages. It is dosed once daily, and the most frequent adverse effects include headaches and insomnia. A prolonged QT interval was observed in a few patients; caution is needed with concomitant use of other medications with known similar effects. Dosage modification is recommended in patients with moderate hepatic impairment and moderate to severe renal impairment. Drug interactions are also observed with the concomitant use of CYP2D6 inhibitors and CYP3A4 inducers. Pitolisant may reduce the efficacy of hormonal contraception, including up to 21 days after its discontinuation (WAKIX. Full prescribing information. Harmony biosciences; revised 12/2022.https://wakixhcp.com/pdf/wakix-­tablets-pi.pdf. Accessed: Sept 24, 2023).
 

Dr. Mechineni is Sleep Attending Physician, Ascension Illinois, Alexian Brothers Medical Center, Chicago. Dr. Sahni is Assistant Professor of Clinical Medicine, Associate Program Director, Sleep Medicine Fellowship; Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago.

TOPLINE:

Challenging conventional wisdom, new research suggests that hitting the snooze button does not lead to cognitive impairment on waking and may actually provide cognitive benefits.

METHODOLOGY:

• Researchers did two studies to determine why intermittent morning alarms are used and how they affect sleep, cognition, cortisol, and mood.
• Study 1 was a survey of 1,732 healthy adults (mean age 34 years; 66% women) designed to elucidate the characteristics of people who snooze and why they choose to delay their waking in this way.
• Study 2 was a within-subject polysomnography study of 31 healthy habitual snoozers (mean age 27 years; 18 women) designed to explore the acute effects of snoozing on sleep architecture, sleepiness, cognitive ability, mood, and cortisol awakening response.

TAKEAWAY:

• Overall, 69% reported using the snooze button or setting multiple alarms at least sometimes, most often on workdays (71%), with an average snooze time per morning of 22 minutes.
• Sleep quality did not differ between snoozers and nonsnoozers, but snoozers were more likely to feel mentally drowsy on waking (odds ratio, 3.0; P < .001) and had slightly shorter sleep time on workdays (13 minutes).
• In the polysomnography study, compared with waking up abruptly, 30 minutes of snoozing in the morning improved or did not affect performance on standard cognitive tests completed directly on final awakening.
• Snoozing resulted in about 6 minutes of lost sleep, but it prevented awakening from slow-wave sleep and had no clear effects on the cortisol awakening response, morning sleepiness, mood, or overnight sleep architecture.

IN PRACTICE:

“The findings indicate that there is no reason to stop snoozing in the morning if you enjoy it, at least not for snooze times around 30 minutes. In fact, it may even help those with morning drowsiness to be slightly more awake once they get up,” corresponding author Tina Sundelin, PhD, of Stockholm University, said in a statement.

SOURCE:

The study was published online in the Journal of Sleep Research.

LIMITATIONS:

Study 1 focused on waking preferences in a convenience sample of adults. Study 2 included only habitual snoozers making it difficult to generalize the findings to people who don’t usually snooze. The study investigated only the effect of 30 minutes of snoozing on the studied parameters. It’s possible that shorter or longer snooze times have different cognitive effects.

DISCLOSURES:

Support for the study was provided by the Stress Research Institute, Stockholm University, and a grant from Vetenskapsrådet. The authors disclosed no relevant conflicts of interest.

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

TOPLINE:

Challenging conventional wisdom, new research suggests that hitting the snooze button does not lead to cognitive impairment on waking and may actually provide cognitive benefits.

METHODOLOGY:

• Researchers did two studies to determine why intermittent morning alarms are used and how they affect sleep, cognition, cortisol, and mood.
• Study 1 was a survey of 1,732 healthy adults (mean age 34 years; 66% women) designed to elucidate the characteristics of people who snooze and why they choose to delay their waking in this way.
• Study 2 was a within-subject polysomnography study of 31 healthy habitual snoozers (mean age 27 years; 18 women) designed to explore the acute effects of snoozing on sleep architecture, sleepiness, cognitive ability, mood, and cortisol awakening response.

TAKEAWAY:

• Overall, 69% reported using the snooze button or setting multiple alarms at least sometimes, most often on workdays (71%), with an average snooze time per morning of 22 minutes.
• Sleep quality did not differ between snoozers and nonsnoozers, but snoozers were more likely to feel mentally drowsy on waking (odds ratio, 3.0; P < .001) and had slightly shorter sleep time on workdays (13 minutes).
• In the polysomnography study, compared with waking up abruptly, 30 minutes of snoozing in the morning improved or did not affect performance on standard cognitive tests completed directly on final awakening.
• Snoozing resulted in about 6 minutes of lost sleep, but it prevented awakening from slow-wave sleep and had no clear effects on the cortisol awakening response, morning sleepiness, mood, or overnight sleep architecture.

IN PRACTICE:

“The findings indicate that there is no reason to stop snoozing in the morning if you enjoy it, at least not for snooze times around 30 minutes. In fact, it may even help those with morning drowsiness to be slightly more awake once they get up,” corresponding author Tina Sundelin, PhD, of Stockholm University, said in a statement.

SOURCE:

The study was published online in the Journal of Sleep Research.

LIMITATIONS:

Study 1 focused on waking preferences in a convenience sample of adults. Study 2 included only habitual snoozers making it difficult to generalize the findings to people who don’t usually snooze. The study investigated only the effect of 30 minutes of snoozing on the studied parameters. It’s possible that shorter or longer snooze times have different cognitive effects.

DISCLOSURES:

Support for the study was provided by the Stress Research Institute, Stockholm University, and a grant from Vetenskapsrådet. The authors disclosed no relevant conflicts of interest.

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

TOPLINE:

Challenging conventional wisdom, new research suggests that hitting the snooze button does not lead to cognitive impairment on waking and may actually provide cognitive benefits.

METHODOLOGY:

• Researchers did two studies to determine why intermittent morning alarms are used and how they affect sleep, cognition, cortisol, and mood.
• Study 1 was a survey of 1,732 healthy adults (mean age 34 years; 66% women) designed to elucidate the characteristics of people who snooze and why they choose to delay their waking in this way.
• Study 2 was a within-subject polysomnography study of 31 healthy habitual snoozers (mean age 27 years; 18 women) designed to explore the acute effects of snoozing on sleep architecture, sleepiness, cognitive ability, mood, and cortisol awakening response.

TAKEAWAY:

• Overall, 69% reported using the snooze button or setting multiple alarms at least sometimes, most often on workdays (71%), with an average snooze time per morning of 22 minutes.
• Sleep quality did not differ between snoozers and nonsnoozers, but snoozers were more likely to feel mentally drowsy on waking (odds ratio, 3.0; P < .001) and had slightly shorter sleep time on workdays (13 minutes).
• In the polysomnography study, compared with waking up abruptly, 30 minutes of snoozing in the morning improved or did not affect performance on standard cognitive tests completed directly on final awakening.
• Snoozing resulted in about 6 minutes of lost sleep, but it prevented awakening from slow-wave sleep and had no clear effects on the cortisol awakening response, morning sleepiness, mood, or overnight sleep architecture.

IN PRACTICE:

“The findings indicate that there is no reason to stop snoozing in the morning if you enjoy it, at least not for snooze times around 30 minutes. In fact, it may even help those with morning drowsiness to be slightly more awake once they get up,” corresponding author Tina Sundelin, PhD, of Stockholm University, said in a statement.

SOURCE:

The study was published online in the Journal of Sleep Research.

LIMITATIONS:

Study 1 focused on waking preferences in a convenience sample of adults. Study 2 included only habitual snoozers making it difficult to generalize the findings to people who don’t usually snooze. The study investigated only the effect of 30 minutes of snoozing on the studied parameters. It’s possible that shorter or longer snooze times have different cognitive effects.

DISCLOSURES:

Support for the study was provided by the Stress Research Institute, Stockholm University, and a grant from Vetenskapsrådet. The authors disclosed no relevant conflicts of interest.

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

TOPLINE:

Solriamfetol – a medication approved for excessive daytime sleepiness caused by narcolepsy or obstructive sleep apnea – significantly improved symptoms of attention-deficit/hyperactivity disorder (ADHD) and clinical impression of ADHD severity in a pilot study of adults with ADHD.

METHODOLOGY:

• Solriamfetol is a dopamine and norepinephrine reuptake inhibitor that shares some of the properties of current ADHD medications.
• Researchers conducted a randomized, double-blind, placebo-controlled, dose-optimization trial of 75- or 150-mg solriamfetol in 60 adults with ADHD. For nearly all of the individuals who received solriamfetol, doses increased to 150 mg after the first week.
• The primary outcome was change in scores on the Adult ADHD Investigator Symptom Rating Scale (AISRS).
• Secondary outcomes included scores on the Clinical Global Impressions (CGI) scale and standard measures of executive function, behavior, and sleep.

TAKEAWAY:

• By week 6, total AISRS score improved 25% for 52% of individuals to took solriamfetol, vs. 17% of those who received placebo. Total AISRS score improved 50% by week 6 in 28% of those who took solriamfetol, vs. 3.4% of those who received placebo.
• By week 6, CGI ratings of “much improved” or “very much improved” occurred in significantly more individuals who received solriamfetol than those who took placebo (45% vs. 7%).
• Significantly more individuals who received solriamfetol than placebo self-reported improvements in executive function (69% vs. 34%). Improvement in wakefulness was noted with solriamfetol, but that did not moderate the change in ADHD symptom burden.
• Solriamfetol was well tolerated, with no significant effect on sleep quality or blood pressure. Adverse effects that occurred at a higher rate in the treatment group than in the placebo group were typical for solriamfetol and sympathomimetic agents used for ADHD.

IN PRACTICE:

Massachusetts General Hospital

“Solriamfetol may be a safe and effective treatment for ADHD in adults. Larger studies replicating these findings could confirm the strong evidence of benefit and the tolerability of this agent as a treatment,” lead author Craig B.H. Surman, MD, director of the clinical and research program in adult ADHD, Massachusetts General Hospital, Boston, said in a statement.

SOURCE:

The study was published online in The Journal of Clinical Psychiatry.

LIMITATIONS:

Limitations include the small sample size and short 6-week duration. More women than men received solriamfetol; it’s unclear how this could have affected the results.

DISCLOSURES:

The study was an investigator-initiated trial supported by Jazz Pharmaceuticals and Axsome Therapeutics. Dr. Surman has received consultant fees, research support, and royalties from multiple companies.

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

TOPLINE:

Solriamfetol – a medication approved for excessive daytime sleepiness caused by narcolepsy or obstructive sleep apnea – significantly improved symptoms of attention-deficit/hyperactivity disorder (ADHD) and clinical impression of ADHD severity in a pilot study of adults with ADHD.

METHODOLOGY:

• Solriamfetol is a dopamine and norepinephrine reuptake inhibitor that shares some of the properties of current ADHD medications.
• Researchers conducted a randomized, double-blind, placebo-controlled, dose-optimization trial of 75- or 150-mg solriamfetol in 60 adults with ADHD. For nearly all of the individuals who received solriamfetol, doses increased to 150 mg after the first week.
• The primary outcome was change in scores on the Adult ADHD Investigator Symptom Rating Scale (AISRS).
• Secondary outcomes included scores on the Clinical Global Impressions (CGI) scale and standard measures of executive function, behavior, and sleep.

TAKEAWAY:

• By week 6, total AISRS score improved 25% for 52% of individuals to took solriamfetol, vs. 17% of those who received placebo. Total AISRS score improved 50% by week 6 in 28% of those who took solriamfetol, vs. 3.4% of those who received placebo.
• By week 6, CGI ratings of “much improved” or “very much improved” occurred in significantly more individuals who received solriamfetol than those who took placebo (45% vs. 7%).
• Significantly more individuals who received solriamfetol than placebo self-reported improvements in executive function (69% vs. 34%). Improvement in wakefulness was noted with solriamfetol, but that did not moderate the change in ADHD symptom burden.
• Solriamfetol was well tolerated, with no significant effect on sleep quality or blood pressure. Adverse effects that occurred at a higher rate in the treatment group than in the placebo group were typical for solriamfetol and sympathomimetic agents used for ADHD.

IN PRACTICE:

Massachusetts General Hospital

“Solriamfetol may be a safe and effective treatment for ADHD in adults. Larger studies replicating these findings could confirm the strong evidence of benefit and the tolerability of this agent as a treatment,” lead author Craig B.H. Surman, MD, director of the clinical and research program in adult ADHD, Massachusetts General Hospital, Boston, said in a statement.

SOURCE:

The study was published online in The Journal of Clinical Psychiatry.

LIMITATIONS:

Limitations include the small sample size and short 6-week duration. More women than men received solriamfetol; it’s unclear how this could have affected the results.

DISCLOSURES:

The study was an investigator-initiated trial supported by Jazz Pharmaceuticals and Axsome Therapeutics. Dr. Surman has received consultant fees, research support, and royalties from multiple companies.

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

TOPLINE:

Solriamfetol – a medication approved for excessive daytime sleepiness caused by narcolepsy or obstructive sleep apnea – significantly improved symptoms of attention-deficit/hyperactivity disorder (ADHD) and clinical impression of ADHD severity in a pilot study of adults with ADHD.

METHODOLOGY:

• Solriamfetol is a dopamine and norepinephrine reuptake inhibitor that shares some of the properties of current ADHD medications.
• Researchers conducted a randomized, double-blind, placebo-controlled, dose-optimization trial of 75- or 150-mg solriamfetol in 60 adults with ADHD. For nearly all of the individuals who received solriamfetol, doses increased to 150 mg after the first week.
• The primary outcome was change in scores on the Adult ADHD Investigator Symptom Rating Scale (AISRS).
• Secondary outcomes included scores on the Clinical Global Impressions (CGI) scale and standard measures of executive function, behavior, and sleep.

TAKEAWAY:

• By week 6, total AISRS score improved 25% for 52% of individuals to took solriamfetol, vs. 17% of those who received placebo. Total AISRS score improved 50% by week 6 in 28% of those who took solriamfetol, vs. 3.4% of those who received placebo.
• By week 6, CGI ratings of “much improved” or “very much improved” occurred in significantly more individuals who received solriamfetol than those who took placebo (45% vs. 7%).
• Significantly more individuals who received solriamfetol than placebo self-reported improvements in executive function (69% vs. 34%). Improvement in wakefulness was noted with solriamfetol, but that did not moderate the change in ADHD symptom burden.
• Solriamfetol was well tolerated, with no significant effect on sleep quality or blood pressure. Adverse effects that occurred at a higher rate in the treatment group than in the placebo group were typical for solriamfetol and sympathomimetic agents used for ADHD.

IN PRACTICE:

Massachusetts General Hospital

“Solriamfetol may be a safe and effective treatment for ADHD in adults. Larger studies replicating these findings could confirm the strong evidence of benefit and the tolerability of this agent as a treatment,” lead author Craig B.H. Surman, MD, director of the clinical and research program in adult ADHD, Massachusetts General Hospital, Boston, said in a statement.

SOURCE:

The study was published online in The Journal of Clinical Psychiatry.

LIMITATIONS:

Limitations include the small sample size and short 6-week duration. More women than men received solriamfetol; it’s unclear how this could have affected the results.

DISCLOSURES:

The study was an investigator-initiated trial supported by Jazz Pharmaceuticals and Axsome Therapeutics. Dr. Surman has received consultant fees, research support, and royalties from multiple companies.

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

Lack of time for self-care and rest are particularly harmful to women’s health. Various speakers at the VII National Conference of the Onda Foundation, Italy’s National Observatory for Women and Gender’s Health, focused on this topic. The conference was dedicated to the social factors that determine health within the context of gender medicine.

In our society, housework and raising a family are responsibilities placed predominantly on the shoulders of women. These responsibilities contribute significantly to women’s daily workload. The most overburdened women are working mothers (according to ISTAT, Italy’s Office for National Statistics, 2019), who are forced to combine their professional responsibilities with family life, dedicating 8 hours and 20 minutes per day to paid and unpaid work overall, compared with the 7 hours and 29 minutes spent by working fathers. Working mothers between ages 25 and 44 years have on average 2 hours and 35 minutes of free time per day.
 

Stress and sleep deprivation

“Under these conditions, the risk of chronic stress is raised, and stress leads to depression. The rate of depression in the female population is double that of the male population,” said Claudio Mencacci, MD, chair of the Italian Society of Neuropsychopharmacology and the Onda Foundation. “What’s more, stress increases the risk of cardiovascular and metabolic diseases, asthma, arthritis, and autoimmune diseases.”

The one thing that is especially damaging to physical and mental health is sleep deprivation, and working mothers get less sleep than do working fathers. “This is partially due to biological factors: hormonal changes that take place toward the end of adolescence in women during the premenstrual period are responsible for an increased rate of sleep disturbance and insomnia,” said Dr. Mencacci. “During pregnancy and the postpartum period, female sex hormones make sleep lighter, reducing time spent in the REM sleep stage. Then there’s the social aspect that plays a decisive role: by and large, it’s mothers who take care of the youngest children at night.”

According to a 2019 German study, during the first 6 years of life of the first child, a mother loses on average 44 minutes sleep per night, compared with the average time spent sleeping before pregnancy; a father loses 14 minutes.

“Another aspect to bear in mind is that, for cultural reasons, women tend to overlook the issue and not seek help, deeming sleep deprivation normal,” said Dr. Mencacci.
 

Caregivers at greatest risk

The negative effects of stress are evident in people continuously caring for a dependent older or disabled family member, so-called caregivers. This is, “A group predominantly made up of women aged between 45 and 55 years,” said Marina Petrini, PhD, of the Italian Health Institute’s Gender Medicine Center of Excellence. Dr. Petrini coordinated a study on stress and health in family caregivers.

“The results obtained reveal a high level of stress, especially among female caregivers, who are more exposed to the risk of severe symptoms of depression, physical disorders, especially those affecting the nervous and immune systems, and who tend to adopt irregular eating patterns and sedentary habits,” said Dr. Petrini.
 

Limited treatment access

Another study presented at the Onda Foundation’s conference, which shows just how much a lack of “me time” can damage your health, is the Access to Diagnostic Medicine and Treatment by Region: the Patient’s Perspective Survey, conducted by market research agency Elma Research on a sample of cancer patients requiring specialist treatment.

“Forty percent of them had to move to a different region from the one they live in to get the care they needed,” said Massimo Massagrande, CEO of Elma Research. “Of that group, 40% had to move to an area not neighboring their own. The impact of area of residence is heavy, in terms of money and logistics – so much so that a large proportion of patients interviewed were forced to turn their back on the best available treatments. For women responding to our survey, the biggest obstacle is the impossibility of reconciling the effects of a move or the prospective of a temporary transfer to another region with their responsibilities for looking after their family.”

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Lack of time for self-care and rest are particularly harmful to women’s health. Various speakers at the VII National Conference of the Onda Foundation, Italy’s National Observatory for Women and Gender’s Health, focused on this topic. The conference was dedicated to the social factors that determine health within the context of gender medicine.

In our society, housework and raising a family are responsibilities placed predominantly on the shoulders of women. These responsibilities contribute significantly to women’s daily workload. The most overburdened women are working mothers (according to ISTAT, Italy’s Office for National Statistics, 2019), who are forced to combine their professional responsibilities with family life, dedicating 8 hours and 20 minutes per day to paid and unpaid work overall, compared with the 7 hours and 29 minutes spent by working fathers. Working mothers between ages 25 and 44 years have on average 2 hours and 35 minutes of free time per day.
 

Stress and sleep deprivation

“Under these conditions, the risk of chronic stress is raised, and stress leads to depression. The rate of depression in the female population is double that of the male population,” said Claudio Mencacci, MD, chair of the Italian Society of Neuropsychopharmacology and the Onda Foundation. “What’s more, stress increases the risk of cardiovascular and metabolic diseases, asthma, arthritis, and autoimmune diseases.”

The one thing that is especially damaging to physical and mental health is sleep deprivation, and working mothers get less sleep than do working fathers. “This is partially due to biological factors: hormonal changes that take place toward the end of adolescence in women during the premenstrual period are responsible for an increased rate of sleep disturbance and insomnia,” said Dr. Mencacci. “During pregnancy and the postpartum period, female sex hormones make sleep lighter, reducing time spent in the REM sleep stage. Then there’s the social aspect that plays a decisive role: by and large, it’s mothers who take care of the youngest children at night.”

According to a 2019 German study, during the first 6 years of life of the first child, a mother loses on average 44 minutes sleep per night, compared with the average time spent sleeping before pregnancy; a father loses 14 minutes.

“Another aspect to bear in mind is that, for cultural reasons, women tend to overlook the issue and not seek help, deeming sleep deprivation normal,” said Dr. Mencacci.
 

Caregivers at greatest risk

The negative effects of stress are evident in people continuously caring for a dependent older or disabled family member, so-called caregivers. This is, “A group predominantly made up of women aged between 45 and 55 years,” said Marina Petrini, PhD, of the Italian Health Institute’s Gender Medicine Center of Excellence. Dr. Petrini coordinated a study on stress and health in family caregivers.

“The results obtained reveal a high level of stress, especially among female caregivers, who are more exposed to the risk of severe symptoms of depression, physical disorders, especially those affecting the nervous and immune systems, and who tend to adopt irregular eating patterns and sedentary habits,” said Dr. Petrini.
 

Limited treatment access

Another study presented at the Onda Foundation’s conference, which shows just how much a lack of “me time” can damage your health, is the Access to Diagnostic Medicine and Treatment by Region: the Patient’s Perspective Survey, conducted by market research agency Elma Research on a sample of cancer patients requiring specialist treatment.

“Forty percent of them had to move to a different region from the one they live in to get the care they needed,” said Massimo Massagrande, CEO of Elma Research. “Of that group, 40% had to move to an area not neighboring their own. The impact of area of residence is heavy, in terms of money and logistics – so much so that a large proportion of patients interviewed were forced to turn their back on the best available treatments. For women responding to our survey, the biggest obstacle is the impossibility of reconciling the effects of a move or the prospective of a temporary transfer to another region with their responsibilities for looking after their family.”

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Lack of time for self-care and rest are particularly harmful to women’s health. Various speakers at the VII National Conference of the Onda Foundation, Italy’s National Observatory for Women and Gender’s Health, focused on this topic. The conference was dedicated to the social factors that determine health within the context of gender medicine.

In our society, housework and raising a family are responsibilities placed predominantly on the shoulders of women. These responsibilities contribute significantly to women’s daily workload. The most overburdened women are working mothers (according to ISTAT, Italy’s Office for National Statistics, 2019), who are forced to combine their professional responsibilities with family life, dedicating 8 hours and 20 minutes per day to paid and unpaid work overall, compared with the 7 hours and 29 minutes spent by working fathers. Working mothers between ages 25 and 44 years have on average 2 hours and 35 minutes of free time per day.
 

Stress and sleep deprivation

“Under these conditions, the risk of chronic stress is raised, and stress leads to depression. The rate of depression in the female population is double that of the male population,” said Claudio Mencacci, MD, chair of the Italian Society of Neuropsychopharmacology and the Onda Foundation. “What’s more, stress increases the risk of cardiovascular and metabolic diseases, asthma, arthritis, and autoimmune diseases.”

The one thing that is especially damaging to physical and mental health is sleep deprivation, and working mothers get less sleep than do working fathers. “This is partially due to biological factors: hormonal changes that take place toward the end of adolescence in women during the premenstrual period are responsible for an increased rate of sleep disturbance and insomnia,” said Dr. Mencacci. “During pregnancy and the postpartum period, female sex hormones make sleep lighter, reducing time spent in the REM sleep stage. Then there’s the social aspect that plays a decisive role: by and large, it’s mothers who take care of the youngest children at night.”

According to a 2019 German study, during the first 6 years of life of the first child, a mother loses on average 44 minutes sleep per night, compared with the average time spent sleeping before pregnancy; a father loses 14 minutes.

“Another aspect to bear in mind is that, for cultural reasons, women tend to overlook the issue and not seek help, deeming sleep deprivation normal,” said Dr. Mencacci.
 

Caregivers at greatest risk

The negative effects of stress are evident in people continuously caring for a dependent older or disabled family member, so-called caregivers. This is, “A group predominantly made up of women aged between 45 and 55 years,” said Marina Petrini, PhD, of the Italian Health Institute’s Gender Medicine Center of Excellence. Dr. Petrini coordinated a study on stress and health in family caregivers.

“The results obtained reveal a high level of stress, especially among female caregivers, who are more exposed to the risk of severe symptoms of depression, physical disorders, especially those affecting the nervous and immune systems, and who tend to adopt irregular eating patterns and sedentary habits,” said Dr. Petrini.
 

Limited treatment access

Another study presented at the Onda Foundation’s conference, which shows just how much a lack of “me time” can damage your health, is the Access to Diagnostic Medicine and Treatment by Region: the Patient’s Perspective Survey, conducted by market research agency Elma Research on a sample of cancer patients requiring specialist treatment.

“Forty percent of them had to move to a different region from the one they live in to get the care they needed,” said Massimo Massagrande, CEO of Elma Research. “Of that group, 40% had to move to an area not neighboring their own. The impact of area of residence is heavy, in terms of money and logistics – so much so that a large proportion of patients interviewed were forced to turn their back on the best available treatments. For women responding to our survey, the biggest obstacle is the impossibility of reconciling the effects of a move or the prospective of a temporary transfer to another region with their responsibilities for looking after their family.”

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Sleep Medicine Network

Respiratory-Related Sleep Disorders Section

The overlap syndrome (OS), which refers to the co-occurrence of OSA and COPD, was first described by Flenley in 1985 (Flenley DC. Clin Chest Med. 1985;6[4]:651). Over the years, numerous studies have demonstrated an increased risk of hospitalization and mortality in patients with OS (Brennan M, et al. 2022;1-10). Despite these findings, limited evidence exists regarding the optimal treatment approach for individuals with OS.

CPAP therapy has demonstrated various physiologic advantages for patients with OS (Srivali N, et al. Sleep Med. 2023;108:55-60), which contribute to diminished dyspnea symptoms, lowered pro-inflammatory markers, improved arterial blood gases, increased 6-minute walk distance, enhanced FEV₁, and decreased mean pulmonary artery pressure (Suri TM, et al. FASEB BioAdv. 2021;3[9]:683-93). CPAP therapy in patients with OS has been linked to a reduction in COPD exacerbations (Voulgaris A, et al. Clin Respir Jour. 2023; 17[3]:165), fewer COPD-related hospitalizations (Marin JM, et al. Am J Respir Crit Care Med. 2010;182[3]:325-31), decreased cardiovascular events (Kendzerska T, et al. Ann ATS. 2019;16[1]:71), and an overall decline in mortality rates (Machado ML, et al. Eur Respir J. 2010;35[1]:132-7).

It is important to acknowledge that, as of now, no randomized clinical trial has specifically addressed the treatment of OS, leaving recommendations largely reliant on observational studies. Conversely, recent guidelines have proposed the utilization of high-intensity noninvasive ventilation (NIV) for hypercapnic patients with COPD. Thus, extensive research is warranted to characterize distinct sleep-related breathing disorders within the OS population and to investigate the effects of CPAP in comparison to other NIV modalities on patients with overlap syndrome.

Solmaz Ehteshami-Afshar, MD

Kirat Gill, MD, Section Member-at-Large

Sleep Medicine Network

Respiratory-Related Sleep Disorders Section

The overlap syndrome (OS), which refers to the co-occurrence of OSA and COPD, was first described by Flenley in 1985 (Flenley DC. Clin Chest Med. 1985;6[4]:651). Over the years, numerous studies have demonstrated an increased risk of hospitalization and mortality in patients with OS (Brennan M, et al. 2022;1-10). Despite these findings, limited evidence exists regarding the optimal treatment approach for individuals with OS.

CPAP therapy has demonstrated various physiologic advantages for patients with OS (Srivali N, et al. Sleep Med. 2023;108:55-60), which contribute to diminished dyspnea symptoms, lowered pro-inflammatory markers, improved arterial blood gases, increased 6-minute walk distance, enhanced FEV₁, and decreased mean pulmonary artery pressure (Suri TM, et al. FASEB BioAdv. 2021;3[9]:683-93). CPAP therapy in patients with OS has been linked to a reduction in COPD exacerbations (Voulgaris A, et al. Clin Respir Jour. 2023; 17[3]:165), fewer COPD-related hospitalizations (Marin JM, et al. Am J Respir Crit Care Med. 2010;182[3]:325-31), decreased cardiovascular events (Kendzerska T, et al. Ann ATS. 2019;16[1]:71), and an overall decline in mortality rates (Machado ML, et al. Eur Respir J. 2010;35[1]:132-7).

It is important to acknowledge that, as of now, no randomized clinical trial has specifically addressed the treatment of OS, leaving recommendations largely reliant on observational studies. Conversely, recent guidelines have proposed the utilization of high-intensity noninvasive ventilation (NIV) for hypercapnic patients with COPD. Thus, extensive research is warranted to characterize distinct sleep-related breathing disorders within the OS population and to investigate the effects of CPAP in comparison to other NIV modalities on patients with overlap syndrome.

Solmaz Ehteshami-Afshar, MD

Kirat Gill, MD, Section Member-at-Large

Sleep Medicine Network

Respiratory-Related Sleep Disorders Section

The overlap syndrome (OS), which refers to the co-occurrence of OSA and COPD, was first described by Flenley in 1985 (Flenley DC. Clin Chest Med. 1985;6[4]:651). Over the years, numerous studies have demonstrated an increased risk of hospitalization and mortality in patients with OS (Brennan M, et al. 2022;1-10). Despite these findings, limited evidence exists regarding the optimal treatment approach for individuals with OS.

CPAP therapy has demonstrated various physiologic advantages for patients with OS (Srivali N, et al. Sleep Med. 2023;108:55-60), which contribute to diminished dyspnea symptoms, lowered pro-inflammatory markers, improved arterial blood gases, increased 6-minute walk distance, enhanced FEV₁, and decreased mean pulmonary artery pressure (Suri TM, et al. FASEB BioAdv. 2021;3[9]:683-93). CPAP therapy in patients with OS has been linked to a reduction in COPD exacerbations (Voulgaris A, et al. Clin Respir Jour. 2023; 17[3]:165), fewer COPD-related hospitalizations (Marin JM, et al. Am J Respir Crit Care Med. 2010;182[3]:325-31), decreased cardiovascular events (Kendzerska T, et al. Ann ATS. 2019;16[1]:71), and an overall decline in mortality rates (Machado ML, et al. Eur Respir J. 2010;35[1]:132-7).

It is important to acknowledge that, as of now, no randomized clinical trial has specifically addressed the treatment of OS, leaving recommendations largely reliant on observational studies. Conversely, recent guidelines have proposed the utilization of high-intensity noninvasive ventilation (NIV) for hypercapnic patients with COPD. Thus, extensive research is warranted to characterize distinct sleep-related breathing disorders within the OS population and to investigate the effects of CPAP in comparison to other NIV modalities on patients with overlap syndrome.

Solmaz Ehteshami-Afshar, MD

Kirat Gill, MD, Section Member-at-Large

In the first study evaluating pediatric sleep-disordered breathing (SDB) from both indoor environment and neighborhood perspectives, multilevel risk factors were revealed as being associated with SDB-related symptoms. Beyond known associations with environmental tobacco smoke (ETS), a novel association with SDB symptoms was observed for exposure to indoor pests such as mice, cockroaches, and rats.

Although it has been well known that pediatric SDB affects low socioeconomic status (SES) children disproportionately, the roles of multilevel risk factor drivers including individual health, household SES, indoor exposures to environmental tobacco smoke, pests, and neighborhood characteristics have not been well studied, Gueye-Ndiaye et al. wrote in CHEST Pulmonary.

Pediatric SDB, a known risk factor for many health, neurobehavioral, and functional outcomes, includes habitual snoring and obstructive sleep apnea and may contribute to health disparities. Adenotonsillar hypertrophy and obesity are the most commonly recognized risk factors for SDB in generally healthy school-aged children. A role for other risk factors, however, is suggested by the fact that Black children have a fourfold increased risk for obstructive sleep apnea (OSA), compared with White children, unexplained by obesity, and have decreased response to treatment of OSA with adenotonsillectomy, compared with White children. Several studies point in the direction of neighborhood disadvantages as factors in heightened SDB prevalence or severity, Gueye-Ndiaye et al. stated.

The authors performed cross-sectional analyses on data recorded from 303 children (aged 6-12 years) enrolled in the Environmental Assessment of Sleep Youth (EASY) study from 2018 to 2022. Among them, 39% were Hispanic, Latino, Latina, or Spanish origin, 30% were Black or African American, 22% were White, and 11% were other. Maternal education attainment of a high school diploma or less was reported in 27%, and 65% of the sample lived in disadvantaged neighborhoods. Twenty-eight percent of children met criteria for objective SDB (Apnea-Hypopnea Index/Oxygen Desaturation Index ≥ 5/hr). Exposure documentation was informed by caregiver reports, assays of measured settled dust from the child’s bedroom, and neighborhood-level census data from which the Childhood Opportunity Index characterizing neighborhood disadvantage (ND) was derived. The study primary outcome was the SDB-related symptom burden assessed by the OSA-18 questionnaire total score.

Compared with children with no adverse indoor exposures to ETS and pests, children with such exposures had an approximately 4-12 point increase in total OSA-18 scores, and the increase among those with exposure to both ETS and pests was about 20 points (approximately a 1.3 standard deviation increase), Gueye-Ndiaye et al. reported.

In models adjusted for age, sex, minority race, and ethnicity, low maternal education was associated with a 7.55 (95% confidence interval, 3.44-11.66; P < .01) increased OSA-18 score. In models adjusted for sociodemographics including maternal education, history of asthma and allergic rhinitis were associated with a 13.63 (95% CI, 9.44-17.82; P < .01) and a 6.95 (95% CI, 2.62-11.29; P < .02) increased OSA-18 score, respectively. The authors noted that prior Canadian studies have shown OSA to be three times as likely in children with mothers reporting less than a high school education than in children with university educated mothers.

Speculating on the drivers of this association, they noted that the poor air quality due to tobacco smoke and allergen exposures to rodents, mold, and cockroaches are known contributors to asthma symptoms. Despite the differing pathogenesis of OSA and asthma, they suggest overlapping risk factors. Irritants and allergens may exacerbate SDB by stimulating immune responses manifested as adenotonsillar hypertrophy and by amplifying nasopharyngeal inflammation, adversely affecting upper airway patency. While ETS was not common in the sample, it was associated strongly with SDB. Gueye-Ndiaye et al. also showed associations between pest exposure, bedroom dust, and SDB symptoms. The findings, they concluded, support the importance of household- and bedroom-environmental conditions and sleep health.

OSA-18 scores were also elevated by about 7-14 points with allergic rhinitis and asthma, respectively. The findings, Gueye-Ndiaye et al. stated, underscore that asthma prevention strategies can be leveraged to address SDB disparities. No amplification of pest exposure effects, however, was found for asthma or allergic rhinitis.

“This is an incredibly important study, one that adds to our understanding of the risk factors that contribute to pediatric sleep health disparities,” said assistant professor of pediatrics Anne C. Coates, MD, Tufts University, Boston. “We have previously understood risk factors for sleep-disordered breathing like adenotonsillar hypertrophy, but this adds other elements like environmental tobacco smoke, pests, and home and neighborhood factors,” she told this news organization. “One of the most important takeaways is that beyond the importance of accurate diagnosis, there is the importance of advocating for our patients to ensure that they have the healthiest homes and neighborhoods. We need to inspire our colleagues to be advocates – for example – for pest mitigation, for antismoking policies, for every policy preventing the factors that contribute to the burden of disease.”

Dr. Coates is coauthor of “Advocacy and Health Equity: The Role of the Pediatric Pulmonologist,” currently in press (Clinics in Chest Medicine), and a member of the CHEST Physician Editorial Board.

The authors noted that a study limitation was that the sample was from one geographic area (Boston). Neither the authors nor Dr. Coates listed any conflicts.
 

In the first study evaluating pediatric sleep-disordered breathing (SDB) from both indoor environment and neighborhood perspectives, multilevel risk factors were revealed as being associated with SDB-related symptoms. Beyond known associations with environmental tobacco smoke (ETS), a novel association with SDB symptoms was observed for exposure to indoor pests such as mice, cockroaches, and rats.

Although it has been well known that pediatric SDB affects low socioeconomic status (SES) children disproportionately, the roles of multilevel risk factor drivers including individual health, household SES, indoor exposures to environmental tobacco smoke, pests, and neighborhood characteristics have not been well studied, Gueye-Ndiaye et al. wrote in CHEST Pulmonary.

Pediatric SDB, a known risk factor for many health, neurobehavioral, and functional outcomes, includes habitual snoring and obstructive sleep apnea and may contribute to health disparities. Adenotonsillar hypertrophy and obesity are the most commonly recognized risk factors for SDB in generally healthy school-aged children. A role for other risk factors, however, is suggested by the fact that Black children have a fourfold increased risk for obstructive sleep apnea (OSA), compared with White children, unexplained by obesity, and have decreased response to treatment of OSA with adenotonsillectomy, compared with White children. Several studies point in the direction of neighborhood disadvantages as factors in heightened SDB prevalence or severity, Gueye-Ndiaye et al. stated.

The authors performed cross-sectional analyses on data recorded from 303 children (aged 6-12 years) enrolled in the Environmental Assessment of Sleep Youth (EASY) study from 2018 to 2022. Among them, 39% were Hispanic, Latino, Latina, or Spanish origin, 30% were Black or African American, 22% were White, and 11% were other. Maternal education attainment of a high school diploma or less was reported in 27%, and 65% of the sample lived in disadvantaged neighborhoods. Twenty-eight percent of children met criteria for objective SDB (Apnea-Hypopnea Index/Oxygen Desaturation Index ≥ 5/hr). Exposure documentation was informed by caregiver reports, assays of measured settled dust from the child’s bedroom, and neighborhood-level census data from which the Childhood Opportunity Index characterizing neighborhood disadvantage (ND) was derived. The study primary outcome was the SDB-related symptom burden assessed by the OSA-18 questionnaire total score.

Compared with children with no adverse indoor exposures to ETS and pests, children with such exposures had an approximately 4-12 point increase in total OSA-18 scores, and the increase among those with exposure to both ETS and pests was about 20 points (approximately a 1.3 standard deviation increase), Gueye-Ndiaye et al. reported.

In models adjusted for age, sex, minority race, and ethnicity, low maternal education was associated with a 7.55 (95% confidence interval, 3.44-11.66; P < .01) increased OSA-18 score. In models adjusted for sociodemographics including maternal education, history of asthma and allergic rhinitis were associated with a 13.63 (95% CI, 9.44-17.82; P < .01) and a 6.95 (95% CI, 2.62-11.29; P < .02) increased OSA-18 score, respectively. The authors noted that prior Canadian studies have shown OSA to be three times as likely in children with mothers reporting less than a high school education than in children with university educated mothers.

Speculating on the drivers of this association, they noted that the poor air quality due to tobacco smoke and allergen exposures to rodents, mold, and cockroaches are known contributors to asthma symptoms. Despite the differing pathogenesis of OSA and asthma, they suggest overlapping risk factors. Irritants and allergens may exacerbate SDB by stimulating immune responses manifested as adenotonsillar hypertrophy and by amplifying nasopharyngeal inflammation, adversely affecting upper airway patency. While ETS was not common in the sample, it was associated strongly with SDB. Gueye-Ndiaye et al. also showed associations between pest exposure, bedroom dust, and SDB symptoms. The findings, they concluded, support the importance of household- and bedroom-environmental conditions and sleep health.

OSA-18 scores were also elevated by about 7-14 points with allergic rhinitis and asthma, respectively. The findings, Gueye-Ndiaye et al. stated, underscore that asthma prevention strategies can be leveraged to address SDB disparities. No amplification of pest exposure effects, however, was found for asthma or allergic rhinitis.

“This is an incredibly important study, one that adds to our understanding of the risk factors that contribute to pediatric sleep health disparities,” said assistant professor of pediatrics Anne C. Coates, MD, Tufts University, Boston. “We have previously understood risk factors for sleep-disordered breathing like adenotonsillar hypertrophy, but this adds other elements like environmental tobacco smoke, pests, and home and neighborhood factors,” she told this news organization. “One of the most important takeaways is that beyond the importance of accurate diagnosis, there is the importance of advocating for our patients to ensure that they have the healthiest homes and neighborhoods. We need to inspire our colleagues to be advocates – for example – for pest mitigation, for antismoking policies, for every policy preventing the factors that contribute to the burden of disease.”

Dr. Coates is coauthor of “Advocacy and Health Equity: The Role of the Pediatric Pulmonologist,” currently in press (Clinics in Chest Medicine), and a member of the CHEST Physician Editorial Board.

The authors noted that a study limitation was that the sample was from one geographic area (Boston). Neither the authors nor Dr. Coates listed any conflicts.
 

In the first study evaluating pediatric sleep-disordered breathing (SDB) from both indoor environment and neighborhood perspectives, multilevel risk factors were revealed as being associated with SDB-related symptoms. Beyond known associations with environmental tobacco smoke (ETS), a novel association with SDB symptoms was observed for exposure to indoor pests such as mice, cockroaches, and rats.

Although it has been well known that pediatric SDB affects low socioeconomic status (SES) children disproportionately, the roles of multilevel risk factor drivers including individual health, household SES, indoor exposures to environmental tobacco smoke, pests, and neighborhood characteristics have not been well studied, Gueye-Ndiaye et al. wrote in CHEST Pulmonary.

Pediatric SDB, a known risk factor for many health, neurobehavioral, and functional outcomes, includes habitual snoring and obstructive sleep apnea and may contribute to health disparities. Adenotonsillar hypertrophy and obesity are the most commonly recognized risk factors for SDB in generally healthy school-aged children. A role for other risk factors, however, is suggested by the fact that Black children have a fourfold increased risk for obstructive sleep apnea (OSA), compared with White children, unexplained by obesity, and have decreased response to treatment of OSA with adenotonsillectomy, compared with White children. Several studies point in the direction of neighborhood disadvantages as factors in heightened SDB prevalence or severity, Gueye-Ndiaye et al. stated.

The authors performed cross-sectional analyses on data recorded from 303 children (aged 6-12 years) enrolled in the Environmental Assessment of Sleep Youth (EASY) study from 2018 to 2022. Among them, 39% were Hispanic, Latino, Latina, or Spanish origin, 30% were Black or African American, 22% were White, and 11% were other. Maternal education attainment of a high school diploma or less was reported in 27%, and 65% of the sample lived in disadvantaged neighborhoods. Twenty-eight percent of children met criteria for objective SDB (Apnea-Hypopnea Index/Oxygen Desaturation Index ≥ 5/hr). Exposure documentation was informed by caregiver reports, assays of measured settled dust from the child’s bedroom, and neighborhood-level census data from which the Childhood Opportunity Index characterizing neighborhood disadvantage (ND) was derived. The study primary outcome was the SDB-related symptom burden assessed by the OSA-18 questionnaire total score.

Compared with children with no adverse indoor exposures to ETS and pests, children with such exposures had an approximately 4-12 point increase in total OSA-18 scores, and the increase among those with exposure to both ETS and pests was about 20 points (approximately a 1.3 standard deviation increase), Gueye-Ndiaye et al. reported.

In models adjusted for age, sex, minority race, and ethnicity, low maternal education was associated with a 7.55 (95% confidence interval, 3.44-11.66; P < .01) increased OSA-18 score. In models adjusted for sociodemographics including maternal education, history of asthma and allergic rhinitis were associated with a 13.63 (95% CI, 9.44-17.82; P < .01) and a 6.95 (95% CI, 2.62-11.29; P < .02) increased OSA-18 score, respectively. The authors noted that prior Canadian studies have shown OSA to be three times as likely in children with mothers reporting less than a high school education than in children with university educated mothers.

Speculating on the drivers of this association, they noted that the poor air quality due to tobacco smoke and allergen exposures to rodents, mold, and cockroaches are known contributors to asthma symptoms. Despite the differing pathogenesis of OSA and asthma, they suggest overlapping risk factors. Irritants and allergens may exacerbate SDB by stimulating immune responses manifested as adenotonsillar hypertrophy and by amplifying nasopharyngeal inflammation, adversely affecting upper airway patency. While ETS was not common in the sample, it was associated strongly with SDB. Gueye-Ndiaye et al. also showed associations between pest exposure, bedroom dust, and SDB symptoms. The findings, they concluded, support the importance of household- and bedroom-environmental conditions and sleep health.

OSA-18 scores were also elevated by about 7-14 points with allergic rhinitis and asthma, respectively. The findings, Gueye-Ndiaye et al. stated, underscore that asthma prevention strategies can be leveraged to address SDB disparities. No amplification of pest exposure effects, however, was found for asthma or allergic rhinitis.

“This is an incredibly important study, one that adds to our understanding of the risk factors that contribute to pediatric sleep health disparities,” said assistant professor of pediatrics Anne C. Coates, MD, Tufts University, Boston. “We have previously understood risk factors for sleep-disordered breathing like adenotonsillar hypertrophy, but this adds other elements like environmental tobacco smoke, pests, and home and neighborhood factors,” she told this news organization. “One of the most important takeaways is that beyond the importance of accurate diagnosis, there is the importance of advocating for our patients to ensure that they have the healthiest homes and neighborhoods. We need to inspire our colleagues to be advocates – for example – for pest mitigation, for antismoking policies, for every policy preventing the factors that contribute to the burden of disease.”

Dr. Coates is coauthor of “Advocacy and Health Equity: The Role of the Pediatric Pulmonologist,” currently in press (Clinics in Chest Medicine), and a member of the CHEST Physician Editorial Board.

The authors noted that a study limitation was that the sample was from one geographic area (Boston). Neither the authors nor Dr. Coates listed any conflicts.
 

BARCELONA – Intermittent benzodiazepine use significantly reduces the risk for falls, fractures, and mortality in older adults compared with chronic use of these medications, results of a large-scale study show.

Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.

Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.

Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.

However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.

The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
 

Wide range of adverse outcomes

The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.

“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.

Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.

Moreover, chronic use is more common in older versus younger patients.

Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.

“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”

To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.

They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.

Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.

Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.

The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.

As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.

Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.

Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.

After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
 

Sex differences

In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).

There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).

A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).

Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).

The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”

He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.

“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.

If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.

“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
 

Confirmatory research

In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.

“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.

Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”

In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”

Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”

“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.

The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.

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

BARCELONA – Intermittent benzodiazepine use significantly reduces the risk for falls, fractures, and mortality in older adults compared with chronic use of these medications, results of a large-scale study show.

Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.

Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.

Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.

However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.

The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
 

Wide range of adverse outcomes

The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.

“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.

Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.

Moreover, chronic use is more common in older versus younger patients.

Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.

“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”

To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.

They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.

Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.

Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.

The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.

As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.

Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.

Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.

After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
 

Sex differences

In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).

There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).

A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).

Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).

The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”

He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.

“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.

If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.

“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
 

Confirmatory research

In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.

“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.

Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”

In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”

Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”

“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.

The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.

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

BARCELONA – Intermittent benzodiazepine use significantly reduces the risk for falls, fractures, and mortality in older adults compared with chronic use of these medications, results of a large-scale study show.

Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.

Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.

Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.

However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.

The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
 

Wide range of adverse outcomes

The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.

“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.

Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.

Moreover, chronic use is more common in older versus younger patients.

Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.

“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”

To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.

They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.

Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.

Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.

The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.

As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.

Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.

Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.

After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
 

Sex differences

In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).

There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).

A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).

Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).

The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”

He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.

“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.

If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.

“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
 

Confirmatory research

In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.

“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.

Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”

In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”

Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”

“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.

The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.

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

Sleep is fundamental to overall health and longevity, with the average person spending about one-third of their life sleeping.¹ Adequate sleep is critical for optimal cognition, memory consolidation, mood regulation, metabolism, appetite regulation, and immune and hormone functioning. According to the American Academy of Sleep Medicine and the Sleep Research Society, adults should sleep at least 7 hours per night on a regular basis “to promote optimal health.”² Yet, between 2013 and 2020, only about 65% of adults in the United States were meeting this amount.³ Insufficient sleep is associated with an increased risk for chronic health conditions, including obesity, diabetes, cardiovascular diseases, and even premature death.⁴

In a population-based longitudinal study of sleep disorders, short sleep duration was associated with increased body mass index (BMI), low blood levels of leptin, and high ghrelin levels.⁵ In addition to physical impairments, poor sleep can impair cognitive performance and lead to vehicular accidents and increased accidents at work.⁴ The potential economic impact that this may have is significant, and includes increased costs and loss of productivity in the workplace.⁶

Many factors may contribute to short sleep duration: environment, mental and physical condition, and social influences such as occupation, family responsibilities, travel, group activities, and personal care. Furthermore, the rapidly evolving and developing media, communication, and entertainment industries are already strongly implicated in poor sleep quality and quantity, both contributing to excessive daytime sleepiness.⁷ Poor sleep quality is most notable in modern societies, and it correlates with the increasing prevalence of obesity, likely due to sleep’s effect on food consumption and physical activity.⁸ Optimizing a person’s sleep will improve overall health and longevity by inhibiting the development of chronic disease.

How insufficient sleep raises the risk for obesity

Not only is sleep beneficial for brain health, memory, learning, and growth, its effect on food consumption and physical activity likely correlates with the increased prevalence of obesity in modern society. Yet the optimal amount of sleep is controversial, and current recommendations of 7 or more hours of sleep per night for adults are derived from expert panels only.² The recommended sleep duration for children is longer, and it varies by age.⁹ The quality of sleep and its impact on neuroendocrine hormones, not just the quantity of sleep, needs to be factored into these recommendations.

Sleep restriction activates the orexigenic system via the hormones leptin and ghrelin. These hormones control the food reward system, essentially increasing hunger and food intake. Leptin, created by white adipose tissue, is responsible for satiety and decreased food consumption.¹⁰ Ghrelin, made by oxyntic glands in the stomach, is responsible for the sensation of hunger.

Poor sleep will increase the risk for obesity and hinder its treatment. Therefore, sleep quality and duration are vital components of obesity management.

In a 2004 study by Spiegel et al,¹¹ leptin and ghrelin levels were measured during 2 days of sleep restriction (4 hours in bed) and sleep extension (10 hours in bed). Sleep restriction was associated with a decrease in leptin levels and an increase in ghrelin levels. The researchers reported that participants experienced an increase in hunger and ­appetite—especially for calorie-dense foods with high carbohydrate content.

Although research design has limitations with predominantly self-reported sleep data, studies have shown that short sleep time leads to increased food intake by increasing hunger signals and craving of unhealthy foods, and by providing more opportunities to eat while awake. It also may lead to decreased physical activity, creating a sedentary lifestyle that further encourages obesity.⁸ Reduced sleep is even correlated to decreased efficacy of weight-loss treatments.¹²

Continue to: Other sleep characteristics weakly correlated with obesity

Other sleep characteristics weakly correlated with obesity are sleep variability, timing, efficiency, quality, and daytime napping.⁸ Sleep variability causes dysregulation of eating patterns, leading to increased food intake. A shift to later sleep and waking times often results in higher consumption of calories after 8 pm¹³; late-night snacks are a part of this sleep–obesity equation.¹⁴

Poor sleep efficiency and quality decreases N3-stage (deep non-REM) sleep, affects the autonomic nervous system, and has been associated with increased abdominal obesity. Daytime napping, which can cause irregular circadian rhythms and sleep schedules, is associated with increased obesity.¹⁵ Thus, each component of sleep needs to be assessed to promote optimal regulation of the orexigenic system.

It is a cycle of poor sleep causing obesity and obesity causing poor sleep.

Another study showed that inadequate sleep not only promotes unhealthy lifestyle habits that can lead to obesity but also decreases the ability to lose weight.¹⁶ This small study with 10 overweight patients provided its subjects with a controlled caloric intake over 2 weeks. Patients spent two 14-day periods 3 months apart in the laboratory, divided into 2 time-in-bed arms of 8.5 and 5.5 hours per night. Neuroendocrine changes caused by decreased sleep were associated with a significant lean body mass loss while conserving energy-dense fat.¹⁶ This study highlights the importance of sleep hygiene counseling when developing a weight-management plan with patients.

Sleep, and its many components, play an integral role in the prevention and treatment of obesity.¹⁷ Poor sleep will increase the risk for obesity and hinder its treatment. Therefore, sleep quality and duration are vital components of obesity management.

The sleep–obesity link in children and the elderly

Childhood obesity is linked to several chronic diseases in adulthood, including type 2 diabetes, cardiovascular disease, nonalcoholic fatty liver disease, asthma, and obstructive sleep apnea (OSA).¹⁸ According to 2017-2018 NHANES (National Health and Nutrition Examination Surveys) data, obesity (BMI ≥ 95th percentile) prevalence among children and adolescents was reported at 19.3% and severe obesity (BMI ≥ 120% of the 95th percentile) at 6.1%. Pediatric overweight prevalence (≥ 85th percentile and < 95th percentile) was 16.1%.¹⁹

Continue to: Although poor sleep is associated...

Although poor sleep is associated with increased risk for obesity, there is no proven cause-effect relationship.²⁰ Nutrition and physical activity have been identified as 2 critical factors in childhood obesity, but sleep health also needs to be investigated. Shorter sleep duration is strongly associated with the development of obesity. Furthermore, children with obesity are more likely to have shorter sleep duration.²¹ A short sleep duration alters plasma levels of insulin, low-density lipoprotein, and high-sensitivity ­C-reactive protein. It is associated with lower diet quality, an increased intake of nutrient-poor foods, and a lower intake of vegetables and fruits.²² Recent studies have shown that interventions to promote earlier bedtimes can improve sleep duration in children.

Older adults have many sleeping issues, including insomnia, circadian rhythm sleep-wake disorders, sleep-related movement disorders, and sleep-breathing disorders. Additionally, the older population has increased sleep latency, decreased sleep efficiency and total sleep time, decreased REM sleep, more frequent nighttime awakenings, and more daytime napping.²³ The increased sleep disturbance with age is mainly related to higher risk factors for sleep disorders than the aging process itself. Sleeping 5 or fewer hours is associated with an increased risk for obesity and central abdominal fat compared with those who sleep 7 to 8 hours per night.²⁴ Similar to children and youth, older adults also show a strong correlation between inadequate sleep and obesity.²⁴

The consequence: A vicious cycle

Obesity in turn leads to shorter sleep duration and more disruptions. This negatively affects the orexigenic system, and the resulting hormonal derangement promotes worsening obesity. It is a cycle of poor sleep causing obesity and obesity causing poor sleep. Insomnia, in combination with shorter (and longer) sleep times, also has been linked with obesity.²⁵ These patients experience more daytime sleepiness, fatigue, and nighttime sleep disturbances, all correlated with decreased quality of life and higher prevalence of medical comorbidities.^8,26 Additional comorbidities secondary to obesity, including gastroesophageal reflux, depression, and asthma, also have been linked to sleep disturbances.⁸

OSA is a common sleep complication associated with obesity. With the increasing prevalence of obesity, the prevalence of OSA is rising.^8,27 Factors that heighten the risk for OSA are male sex, age 40 to 70 years, postmenopausal status, elevated BMI, and craniofacial and upper airway abnormality.²⁸ However, the US Preventive Services Task Force found insufficient evidence to screen for or treat OSA in asymptomatic adults.²⁸ Signs and symptoms of OSA include nighttime awakenings with choking, loud snoring, and feeling unrefreshed after sleep.²⁹

Approximately half of primary care clinicians do not screen at-risk patients for OSA, and 90% do not use validated OSA screening tools.

OSA is caused by the intermittent narrowing and obstruction of the pharyngeal airway due to anatomical and structural irregularities or neuromuscular impairments. Untreated OSA is associated with cardiovascular disease and cardiac arrhythmias such as atrial fibrillation. Even with this correlation between obesity and sleep, it is estimated that 80% of OSA remains undiagnosed.³⁰ Approximately half of primary care clinicians do not screen at-risk patients for OSA, and 90% do not use validated OSA screening tools.³¹ Screening tools that have been validated are the STOP, STOP-BANG, Epworth Sleepiness Scale, and 4-Variable Screening Tool. However, the US Department of Veterans Affairs and the US Department of Defense have a more recent guideline recommending STOP as an easier-to-administer screen for OSA.³² A positive result with a screening tool should be confirmed with polysomnography.³²

Continue to: Intervention for OSA

Intervention for OSA. The longest randomized controlled study to date, Sleep AHEAD, evaluated over a period of 10 years the effect of weight loss on OSA severity achieved with either an intensive lifestyle intervention (ILI) or with diabetes support and education (DSE).³³ OSA severity is rated on an Apnea-Hypopnea Index (AHI), with scores reflecting the number of sleep apnea events per hour. This study demonstrated that weight loss was associated with decreased OSA severity. At 4-year follow-up, the greater the weight loss with ILI intervention, the lower the patients’ OSA severity scores. The study found an average decrease in AHI of 0.68 events per hour for every kilogram of weight loss in the ILI group (P < .0001).^33,34 Over the follow-up visits, the ILI participants had 7.4 events per hour, a more significantly reduced AHI than the DSE participants (P < .0001).^33,34

Additionally, a small cohort of study participants achieved OSA remission (ILI, 34.4%; DSE, 22.2%), indicated by a low AHI score (< 5 events per hour). At the conclusion of the study, OSA severity decreased to a greater degree with ILI intervention.^33,34

Alcohol and drug use can negatively influence sleep patterns and obesity. Higher alcohol consumption is associated with poorer sleep quality and higher chances of developing short sleep duration and snoring.³⁵ Alcohol, a muscle relaxant, causes upper airway narrowing and reduced tongue muscle tone, thereby increasing snoring and OSA as demonstrated by increased AHI on polysomnography after alcohol intake. Alcohol also changes sleep architecture by increasing slow-wave sleep, decreasing REM sleep duration, and increasing sleep arousal in the second half of the night.³⁶ Disrupted circadian rhythm after alcohol consumption was correlated with increased adenosine neurotransmitters derived from ethanol metabolism.³⁷ Alcohol dependence may be related to other psychiatric symptoms, and chronic alcohol use eventually alters sleep mechanisms leading to persistent insomnia, further perpetuating adverse outcomes such as suicidal ideation.³⁶ There are positive associations between beer drinking and measures of abdominal adiposity in men, and “the combination of short sleep duration [and] disinhibited eating … is associated with greater alcohol intake and excess weight.”³⁸

Therefore, counsel patients to avoid alcohol since it is a modifiable risk factor with pervasive adverse health effects.

Many drugs have a profound effect on sleep patterns. Illicit drug use in particular can affect the brain’s neurotransmitter serotonin system. For example, ecstasy users have an increased risk for OSA.³⁹ People with cocaine and heroin use disorder tend to have more sleep-maintenance insomnia.⁴⁰

Continue to: In contrast, those with alcohol...

In contrast, those with alcohol or cannabis use disorder tend to have more sleep-onset insomnia.⁴⁰ Not only do illicit drugs interrupt sleep, but daily tobacco use also has been correlated with increased insomnia and shorter sleep duration since nicotine is a stimulant.⁴¹

Insomnia is commonly treated with sedative antidepressants and hypnotics—eg, mirtazapine and olanzapine—that contribute to weight gain.⁴² In addition, other common pharmaceuticals used for sleep disorders, such as diphenhydramine, have sedative properties and tend to lead to weight gain.⁴³ Because so many medications affect sleep and weight, carefully review patients’ medication lists and switch offending agents to weight-neutral drugs if possible.

Treatment and tools to improve sleep in patients with obesity

Given the strong correlation between obesity and sleep disorders, validated screening tools should be used to assess sleep quality, including onset and potential symptoms associated with poor sleep (TABLE 1⁴⁴). For weight management to succeed in patients with obesity, it is crucial to address sleep in addition to nutrition and physical activity.^17,45

It falls upon the clinician and patient to weigh the benefits and burdens of the pharmacologic treatments of insomnia.

Physical activity has many benefits to overall health, especially for chronic diseases such as type 2 diabetes and hypertension. The Centers for Disease Control and Prevention recommends at least 150 minutes of ­moderate-intensity aerobic activity or 75 minutes of vigorous-intensity aerobic exercise per week in addition to muscle-strengthening activities 2 or more days per week.⁴⁶ However, approximately 300 minutes of moderate-intensity activity per week is suggested for successful weight loss with exercise alone.⁴⁷

Physical activity and diet in combination are vital, but diet restriction has a more substantial effect on weight loss than physical activity alone.⁴⁸ Still, physical activity is essential in helping maintain and prevent weight regain.

Continue to: Nonpharmacologic interventions

Nonpharmacologic interventions include promoting greater sleep quality and quantity by emphasizing good sleep hygiene practices. Developing a practical and effective bedtime routine, creating a quiet sleep environment, and practicing healthy daily habits are essential components to sleep hygiene(TABLE 2^49,50). Relaxation techniques and cognitive behavioral therapy (CBT) also can help. CBT for insomnia (CBT-I) is the first-line intervention for chronic insomnia.⁵¹ Sleep restriction is a type of CBT used to treat insomnia, encouraging short-term sleep loss in the hopes of improving insomnia. A trial by Logue et al showed that patients with overweight and obesity randomized to undergo CBT with better sleep hygiene (nonpharmacologic) interventions had a greater mean weight loss percentage (5% vs 2%; P = .04) than did those who received CBT alone.⁵²

Eastern medicine including herbal interventions lack evidence of efficacy and safety. Further studies need to be done on the effects that chamomile, kava, valerian root (Valeriana officinalis), tryptophan, and Wu Ling (from mycelia Xylaria nigripes) might have on sleep.⁵³

Proceed cautiously with medication. The American College of Physicians recommends a shared decision-making approach when considering pharmacologic therapy for chronic insomnia and the American Academy of Sleep Medicine (AASM) offers guidance on options.^51,54 However, the evidence behind AASM sleep pharmacologic recommendations is weak, implying a lesser degree of confidence in the outcome and, therefore, in its appropriateness. Thus, it falls upon the clinician and patient to weigh the benefits and burdens of the pharmacologic treatments of insomnia. If indicated, medications suggested to treat sleep onset and sleep maintenance insomnia are eszopiclone, zolpidem, and temazepam. Zaleplon, triazolam, and ramelteon may improve sleep initiation. Suvorexant and doxepin are used for sleep-maintenance insomnia.⁵⁴ Exploring patient preferences, cost of treatment, health care options, and available resources should all be considered.

CORRESPONDENCE
Ecler Ercole Jaqua, MD, MBA, FAAFP, AGSF, FACLM, DipABOM, Loma Linda University Health, 25455 Barton Road, Suite 206A, Loma Linda, CA 92354; [email protected]

Sleep is fundamental to overall health and longevity, with the average person spending about one-third of their life sleeping.¹ Adequate sleep is critical for optimal cognition, memory consolidation, mood regulation, metabolism, appetite regulation, and immune and hormone functioning. According to the American Academy of Sleep Medicine and the Sleep Research Society, adults should sleep at least 7 hours per night on a regular basis “to promote optimal health.”² Yet, between 2013 and 2020, only about 65% of adults in the United States were meeting this amount.³ Insufficient sleep is associated with an increased risk for chronic health conditions, including obesity, diabetes, cardiovascular diseases, and even premature death.⁴

In a population-based longitudinal study of sleep disorders, short sleep duration was associated with increased body mass index (BMI), low blood levels of leptin, and high ghrelin levels.⁵ In addition to physical impairments, poor sleep can impair cognitive performance and lead to vehicular accidents and increased accidents at work.⁴ The potential economic impact that this may have is significant, and includes increased costs and loss of productivity in the workplace.⁶

Many factors may contribute to short sleep duration: environment, mental and physical condition, and social influences such as occupation, family responsibilities, travel, group activities, and personal care. Furthermore, the rapidly evolving and developing media, communication, and entertainment industries are already strongly implicated in poor sleep quality and quantity, both contributing to excessive daytime sleepiness.⁷ Poor sleep quality is most notable in modern societies, and it correlates with the increasing prevalence of obesity, likely due to sleep’s effect on food consumption and physical activity.⁸ Optimizing a person’s sleep will improve overall health and longevity by inhibiting the development of chronic disease.

How insufficient sleep raises the risk for obesity

Not only is sleep beneficial for brain health, memory, learning, and growth, its effect on food consumption and physical activity likely correlates with the increased prevalence of obesity in modern society. Yet the optimal amount of sleep is controversial, and current recommendations of 7 or more hours of sleep per night for adults are derived from expert panels only.² The recommended sleep duration for children is longer, and it varies by age.⁹ The quality of sleep and its impact on neuroendocrine hormones, not just the quantity of sleep, needs to be factored into these recommendations.

Sleep restriction activates the orexigenic system via the hormones leptin and ghrelin. These hormones control the food reward system, essentially increasing hunger and food intake. Leptin, created by white adipose tissue, is responsible for satiety and decreased food consumption.¹⁰ Ghrelin, made by oxyntic glands in the stomach, is responsible for the sensation of hunger.

Poor sleep will increase the risk for obesity and hinder its treatment. Therefore, sleep quality and duration are vital components of obesity management.

In a 2004 study by Spiegel et al,¹¹ leptin and ghrelin levels were measured during 2 days of sleep restriction (4 hours in bed) and sleep extension (10 hours in bed). Sleep restriction was associated with a decrease in leptin levels and an increase in ghrelin levels. The researchers reported that participants experienced an increase in hunger and ­appetite—especially for calorie-dense foods with high carbohydrate content.

Although research design has limitations with predominantly self-reported sleep data, studies have shown that short sleep time leads to increased food intake by increasing hunger signals and craving of unhealthy foods, and by providing more opportunities to eat while awake. It also may lead to decreased physical activity, creating a sedentary lifestyle that further encourages obesity.⁸ Reduced sleep is even correlated to decreased efficacy of weight-loss treatments.¹²

Continue to: Other sleep characteristics weakly correlated with obesity

Other sleep characteristics weakly correlated with obesity are sleep variability, timing, efficiency, quality, and daytime napping.⁸ Sleep variability causes dysregulation of eating patterns, leading to increased food intake. A shift to later sleep and waking times often results in higher consumption of calories after 8 pm¹³; late-night snacks are a part of this sleep–obesity equation.¹⁴

Poor sleep efficiency and quality decreases N3-stage (deep non-REM) sleep, affects the autonomic nervous system, and has been associated with increased abdominal obesity. Daytime napping, which can cause irregular circadian rhythms and sleep schedules, is associated with increased obesity.¹⁵ Thus, each component of sleep needs to be assessed to promote optimal regulation of the orexigenic system.

It is a cycle of poor sleep causing obesity and obesity causing poor sleep.

Another study showed that inadequate sleep not only promotes unhealthy lifestyle habits that can lead to obesity but also decreases the ability to lose weight.¹⁶ This small study with 10 overweight patients provided its subjects with a controlled caloric intake over 2 weeks. Patients spent two 14-day periods 3 months apart in the laboratory, divided into 2 time-in-bed arms of 8.5 and 5.5 hours per night. Neuroendocrine changes caused by decreased sleep were associated with a significant lean body mass loss while conserving energy-dense fat.¹⁶ This study highlights the importance of sleep hygiene counseling when developing a weight-management plan with patients.

Sleep, and its many components, play an integral role in the prevention and treatment of obesity.¹⁷ Poor sleep will increase the risk for obesity and hinder its treatment. Therefore, sleep quality and duration are vital components of obesity management.

The sleep–obesity link in children and the elderly

Childhood obesity is linked to several chronic diseases in adulthood, including type 2 diabetes, cardiovascular disease, nonalcoholic fatty liver disease, asthma, and obstructive sleep apnea (OSA).¹⁸ According to 2017-2018 NHANES (National Health and Nutrition Examination Surveys) data, obesity (BMI ≥ 95th percentile) prevalence among children and adolescents was reported at 19.3% and severe obesity (BMI ≥ 120% of the 95th percentile) at 6.1%. Pediatric overweight prevalence (≥ 85th percentile and < 95th percentile) was 16.1%.¹⁹

Continue to: Although poor sleep is associated...

Although poor sleep is associated with increased risk for obesity, there is no proven cause-effect relationship.²⁰ Nutrition and physical activity have been identified as 2 critical factors in childhood obesity, but sleep health also needs to be investigated. Shorter sleep duration is strongly associated with the development of obesity. Furthermore, children with obesity are more likely to have shorter sleep duration.²¹ A short sleep duration alters plasma levels of insulin, low-density lipoprotein, and high-sensitivity ­C-reactive protein. It is associated with lower diet quality, an increased intake of nutrient-poor foods, and a lower intake of vegetables and fruits.²² Recent studies have shown that interventions to promote earlier bedtimes can improve sleep duration in children.

Older adults have many sleeping issues, including insomnia, circadian rhythm sleep-wake disorders, sleep-related movement disorders, and sleep-breathing disorders. Additionally, the older population has increased sleep latency, decreased sleep efficiency and total sleep time, decreased REM sleep, more frequent nighttime awakenings, and more daytime napping.²³ The increased sleep disturbance with age is mainly related to higher risk factors for sleep disorders than the aging process itself. Sleeping 5 or fewer hours is associated with an increased risk for obesity and central abdominal fat compared with those who sleep 7 to 8 hours per night.²⁴ Similar to children and youth, older adults also show a strong correlation between inadequate sleep and obesity.²⁴

The consequence: A vicious cycle

Obesity in turn leads to shorter sleep duration and more disruptions. This negatively affects the orexigenic system, and the resulting hormonal derangement promotes worsening obesity. It is a cycle of poor sleep causing obesity and obesity causing poor sleep. Insomnia, in combination with shorter (and longer) sleep times, also has been linked with obesity.²⁵ These patients experience more daytime sleepiness, fatigue, and nighttime sleep disturbances, all correlated with decreased quality of life and higher prevalence of medical comorbidities.^8,26 Additional comorbidities secondary to obesity, including gastroesophageal reflux, depression, and asthma, also have been linked to sleep disturbances.⁸

OSA is a common sleep complication associated with obesity. With the increasing prevalence of obesity, the prevalence of OSA is rising.^8,27 Factors that heighten the risk for OSA are male sex, age 40 to 70 years, postmenopausal status, elevated BMI, and craniofacial and upper airway abnormality.²⁸ However, the US Preventive Services Task Force found insufficient evidence to screen for or treat OSA in asymptomatic adults.²⁸ Signs and symptoms of OSA include nighttime awakenings with choking, loud snoring, and feeling unrefreshed after sleep.²⁹

Approximately half of primary care clinicians do not screen at-risk patients for OSA, and 90% do not use validated OSA screening tools.

OSA is caused by the intermittent narrowing and obstruction of the pharyngeal airway due to anatomical and structural irregularities or neuromuscular impairments. Untreated OSA is associated with cardiovascular disease and cardiac arrhythmias such as atrial fibrillation. Even with this correlation between obesity and sleep, it is estimated that 80% of OSA remains undiagnosed.³⁰ Approximately half of primary care clinicians do not screen at-risk patients for OSA, and 90% do not use validated OSA screening tools.³¹ Screening tools that have been validated are the STOP, STOP-BANG, Epworth Sleepiness Scale, and 4-Variable Screening Tool. However, the US Department of Veterans Affairs and the US Department of Defense have a more recent guideline recommending STOP as an easier-to-administer screen for OSA.³² A positive result with a screening tool should be confirmed with polysomnography.³²

Continue to: Intervention for OSA

Intervention for OSA. The longest randomized controlled study to date, Sleep AHEAD, evaluated over a period of 10 years the effect of weight loss on OSA severity achieved with either an intensive lifestyle intervention (ILI) or with diabetes support and education (DSE).³³ OSA severity is rated on an Apnea-Hypopnea Index (AHI), with scores reflecting the number of sleep apnea events per hour. This study demonstrated that weight loss was associated with decreased OSA severity. At 4-year follow-up, the greater the weight loss with ILI intervention, the lower the patients’ OSA severity scores. The study found an average decrease in AHI of 0.68 events per hour for every kilogram of weight loss in the ILI group (P < .0001).^33,34 Over the follow-up visits, the ILI participants had 7.4 events per hour, a more significantly reduced AHI than the DSE participants (P < .0001).^33,34

Additionally, a small cohort of study participants achieved OSA remission (ILI, 34.4%; DSE, 22.2%), indicated by a low AHI score (< 5 events per hour). At the conclusion of the study, OSA severity decreased to a greater degree with ILI intervention.^33,34

Alcohol and drug use can negatively influence sleep patterns and obesity. Higher alcohol consumption is associated with poorer sleep quality and higher chances of developing short sleep duration and snoring.³⁵ Alcohol, a muscle relaxant, causes upper airway narrowing and reduced tongue muscle tone, thereby increasing snoring and OSA as demonstrated by increased AHI on polysomnography after alcohol intake. Alcohol also changes sleep architecture by increasing slow-wave sleep, decreasing REM sleep duration, and increasing sleep arousal in the second half of the night.³⁶ Disrupted circadian rhythm after alcohol consumption was correlated with increased adenosine neurotransmitters derived from ethanol metabolism.³⁷ Alcohol dependence may be related to other psychiatric symptoms, and chronic alcohol use eventually alters sleep mechanisms leading to persistent insomnia, further perpetuating adverse outcomes such as suicidal ideation.³⁶ There are positive associations between beer drinking and measures of abdominal adiposity in men, and “the combination of short sleep duration [and] disinhibited eating … is associated with greater alcohol intake and excess weight.”³⁸

Therefore, counsel patients to avoid alcohol since it is a modifiable risk factor with pervasive adverse health effects.

Many drugs have a profound effect on sleep patterns. Illicit drug use in particular can affect the brain’s neurotransmitter serotonin system. For example, ecstasy users have an increased risk for OSA.³⁹ People with cocaine and heroin use disorder tend to have more sleep-maintenance insomnia.⁴⁰

Continue to: In contrast, those with alcohol...

In contrast, those with alcohol or cannabis use disorder tend to have more sleep-onset insomnia.⁴⁰ Not only do illicit drugs interrupt sleep, but daily tobacco use also has been correlated with increased insomnia and shorter sleep duration since nicotine is a stimulant.⁴¹

Insomnia is commonly treated with sedative antidepressants and hypnotics—eg, mirtazapine and olanzapine—that contribute to weight gain.⁴² In addition, other common pharmaceuticals used for sleep disorders, such as diphenhydramine, have sedative properties and tend to lead to weight gain.⁴³ Because so many medications affect sleep and weight, carefully review patients’ medication lists and switch offending agents to weight-neutral drugs if possible.

Treatment and tools to improve sleep in patients with obesity

Given the strong correlation between obesity and sleep disorders, validated screening tools should be used to assess sleep quality, including onset and potential symptoms associated with poor sleep (TABLE 1⁴⁴). For weight management to succeed in patients with obesity, it is crucial to address sleep in addition to nutrition and physical activity.^17,45

It falls upon the clinician and patient to weigh the benefits and burdens of the pharmacologic treatments of insomnia.

Physical activity has many benefits to overall health, especially for chronic diseases such as type 2 diabetes and hypertension. The Centers for Disease Control and Prevention recommends at least 150 minutes of ­moderate-intensity aerobic activity or 75 minutes of vigorous-intensity aerobic exercise per week in addition to muscle-strengthening activities 2 or more days per week.⁴⁶ However, approximately 300 minutes of moderate-intensity activity per week is suggested for successful weight loss with exercise alone.⁴⁷

Physical activity and diet in combination are vital, but diet restriction has a more substantial effect on weight loss than physical activity alone.⁴⁸ Still, physical activity is essential in helping maintain and prevent weight regain.

Continue to: Nonpharmacologic interventions

Nonpharmacologic interventions include promoting greater sleep quality and quantity by emphasizing good sleep hygiene practices. Developing a practical and effective bedtime routine, creating a quiet sleep environment, and practicing healthy daily habits are essential components to sleep hygiene(TABLE 2^49,50). Relaxation techniques and cognitive behavioral therapy (CBT) also can help. CBT for insomnia (CBT-I) is the first-line intervention for chronic insomnia.⁵¹ Sleep restriction is a type of CBT used to treat insomnia, encouraging short-term sleep loss in the hopes of improving insomnia. A trial by Logue et al showed that patients with overweight and obesity randomized to undergo CBT with better sleep hygiene (nonpharmacologic) interventions had a greater mean weight loss percentage (5% vs 2%; P = .04) than did those who received CBT alone.⁵²

Eastern medicine including herbal interventions lack evidence of efficacy and safety. Further studies need to be done on the effects that chamomile, kava, valerian root (Valeriana officinalis), tryptophan, and Wu Ling (from mycelia Xylaria nigripes) might have on sleep.⁵³

Proceed cautiously with medication. The American College of Physicians recommends a shared decision-making approach when considering pharmacologic therapy for chronic insomnia and the American Academy of Sleep Medicine (AASM) offers guidance on options.^51,54 However, the evidence behind AASM sleep pharmacologic recommendations is weak, implying a lesser degree of confidence in the outcome and, therefore, in its appropriateness. Thus, it falls upon the clinician and patient to weigh the benefits and burdens of the pharmacologic treatments of insomnia. If indicated, medications suggested to treat sleep onset and sleep maintenance insomnia are eszopiclone, zolpidem, and temazepam. Zaleplon, triazolam, and ramelteon may improve sleep initiation. Suvorexant and doxepin are used for sleep-maintenance insomnia.⁵⁴ Exploring patient preferences, cost of treatment, health care options, and available resources should all be considered.

CORRESPONDENCE
Ecler Ercole Jaqua, MD, MBA, FAAFP, AGSF, FACLM, DipABOM, Loma Linda University Health, 25455 Barton Road, Suite 206A, Loma Linda, CA 92354; [email protected]

Sleep is fundamental to overall health and longevity, with the average person spending about one-third of their life sleeping.¹ Adequate sleep is critical for optimal cognition, memory consolidation, mood regulation, metabolism, appetite regulation, and immune and hormone functioning. According to the American Academy of Sleep Medicine and the Sleep Research Society, adults should sleep at least 7 hours per night on a regular basis “to promote optimal health.”² Yet, between 2013 and 2020, only about 65% of adults in the United States were meeting this amount.³ Insufficient sleep is associated with an increased risk for chronic health conditions, including obesity, diabetes, cardiovascular diseases, and even premature death.⁴

In a population-based longitudinal study of sleep disorders, short sleep duration was associated with increased body mass index (BMI), low blood levels of leptin, and high ghrelin levels.⁵ In addition to physical impairments, poor sleep can impair cognitive performance and lead to vehicular accidents and increased accidents at work.⁴ The potential economic impact that this may have is significant, and includes increased costs and loss of productivity in the workplace.⁶

Many factors may contribute to short sleep duration: environment, mental and physical condition, and social influences such as occupation, family responsibilities, travel, group activities, and personal care. Furthermore, the rapidly evolving and developing media, communication, and entertainment industries are already strongly implicated in poor sleep quality and quantity, both contributing to excessive daytime sleepiness.⁷ Poor sleep quality is most notable in modern societies, and it correlates with the increasing prevalence of obesity, likely due to sleep’s effect on food consumption and physical activity.⁸ Optimizing a person’s sleep will improve overall health and longevity by inhibiting the development of chronic disease.

How insufficient sleep raises the risk for obesity

Not only is sleep beneficial for brain health, memory, learning, and growth, its effect on food consumption and physical activity likely correlates with the increased prevalence of obesity in modern society. Yet the optimal amount of sleep is controversial, and current recommendations of 7 or more hours of sleep per night for adults are derived from expert panels only.² The recommended sleep duration for children is longer, and it varies by age.⁹ The quality of sleep and its impact on neuroendocrine hormones, not just the quantity of sleep, needs to be factored into these recommendations.

Sleep restriction activates the orexigenic system via the hormones leptin and ghrelin. These hormones control the food reward system, essentially increasing hunger and food intake. Leptin, created by white adipose tissue, is responsible for satiety and decreased food consumption.¹⁰ Ghrelin, made by oxyntic glands in the stomach, is responsible for the sensation of hunger.

Poor sleep will increase the risk for obesity and hinder its treatment. Therefore, sleep quality and duration are vital components of obesity management.

In a 2004 study by Spiegel et al,¹¹ leptin and ghrelin levels were measured during 2 days of sleep restriction (4 hours in bed) and sleep extension (10 hours in bed). Sleep restriction was associated with a decrease in leptin levels and an increase in ghrelin levels. The researchers reported that participants experienced an increase in hunger and ­appetite—especially for calorie-dense foods with high carbohydrate content.

Although research design has limitations with predominantly self-reported sleep data, studies have shown that short sleep time leads to increased food intake by increasing hunger signals and craving of unhealthy foods, and by providing more opportunities to eat while awake. It also may lead to decreased physical activity, creating a sedentary lifestyle that further encourages obesity.⁸ Reduced sleep is even correlated to decreased efficacy of weight-loss treatments.¹²

Continue to: Other sleep characteristics weakly correlated with obesity

Other sleep characteristics weakly correlated with obesity are sleep variability, timing, efficiency, quality, and daytime napping.⁸ Sleep variability causes dysregulation of eating patterns, leading to increased food intake. A shift to later sleep and waking times often results in higher consumption of calories after 8 pm¹³; late-night snacks are a part of this sleep–obesity equation.¹⁴

Poor sleep efficiency and quality decreases N3-stage (deep non-REM) sleep, affects the autonomic nervous system, and has been associated with increased abdominal obesity. Daytime napping, which can cause irregular circadian rhythms and sleep schedules, is associated with increased obesity.¹⁵ Thus, each component of sleep needs to be assessed to promote optimal regulation of the orexigenic system.

It is a cycle of poor sleep causing obesity and obesity causing poor sleep.

Another study showed that inadequate sleep not only promotes unhealthy lifestyle habits that can lead to obesity but also decreases the ability to lose weight.¹⁶ This small study with 10 overweight patients provided its subjects with a controlled caloric intake over 2 weeks. Patients spent two 14-day periods 3 months apart in the laboratory, divided into 2 time-in-bed arms of 8.5 and 5.5 hours per night. Neuroendocrine changes caused by decreased sleep were associated with a significant lean body mass loss while conserving energy-dense fat.¹⁶ This study highlights the importance of sleep hygiene counseling when developing a weight-management plan with patients.

Sleep, and its many components, play an integral role in the prevention and treatment of obesity.¹⁷ Poor sleep will increase the risk for obesity and hinder its treatment. Therefore, sleep quality and duration are vital components of obesity management.

The sleep–obesity link in children and the elderly

Childhood obesity is linked to several chronic diseases in adulthood, including type 2 diabetes, cardiovascular disease, nonalcoholic fatty liver disease, asthma, and obstructive sleep apnea (OSA).¹⁸ According to 2017-2018 NHANES (National Health and Nutrition Examination Surveys) data, obesity (BMI ≥ 95th percentile) prevalence among children and adolescents was reported at 19.3% and severe obesity (BMI ≥ 120% of the 95th percentile) at 6.1%. Pediatric overweight prevalence (≥ 85th percentile and < 95th percentile) was 16.1%.¹⁹

Continue to: Although poor sleep is associated...

Although poor sleep is associated with increased risk for obesity, there is no proven cause-effect relationship.²⁰ Nutrition and physical activity have been identified as 2 critical factors in childhood obesity, but sleep health also needs to be investigated. Shorter sleep duration is strongly associated with the development of obesity. Furthermore, children with obesity are more likely to have shorter sleep duration.²¹ A short sleep duration alters plasma levels of insulin, low-density lipoprotein, and high-sensitivity ­C-reactive protein. It is associated with lower diet quality, an increased intake of nutrient-poor foods, and a lower intake of vegetables and fruits.²² Recent studies have shown that interventions to promote earlier bedtimes can improve sleep duration in children.

Older adults have many sleeping issues, including insomnia, circadian rhythm sleep-wake disorders, sleep-related movement disorders, and sleep-breathing disorders. Additionally, the older population has increased sleep latency, decreased sleep efficiency and total sleep time, decreased REM sleep, more frequent nighttime awakenings, and more daytime napping.²³ The increased sleep disturbance with age is mainly related to higher risk factors for sleep disorders than the aging process itself. Sleeping 5 or fewer hours is associated with an increased risk for obesity and central abdominal fat compared with those who sleep 7 to 8 hours per night.²⁴ Similar to children and youth, older adults also show a strong correlation between inadequate sleep and obesity.²⁴

The consequence: A vicious cycle

Obesity in turn leads to shorter sleep duration and more disruptions. This negatively affects the orexigenic system, and the resulting hormonal derangement promotes worsening obesity. It is a cycle of poor sleep causing obesity and obesity causing poor sleep. Insomnia, in combination with shorter (and longer) sleep times, also has been linked with obesity.²⁵ These patients experience more daytime sleepiness, fatigue, and nighttime sleep disturbances, all correlated with decreased quality of life and higher prevalence of medical comorbidities.^8,26 Additional comorbidities secondary to obesity, including gastroesophageal reflux, depression, and asthma, also have been linked to sleep disturbances.⁸

OSA is a common sleep complication associated with obesity. With the increasing prevalence of obesity, the prevalence of OSA is rising.^8,27 Factors that heighten the risk for OSA are male sex, age 40 to 70 years, postmenopausal status, elevated BMI, and craniofacial and upper airway abnormality.²⁸ However, the US Preventive Services Task Force found insufficient evidence to screen for or treat OSA in asymptomatic adults.²⁸ Signs and symptoms of OSA include nighttime awakenings with choking, loud snoring, and feeling unrefreshed after sleep.²⁹

Approximately half of primary care clinicians do not screen at-risk patients for OSA, and 90% do not use validated OSA screening tools.

OSA is caused by the intermittent narrowing and obstruction of the pharyngeal airway due to anatomical and structural irregularities or neuromuscular impairments. Untreated OSA is associated with cardiovascular disease and cardiac arrhythmias such as atrial fibrillation. Even with this correlation between obesity and sleep, it is estimated that 80% of OSA remains undiagnosed.³⁰ Approximately half of primary care clinicians do not screen at-risk patients for OSA, and 90% do not use validated OSA screening tools.³¹ Screening tools that have been validated are the STOP, STOP-BANG, Epworth Sleepiness Scale, and 4-Variable Screening Tool. However, the US Department of Veterans Affairs and the US Department of Defense have a more recent guideline recommending STOP as an easier-to-administer screen for OSA.³² A positive result with a screening tool should be confirmed with polysomnography.³²

Continue to: Intervention for OSA

Intervention for OSA. The longest randomized controlled study to date, Sleep AHEAD, evaluated over a period of 10 years the effect of weight loss on OSA severity achieved with either an intensive lifestyle intervention (ILI) or with diabetes support and education (DSE).³³ OSA severity is rated on an Apnea-Hypopnea Index (AHI), with scores reflecting the number of sleep apnea events per hour. This study demonstrated that weight loss was associated with decreased OSA severity. At 4-year follow-up, the greater the weight loss with ILI intervention, the lower the patients’ OSA severity scores. The study found an average decrease in AHI of 0.68 events per hour for every kilogram of weight loss in the ILI group (P < .0001).^33,34 Over the follow-up visits, the ILI participants had 7.4 events per hour, a more significantly reduced AHI than the DSE participants (P < .0001).^33,34

Additionally, a small cohort of study participants achieved OSA remission (ILI, 34.4%; DSE, 22.2%), indicated by a low AHI score (< 5 events per hour). At the conclusion of the study, OSA severity decreased to a greater degree with ILI intervention.^33,34

Alcohol and drug use can negatively influence sleep patterns and obesity. Higher alcohol consumption is associated with poorer sleep quality and higher chances of developing short sleep duration and snoring.³⁵ Alcohol, a muscle relaxant, causes upper airway narrowing and reduced tongue muscle tone, thereby increasing snoring and OSA as demonstrated by increased AHI on polysomnography after alcohol intake. Alcohol also changes sleep architecture by increasing slow-wave sleep, decreasing REM sleep duration, and increasing sleep arousal in the second half of the night.³⁶ Disrupted circadian rhythm after alcohol consumption was correlated with increased adenosine neurotransmitters derived from ethanol metabolism.³⁷ Alcohol dependence may be related to other psychiatric symptoms, and chronic alcohol use eventually alters sleep mechanisms leading to persistent insomnia, further perpetuating adverse outcomes such as suicidal ideation.³⁶ There are positive associations between beer drinking and measures of abdominal adiposity in men, and “the combination of short sleep duration [and] disinhibited eating … is associated with greater alcohol intake and excess weight.”³⁸

Therefore, counsel patients to avoid alcohol since it is a modifiable risk factor with pervasive adverse health effects.

Many drugs have a profound effect on sleep patterns. Illicit drug use in particular can affect the brain’s neurotransmitter serotonin system. For example, ecstasy users have an increased risk for OSA.³⁹ People with cocaine and heroin use disorder tend to have more sleep-maintenance insomnia.⁴⁰

Continue to: In contrast, those with alcohol...

In contrast, those with alcohol or cannabis use disorder tend to have more sleep-onset insomnia.⁴⁰ Not only do illicit drugs interrupt sleep, but daily tobacco use also has been correlated with increased insomnia and shorter sleep duration since nicotine is a stimulant.⁴¹

Insomnia is commonly treated with sedative antidepressants and hypnotics—eg, mirtazapine and olanzapine—that contribute to weight gain.⁴² In addition, other common pharmaceuticals used for sleep disorders, such as diphenhydramine, have sedative properties and tend to lead to weight gain.⁴³ Because so many medications affect sleep and weight, carefully review patients’ medication lists and switch offending agents to weight-neutral drugs if possible.

Treatment and tools to improve sleep in patients with obesity

Given the strong correlation between obesity and sleep disorders, validated screening tools should be used to assess sleep quality, including onset and potential symptoms associated with poor sleep (TABLE 1⁴⁴). For weight management to succeed in patients with obesity, it is crucial to address sleep in addition to nutrition and physical activity.^17,45

It falls upon the clinician and patient to weigh the benefits and burdens of the pharmacologic treatments of insomnia.

Physical activity has many benefits to overall health, especially for chronic diseases such as type 2 diabetes and hypertension. The Centers for Disease Control and Prevention recommends at least 150 minutes of ­moderate-intensity aerobic activity or 75 minutes of vigorous-intensity aerobic exercise per week in addition to muscle-strengthening activities 2 or more days per week.⁴⁶ However, approximately 300 minutes of moderate-intensity activity per week is suggested for successful weight loss with exercise alone.⁴⁷

Physical activity and diet in combination are vital, but diet restriction has a more substantial effect on weight loss than physical activity alone.⁴⁸ Still, physical activity is essential in helping maintain and prevent weight regain.

Continue to: Nonpharmacologic interventions

Nonpharmacologic interventions include promoting greater sleep quality and quantity by emphasizing good sleep hygiene practices. Developing a practical and effective bedtime routine, creating a quiet sleep environment, and practicing healthy daily habits are essential components to sleep hygiene(TABLE 2^49,50). Relaxation techniques and cognitive behavioral therapy (CBT) also can help. CBT for insomnia (CBT-I) is the first-line intervention for chronic insomnia.⁵¹ Sleep restriction is a type of CBT used to treat insomnia, encouraging short-term sleep loss in the hopes of improving insomnia. A trial by Logue et al showed that patients with overweight and obesity randomized to undergo CBT with better sleep hygiene (nonpharmacologic) interventions had a greater mean weight loss percentage (5% vs 2%; P = .04) than did those who received CBT alone.⁵²

Eastern medicine including herbal interventions lack evidence of efficacy and safety. Further studies need to be done on the effects that chamomile, kava, valerian root (Valeriana officinalis), tryptophan, and Wu Ling (from mycelia Xylaria nigripes) might have on sleep.⁵³

Proceed cautiously with medication. The American College of Physicians recommends a shared decision-making approach when considering pharmacologic therapy for chronic insomnia and the American Academy of Sleep Medicine (AASM) offers guidance on options.^51,54 However, the evidence behind AASM sleep pharmacologic recommendations is weak, implying a lesser degree of confidence in the outcome and, therefore, in its appropriateness. Thus, it falls upon the clinician and patient to weigh the benefits and burdens of the pharmacologic treatments of insomnia. If indicated, medications suggested to treat sleep onset and sleep maintenance insomnia are eszopiclone, zolpidem, and temazepam. Zaleplon, triazolam, and ramelteon may improve sleep initiation. Suvorexant and doxepin are used for sleep-maintenance insomnia.⁵⁴ Exploring patient preferences, cost of treatment, health care options, and available resources should all be considered.

CORRESPONDENCE
Ecler Ercole Jaqua, MD, MBA, FAAFP, AGSF, FACLM, DipABOM, Loma Linda University Health, 25455 Barton Road, Suite 206A, Loma Linda, CA 92354; [email protected]

This transcript has been edited for clarity.

The ongoing longitudinal Nurses’ Health Study has served as an incredible database for evaluating disease states prospectively over decades, thanks to the robust input of its participants. Most recently, this allowed for an important analysis of the association between gastroesophageal reflux (GER) symptoms and sleep quality, the results of which were published in JAMA Network Open.

Approximately 49,000 women with a median age of 59 years (range, 48-69 years) provided data for this analysis. Starting in 2005, they were asked about their experience of GER symptoms. In 2017, they were also asked to respond to a questionnaire, a modified Pittsburgh Sleep Quality Index (PSQI). This is a tool we’ve used a lot in prospective studies looking at gastrointestinal diseases and sleep-related abnormalities. It’s unique in that it looks not only at sleep but also at next-day function and daytime sleepiness, which is important here for its implications related to reflux disease and sleep fragmentation.

In assessing these outcomes, the investigators found that the relative risk for association with sleep fragmentation was approximately 15% greater in those with GER symptoms occurring one to three times a month. For those with GER symptoms occurring once a week and more than once a week, the approximate relative risk increased by 30% and 53%, respectively. Clearly, the association of GER symptoms and relative sleep quality was really important.

It should be noted that the PSQI is a disease-independent, validated instrument. It’s not specific to GER disease or any diseases. It’s cross validated across 17 different languages. I think what’s most important about its use in the assessment here is the incorporation of next-day function and asking participants about daytime sleepiness, which we’ll discuss in more detail shortly.
 

The many causes of interrupted sleep

We’ve all experienced sleep fragmentation, whether in the form of having been on call during our medical training or common experiences like hearing a child cry in the night, a noisy truck pass by, or a dog barking. You may or may not remember that these happened the next day, but they’ve nonetheless interrupted your sleep efficiency.

When you transition laterally across the stages of sleep, that’s what establishes the circadian rhythm and ensures sleep hygiene. Typically, we require approximately 7 hours of restful sleep to do that. But if you fragment or interrupt this process, you more or less move your way erratically through the night, disrupting sleep hygiene and efficiency.

If you have a cognitive awakening during those disruptions, you may recall those events the next day. Or, you may not remember it at all, and such amnestic events are normal for some people with sleep disruptions.

You may also have a sensory arousal, whether it’s due to GER symptoms, auditory stimuli, bumping your toe, or whatever disruptive event. Any of these can cause you to lose that laterality of smooth transition through sleep.

Approximately 20% of the U.S. population have reported GER symptoms at least once a week. Incident data indicate that number may be increasing by as much as 5% a year. Much of that increase is tied to obesity. But nonetheless, it’s a problem on the rise.

It’s important to know this as we start to look at sleep. If GER is acting as a trigger to sleep disruption, you need to ask your patients with this condition about next-day function.

In particular, the next-day function questions to ask are, “How do you feel when you get up? Are you awake and refreshed? Do you have early fatigue? Do you drag yourself out of bed, have daytime somnolence, loss of concentration, or irritability?”

Those are key parameters we can use for looking back to the night before and gauging sleep efficiency. If you’re not asking those questions, you may miss out on identifying a patient having sleep fragmentation.
 

Sleep’s role in inflammatory disease processes

I now perform an interval assessment of this type not just in my patients with GER disease but across all my patients. I do so because sleep is physiologically important in so many ways.

In patients who have nonalcoholic fatty liver disease and a variety of other liver diseases, we’re finding an increased association with sleep fragmentation outside of sleep apnea.

The same is true with irritable bowel and other functional diseases.

When you have sleep fragmentation in inflammatory bowel disease, you turn on a variety of inflammatory proteins (e.g., C-reactive protein) and cytokines, such as interleukins and tumor necrosis factor alpha. These processes may actually tip somebody over to a pro-inflammatory state.

When it comes to what might be considered a relatively simpler condition like GER disease, Ronnie Fass and colleagues showed a number of years ago via Bernstein testing performed in patients with both fragmented and normal sleep that the sensory thresholds all get lowered in the former group. This is irrespective of whether you have a functional symptom or you’re awakened by bumping your toe, a headache, or having heartburn; your sensory thresholds are lower. As a result, the same stimulus provides a higher sense of awareness. By ramping up that awareness, you increase the interference with the next-day function.

We’ve shown that sleep fragmentation affects a variety of things, including immune function. This may be why many people get sick when they travel in between time zones.

There are also implications relating to things like obesity. When you have sleep dysfunction, you have effects on leptin and ghrelin, contrary to what you would normally want to have. This, in turn, causes adverse effects on stimulation or suppression of satiety or appetite. These are things that I counsel my patients about when I talk about reflux as well as those trying to lose weight.

Sleep disruption affects cortisol stimulation and has a significant correlation with type 2 diabetes, cardiovascular diseases, and even mortality statistics. 
 

Advice for counseling patients

This latest analysis from the Nurses’ Health Study reminds us that a lot of people have reflux and a lot of people have sleep fragmentation. We need to do better in asking our patients if they have symptoms specific not only to reflux but also to potentially sleep-related complications.

The more we do that, the more we individualize patient treatment rather than treating them as a disease state. This, in turn, will allow us to practice personalized medicine. The more we can engage our patients with reflux disease by asking the right questions about next-day function, the better we can do in improving their outcomes.

It’s time for us all to open our eyes to the value of closing them. Let’s talk to our patients with reflux disease in a little bit of a different light, providing a new perspective on strategies we can use to mitigate and deal with those symptoms, thereby preventing the consequences of sleep fragmentation.

Hopefully, this overview gives you some guidance the next time you have a conversation with your patients. It will apply across many, many disease states, and in almost everything we do in gastroenterology.

David A. Johnson, MD, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk, Va., and a past president of the American College of Gastroenterology. He reported advising with ISOTHRIVE and Johnson & Johnson.

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

This transcript has been edited for clarity.

The ongoing longitudinal Nurses’ Health Study has served as an incredible database for evaluating disease states prospectively over decades, thanks to the robust input of its participants. Most recently, this allowed for an important analysis of the association between gastroesophageal reflux (GER) symptoms and sleep quality, the results of which were published in JAMA Network Open.

Approximately 49,000 women with a median age of 59 years (range, 48-69 years) provided data for this analysis. Starting in 2005, they were asked about their experience of GER symptoms. In 2017, they were also asked to respond to a questionnaire, a modified Pittsburgh Sleep Quality Index (PSQI). This is a tool we’ve used a lot in prospective studies looking at gastrointestinal diseases and sleep-related abnormalities. It’s unique in that it looks not only at sleep but also at next-day function and daytime sleepiness, which is important here for its implications related to reflux disease and sleep fragmentation.

In assessing these outcomes, the investigators found that the relative risk for association with sleep fragmentation was approximately 15% greater in those with GER symptoms occurring one to three times a month. For those with GER symptoms occurring once a week and more than once a week, the approximate relative risk increased by 30% and 53%, respectively. Clearly, the association of GER symptoms and relative sleep quality was really important.

It should be noted that the PSQI is a disease-independent, validated instrument. It’s not specific to GER disease or any diseases. It’s cross validated across 17 different languages. I think what’s most important about its use in the assessment here is the incorporation of next-day function and asking participants about daytime sleepiness, which we’ll discuss in more detail shortly.
 

The many causes of interrupted sleep

We’ve all experienced sleep fragmentation, whether in the form of having been on call during our medical training or common experiences like hearing a child cry in the night, a noisy truck pass by, or a dog barking. You may or may not remember that these happened the next day, but they’ve nonetheless interrupted your sleep efficiency.

When you transition laterally across the stages of sleep, that’s what establishes the circadian rhythm and ensures sleep hygiene. Typically, we require approximately 7 hours of restful sleep to do that. But if you fragment or interrupt this process, you more or less move your way erratically through the night, disrupting sleep hygiene and efficiency.

If you have a cognitive awakening during those disruptions, you may recall those events the next day. Or, you may not remember it at all, and such amnestic events are normal for some people with sleep disruptions.

You may also have a sensory arousal, whether it’s due to GER symptoms, auditory stimuli, bumping your toe, or whatever disruptive event. Any of these can cause you to lose that laterality of smooth transition through sleep.

Approximately 20% of the U.S. population have reported GER symptoms at least once a week. Incident data indicate that number may be increasing by as much as 5% a year. Much of that increase is tied to obesity. But nonetheless, it’s a problem on the rise.

It’s important to know this as we start to look at sleep. If GER is acting as a trigger to sleep disruption, you need to ask your patients with this condition about next-day function.

In particular, the next-day function questions to ask are, “How do you feel when you get up? Are you awake and refreshed? Do you have early fatigue? Do you drag yourself out of bed, have daytime somnolence, loss of concentration, or irritability?”

Those are key parameters we can use for looking back to the night before and gauging sleep efficiency. If you’re not asking those questions, you may miss out on identifying a patient having sleep fragmentation.
 

Sleep’s role in inflammatory disease processes

I now perform an interval assessment of this type not just in my patients with GER disease but across all my patients. I do so because sleep is physiologically important in so many ways.

In patients who have nonalcoholic fatty liver disease and a variety of other liver diseases, we’re finding an increased association with sleep fragmentation outside of sleep apnea.

The same is true with irritable bowel and other functional diseases.

When you have sleep fragmentation in inflammatory bowel disease, you turn on a variety of inflammatory proteins (e.g., C-reactive protein) and cytokines, such as interleukins and tumor necrosis factor alpha. These processes may actually tip somebody over to a pro-inflammatory state.

When it comes to what might be considered a relatively simpler condition like GER disease, Ronnie Fass and colleagues showed a number of years ago via Bernstein testing performed in patients with both fragmented and normal sleep that the sensory thresholds all get lowered in the former group. This is irrespective of whether you have a functional symptom or you’re awakened by bumping your toe, a headache, or having heartburn; your sensory thresholds are lower. As a result, the same stimulus provides a higher sense of awareness. By ramping up that awareness, you increase the interference with the next-day function.

We’ve shown that sleep fragmentation affects a variety of things, including immune function. This may be why many people get sick when they travel in between time zones.

There are also implications relating to things like obesity. When you have sleep dysfunction, you have effects on leptin and ghrelin, contrary to what you would normally want to have. This, in turn, causes adverse effects on stimulation or suppression of satiety or appetite. These are things that I counsel my patients about when I talk about reflux as well as those trying to lose weight.

Sleep disruption affects cortisol stimulation and has a significant correlation with type 2 diabetes, cardiovascular diseases, and even mortality statistics. 
 

Advice for counseling patients

This latest analysis from the Nurses’ Health Study reminds us that a lot of people have reflux and a lot of people have sleep fragmentation. We need to do better in asking our patients if they have symptoms specific not only to reflux but also to potentially sleep-related complications.

The more we do that, the more we individualize patient treatment rather than treating them as a disease state. This, in turn, will allow us to practice personalized medicine. The more we can engage our patients with reflux disease by asking the right questions about next-day function, the better we can do in improving their outcomes.

It’s time for us all to open our eyes to the value of closing them. Let’s talk to our patients with reflux disease in a little bit of a different light, providing a new perspective on strategies we can use to mitigate and deal with those symptoms, thereby preventing the consequences of sleep fragmentation.

Hopefully, this overview gives you some guidance the next time you have a conversation with your patients. It will apply across many, many disease states, and in almost everything we do in gastroenterology.

David A. Johnson, MD, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk, Va., and a past president of the American College of Gastroenterology. He reported advising with ISOTHRIVE and Johnson & Johnson.

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

This transcript has been edited for clarity.

The ongoing longitudinal Nurses’ Health Study has served as an incredible database for evaluating disease states prospectively over decades, thanks to the robust input of its participants. Most recently, this allowed for an important analysis of the association between gastroesophageal reflux (GER) symptoms and sleep quality, the results of which were published in JAMA Network Open.

Approximately 49,000 women with a median age of 59 years (range, 48-69 years) provided data for this analysis. Starting in 2005, they were asked about their experience of GER symptoms. In 2017, they were also asked to respond to a questionnaire, a modified Pittsburgh Sleep Quality Index (PSQI). This is a tool we’ve used a lot in prospective studies looking at gastrointestinal diseases and sleep-related abnormalities. It’s unique in that it looks not only at sleep but also at next-day function and daytime sleepiness, which is important here for its implications related to reflux disease and sleep fragmentation.

In assessing these outcomes, the investigators found that the relative risk for association with sleep fragmentation was approximately 15% greater in those with GER symptoms occurring one to three times a month. For those with GER symptoms occurring once a week and more than once a week, the approximate relative risk increased by 30% and 53%, respectively. Clearly, the association of GER symptoms and relative sleep quality was really important.

It should be noted that the PSQI is a disease-independent, validated instrument. It’s not specific to GER disease or any diseases. It’s cross validated across 17 different languages. I think what’s most important about its use in the assessment here is the incorporation of next-day function and asking participants about daytime sleepiness, which we’ll discuss in more detail shortly.
 

The many causes of interrupted sleep

We’ve all experienced sleep fragmentation, whether in the form of having been on call during our medical training or common experiences like hearing a child cry in the night, a noisy truck pass by, or a dog barking. You may or may not remember that these happened the next day, but they’ve nonetheless interrupted your sleep efficiency.

When you transition laterally across the stages of sleep, that’s what establishes the circadian rhythm and ensures sleep hygiene. Typically, we require approximately 7 hours of restful sleep to do that. But if you fragment or interrupt this process, you more or less move your way erratically through the night, disrupting sleep hygiene and efficiency.

If you have a cognitive awakening during those disruptions, you may recall those events the next day. Or, you may not remember it at all, and such amnestic events are normal for some people with sleep disruptions.

You may also have a sensory arousal, whether it’s due to GER symptoms, auditory stimuli, bumping your toe, or whatever disruptive event. Any of these can cause you to lose that laterality of smooth transition through sleep.

Approximately 20% of the U.S. population have reported GER symptoms at least once a week. Incident data indicate that number may be increasing by as much as 5% a year. Much of that increase is tied to obesity. But nonetheless, it’s a problem on the rise.

It’s important to know this as we start to look at sleep. If GER is acting as a trigger to sleep disruption, you need to ask your patients with this condition about next-day function.

In particular, the next-day function questions to ask are, “How do you feel when you get up? Are you awake and refreshed? Do you have early fatigue? Do you drag yourself out of bed, have daytime somnolence, loss of concentration, or irritability?”

Those are key parameters we can use for looking back to the night before and gauging sleep efficiency. If you’re not asking those questions, you may miss out on identifying a patient having sleep fragmentation.
 

Sleep’s role in inflammatory disease processes

I now perform an interval assessment of this type not just in my patients with GER disease but across all my patients. I do so because sleep is physiologically important in so many ways.

In patients who have nonalcoholic fatty liver disease and a variety of other liver diseases, we’re finding an increased association with sleep fragmentation outside of sleep apnea.

The same is true with irritable bowel and other functional diseases.

When you have sleep fragmentation in inflammatory bowel disease, you turn on a variety of inflammatory proteins (e.g., C-reactive protein) and cytokines, such as interleukins and tumor necrosis factor alpha. These processes may actually tip somebody over to a pro-inflammatory state.

When it comes to what might be considered a relatively simpler condition like GER disease, Ronnie Fass and colleagues showed a number of years ago via Bernstein testing performed in patients with both fragmented and normal sleep that the sensory thresholds all get lowered in the former group. This is irrespective of whether you have a functional symptom or you’re awakened by bumping your toe, a headache, or having heartburn; your sensory thresholds are lower. As a result, the same stimulus provides a higher sense of awareness. By ramping up that awareness, you increase the interference with the next-day function.

We’ve shown that sleep fragmentation affects a variety of things, including immune function. This may be why many people get sick when they travel in between time zones.

There are also implications relating to things like obesity. When you have sleep dysfunction, you have effects on leptin and ghrelin, contrary to what you would normally want to have. This, in turn, causes adverse effects on stimulation or suppression of satiety or appetite. These are things that I counsel my patients about when I talk about reflux as well as those trying to lose weight.

Sleep disruption affects cortisol stimulation and has a significant correlation with type 2 diabetes, cardiovascular diseases, and even mortality statistics. 
 

Advice for counseling patients

This latest analysis from the Nurses’ Health Study reminds us that a lot of people have reflux and a lot of people have sleep fragmentation. We need to do better in asking our patients if they have symptoms specific not only to reflux but also to potentially sleep-related complications.

The more we do that, the more we individualize patient treatment rather than treating them as a disease state. This, in turn, will allow us to practice personalized medicine. The more we can engage our patients with reflux disease by asking the right questions about next-day function, the better we can do in improving their outcomes.

It’s time for us all to open our eyes to the value of closing them. Let’s talk to our patients with reflux disease in a little bit of a different light, providing a new perspective on strategies we can use to mitigate and deal with those symptoms, thereby preventing the consequences of sleep fragmentation.

Hopefully, this overview gives you some guidance the next time you have a conversation with your patients. It will apply across many, many disease states, and in almost everything we do in gastroenterology.

David A. Johnson, MD, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk, Va., and a past president of the American College of Gastroenterology. He reported advising with ISOTHRIVE and Johnson & Johnson.

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