Sleep Medicine

“Night owls” have an increased risk for developing type 2 diabetes and are more likely to smoke more, exercise less, and have poor sleep habits, compared with their “early bird” counterparts, according to a new study, published in Annals of Internal Medicine.

The work focused on participants’ self-assessed chronotype – an individuals’ circadian preference, or natural preference to sleep and wake up earlier or later, commonly known as being an early bird or a night owl.

Analyzing the self-reported lifestyle behaviors and sleeping habits of more than 60,000 middle-aged female nurses, researchers from Brigham and Women’s Hospital and Harvard Medical School, both in Boston, found that those with a preference for waking up later had a 72% higher risk for diabetes and were 54% more likely to have unhealthy lifestyle behaviors, compared with participants who tended to wake up earlier.

After adjustment for six lifestyle factors – diet, alcohol use, body mass index (BMI), physical activity, smoking status, and sleep duration – the association between diabetes risk and evening chronotype weakened to a 19% higher risk of developing type 2 diabetes.

In a subgroup analysis, this association was stronger among women who either had had no night shifts over the previous 2 years or had worked night shifts for less than 10 years in their careers. For nurses who had worked night shifts recently, the study found no association between evening chronotype and diabetes risk.

The participants, drawn from the Nurses’ Health Study II, were between 45 and 62 years age, with no history of cancer, cardiovascular disease, or diabetes. Researchers followed the group from 2009 until 2017.
 

Is there a mismatch between natural circadian rhythm and work schedule?

The authors, led by Sina Kianersi, DVM, PhD, of Harvard Medical School, Boston, suggest that their results may be linked to a mismatch between a person’s circadian rhythm and their physical and social environment – for example, if someone lives on a schedule opposite to their circadian preference.

In one 2015 study, female nurses who had worked daytime shifts for more than 10 years but had an evening chronotype had the highest diabetes risk, compared with early chronotypes (51% more likely to develop type 2 diabetes).

In a 2022 study, an evening chronotype was associated with a 30% elevated risk for type 2 diabetes. The authors speculated that circadian misalignment could be to blame – for example, being a night owl but working early morning – which can disrupt glycemic and lipid metabolism.

Previous studies have found that shorter or irregular sleep habits are associated with a higher risk of type 2 diabetes. Other studies have also found that people with an evening chronotype are more likely than early birds to have unhealthy eating habits, have lower levels of physical activity, and smoke and drink.

This new study did not find that an evening chronotype was associated with unhealthy drinking, which the authors defined as having one or more drinks per day.

In an accompanying editorial, two physicians from the Harvard T.H. Chan School of Public Health in Boston caution that the statistical design of the study limits its ability to establish causation.

“Chronotype could change later, which might correlate with lifestyle changes,” write Kehuan Lin, MS, Mingyang Song, MBBS, and Edward Giovannucci, MD. “Experimental trials are required to determine whether chronotype is a marker of unhealthy lifestyle or an independent determinant.”

They also suggest that psychological factors and the type of work being performed by the participants could be potential confounders.

The authors of the study note that their findings might not be generalizable to groups other than middle-aged White female nurses. The study population also had a relatively high level of education and were socioeconomically advantaged.

Self-reporting chronotypes with a single question could also result in misclassification and measurement error, the authors acknowledge.

The findings underscore the value of assessing an individuals’ chronotype for scheduling shift work – for example, assigning night owls to night shifts may improve their metabolic health and sleeping habits, according to the authors of the study.

“Given the importance of lifestyle modification in diabetes prevention, future research is warranted to investigate whether improving lifestyle behaviors could effectively reduce diabetes risk in persons with an evening chronotype,” the authors conclude.

The study was supported by grants from the National Institutes of Health and the European Research Council.

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

“Night owls” have an increased risk for developing type 2 diabetes and are more likely to smoke more, exercise less, and have poor sleep habits, compared with their “early bird” counterparts, according to a new study, published in Annals of Internal Medicine.

The work focused on participants’ self-assessed chronotype – an individuals’ circadian preference, or natural preference to sleep and wake up earlier or later, commonly known as being an early bird or a night owl.

Analyzing the self-reported lifestyle behaviors and sleeping habits of more than 60,000 middle-aged female nurses, researchers from Brigham and Women’s Hospital and Harvard Medical School, both in Boston, found that those with a preference for waking up later had a 72% higher risk for diabetes and were 54% more likely to have unhealthy lifestyle behaviors, compared with participants who tended to wake up earlier.

After adjustment for six lifestyle factors – diet, alcohol use, body mass index (BMI), physical activity, smoking status, and sleep duration – the association between diabetes risk and evening chronotype weakened to a 19% higher risk of developing type 2 diabetes.

In a subgroup analysis, this association was stronger among women who either had had no night shifts over the previous 2 years or had worked night shifts for less than 10 years in their careers. For nurses who had worked night shifts recently, the study found no association between evening chronotype and diabetes risk.

The participants, drawn from the Nurses’ Health Study II, were between 45 and 62 years age, with no history of cancer, cardiovascular disease, or diabetes. Researchers followed the group from 2009 until 2017.
 

Is there a mismatch between natural circadian rhythm and work schedule?

The authors, led by Sina Kianersi, DVM, PhD, of Harvard Medical School, Boston, suggest that their results may be linked to a mismatch between a person’s circadian rhythm and their physical and social environment – for example, if someone lives on a schedule opposite to their circadian preference.

In one 2015 study, female nurses who had worked daytime shifts for more than 10 years but had an evening chronotype had the highest diabetes risk, compared with early chronotypes (51% more likely to develop type 2 diabetes).

In a 2022 study, an evening chronotype was associated with a 30% elevated risk for type 2 diabetes. The authors speculated that circadian misalignment could be to blame – for example, being a night owl but working early morning – which can disrupt glycemic and lipid metabolism.

Previous studies have found that shorter or irregular sleep habits are associated with a higher risk of type 2 diabetes. Other studies have also found that people with an evening chronotype are more likely than early birds to have unhealthy eating habits, have lower levels of physical activity, and smoke and drink.

This new study did not find that an evening chronotype was associated with unhealthy drinking, which the authors defined as having one or more drinks per day.

In an accompanying editorial, two physicians from the Harvard T.H. Chan School of Public Health in Boston caution that the statistical design of the study limits its ability to establish causation.

“Chronotype could change later, which might correlate with lifestyle changes,” write Kehuan Lin, MS, Mingyang Song, MBBS, and Edward Giovannucci, MD. “Experimental trials are required to determine whether chronotype is a marker of unhealthy lifestyle or an independent determinant.”

They also suggest that psychological factors and the type of work being performed by the participants could be potential confounders.

The authors of the study note that their findings might not be generalizable to groups other than middle-aged White female nurses. The study population also had a relatively high level of education and were socioeconomically advantaged.

Self-reporting chronotypes with a single question could also result in misclassification and measurement error, the authors acknowledge.

The findings underscore the value of assessing an individuals’ chronotype for scheduling shift work – for example, assigning night owls to night shifts may improve their metabolic health and sleeping habits, according to the authors of the study.

“Given the importance of lifestyle modification in diabetes prevention, future research is warranted to investigate whether improving lifestyle behaviors could effectively reduce diabetes risk in persons with an evening chronotype,” the authors conclude.

The study was supported by grants from the National Institutes of Health and the European Research Council.

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

“Night owls” have an increased risk for developing type 2 diabetes and are more likely to smoke more, exercise less, and have poor sleep habits, compared with their “early bird” counterparts, according to a new study, published in Annals of Internal Medicine.

The work focused on participants’ self-assessed chronotype – an individuals’ circadian preference, or natural preference to sleep and wake up earlier or later, commonly known as being an early bird or a night owl.

Analyzing the self-reported lifestyle behaviors and sleeping habits of more than 60,000 middle-aged female nurses, researchers from Brigham and Women’s Hospital and Harvard Medical School, both in Boston, found that those with a preference for waking up later had a 72% higher risk for diabetes and were 54% more likely to have unhealthy lifestyle behaviors, compared with participants who tended to wake up earlier.

After adjustment for six lifestyle factors – diet, alcohol use, body mass index (BMI), physical activity, smoking status, and sleep duration – the association between diabetes risk and evening chronotype weakened to a 19% higher risk of developing type 2 diabetes.

In a subgroup analysis, this association was stronger among women who either had had no night shifts over the previous 2 years or had worked night shifts for less than 10 years in their careers. For nurses who had worked night shifts recently, the study found no association between evening chronotype and diabetes risk.

The participants, drawn from the Nurses’ Health Study II, were between 45 and 62 years age, with no history of cancer, cardiovascular disease, or diabetes. Researchers followed the group from 2009 until 2017.
 

Is there a mismatch between natural circadian rhythm and work schedule?

The authors, led by Sina Kianersi, DVM, PhD, of Harvard Medical School, Boston, suggest that their results may be linked to a mismatch between a person’s circadian rhythm and their physical and social environment – for example, if someone lives on a schedule opposite to their circadian preference.

In one 2015 study, female nurses who had worked daytime shifts for more than 10 years but had an evening chronotype had the highest diabetes risk, compared with early chronotypes (51% more likely to develop type 2 diabetes).

In a 2022 study, an evening chronotype was associated with a 30% elevated risk for type 2 diabetes. The authors speculated that circadian misalignment could be to blame – for example, being a night owl but working early morning – which can disrupt glycemic and lipid metabolism.

Previous studies have found that shorter or irregular sleep habits are associated with a higher risk of type 2 diabetes. Other studies have also found that people with an evening chronotype are more likely than early birds to have unhealthy eating habits, have lower levels of physical activity, and smoke and drink.

This new study did not find that an evening chronotype was associated with unhealthy drinking, which the authors defined as having one or more drinks per day.

In an accompanying editorial, two physicians from the Harvard T.H. Chan School of Public Health in Boston caution that the statistical design of the study limits its ability to establish causation.

“Chronotype could change later, which might correlate with lifestyle changes,” write Kehuan Lin, MS, Mingyang Song, MBBS, and Edward Giovannucci, MD. “Experimental trials are required to determine whether chronotype is a marker of unhealthy lifestyle or an independent determinant.”

They also suggest that psychological factors and the type of work being performed by the participants could be potential confounders.

The authors of the study note that their findings might not be generalizable to groups other than middle-aged White female nurses. The study population also had a relatively high level of education and were socioeconomically advantaged.

Self-reporting chronotypes with a single question could also result in misclassification and measurement error, the authors acknowledge.

The findings underscore the value of assessing an individuals’ chronotype for scheduling shift work – for example, assigning night owls to night shifts may improve their metabolic health and sleeping habits, according to the authors of the study.

“Given the importance of lifestyle modification in diabetes prevention, future research is warranted to investigate whether improving lifestyle behaviors could effectively reduce diabetes risk in persons with an evening chronotype,” the authors conclude.

The study was supported by grants from the National Institutes of Health and the European Research Council.

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

It is estimated that almost one billion people globally are affected by obstructive sleep apnea (OSA) (Benjafield A, et al. Lancet Respir Med. 2019;7[8]:687-98). Despite such high prevalence, the treatment options for OSA are somewhat limited. Continuous positive airway pressure (CPAP), the gold standard therapy, is not viable for many due to difficulties tolerating the device or mask, and thus may not be a realistic long-term solution. As per certain estimates, nearly 50% of CPAP users discontinue treatment by the fifth year (Schoch O, et al. Respiration. 2014;87[2]:121-8). Furthermore, alternative options such as mandibular advancement devices, positional therapy, weight loss, and maxillofacial or palate surgery, also have unique challenges and limitations.

CHEST

First described in 2001, hypoglossal nerve stimulation (HGNS) is a relatively new and emerging technology for the treatment of OSA (Schwartz A, et al. Arch Otolaryngol Head Neck Surg. 2001 Oct;127[10]:1216-23). HGNS therapy was approved by the Food and Drug Administration in 2014 for the treatment of moderate to severe OSA. The therapy involves surgical implantation of the HGNS device, optimization of device settings, and evaluation for treatment response. A physician-led multidisciplinary Hypoglossal Nerve Stimulation Clinic involves collaboration from essential stakeholders, most importantly sleep medicine providers, clinic staff, sleep technologists, and ENT sleep surgeons. Goals of the multidisciplinary program are to ensure timely follow-up, optimization of device settings, and maximizing treatment efficacy. This review describes steps involved in developing a successful multidisciplinary HGNS program within a sleep medicine practice.
 

Patient selection and evaluation

There is growing interest in HGNS relative to conventional CPAP therapy, with many patients presenting to clinic to inquire about this therapy. However, not all patients are candidates for HGNS therapy. Prioritizing appropriate patient selection and education are key first steps. The initial assessments usually occur with a sleep medicine specialist. It begins with confirmation of the diagnosis of OSA in all patients and a concerted effort to troubleshoot and address any barriers to CPAP use before consideration of surgery. Patients who are unwilling to use or unable to tolerate CPAP therapy undergo further evaluation for HGNS therapy. It is important to ensure that patients are also screened for other sleep disorders, such as insomnia or restless leg syndrome, to rule out its contribution to daytime (or nighttime) symptoms.

Other salient inclusion criteria include an apnea-hypopnea index (AHI) between 15-100 events per hour (previously 65), at least 18 years of age, and a body mass index (BMI) less than 40 kg/m² (previously 32). Qualifying patients undergo an updated polysomnography if a recent study is not available. If the polysomnography reveals central and mixed apneas comprising less than 25 percent of the total AHI, patients are referred to ENT Sleep Surgery, and drug-induced sleep endoscopy is offered to examine upper airway anatomy. When a complete concentric collapse of the soft palate is seen on drug-induced sleep endoscopy, surgery is contraindicated. Prior palate surgery or maxillomandibular advancement (MMA) are not contraindications to HGNS therapy.

The patients receive comprehensive information on the nature of the surgery, expected recovery course, and device activation timeline. Perhaps most importantly, the patients receive structured education on HGNS therapy and potential outcomes to set realistic expectations. In the STAR trial, patients experienced a reduction in the AHI of approximately 70% (Strollo P, et al. N Engl J Med. 2014;370[2]:139-49). It is important to note that a response to therapy was defined as a reduction in the AHI by at least 50% and a value less than 20 events/hour (Strollo P, et al. Sleep. 2015;38[10]:1593-8). Therefore, patients who are expecting complete resolution of snoring and/or OSA may not be ideal candidates for surgery. Furthermore, patients who continue to experience fatigue and sleepiness on CPAP despite control of OSA may not experience amelioration of these symptoms with HGNS therapy.
 

Surgery and device management

The surgery, performed under general anesthesia, lasts approximately 3 hours, and may be followed by an overnight hospital stay depending on patient’s comorbidities. The device implantation involves placement of an implantable pulse generator (IPG) in the chest wall and leads to the hypoglossal nerve. The IPG is similar to a pacemaker and functions to stimulate the ipsilateral hypoglossal nerve innervating the tongue during sleep. The most common postoperative complications noted in the STAR trial data include incision site pain and swelling as well as temporary tongue weakness or paresthesia. Postoperative restrictions are minimal and include no heavy lifting for one month after surgery.

One week postsurgery, patients return to the ENT Sleep Surgery Clinic for follow-up, at which time the incisions as well as tongue strength and sensation are evaluated. In a subsequent visit between 4 and 6 weeks postsurgery, patients are evaluated in a joint Sleep Medicine and ENT clinic. They undergo device education and activation of the IPG using a dedicated programmer obtained from the device manufacturer. Device comfort features such as start delay and pause time are also programmed. Furthermore, appropriate tongue movement, lead placement, and voltage range settings are assessed during the visit. The ENT surgery team reevaluates the incision sites and assesses for tongue function and sensation. Patients are instructed to increase the voltage incrementally every week as tolerated with the goal of using the device nightly for the entirety of sleep. If patients tolerate the therapy well during the 2- to 3-month follow-up, a sleep study is scheduled to evaluate treatment effectiveness at the peak tolerable voltage. For those struggling with the therapy, adjustments to electrode configurations should be considered for pulse width, and rate. Occasionally, patients may require awake endoscopy and/or an advanced HGNS titration while asleep to determine the most appropriate settings to optimally control sleep apnea.

Until recently, patients implanted with an early version of the HGNS were limited to magnetic resonance imaging (MRI) scans of the head, neck, and extremities only. However, patients with the latest model IPGs can now undergo full-body MRI scans. It is important to note that the MRI’s Tesla cannot exceed 1.5T, necessitating specific imaging centers. Other constraints include the inability to adjust device settings remotely, which could mean long travel for minor setting adjustments such as altering start delay or pause times. Furthermore, provider education on operating and managing the device can be time consuming and may also be a barrier to implementation in a clinic. Also challenging may be the availability of an ENT surgery, which plays a critical role in the implantation of the devices and follow-up.

Currently, Inspire Medical Systems is the only FDA-approved hypoglossal nerve stimulation device available in the United States, and globally, more than 45,000 patients have been implanted. However, the field of neurostimulation is rapidly growing. Companies like LivaNova have secured Investigational Device Exemption for their HGNS device. The Genio system by Nyxoah is evaluating the use of bilateral hypoglossal nerve stimulation in patients with OSA and complete concentric collapse of the palate. A multidisciplinary Hypoglossal Nerve Stimulation Clinic is an important component of a comprehensive sleep medicine clinic for patient care and medical education. In the appropriate patient, this emerging technology may provide improvement in OSA severity and symptoms.
 

Dr. Gill is Clinical Associate Professor, Division of Sleep Medicine, Stanford (Calif.) University.

It is estimated that almost one billion people globally are affected by obstructive sleep apnea (OSA) (Benjafield A, et al. Lancet Respir Med. 2019;7[8]:687-98). Despite such high prevalence, the treatment options for OSA are somewhat limited. Continuous positive airway pressure (CPAP), the gold standard therapy, is not viable for many due to difficulties tolerating the device or mask, and thus may not be a realistic long-term solution. As per certain estimates, nearly 50% of CPAP users discontinue treatment by the fifth year (Schoch O, et al. Respiration. 2014;87[2]:121-8). Furthermore, alternative options such as mandibular advancement devices, positional therapy, weight loss, and maxillofacial or palate surgery, also have unique challenges and limitations.

CHEST

First described in 2001, hypoglossal nerve stimulation (HGNS) is a relatively new and emerging technology for the treatment of OSA (Schwartz A, et al. Arch Otolaryngol Head Neck Surg. 2001 Oct;127[10]:1216-23). HGNS therapy was approved by the Food and Drug Administration in 2014 for the treatment of moderate to severe OSA. The therapy involves surgical implantation of the HGNS device, optimization of device settings, and evaluation for treatment response. A physician-led multidisciplinary Hypoglossal Nerve Stimulation Clinic involves collaboration from essential stakeholders, most importantly sleep medicine providers, clinic staff, sleep technologists, and ENT sleep surgeons. Goals of the multidisciplinary program are to ensure timely follow-up, optimization of device settings, and maximizing treatment efficacy. This review describes steps involved in developing a successful multidisciplinary HGNS program within a sleep medicine practice.
 

Patient selection and evaluation

There is growing interest in HGNS relative to conventional CPAP therapy, with many patients presenting to clinic to inquire about this therapy. However, not all patients are candidates for HGNS therapy. Prioritizing appropriate patient selection and education are key first steps. The initial assessments usually occur with a sleep medicine specialist. It begins with confirmation of the diagnosis of OSA in all patients and a concerted effort to troubleshoot and address any barriers to CPAP use before consideration of surgery. Patients who are unwilling to use or unable to tolerate CPAP therapy undergo further evaluation for HGNS therapy. It is important to ensure that patients are also screened for other sleep disorders, such as insomnia or restless leg syndrome, to rule out its contribution to daytime (or nighttime) symptoms.

Other salient inclusion criteria include an apnea-hypopnea index (AHI) between 15-100 events per hour (previously 65), at least 18 years of age, and a body mass index (BMI) less than 40 kg/m² (previously 32). Qualifying patients undergo an updated polysomnography if a recent study is not available. If the polysomnography reveals central and mixed apneas comprising less than 25 percent of the total AHI, patients are referred to ENT Sleep Surgery, and drug-induced sleep endoscopy is offered to examine upper airway anatomy. When a complete concentric collapse of the soft palate is seen on drug-induced sleep endoscopy, surgery is contraindicated. Prior palate surgery or maxillomandibular advancement (MMA) are not contraindications to HGNS therapy.

The patients receive comprehensive information on the nature of the surgery, expected recovery course, and device activation timeline. Perhaps most importantly, the patients receive structured education on HGNS therapy and potential outcomes to set realistic expectations. In the STAR trial, patients experienced a reduction in the AHI of approximately 70% (Strollo P, et al. N Engl J Med. 2014;370[2]:139-49). It is important to note that a response to therapy was defined as a reduction in the AHI by at least 50% and a value less than 20 events/hour (Strollo P, et al. Sleep. 2015;38[10]:1593-8). Therefore, patients who are expecting complete resolution of snoring and/or OSA may not be ideal candidates for surgery. Furthermore, patients who continue to experience fatigue and sleepiness on CPAP despite control of OSA may not experience amelioration of these symptoms with HGNS therapy.
 

Surgery and device management

The surgery, performed under general anesthesia, lasts approximately 3 hours, and may be followed by an overnight hospital stay depending on patient’s comorbidities. The device implantation involves placement of an implantable pulse generator (IPG) in the chest wall and leads to the hypoglossal nerve. The IPG is similar to a pacemaker and functions to stimulate the ipsilateral hypoglossal nerve innervating the tongue during sleep. The most common postoperative complications noted in the STAR trial data include incision site pain and swelling as well as temporary tongue weakness or paresthesia. Postoperative restrictions are minimal and include no heavy lifting for one month after surgery.

One week postsurgery, patients return to the ENT Sleep Surgery Clinic for follow-up, at which time the incisions as well as tongue strength and sensation are evaluated. In a subsequent visit between 4 and 6 weeks postsurgery, patients are evaluated in a joint Sleep Medicine and ENT clinic. They undergo device education and activation of the IPG using a dedicated programmer obtained from the device manufacturer. Device comfort features such as start delay and pause time are also programmed. Furthermore, appropriate tongue movement, lead placement, and voltage range settings are assessed during the visit. The ENT surgery team reevaluates the incision sites and assesses for tongue function and sensation. Patients are instructed to increase the voltage incrementally every week as tolerated with the goal of using the device nightly for the entirety of sleep. If patients tolerate the therapy well during the 2- to 3-month follow-up, a sleep study is scheduled to evaluate treatment effectiveness at the peak tolerable voltage. For those struggling with the therapy, adjustments to electrode configurations should be considered for pulse width, and rate. Occasionally, patients may require awake endoscopy and/or an advanced HGNS titration while asleep to determine the most appropriate settings to optimally control sleep apnea.

Until recently, patients implanted with an early version of the HGNS were limited to magnetic resonance imaging (MRI) scans of the head, neck, and extremities only. However, patients with the latest model IPGs can now undergo full-body MRI scans. It is important to note that the MRI’s Tesla cannot exceed 1.5T, necessitating specific imaging centers. Other constraints include the inability to adjust device settings remotely, which could mean long travel for minor setting adjustments such as altering start delay or pause times. Furthermore, provider education on operating and managing the device can be time consuming and may also be a barrier to implementation in a clinic. Also challenging may be the availability of an ENT surgery, which plays a critical role in the implantation of the devices and follow-up.

Currently, Inspire Medical Systems is the only FDA-approved hypoglossal nerve stimulation device available in the United States, and globally, more than 45,000 patients have been implanted. However, the field of neurostimulation is rapidly growing. Companies like LivaNova have secured Investigational Device Exemption for their HGNS device. The Genio system by Nyxoah is evaluating the use of bilateral hypoglossal nerve stimulation in patients with OSA and complete concentric collapse of the palate. A multidisciplinary Hypoglossal Nerve Stimulation Clinic is an important component of a comprehensive sleep medicine clinic for patient care and medical education. In the appropriate patient, this emerging technology may provide improvement in OSA severity and symptoms.
 

Dr. Gill is Clinical Associate Professor, Division of Sleep Medicine, Stanford (Calif.) University.

It is estimated that almost one billion people globally are affected by obstructive sleep apnea (OSA) (Benjafield A, et al. Lancet Respir Med. 2019;7[8]:687-98). Despite such high prevalence, the treatment options for OSA are somewhat limited. Continuous positive airway pressure (CPAP), the gold standard therapy, is not viable for many due to difficulties tolerating the device or mask, and thus may not be a realistic long-term solution. As per certain estimates, nearly 50% of CPAP users discontinue treatment by the fifth year (Schoch O, et al. Respiration. 2014;87[2]:121-8). Furthermore, alternative options such as mandibular advancement devices, positional therapy, weight loss, and maxillofacial or palate surgery, also have unique challenges and limitations.

CHEST

First described in 2001, hypoglossal nerve stimulation (HGNS) is a relatively new and emerging technology for the treatment of OSA (Schwartz A, et al. Arch Otolaryngol Head Neck Surg. 2001 Oct;127[10]:1216-23). HGNS therapy was approved by the Food and Drug Administration in 2014 for the treatment of moderate to severe OSA. The therapy involves surgical implantation of the HGNS device, optimization of device settings, and evaluation for treatment response. A physician-led multidisciplinary Hypoglossal Nerve Stimulation Clinic involves collaboration from essential stakeholders, most importantly sleep medicine providers, clinic staff, sleep technologists, and ENT sleep surgeons. Goals of the multidisciplinary program are to ensure timely follow-up, optimization of device settings, and maximizing treatment efficacy. This review describes steps involved in developing a successful multidisciplinary HGNS program within a sleep medicine practice.
 

Patient selection and evaluation

There is growing interest in HGNS relative to conventional CPAP therapy, with many patients presenting to clinic to inquire about this therapy. However, not all patients are candidates for HGNS therapy. Prioritizing appropriate patient selection and education are key first steps. The initial assessments usually occur with a sleep medicine specialist. It begins with confirmation of the diagnosis of OSA in all patients and a concerted effort to troubleshoot and address any barriers to CPAP use before consideration of surgery. Patients who are unwilling to use or unable to tolerate CPAP therapy undergo further evaluation for HGNS therapy. It is important to ensure that patients are also screened for other sleep disorders, such as insomnia or restless leg syndrome, to rule out its contribution to daytime (or nighttime) symptoms.

Other salient inclusion criteria include an apnea-hypopnea index (AHI) between 15-100 events per hour (previously 65), at least 18 years of age, and a body mass index (BMI) less than 40 kg/m² (previously 32). Qualifying patients undergo an updated polysomnography if a recent study is not available. If the polysomnography reveals central and mixed apneas comprising less than 25 percent of the total AHI, patients are referred to ENT Sleep Surgery, and drug-induced sleep endoscopy is offered to examine upper airway anatomy. When a complete concentric collapse of the soft palate is seen on drug-induced sleep endoscopy, surgery is contraindicated. Prior palate surgery or maxillomandibular advancement (MMA) are not contraindications to HGNS therapy.

The patients receive comprehensive information on the nature of the surgery, expected recovery course, and device activation timeline. Perhaps most importantly, the patients receive structured education on HGNS therapy and potential outcomes to set realistic expectations. In the STAR trial, patients experienced a reduction in the AHI of approximately 70% (Strollo P, et al. N Engl J Med. 2014;370[2]:139-49). It is important to note that a response to therapy was defined as a reduction in the AHI by at least 50% and a value less than 20 events/hour (Strollo P, et al. Sleep. 2015;38[10]:1593-8). Therefore, patients who are expecting complete resolution of snoring and/or OSA may not be ideal candidates for surgery. Furthermore, patients who continue to experience fatigue and sleepiness on CPAP despite control of OSA may not experience amelioration of these symptoms with HGNS therapy.
 

Surgery and device management

The surgery, performed under general anesthesia, lasts approximately 3 hours, and may be followed by an overnight hospital stay depending on patient’s comorbidities. The device implantation involves placement of an implantable pulse generator (IPG) in the chest wall and leads to the hypoglossal nerve. The IPG is similar to a pacemaker and functions to stimulate the ipsilateral hypoglossal nerve innervating the tongue during sleep. The most common postoperative complications noted in the STAR trial data include incision site pain and swelling as well as temporary tongue weakness or paresthesia. Postoperative restrictions are minimal and include no heavy lifting for one month after surgery.

One week postsurgery, patients return to the ENT Sleep Surgery Clinic for follow-up, at which time the incisions as well as tongue strength and sensation are evaluated. In a subsequent visit between 4 and 6 weeks postsurgery, patients are evaluated in a joint Sleep Medicine and ENT clinic. They undergo device education and activation of the IPG using a dedicated programmer obtained from the device manufacturer. Device comfort features such as start delay and pause time are also programmed. Furthermore, appropriate tongue movement, lead placement, and voltage range settings are assessed during the visit. The ENT surgery team reevaluates the incision sites and assesses for tongue function and sensation. Patients are instructed to increase the voltage incrementally every week as tolerated with the goal of using the device nightly for the entirety of sleep. If patients tolerate the therapy well during the 2- to 3-month follow-up, a sleep study is scheduled to evaluate treatment effectiveness at the peak tolerable voltage. For those struggling with the therapy, adjustments to electrode configurations should be considered for pulse width, and rate. Occasionally, patients may require awake endoscopy and/or an advanced HGNS titration while asleep to determine the most appropriate settings to optimally control sleep apnea.

Until recently, patients implanted with an early version of the HGNS were limited to magnetic resonance imaging (MRI) scans of the head, neck, and extremities only. However, patients with the latest model IPGs can now undergo full-body MRI scans. It is important to note that the MRI’s Tesla cannot exceed 1.5T, necessitating specific imaging centers. Other constraints include the inability to adjust device settings remotely, which could mean long travel for minor setting adjustments such as altering start delay or pause times. Furthermore, provider education on operating and managing the device can be time consuming and may also be a barrier to implementation in a clinic. Also challenging may be the availability of an ENT surgery, which plays a critical role in the implantation of the devices and follow-up.

Currently, Inspire Medical Systems is the only FDA-approved hypoglossal nerve stimulation device available in the United States, and globally, more than 45,000 patients have been implanted. However, the field of neurostimulation is rapidly growing. Companies like LivaNova have secured Investigational Device Exemption for their HGNS device. The Genio system by Nyxoah is evaluating the use of bilateral hypoglossal nerve stimulation in patients with OSA and complete concentric collapse of the palate. A multidisciplinary Hypoglossal Nerve Stimulation Clinic is an important component of a comprehensive sleep medicine clinic for patient care and medical education. In the appropriate patient, this emerging technology may provide improvement in OSA severity and symptoms.
 

Dr. Gill is Clinical Associate Professor, Division of Sleep Medicine, Stanford (Calif.) University.

Adults with asthma who were newly prescribed mepolizumab showed significant improvement in symptoms after 1 year regardless of comorbidities, based on data from 822 individuals.

Comorbidities including chronic rhinosinusitis with polyps (CRSwNP), gastroesophageal reflux disease GERD), anxiety and depression, and chronic obstructive pulmonary disorder (COPD) are common in patients with severe asthma and add to the disease burden, wrote Mark C. Liu, MD, of Johns Hopkins University, Baltimore, and colleagues.

“Some comorbidities, such as CRSwNP, share pathophysiological mechanisms with severe asthma, with interleukin-5 (IL-5),” and treatments targeting IL-5 could improve outcomes, they said.

In the real-world REALITI-A study, mepolizumab, a humanized monoclonal antibody that targets IL-5, significantly reduced asthma exacerbation and oral corticosteroid use in severe asthma patients, they said.

To assess the impact of mepolizumab on patients with comorbidities, the researchers conducted a post hoc analysis of 822 adults with severe asthma, including 321 with CRSwNP, 309 with GERD, 203 with depression/anxiety, and 81 with COPD. The findings were published in the Journal of Allergy and Clinical Immunology: In Practice.

The main outcomes were the rate of clinically significant asthma exacerbations (CSEs) between the 12 months before and after mepolizumab initiation, and the changes from baseline in the daily maintenance use of oral corticosteroids (OCS).

Across all comorbidities, the rate of CSEs decreased significantly from the pretreatment period to the follow-up period, from 4.28 events per year to 1.23 events per year.

“A numerically greater reduction in the rate of CSEs was reported for patients with versus without CRSwNP, whereas the reverse was reported for patients with versus without COPD and depression/anxiety, although the confidence intervals were large for the with COPD subgroup,” the researchers wrote.

The median maintenance dose of oral corticosteroids decreased by at least 50% across all comorbidities after mepolizumab treatment; patients with CRSwNP had the greatest reduction (83%).

In addition, scores on the Asthma Control Questionnaire–5 decreased by at least 0.63 points, and least squared (LS) mean changes in forced expiratory volume per second (FEV₁) increased from baseline across all comorbidities after mepolizumab treatment by at least 74 mL.

Although patients with versus without CRSwNP had greater improvements, patients without GERD, depression/anxiety, and COPD had greater improvements than did those without the respective conditions with the exception of greater FEV₁ improvement in patients with vs. without COPD.

“Patients with severe asthma and comorbid CRSwNP are recognized as having a high disease burden, as demonstrated by more frequent exacerbations,” the researchers wrote in their discussion. “Mepolizumab may serve to reduce the disease burden of this high-risk group by targeting the common pathophysiological pathway of IL-5 and eosinophilic-driven inflammation because it has proven clinical benefits in treating asthma and CRSwNP separately and together,” and the current study findings support the use of mepolizumab for this population in particular, they said.

The findings were limited by several factors including the incomplete data for voluntary assessments, the post hoc design and relatively small numbers of patients in various subgroups, notably COPD, and the potential inaccurate diagnosis of COPD, the researchers noted.

“Nevertheless, because the amount of improvement in each outcome following mepolizumab treatment differed depending on the comorbidity in question, our findings highlight the impact that comorbidities and their prevalence and severity have on outcomes,” and the overall success of mepolizumab across clinical characteristics and comorbidities supports the generalizability of the findings to the larger population of adults with severe asthma, they concluded.

The study was supported by GlaxoSmithKline. Dr. Liu disclosed research funding from GSK, Boehringer Ingelheim, and Gossamer Bio, and participation on advisory boards for AstraZeneca, GSK, and Gossamer Bio.

Adults with asthma who were newly prescribed mepolizumab showed significant improvement in symptoms after 1 year regardless of comorbidities, based on data from 822 individuals.

Comorbidities including chronic rhinosinusitis with polyps (CRSwNP), gastroesophageal reflux disease GERD), anxiety and depression, and chronic obstructive pulmonary disorder (COPD) are common in patients with severe asthma and add to the disease burden, wrote Mark C. Liu, MD, of Johns Hopkins University, Baltimore, and colleagues.

“Some comorbidities, such as CRSwNP, share pathophysiological mechanisms with severe asthma, with interleukin-5 (IL-5),” and treatments targeting IL-5 could improve outcomes, they said.

In the real-world REALITI-A study, mepolizumab, a humanized monoclonal antibody that targets IL-5, significantly reduced asthma exacerbation and oral corticosteroid use in severe asthma patients, they said.

To assess the impact of mepolizumab on patients with comorbidities, the researchers conducted a post hoc analysis of 822 adults with severe asthma, including 321 with CRSwNP, 309 with GERD, 203 with depression/anxiety, and 81 with COPD. The findings were published in the Journal of Allergy and Clinical Immunology: In Practice.

The main outcomes were the rate of clinically significant asthma exacerbations (CSEs) between the 12 months before and after mepolizumab initiation, and the changes from baseline in the daily maintenance use of oral corticosteroids (OCS).

Across all comorbidities, the rate of CSEs decreased significantly from the pretreatment period to the follow-up period, from 4.28 events per year to 1.23 events per year.

“A numerically greater reduction in the rate of CSEs was reported for patients with versus without CRSwNP, whereas the reverse was reported for patients with versus without COPD and depression/anxiety, although the confidence intervals were large for the with COPD subgroup,” the researchers wrote.

The median maintenance dose of oral corticosteroids decreased by at least 50% across all comorbidities after mepolizumab treatment; patients with CRSwNP had the greatest reduction (83%).

In addition, scores on the Asthma Control Questionnaire–5 decreased by at least 0.63 points, and least squared (LS) mean changes in forced expiratory volume per second (FEV₁) increased from baseline across all comorbidities after mepolizumab treatment by at least 74 mL.

Although patients with versus without CRSwNP had greater improvements, patients without GERD, depression/anxiety, and COPD had greater improvements than did those without the respective conditions with the exception of greater FEV₁ improvement in patients with vs. without COPD.

“Patients with severe asthma and comorbid CRSwNP are recognized as having a high disease burden, as demonstrated by more frequent exacerbations,” the researchers wrote in their discussion. “Mepolizumab may serve to reduce the disease burden of this high-risk group by targeting the common pathophysiological pathway of IL-5 and eosinophilic-driven inflammation because it has proven clinical benefits in treating asthma and CRSwNP separately and together,” and the current study findings support the use of mepolizumab for this population in particular, they said.

The findings were limited by several factors including the incomplete data for voluntary assessments, the post hoc design and relatively small numbers of patients in various subgroups, notably COPD, and the potential inaccurate diagnosis of COPD, the researchers noted.

“Nevertheless, because the amount of improvement in each outcome following mepolizumab treatment differed depending on the comorbidity in question, our findings highlight the impact that comorbidities and their prevalence and severity have on outcomes,” and the overall success of mepolizumab across clinical characteristics and comorbidities supports the generalizability of the findings to the larger population of adults with severe asthma, they concluded.

The study was supported by GlaxoSmithKline. Dr. Liu disclosed research funding from GSK, Boehringer Ingelheim, and Gossamer Bio, and participation on advisory boards for AstraZeneca, GSK, and Gossamer Bio.

Adults with asthma who were newly prescribed mepolizumab showed significant improvement in symptoms after 1 year regardless of comorbidities, based on data from 822 individuals.

Comorbidities including chronic rhinosinusitis with polyps (CRSwNP), gastroesophageal reflux disease GERD), anxiety and depression, and chronic obstructive pulmonary disorder (COPD) are common in patients with severe asthma and add to the disease burden, wrote Mark C. Liu, MD, of Johns Hopkins University, Baltimore, and colleagues.

“Some comorbidities, such as CRSwNP, share pathophysiological mechanisms with severe asthma, with interleukin-5 (IL-5),” and treatments targeting IL-5 could improve outcomes, they said.

In the real-world REALITI-A study, mepolizumab, a humanized monoclonal antibody that targets IL-5, significantly reduced asthma exacerbation and oral corticosteroid use in severe asthma patients, they said.

To assess the impact of mepolizumab on patients with comorbidities, the researchers conducted a post hoc analysis of 822 adults with severe asthma, including 321 with CRSwNP, 309 with GERD, 203 with depression/anxiety, and 81 with COPD. The findings were published in the Journal of Allergy and Clinical Immunology: In Practice.

The main outcomes were the rate of clinically significant asthma exacerbations (CSEs) between the 12 months before and after mepolizumab initiation, and the changes from baseline in the daily maintenance use of oral corticosteroids (OCS).

Across all comorbidities, the rate of CSEs decreased significantly from the pretreatment period to the follow-up period, from 4.28 events per year to 1.23 events per year.

“A numerically greater reduction in the rate of CSEs was reported for patients with versus without CRSwNP, whereas the reverse was reported for patients with versus without COPD and depression/anxiety, although the confidence intervals were large for the with COPD subgroup,” the researchers wrote.

The median maintenance dose of oral corticosteroids decreased by at least 50% across all comorbidities after mepolizumab treatment; patients with CRSwNP had the greatest reduction (83%).

In addition, scores on the Asthma Control Questionnaire–5 decreased by at least 0.63 points, and least squared (LS) mean changes in forced expiratory volume per second (FEV₁) increased from baseline across all comorbidities after mepolizumab treatment by at least 74 mL.

Although patients with versus without CRSwNP had greater improvements, patients without GERD, depression/anxiety, and COPD had greater improvements than did those without the respective conditions with the exception of greater FEV₁ improvement in patients with vs. without COPD.

“Patients with severe asthma and comorbid CRSwNP are recognized as having a high disease burden, as demonstrated by more frequent exacerbations,” the researchers wrote in their discussion. “Mepolizumab may serve to reduce the disease burden of this high-risk group by targeting the common pathophysiological pathway of IL-5 and eosinophilic-driven inflammation because it has proven clinical benefits in treating asthma and CRSwNP separately and together,” and the current study findings support the use of mepolizumab for this population in particular, they said.

The findings were limited by several factors including the incomplete data for voluntary assessments, the post hoc design and relatively small numbers of patients in various subgroups, notably COPD, and the potential inaccurate diagnosis of COPD, the researchers noted.

“Nevertheless, because the amount of improvement in each outcome following mepolizumab treatment differed depending on the comorbidity in question, our findings highlight the impact that comorbidities and their prevalence and severity have on outcomes,” and the overall success of mepolizumab across clinical characteristics and comorbidities supports the generalizability of the findings to the larger population of adults with severe asthma, they concluded.

The study was supported by GlaxoSmithKline. Dr. Liu disclosed research funding from GSK, Boehringer Ingelheim, and Gossamer Bio, and participation on advisory boards for AstraZeneca, GSK, and Gossamer Bio.

TOPLINE:

Both short and long sleep durations appear to increase the risk for type 2 diabetes, independent of lifestyle and cardiovascular risk factors, suggests an analysis of a Dutch study.

METHODOLOGY:

• Data on 5,561 participants aged 40–75 years from The Maastricht Study who completed the baseline survey between November 2010 and January 2018 and had full data available were included.
• Sleep duration was assessed as the in-bed time in minutes, using a median of 7 nights’ data from an activPAL3 (PAL Technologies) accelerometer, which is worn on the thigh.
• Glucose metabolism was determined via an oral glucose tolerance test and categorized as prediabetes or type 2 diabetes in line with World Health Organization diagnostic criteria.
• The association between sleep duration and type 2 diabetes was assessed on multivariate logistic regression analysis, taking into account a range of potential confounding factors.

TAKEAWAY:

• The mean age of the participants was 60.1 years, and there was an even split between men and women. In all, 832 had prediabetes and 1,341 type 2 diabetes, and the mean sleep duration was 8.3 hours.
• The results indicated there was a U-shaped relationship between sleep duration and type 2 diabetes, so that both long and short sleep durations increased the risk.
• In the fully adjusted model, a sleep duration of 5 hours was associated with an odds ratio for type 2 diabetes versus 8 hours sleep of 2.9. For a sleep duration of 12 hours, the odds ratio was 1.8.
• The association between sleep duration and diabetes was not significant.

IN PRACTICE:

The results “support the idea that sleep duration could be a relevant risk factor for type 2 diabetes independent of lifestyle risk factors, including diet, physical activity, smoking behavior, and alcohol consumption,” wrote the authors.

“These findings underpin the importance of promoting healthy sleep habits to avoid sleep deprivation,” they added.
 

STUDY DETAILS:

The research was led by Jeroen D. Albers, MSc, department of social medicine, Maastricht (the Netherlands) University, and published in Sleep Health. It is an analysis of The Maastricht Study.

LIMITATIONS:

The study is limited by its cross-sectional nature, particularly because there are “plausible causal paths between sleep duration and type 2 in both directions,” the authors note. The accelerometer used in the study also cannot reliably distinguish between waking and sleeping time in bed, with the potential for misclassification. Daytime naps were also not included, and long-term changes sleep patterns were not measured. In addition, it was not possible to control for some potential confounding factors.

DISCLOSURES:

The Maastricht Study was supported by the European Regional Development Fund via OP-Zuid, the Province of Limburg, the Dutch Ministry of Economic Affairs, Stichting De Weijerhorst, the Pearl String Initiative Diabetes, the School for Cardiovascular Diseases, the School for Public Health and Primary Care, the School for Nutrition and Translational Research in Metabolism, Stichting Annadal, Health Foundation Limburg, and unrestricted grants from Janssen-Cilag, Novo Nordisk, and Sanofi Aventis Netherlands. One author declares a relationship with Novo Nordisk outside the submitted work. No other relevant financial relationships were declared.

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

TOPLINE:

Both short and long sleep durations appear to increase the risk for type 2 diabetes, independent of lifestyle and cardiovascular risk factors, suggests an analysis of a Dutch study.

METHODOLOGY:

• Data on 5,561 participants aged 40–75 years from The Maastricht Study who completed the baseline survey between November 2010 and January 2018 and had full data available were included.
• Sleep duration was assessed as the in-bed time in minutes, using a median of 7 nights’ data from an activPAL3 (PAL Technologies) accelerometer, which is worn on the thigh.
• Glucose metabolism was determined via an oral glucose tolerance test and categorized as prediabetes or type 2 diabetes in line with World Health Organization diagnostic criteria.
• The association between sleep duration and type 2 diabetes was assessed on multivariate logistic regression analysis, taking into account a range of potential confounding factors.

TAKEAWAY:

• The mean age of the participants was 60.1 years, and there was an even split between men and women. In all, 832 had prediabetes and 1,341 type 2 diabetes, and the mean sleep duration was 8.3 hours.
• The results indicated there was a U-shaped relationship between sleep duration and type 2 diabetes, so that both long and short sleep durations increased the risk.
• In the fully adjusted model, a sleep duration of 5 hours was associated with an odds ratio for type 2 diabetes versus 8 hours sleep of 2.9. For a sleep duration of 12 hours, the odds ratio was 1.8.
• The association between sleep duration and diabetes was not significant.

IN PRACTICE:

The results “support the idea that sleep duration could be a relevant risk factor for type 2 diabetes independent of lifestyle risk factors, including diet, physical activity, smoking behavior, and alcohol consumption,” wrote the authors.

“These findings underpin the importance of promoting healthy sleep habits to avoid sleep deprivation,” they added.
 

STUDY DETAILS:

The research was led by Jeroen D. Albers, MSc, department of social medicine, Maastricht (the Netherlands) University, and published in Sleep Health. It is an analysis of The Maastricht Study.

LIMITATIONS:

The study is limited by its cross-sectional nature, particularly because there are “plausible causal paths between sleep duration and type 2 in both directions,” the authors note. The accelerometer used in the study also cannot reliably distinguish between waking and sleeping time in bed, with the potential for misclassification. Daytime naps were also not included, and long-term changes sleep patterns were not measured. In addition, it was not possible to control for some potential confounding factors.

DISCLOSURES:

The Maastricht Study was supported by the European Regional Development Fund via OP-Zuid, the Province of Limburg, the Dutch Ministry of Economic Affairs, Stichting De Weijerhorst, the Pearl String Initiative Diabetes, the School for Cardiovascular Diseases, the School for Public Health and Primary Care, the School for Nutrition and Translational Research in Metabolism, Stichting Annadal, Health Foundation Limburg, and unrestricted grants from Janssen-Cilag, Novo Nordisk, and Sanofi Aventis Netherlands. One author declares a relationship with Novo Nordisk outside the submitted work. No other relevant financial relationships were declared.

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

TOPLINE:

Both short and long sleep durations appear to increase the risk for type 2 diabetes, independent of lifestyle and cardiovascular risk factors, suggests an analysis of a Dutch study.

METHODOLOGY:

• Data on 5,561 participants aged 40–75 years from The Maastricht Study who completed the baseline survey between November 2010 and January 2018 and had full data available were included.
• Sleep duration was assessed as the in-bed time in minutes, using a median of 7 nights’ data from an activPAL3 (PAL Technologies) accelerometer, which is worn on the thigh.
• Glucose metabolism was determined via an oral glucose tolerance test and categorized as prediabetes or type 2 diabetes in line with World Health Organization diagnostic criteria.
• The association between sleep duration and type 2 diabetes was assessed on multivariate logistic regression analysis, taking into account a range of potential confounding factors.

TAKEAWAY:

• The mean age of the participants was 60.1 years, and there was an even split between men and women. In all, 832 had prediabetes and 1,341 type 2 diabetes, and the mean sleep duration was 8.3 hours.
• The results indicated there was a U-shaped relationship between sleep duration and type 2 diabetes, so that both long and short sleep durations increased the risk.
• In the fully adjusted model, a sleep duration of 5 hours was associated with an odds ratio for type 2 diabetes versus 8 hours sleep of 2.9. For a sleep duration of 12 hours, the odds ratio was 1.8.
• The association between sleep duration and diabetes was not significant.

IN PRACTICE:

The results “support the idea that sleep duration could be a relevant risk factor for type 2 diabetes independent of lifestyle risk factors, including diet, physical activity, smoking behavior, and alcohol consumption,” wrote the authors.

“These findings underpin the importance of promoting healthy sleep habits to avoid sleep deprivation,” they added.
 

STUDY DETAILS:

The research was led by Jeroen D. Albers, MSc, department of social medicine, Maastricht (the Netherlands) University, and published in Sleep Health. It is an analysis of The Maastricht Study.

LIMITATIONS:

The study is limited by its cross-sectional nature, particularly because there are “plausible causal paths between sleep duration and type 2 in both directions,” the authors note. The accelerometer used in the study also cannot reliably distinguish between waking and sleeping time in bed, with the potential for misclassification. Daytime naps were also not included, and long-term changes sleep patterns were not measured. In addition, it was not possible to control for some potential confounding factors.

DISCLOSURES:

The Maastricht Study was supported by the European Regional Development Fund via OP-Zuid, the Province of Limburg, the Dutch Ministry of Economic Affairs, Stichting De Weijerhorst, the Pearl String Initiative Diabetes, the School for Cardiovascular Diseases, the School for Public Health and Primary Care, the School for Nutrition and Translational Research in Metabolism, Stichting Annadal, Health Foundation Limburg, and unrestricted grants from Janssen-Cilag, Novo Nordisk, and Sanofi Aventis Netherlands. One author declares a relationship with Novo Nordisk outside the submitted work. No other relevant financial relationships were declared.

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

Early in his career as a pain researcher, Daniel Whibley, PhD, was struck by an article that drew parallels between methods of torture and the experiences of patients with insomnia and chronic pain.

The author of that article, Nicole Tang, DPhil, observed that two methods used by torturers – pain infliction and sleep deprivation – harm people in ways that also are experienced by many patients with pain and sleep conditions.

Patients are “essentially living in this perpetually undesirable, at best, situation where both of these features are playing out in their lives,” said Dr. Whibley, a research assistant professor of physical medicine and rehabilitation at the University of Michigan, Ann Arbor.

The problems create a “kind of vicious circle,” he said. Pain disrupts sleep. Insufficient sleep worsens pain.

Studies have established important relationships between the conditions, but investigators are still trying to clarify the mechanisms that connect them and the best ways to intervene to improve patient outcomes.

To that end, Dr. Whibley has developed an intervention known as Move & Snooze to benefit patients with pain associated with osteoarthritis.

The program includes remote exercise coaching and an automated 6-week course of digital cognitive-behavioral therapy for insomnia (CBT-I). Dr. Whibley’s hypothesis is that addressing sleep disturbances will help patients stay engaged with the physical activity component of the program and help with pain management.

He and his colleagues have tested the intervention in a feasibility study and are in the process of securing grant funding to test it in a large, nationwide trial.
 

Losing sleep for science

Michael Smith, PhD, is examining the sleep-pain connection from a different angle.

Dr. Smith, the director of the Behavioral Medicine Research Laboratory at Johns Hopkins University, Baltimore, is recruiting healthy adults to endure restless nights and painful stimuli.

His team is conducting a study known as Sleep-MOR that aims to reveal how different types of sleep disturbances influence pain and a person’s response to opioids.

Nearly three dozen participants have completed the study so far, Dr. Smith said, out of what he hopes will be 200 in all.

Participants are randomly assigned to sleep normally or to undergo an experimental condition that is designed to mimic the sleep disturbances of insomnia or obstructive sleep apnea (OSA).

In a “forced awakening” group, participants are awakened for 20-minute intervals every hour and for a full hour-long window during the night. In this condition, they could sleep for about four hours in all. Forced awakening is intended to represent insomnia

A “sleep fragmentation” group is meant to represent patients with OSA. About 30 times per hour, tones and tactile buzzers rouse sleeping participants without fully waking them up. Although the experiment involves brief arousals such as those experienced by patients with OSA, it does not capture another important feature of sleep apnea – the cessation of breathing, Dr. Smith noted.

The next day, researchers perform pain testing and brain imaging and see how opioid receptors respond to pain medication.

“Some of the forms of sleep loss that we are studying may actually alter the efficacy of the binding of those receptors, and that might then require you to have higher doses of an opioid to get the same effect,” Dr. Smith said. “That’s our hypothesis.”

If that bears out, disturbed sleep may play a role in the development of opioid use disorder and have implications for patients who receive opioids after surgery, he said.

In the lab, researchers examine pain thresholds using techniques such as thermal pain testing, in which a thermode attached to a participant’s arm heats up. The temperature “slowly goes up and the patient just says: ‘Ouch,’ when it first hurts. Then we have their pain threshold,” Dr. Smith said.
 

A bidirectional relationship

Epidemiologic studies have found that, if you follow women who do not have pain, those with complaints about sleep are more than twice as likely to develop fibromyalgia.

Dr. Smith’s group and others have shown that if you deprive a healthy person of sleep, they become more sensitive to pain.

Inflammation could be one possible reason for this effect. In one study, participants who experienced forced awakening experienced less slow-wave sleep, which was tied to more inflammation in the morning. Increased inflammation was linked to greater pain sensitivity.

“We are starting to piece together some of the pathways. That’s just one,” Dr. Smith said.

A recent study by researchers at Harvard University and elsewhere investigated how sleep disturbances affected three pain pathways. In that study, the results varied by sex. The data indicate that optimal treatment approaches might differ for men and women, the researchers said.
 

Waking up to the problem

Sleep problems can be neglected in medical school and in the clinic. “People just have other things to focus on that they clearly know what they can do about it,” Dr. Smith said.

But clinicians should not hesitate to screen for conditions such as insomnia or OSA and refer patients to a specialist. If a patient has had pain for 6 months and treatments are not working, the chance that they have a treatable sleep disorder “is very high, above 50%,” Dr. Smith said. Many could have more than one sleep disorder, he added.

Continuous positive airway pressure for OSA and CBT for insomnia can improve sleep. Dr. Smith said he expects these measures will improve overall pain management as well.

If treating a sleep disorder fails to help with pain, however, it may still help prevent other sleep-related problems, such as depression, poor glucose control, and heart disease. It also could improve patients’ ability to function day to day, he said.

Evidence on whether treating sleep problems reduces pain has so far been mixed.

“We’ve done some studies showing that if you have CBT-I and you have knee arthritis, improvements in the amount of time you spend awake at night translate into improvements in pain at 6 months. There is a signal there, but it’s not as strong as we would like,” he said. “It may be that it takes longer than anyone would like” to have an effect.

A structured intervention such as CBT-I is likely more beneficial than education about sleep hygiene alone in resolving sleep disturbances, Dr. Whibley said. CBT-I includes active components such as sleep restriction therapy and stimulus control therapy and is recommended by the American Academy of Sleep Medicine as the first-line treatment for chronic insomnia (J Clin Sleep Med. 2008 Oct 15;4[5]:487-504).

Patients should consider the role that sleep may play in their chronic pain condition, he said.

“An increasing number of researchers and clinicians are becoming more interested in this as a foundational pillar of health, alongside activity and diet,” Dr. Whibley said. “Sleep is recognized as just as important but doesn’t seem to get the airtime.”

Clinicians, he added, should regularly assess their patients’ sleep and know where to refer those whom they feel would benefit from more advanced management: “They [should] know that they have at least got it on their radar to check as one of the important pillars of health that you should be able to control.”
 

Sleep trials seeking pain patients

Researchers around the United States are conducting dozens of studies related to sleep and pain. The following trials are recruiting participants, according to ClinicalTrials.gov.

Sleep and Pain Interventions in Women With Fibromyalgia (SPIN-II). Investigators at the University of Missouri–Columbia are examining two cognitive-behavioral treatments for women with fibromyalgia and insomnia. “This trial will yield important information about the roles of sleep, arousal, and brain structure and function in the development and maintenance of chronic pain in women with fibromyalgia,” the researchers say.

Prospective Randomized Trial of CPAP for SDB in Patients Who Use Opioids (PRESTO). At the University of California, San Diego, researchers are investigating whether patients with chronic pain who use opioids and have sleep-disordered breathing may benefit from treatment with continuous positive airway pressure. They plan to assess the intervention’s effects on sleep quality, pain, and quality of life. They also will see which patients are least likely to benefit from this treatment approach.

Latent Aging Mechanisms in Pain and Sleep (LAMPS). Researchers at the University of Florida are studying the effects of oral gamma-aminobutyric acid in older adults with chronic pain and sleep difficulties.

Sleep and Pain in Sickle Cell Disease. At Johns Hopkins University, investigators are evaluating how behavioral sleep interventions influence pain and brain function in patients with sickle cell disease.

Pain in Long COVID-19: The Role of Sleep. Researchers at Beth Israel Deaconess Medical Center are conducting an observational study of patients with long COVID who have pain and sleep disturbances. The study aims “to understand the role of sleep in the development and persistence of pain symptoms in long COVID.”

Intervention for Sleep and Pain in Youth: A Randomized Controlled Trial (I-SPY-RCT). Adolescents with migraine are being recruited by a team at Seattle Children’s Hospital for a randomized controlled trial. The study will examine the effects of CBT-I as well as the combined effect of CBT-I and pain interventions on reducing insomnia symptoms and headache-related disability in this population.

A version of this article appeared on Medscape.com.

Early in his career as a pain researcher, Daniel Whibley, PhD, was struck by an article that drew parallels between methods of torture and the experiences of patients with insomnia and chronic pain.

The author of that article, Nicole Tang, DPhil, observed that two methods used by torturers – pain infliction and sleep deprivation – harm people in ways that also are experienced by many patients with pain and sleep conditions.

Patients are “essentially living in this perpetually undesirable, at best, situation where both of these features are playing out in their lives,” said Dr. Whibley, a research assistant professor of physical medicine and rehabilitation at the University of Michigan, Ann Arbor.

The problems create a “kind of vicious circle,” he said. Pain disrupts sleep. Insufficient sleep worsens pain.

Studies have established important relationships between the conditions, but investigators are still trying to clarify the mechanisms that connect them and the best ways to intervene to improve patient outcomes.

To that end, Dr. Whibley has developed an intervention known as Move & Snooze to benefit patients with pain associated with osteoarthritis.

The program includes remote exercise coaching and an automated 6-week course of digital cognitive-behavioral therapy for insomnia (CBT-I). Dr. Whibley’s hypothesis is that addressing sleep disturbances will help patients stay engaged with the physical activity component of the program and help with pain management.

He and his colleagues have tested the intervention in a feasibility study and are in the process of securing grant funding to test it in a large, nationwide trial.
 

Losing sleep for science

Michael Smith, PhD, is examining the sleep-pain connection from a different angle.

Dr. Smith, the director of the Behavioral Medicine Research Laboratory at Johns Hopkins University, Baltimore, is recruiting healthy adults to endure restless nights and painful stimuli.

His team is conducting a study known as Sleep-MOR that aims to reveal how different types of sleep disturbances influence pain and a person’s response to opioids.

Nearly three dozen participants have completed the study so far, Dr. Smith said, out of what he hopes will be 200 in all.

Participants are randomly assigned to sleep normally or to undergo an experimental condition that is designed to mimic the sleep disturbances of insomnia or obstructive sleep apnea (OSA).

In a “forced awakening” group, participants are awakened for 20-minute intervals every hour and for a full hour-long window during the night. In this condition, they could sleep for about four hours in all. Forced awakening is intended to represent insomnia

A “sleep fragmentation” group is meant to represent patients with OSA. About 30 times per hour, tones and tactile buzzers rouse sleeping participants without fully waking them up. Although the experiment involves brief arousals such as those experienced by patients with OSA, it does not capture another important feature of sleep apnea – the cessation of breathing, Dr. Smith noted.

The next day, researchers perform pain testing and brain imaging and see how opioid receptors respond to pain medication.

“Some of the forms of sleep loss that we are studying may actually alter the efficacy of the binding of those receptors, and that might then require you to have higher doses of an opioid to get the same effect,” Dr. Smith said. “That’s our hypothesis.”

If that bears out, disturbed sleep may play a role in the development of opioid use disorder and have implications for patients who receive opioids after surgery, he said.

In the lab, researchers examine pain thresholds using techniques such as thermal pain testing, in which a thermode attached to a participant’s arm heats up. The temperature “slowly goes up and the patient just says: ‘Ouch,’ when it first hurts. Then we have their pain threshold,” Dr. Smith said.
 

A bidirectional relationship

Epidemiologic studies have found that, if you follow women who do not have pain, those with complaints about sleep are more than twice as likely to develop fibromyalgia.

Dr. Smith’s group and others have shown that if you deprive a healthy person of sleep, they become more sensitive to pain.

Inflammation could be one possible reason for this effect. In one study, participants who experienced forced awakening experienced less slow-wave sleep, which was tied to more inflammation in the morning. Increased inflammation was linked to greater pain sensitivity.

“We are starting to piece together some of the pathways. That’s just one,” Dr. Smith said.

A recent study by researchers at Harvard University and elsewhere investigated how sleep disturbances affected three pain pathways. In that study, the results varied by sex. The data indicate that optimal treatment approaches might differ for men and women, the researchers said.
 

Waking up to the problem

Sleep problems can be neglected in medical school and in the clinic. “People just have other things to focus on that they clearly know what they can do about it,” Dr. Smith said.

But clinicians should not hesitate to screen for conditions such as insomnia or OSA and refer patients to a specialist. If a patient has had pain for 6 months and treatments are not working, the chance that they have a treatable sleep disorder “is very high, above 50%,” Dr. Smith said. Many could have more than one sleep disorder, he added.

Continuous positive airway pressure for OSA and CBT for insomnia can improve sleep. Dr. Smith said he expects these measures will improve overall pain management as well.

If treating a sleep disorder fails to help with pain, however, it may still help prevent other sleep-related problems, such as depression, poor glucose control, and heart disease. It also could improve patients’ ability to function day to day, he said.

Evidence on whether treating sleep problems reduces pain has so far been mixed.

“We’ve done some studies showing that if you have CBT-I and you have knee arthritis, improvements in the amount of time you spend awake at night translate into improvements in pain at 6 months. There is a signal there, but it’s not as strong as we would like,” he said. “It may be that it takes longer than anyone would like” to have an effect.

A structured intervention such as CBT-I is likely more beneficial than education about sleep hygiene alone in resolving sleep disturbances, Dr. Whibley said. CBT-I includes active components such as sleep restriction therapy and stimulus control therapy and is recommended by the American Academy of Sleep Medicine as the first-line treatment for chronic insomnia (J Clin Sleep Med. 2008 Oct 15;4[5]:487-504).

Patients should consider the role that sleep may play in their chronic pain condition, he said.

“An increasing number of researchers and clinicians are becoming more interested in this as a foundational pillar of health, alongside activity and diet,” Dr. Whibley said. “Sleep is recognized as just as important but doesn’t seem to get the airtime.”

Clinicians, he added, should regularly assess their patients’ sleep and know where to refer those whom they feel would benefit from more advanced management: “They [should] know that they have at least got it on their radar to check as one of the important pillars of health that you should be able to control.”
 

Sleep trials seeking pain patients

Researchers around the United States are conducting dozens of studies related to sleep and pain. The following trials are recruiting participants, according to ClinicalTrials.gov.

Sleep and Pain Interventions in Women With Fibromyalgia (SPIN-II). Investigators at the University of Missouri–Columbia are examining two cognitive-behavioral treatments for women with fibromyalgia and insomnia. “This trial will yield important information about the roles of sleep, arousal, and brain structure and function in the development and maintenance of chronic pain in women with fibromyalgia,” the researchers say.

Prospective Randomized Trial of CPAP for SDB in Patients Who Use Opioids (PRESTO). At the University of California, San Diego, researchers are investigating whether patients with chronic pain who use opioids and have sleep-disordered breathing may benefit from treatment with continuous positive airway pressure. They plan to assess the intervention’s effects on sleep quality, pain, and quality of life. They also will see which patients are least likely to benefit from this treatment approach.

Latent Aging Mechanisms in Pain and Sleep (LAMPS). Researchers at the University of Florida are studying the effects of oral gamma-aminobutyric acid in older adults with chronic pain and sleep difficulties.

Sleep and Pain in Sickle Cell Disease. At Johns Hopkins University, investigators are evaluating how behavioral sleep interventions influence pain and brain function in patients with sickle cell disease.

Pain in Long COVID-19: The Role of Sleep. Researchers at Beth Israel Deaconess Medical Center are conducting an observational study of patients with long COVID who have pain and sleep disturbances. The study aims “to understand the role of sleep in the development and persistence of pain symptoms in long COVID.”

Intervention for Sleep and Pain in Youth: A Randomized Controlled Trial (I-SPY-RCT). Adolescents with migraine are being recruited by a team at Seattle Children’s Hospital for a randomized controlled trial. The study will examine the effects of CBT-I as well as the combined effect of CBT-I and pain interventions on reducing insomnia symptoms and headache-related disability in this population.

A version of this article appeared on Medscape.com.

Early in his career as a pain researcher, Daniel Whibley, PhD, was struck by an article that drew parallels between methods of torture and the experiences of patients with insomnia and chronic pain.

The author of that article, Nicole Tang, DPhil, observed that two methods used by torturers – pain infliction and sleep deprivation – harm people in ways that also are experienced by many patients with pain and sleep conditions.

Patients are “essentially living in this perpetually undesirable, at best, situation where both of these features are playing out in their lives,” said Dr. Whibley, a research assistant professor of physical medicine and rehabilitation at the University of Michigan, Ann Arbor.

The problems create a “kind of vicious circle,” he said. Pain disrupts sleep. Insufficient sleep worsens pain.

Studies have established important relationships between the conditions, but investigators are still trying to clarify the mechanisms that connect them and the best ways to intervene to improve patient outcomes.

To that end, Dr. Whibley has developed an intervention known as Move & Snooze to benefit patients with pain associated with osteoarthritis.

The program includes remote exercise coaching and an automated 6-week course of digital cognitive-behavioral therapy for insomnia (CBT-I). Dr. Whibley’s hypothesis is that addressing sleep disturbances will help patients stay engaged with the physical activity component of the program and help with pain management.

He and his colleagues have tested the intervention in a feasibility study and are in the process of securing grant funding to test it in a large, nationwide trial.
 

Losing sleep for science

Michael Smith, PhD, is examining the sleep-pain connection from a different angle.

Dr. Smith, the director of the Behavioral Medicine Research Laboratory at Johns Hopkins University, Baltimore, is recruiting healthy adults to endure restless nights and painful stimuli.

His team is conducting a study known as Sleep-MOR that aims to reveal how different types of sleep disturbances influence pain and a person’s response to opioids.

Nearly three dozen participants have completed the study so far, Dr. Smith said, out of what he hopes will be 200 in all.

Participants are randomly assigned to sleep normally or to undergo an experimental condition that is designed to mimic the sleep disturbances of insomnia or obstructive sleep apnea (OSA).

In a “forced awakening” group, participants are awakened for 20-minute intervals every hour and for a full hour-long window during the night. In this condition, they could sleep for about four hours in all. Forced awakening is intended to represent insomnia

A “sleep fragmentation” group is meant to represent patients with OSA. About 30 times per hour, tones and tactile buzzers rouse sleeping participants without fully waking them up. Although the experiment involves brief arousals such as those experienced by patients with OSA, it does not capture another important feature of sleep apnea – the cessation of breathing, Dr. Smith noted.

The next day, researchers perform pain testing and brain imaging and see how opioid receptors respond to pain medication.

“Some of the forms of sleep loss that we are studying may actually alter the efficacy of the binding of those receptors, and that might then require you to have higher doses of an opioid to get the same effect,” Dr. Smith said. “That’s our hypothesis.”

If that bears out, disturbed sleep may play a role in the development of opioid use disorder and have implications for patients who receive opioids after surgery, he said.

In the lab, researchers examine pain thresholds using techniques such as thermal pain testing, in which a thermode attached to a participant’s arm heats up. The temperature “slowly goes up and the patient just says: ‘Ouch,’ when it first hurts. Then we have their pain threshold,” Dr. Smith said.
 

A bidirectional relationship

Epidemiologic studies have found that, if you follow women who do not have pain, those with complaints about sleep are more than twice as likely to develop fibromyalgia.

Dr. Smith’s group and others have shown that if you deprive a healthy person of sleep, they become more sensitive to pain.

Inflammation could be one possible reason for this effect. In one study, participants who experienced forced awakening experienced less slow-wave sleep, which was tied to more inflammation in the morning. Increased inflammation was linked to greater pain sensitivity.

“We are starting to piece together some of the pathways. That’s just one,” Dr. Smith said.

A recent study by researchers at Harvard University and elsewhere investigated how sleep disturbances affected three pain pathways. In that study, the results varied by sex. The data indicate that optimal treatment approaches might differ for men and women, the researchers said.
 

Waking up to the problem

Sleep problems can be neglected in medical school and in the clinic. “People just have other things to focus on that they clearly know what they can do about it,” Dr. Smith said.

But clinicians should not hesitate to screen for conditions such as insomnia or OSA and refer patients to a specialist. If a patient has had pain for 6 months and treatments are not working, the chance that they have a treatable sleep disorder “is very high, above 50%,” Dr. Smith said. Many could have more than one sleep disorder, he added.

Continuous positive airway pressure for OSA and CBT for insomnia can improve sleep. Dr. Smith said he expects these measures will improve overall pain management as well.

If treating a sleep disorder fails to help with pain, however, it may still help prevent other sleep-related problems, such as depression, poor glucose control, and heart disease. It also could improve patients’ ability to function day to day, he said.

Evidence on whether treating sleep problems reduces pain has so far been mixed.

“We’ve done some studies showing that if you have CBT-I and you have knee arthritis, improvements in the amount of time you spend awake at night translate into improvements in pain at 6 months. There is a signal there, but it’s not as strong as we would like,” he said. “It may be that it takes longer than anyone would like” to have an effect.

A structured intervention such as CBT-I is likely more beneficial than education about sleep hygiene alone in resolving sleep disturbances, Dr. Whibley said. CBT-I includes active components such as sleep restriction therapy and stimulus control therapy and is recommended by the American Academy of Sleep Medicine as the first-line treatment for chronic insomnia (J Clin Sleep Med. 2008 Oct 15;4[5]:487-504).

Patients should consider the role that sleep may play in their chronic pain condition, he said.

“An increasing number of researchers and clinicians are becoming more interested in this as a foundational pillar of health, alongside activity and diet,” Dr. Whibley said. “Sleep is recognized as just as important but doesn’t seem to get the airtime.”

Clinicians, he added, should regularly assess their patients’ sleep and know where to refer those whom they feel would benefit from more advanced management: “They [should] know that they have at least got it on their radar to check as one of the important pillars of health that you should be able to control.”
 

Sleep trials seeking pain patients

Researchers around the United States are conducting dozens of studies related to sleep and pain. The following trials are recruiting participants, according to ClinicalTrials.gov.

Sleep and Pain Interventions in Women With Fibromyalgia (SPIN-II). Investigators at the University of Missouri–Columbia are examining two cognitive-behavioral treatments for women with fibromyalgia and insomnia. “This trial will yield important information about the roles of sleep, arousal, and brain structure and function in the development and maintenance of chronic pain in women with fibromyalgia,” the researchers say.

Prospective Randomized Trial of CPAP for SDB in Patients Who Use Opioids (PRESTO). At the University of California, San Diego, researchers are investigating whether patients with chronic pain who use opioids and have sleep-disordered breathing may benefit from treatment with continuous positive airway pressure. They plan to assess the intervention’s effects on sleep quality, pain, and quality of life. They also will see which patients are least likely to benefit from this treatment approach.

Latent Aging Mechanisms in Pain and Sleep (LAMPS). Researchers at the University of Florida are studying the effects of oral gamma-aminobutyric acid in older adults with chronic pain and sleep difficulties.

Sleep and Pain in Sickle Cell Disease. At Johns Hopkins University, investigators are evaluating how behavioral sleep interventions influence pain and brain function in patients with sickle cell disease.

Pain in Long COVID-19: The Role of Sleep. Researchers at Beth Israel Deaconess Medical Center are conducting an observational study of patients with long COVID who have pain and sleep disturbances. The study aims “to understand the role of sleep in the development and persistence of pain symptoms in long COVID.”

Intervention for Sleep and Pain in Youth: A Randomized Controlled Trial (I-SPY-RCT). Adolescents with migraine are being recruited by a team at Seattle Children’s Hospital for a randomized controlled trial. The study will examine the effects of CBT-I as well as the combined effect of CBT-I and pain interventions on reducing insomnia symptoms and headache-related disability in this population.

A version of this article appeared on Medscape.com.

Several features of sleep disturbance, including nightmares, sleep onset latency, and sleep quality, were associated with a significantly increased risk of suicidal ideation (SI), based on data from 102 individuals.

Suicide remains the second leading cause of death in young adults, but factors that may predict increased suicide risk have not been characterized, wrote Rebecca C. Cox, PhD, of the University of Colorado Boulder, and colleagues.

“Sleep disturbance is a promising modifiable risk factor for acute changes in suicide risk,” they noted. “Previous research has found multiple aspects of sleep disturbance are linked to elevated SI, including insomnia symptoms, both short and long sleep duration, nocturnal wakefulness, and nightmares.”

However, data on the impact of nightly sleep disturbance on suicide risk are limited, the researchers said. They hypothesized that use of ecological momentary assessment (EMA) to assess daily variability in sleep might offer more insight into the relationship between various components of sleep disturbance and changes in suicide risk.

In a study published in Psychiatry Research , the investigators recruited 102 young adults aged 18-35 years who had a history of suicidal behavior; 74.5% were female, 64.7% were White. Participants completed seven semi-random surveys per day for between wake and sleep schedules over 21 days. Each survey asked participants to report on whether they had experienced suicidal ideation (SI) since the last survey. The researchers examined within-person and between-person sleep variables including bedtime, sleep onset latency, sleep onset, number of awakenings, wake after sleep onset, sleep duration, sleep timing, sleep quality, and nightmares.

Overall, nightmares had a significant, positive effect on passive SI at both within- and between-person levels, but no significant effect on active SI. Sleep latency showed a significant, positive effect on passive and active SI at the between-person level, meaning that “participants who took longer to fall asleep on average were more likely to experience passive and active SI during the sampling period,” the researchers noted.

In addition, days following nights of more time awake between sleep onset and offset were days with increased likelihood of passive and active SI. Similarly, days following nights of worse sleep quality than normally reported for an individual were days with increased likelihood of passive and active SI. Sleep timing and duration had no significant effects on SI at the within- or between-person level.

“Notably, tests of reverse models found no relation between daily passive or active SI and any component of the subsequent night’s sleep, suggesting a unidirectional relation between sleep disturbance and subsequent SI,” the researchers wrote in their discussion. If future research replicates the study findings, the results could support the inclusion of sleep difficulties on standard risk assessments as a way to identify risk for SI and initiate prevention approaches, they said.

The findings were limited by several factors including the potential for unmeasured variables impacting the associations between sleep and SI, the researchers noted. Other limitations included the lack of data on more severe levels of SI such as planning and intent, and on suicidal behaviors such as preparatory behaviors, aborted attempts, and actual attempts. The findings also may not generalize to other age groups such as children, adolescents, or older adults, they said.

More research is needed to determine which sleep disturbance components are acute risk factors for which suicide-related outcomes, the researchers said. However, the study is the first to provide evidence for daily sleep disturbances as a near-term predictor of SI in young adults, they concluded.

The study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.

Several features of sleep disturbance, including nightmares, sleep onset latency, and sleep quality, were associated with a significantly increased risk of suicidal ideation (SI), based on data from 102 individuals.

Suicide remains the second leading cause of death in young adults, but factors that may predict increased suicide risk have not been characterized, wrote Rebecca C. Cox, PhD, of the University of Colorado Boulder, and colleagues.

“Sleep disturbance is a promising modifiable risk factor for acute changes in suicide risk,” they noted. “Previous research has found multiple aspects of sleep disturbance are linked to elevated SI, including insomnia symptoms, both short and long sleep duration, nocturnal wakefulness, and nightmares.”

However, data on the impact of nightly sleep disturbance on suicide risk are limited, the researchers said. They hypothesized that use of ecological momentary assessment (EMA) to assess daily variability in sleep might offer more insight into the relationship between various components of sleep disturbance and changes in suicide risk.

In a study published in Psychiatry Research , the investigators recruited 102 young adults aged 18-35 years who had a history of suicidal behavior; 74.5% were female, 64.7% were White. Participants completed seven semi-random surveys per day for between wake and sleep schedules over 21 days. Each survey asked participants to report on whether they had experienced suicidal ideation (SI) since the last survey. The researchers examined within-person and between-person sleep variables including bedtime, sleep onset latency, sleep onset, number of awakenings, wake after sleep onset, sleep duration, sleep timing, sleep quality, and nightmares.

Overall, nightmares had a significant, positive effect on passive SI at both within- and between-person levels, but no significant effect on active SI. Sleep latency showed a significant, positive effect on passive and active SI at the between-person level, meaning that “participants who took longer to fall asleep on average were more likely to experience passive and active SI during the sampling period,” the researchers noted.

In addition, days following nights of more time awake between sleep onset and offset were days with increased likelihood of passive and active SI. Similarly, days following nights of worse sleep quality than normally reported for an individual were days with increased likelihood of passive and active SI. Sleep timing and duration had no significant effects on SI at the within- or between-person level.

“Notably, tests of reverse models found no relation between daily passive or active SI and any component of the subsequent night’s sleep, suggesting a unidirectional relation between sleep disturbance and subsequent SI,” the researchers wrote in their discussion. If future research replicates the study findings, the results could support the inclusion of sleep difficulties on standard risk assessments as a way to identify risk for SI and initiate prevention approaches, they said.

The findings were limited by several factors including the potential for unmeasured variables impacting the associations between sleep and SI, the researchers noted. Other limitations included the lack of data on more severe levels of SI such as planning and intent, and on suicidal behaviors such as preparatory behaviors, aborted attempts, and actual attempts. The findings also may not generalize to other age groups such as children, adolescents, or older adults, they said.

More research is needed to determine which sleep disturbance components are acute risk factors for which suicide-related outcomes, the researchers said. However, the study is the first to provide evidence for daily sleep disturbances as a near-term predictor of SI in young adults, they concluded.

The study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.

Several features of sleep disturbance, including nightmares, sleep onset latency, and sleep quality, were associated with a significantly increased risk of suicidal ideation (SI), based on data from 102 individuals.

Suicide remains the second leading cause of death in young adults, but factors that may predict increased suicide risk have not been characterized, wrote Rebecca C. Cox, PhD, of the University of Colorado Boulder, and colleagues.

“Sleep disturbance is a promising modifiable risk factor for acute changes in suicide risk,” they noted. “Previous research has found multiple aspects of sleep disturbance are linked to elevated SI, including insomnia symptoms, both short and long sleep duration, nocturnal wakefulness, and nightmares.”

However, data on the impact of nightly sleep disturbance on suicide risk are limited, the researchers said. They hypothesized that use of ecological momentary assessment (EMA) to assess daily variability in sleep might offer more insight into the relationship between various components of sleep disturbance and changes in suicide risk.

In a study published in Psychiatry Research , the investigators recruited 102 young adults aged 18-35 years who had a history of suicidal behavior; 74.5% were female, 64.7% were White. Participants completed seven semi-random surveys per day for between wake and sleep schedules over 21 days. Each survey asked participants to report on whether they had experienced suicidal ideation (SI) since the last survey. The researchers examined within-person and between-person sleep variables including bedtime, sleep onset latency, sleep onset, number of awakenings, wake after sleep onset, sleep duration, sleep timing, sleep quality, and nightmares.

Overall, nightmares had a significant, positive effect on passive SI at both within- and between-person levels, but no significant effect on active SI. Sleep latency showed a significant, positive effect on passive and active SI at the between-person level, meaning that “participants who took longer to fall asleep on average were more likely to experience passive and active SI during the sampling period,” the researchers noted.

In addition, days following nights of more time awake between sleep onset and offset were days with increased likelihood of passive and active SI. Similarly, days following nights of worse sleep quality than normally reported for an individual were days with increased likelihood of passive and active SI. Sleep timing and duration had no significant effects on SI at the within- or between-person level.

“Notably, tests of reverse models found no relation between daily passive or active SI and any component of the subsequent night’s sleep, suggesting a unidirectional relation between sleep disturbance and subsequent SI,” the researchers wrote in their discussion. If future research replicates the study findings, the results could support the inclusion of sleep difficulties on standard risk assessments as a way to identify risk for SI and initiate prevention approaches, they said.

The findings were limited by several factors including the potential for unmeasured variables impacting the associations between sleep and SI, the researchers noted. Other limitations included the lack of data on more severe levels of SI such as planning and intent, and on suicidal behaviors such as preparatory behaviors, aborted attempts, and actual attempts. The findings also may not generalize to other age groups such as children, adolescents, or older adults, they said.

More research is needed to determine which sleep disturbance components are acute risk factors for which suicide-related outcomes, the researchers said. However, the study is the first to provide evidence for daily sleep disturbances as a near-term predictor of SI in young adults, they concluded.

The study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.

Despite claims by their makers, blue light glasses probably don’t reduce eyestrain for people who spend a lot of time looking at computer screens or their phones, a new study says. The glasses probably don’t improve wearers’ sleep habits either, according to the study. 

Blue light glasses are usually marketed as being able to filter out the potentially harmful effects of blue light from screens, such as eyestrain, dry eye, and sleep problems. Interest in blue light glasses increased during the COVID-19 pandemic as more people stayed home and looked at their computers and phones. They’re often prescribed by optometrists.

The study, published in the Cochrane Database of Systematic Reviews, looked at data collected from 17 clinical trials in six countries that recruited 619 people. 

“We found there may be no short-term advantages with using blue light–filtering spectacle lenses to reduce visual fatigue associated with computer use, compared to non–blue-light–filtering lenses,” senior author Laura Downie, PhD, an associate professor of optometry and vision sciences at the University of Melbourne, said in a statement.

“It is also currently unclear whether these lenses affect vision quality or sleep-related outcomes, and no conclusions could be drawn about any potential effects on retinal health in the longer term. People should be aware of these findings when deciding whether to purchase these spectacles.”

Researchers noted that one reason the glasses don’t help is that the amount of blue light received from computer screens and other artificial sources is only about a thousandth of what people get from natural daylight. On top of that, blue light lenses usually filter out only about 10%-25% of blue light.

“Our findings do not support the prescription of blue light–filtering lenses to the general population,” Dr. Downie said. 

Eye experts say people can cut down on eyestrain by simply cutting down on the amount of time they look at screens, or by taking regular breaks. To improve sleep, stop looking at screens for a few hours before bedtime.

The researchers noted limitations in their analysis. None of the studies investigated contrast sensitivity, color discrimination, discomfort glare, macular health, serum melatonin levels, or overall patient visual satisfaction.

Also, the length of the different studies varied. More studies of the use of blue light–filtering glasses is needed, the researchers said.

The study received funding from Australia’s National Health and Medical Research Council, the Public Health Agency in the United Kingdom, and Queen’s University Belfast. Two coauthors reported receiving payment from the College of Optometrists.

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

Despite claims by their makers, blue light glasses probably don’t reduce eyestrain for people who spend a lot of time looking at computer screens or their phones, a new study says. The glasses probably don’t improve wearers’ sleep habits either, according to the study. 

Blue light glasses are usually marketed as being able to filter out the potentially harmful effects of blue light from screens, such as eyestrain, dry eye, and sleep problems. Interest in blue light glasses increased during the COVID-19 pandemic as more people stayed home and looked at their computers and phones. They’re often prescribed by optometrists.

The study, published in the Cochrane Database of Systematic Reviews, looked at data collected from 17 clinical trials in six countries that recruited 619 people. 

“We found there may be no short-term advantages with using blue light–filtering spectacle lenses to reduce visual fatigue associated with computer use, compared to non–blue-light–filtering lenses,” senior author Laura Downie, PhD, an associate professor of optometry and vision sciences at the University of Melbourne, said in a statement.

“It is also currently unclear whether these lenses affect vision quality or sleep-related outcomes, and no conclusions could be drawn about any potential effects on retinal health in the longer term. People should be aware of these findings when deciding whether to purchase these spectacles.”

Researchers noted that one reason the glasses don’t help is that the amount of blue light received from computer screens and other artificial sources is only about a thousandth of what people get from natural daylight. On top of that, blue light lenses usually filter out only about 10%-25% of blue light.

“Our findings do not support the prescription of blue light–filtering lenses to the general population,” Dr. Downie said. 

Eye experts say people can cut down on eyestrain by simply cutting down on the amount of time they look at screens, or by taking regular breaks. To improve sleep, stop looking at screens for a few hours before bedtime.

The researchers noted limitations in their analysis. None of the studies investigated contrast sensitivity, color discrimination, discomfort glare, macular health, serum melatonin levels, or overall patient visual satisfaction.

Also, the length of the different studies varied. More studies of the use of blue light–filtering glasses is needed, the researchers said.

The study received funding from Australia’s National Health and Medical Research Council, the Public Health Agency in the United Kingdom, and Queen’s University Belfast. Two coauthors reported receiving payment from the College of Optometrists.

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

Despite claims by their makers, blue light glasses probably don’t reduce eyestrain for people who spend a lot of time looking at computer screens or their phones, a new study says. The glasses probably don’t improve wearers’ sleep habits either, according to the study. 

Blue light glasses are usually marketed as being able to filter out the potentially harmful effects of blue light from screens, such as eyestrain, dry eye, and sleep problems. Interest in blue light glasses increased during the COVID-19 pandemic as more people stayed home and looked at their computers and phones. They’re often prescribed by optometrists.

The study, published in the Cochrane Database of Systematic Reviews, looked at data collected from 17 clinical trials in six countries that recruited 619 people. 

“We found there may be no short-term advantages with using blue light–filtering spectacle lenses to reduce visual fatigue associated with computer use, compared to non–blue-light–filtering lenses,” senior author Laura Downie, PhD, an associate professor of optometry and vision sciences at the University of Melbourne, said in a statement.

“It is also currently unclear whether these lenses affect vision quality or sleep-related outcomes, and no conclusions could be drawn about any potential effects on retinal health in the longer term. People should be aware of these findings when deciding whether to purchase these spectacles.”

Researchers noted that one reason the glasses don’t help is that the amount of blue light received from computer screens and other artificial sources is only about a thousandth of what people get from natural daylight. On top of that, blue light lenses usually filter out only about 10%-25% of blue light.

“Our findings do not support the prescription of blue light–filtering lenses to the general population,” Dr. Downie said. 

Eye experts say people can cut down on eyestrain by simply cutting down on the amount of time they look at screens, or by taking regular breaks. To improve sleep, stop looking at screens for a few hours before bedtime.

The researchers noted limitations in their analysis. None of the studies investigated contrast sensitivity, color discrimination, discomfort glare, macular health, serum melatonin levels, or overall patient visual satisfaction.

Also, the length of the different studies varied. More studies of the use of blue light–filtering glasses is needed, the researchers said.

The study received funding from Australia’s National Health and Medical Research Council, the Public Health Agency in the United Kingdom, and Queen’s University Belfast. Two coauthors reported receiving payment from the College of Optometrists.

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

Inhaling a pleasant aroma during sleep has been linked to a “dramatic” improvement in memory, early research suggests.

In a small, randomized controlled trial researchers found that when cognitively normal individuals were exposed to the scent of an essential oil for 2 hours every night over 6 months, they experienced a 226% improvement in memory compared with a control group who received only a trace amount of the diffused scent.

In addition, functional magnetic resonance imaging (fMRI) showed that those in the enriched group had improved functioning of the left uncinate fasciculus, an area of the brain linked to memory and cognition, which typically declines with age.

“To my knowledge, that level of [memory] improvement is far greater than anything that has been reported for healthy older adults and we also found a critical memory pathway in their brains improved to a similar extent relative to unenriched older adults,” senior investigator Michael Leon, PhD, professor emeritus, University of California, Irvine, said in an interview.

The study was published online in Frontiers of Neuroscience.
 

The brain’s “superhighway”

Olfactory enrichment “involves the daily exposure of individuals to multiple odorants” and has been shown in mouse models to improve memory and neurogenesis, the investigators noted.

A previous study showed that exposure to individual essential oils for 30 minutes a day over 3 months induced neurogenesis in the olfactory bulb and the hippocampus.

“The olfactory system is the only sense that has a direct ‘superhighway’ input to the memory centers areas of the brain; all the other senses have to reach those brain areas through what you might call the ‘side streets’ of the brain, and so consequently, they have much less impact on maintaining the health of those memory centers.”

When olfaction is compromised, “the memory centers of the brain start to deteriorate and, conversely, when people are given olfactory enrichment, their memory areas become larger and more functional,” he added.

Olfactory dysfunction is the first symptom of Alzheimer’s disease (AD) and is also found in virtually all neurological and psychiatric disorders.

“I’ve counted 68 of them – including anorexia, anxiety, [attention-deficit/hyperactivity disorder], depression, epilepsy, and stroke. In fact, by mid-life, your all-cause mortality can be predicted by your ability to smell things,” Dr. Leon said.

Dr. Leon and colleagues previously developed an effective treatment for autism using environmental enrichment that focused on odor stimulation, along with stimulating other senses. “We then considered the possibility that olfactory enrichment alone might improve brain function.”
 

Rose, orange, eucalyptus …

For the study, the researchers randomly assigned 43 older adults, aged 60-85 years, to receive either nightly exposure to essential oil scents delivered via a diffuser (n = 20; mean [SD] age, 70.1 [6.6] years) or to a sham control with only trace amounts of odorants (n = 23; mean age, 69.2 [7.1] years) for a period of 6 months.

The intervention group was exposed to a single odorant, delivered through a diffuser, for 2 hours nightly, rotating through seven pleasant aromas each week. They included rose, orange, eucalyptus, lemon, peppermint, rosemary, and lavender scents.

All participants completed a battery of tests at baseline, including the Mini-Mental State Examination (MMSE), which confirmed normal cognitive functioning. At baseline and after a 6-month follow-up, participants completed the Rey Auditory Verbal Learning Test (RAVLT) as well as three subsets of the Wechsler Adult Intelligence Scale–Third Edition (WAIS-III).

Olfactory system function was assessed using “Sniffin Sticks,” allowing the researchers to determine if olfactory enrichment enhanced olfactory performance.

Participants underwent fMRI at baseline and again at 6 months.

Brain imaging results showed a “clear, statistically significant 226% difference between enriched and control older adults in performance on the RAVLT, which evaluates learning and memory (timepoint × group interaction; F = 6.63; P = .02; Cohen’s d = 1.08; a “large effect size”).

They also found a significant change in the mean diffusivity of the left uncinate fasciculus in the enriched group compared with the controls (timepoint × group interaction; F = 4.39; P = .043; h 2 p = .101; a “medium-size effect”).

The uncinate fasciculus is a “major pathway” connecting the basolateral amygdala and the entorhinal cortex to the prefrontal cortex. This pathway deteriorates in aging and in AD and “has been suggested to play a role in mediating episodic memory, language, socio-emotional processing, and selecting among competing memories during retrieval.”

No significant differences were found between the groups in olfactory ability.

Limitations of the study include its small sample size. The investigators hope the findings will “stimulate larger scale clinical trials systematically testing the therapeutic efficacy of olfactory enrichment in treating memory loss in older adults.”
 

Exciting but preliminary

Commenting for this article, Donald Wilson, PhD, professor of child and adolescent psychiatry and of neuroscience and physiology, the Child Study Center, NYU Langone Medical Center, New York, said that multiple studies have “demonstrated that problems with sense of smell are associated with and sometimes can precede other symptoms for many disorders, including AD, Parkinson’s disease, and depression.”

Recent work has suggested that this relationship can be “bidirectional” – for example, losing one’s sense of smell might promote depression, while depressive disorder might lead to impaired smell, according to Dr. Wilson, also director and senior research scientist, the Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research. He was not involved with the study.

This “two-way interaction” may raise the possibility that “improving olfaction could impact nonolfactory disorders.”

This paper “brings together” previous research findings to show that odors during bedtime can improve some aspects of cognitive function and circuits that are known to be important for memory and cognition – which Dr. Wilson called “a very exciting, though relatively preliminary, finding.”

A caveat is that several measures of cognitive function were assessed and only one (verbal memory) showed clear improvement.

Nevertheless, there’s “very strong interest now in the olfactory and nonolfactory aspects of odor training and this training expands the training possibilities to sleep. This could be a powerful tool for cognitive improvement and/or rescue if follow-up studies support these findings,” Dr. Wilson said.

A version of this article appeared on Medscape.com.

Inhaling a pleasant aroma during sleep has been linked to a “dramatic” improvement in memory, early research suggests.

In a small, randomized controlled trial researchers found that when cognitively normal individuals were exposed to the scent of an essential oil for 2 hours every night over 6 months, they experienced a 226% improvement in memory compared with a control group who received only a trace amount of the diffused scent.

In addition, functional magnetic resonance imaging (fMRI) showed that those in the enriched group had improved functioning of the left uncinate fasciculus, an area of the brain linked to memory and cognition, which typically declines with age.

“To my knowledge, that level of [memory] improvement is far greater than anything that has been reported for healthy older adults and we also found a critical memory pathway in their brains improved to a similar extent relative to unenriched older adults,” senior investigator Michael Leon, PhD, professor emeritus, University of California, Irvine, said in an interview.

The study was published online in Frontiers of Neuroscience.
 

The brain’s “superhighway”

Olfactory enrichment “involves the daily exposure of individuals to multiple odorants” and has been shown in mouse models to improve memory and neurogenesis, the investigators noted.

A previous study showed that exposure to individual essential oils for 30 minutes a day over 3 months induced neurogenesis in the olfactory bulb and the hippocampus.

“The olfactory system is the only sense that has a direct ‘superhighway’ input to the memory centers areas of the brain; all the other senses have to reach those brain areas through what you might call the ‘side streets’ of the brain, and so consequently, they have much less impact on maintaining the health of those memory centers.”

When olfaction is compromised, “the memory centers of the brain start to deteriorate and, conversely, when people are given olfactory enrichment, their memory areas become larger and more functional,” he added.

Olfactory dysfunction is the first symptom of Alzheimer’s disease (AD) and is also found in virtually all neurological and psychiatric disorders.

“I’ve counted 68 of them – including anorexia, anxiety, [attention-deficit/hyperactivity disorder], depression, epilepsy, and stroke. In fact, by mid-life, your all-cause mortality can be predicted by your ability to smell things,” Dr. Leon said.

Dr. Leon and colleagues previously developed an effective treatment for autism using environmental enrichment that focused on odor stimulation, along with stimulating other senses. “We then considered the possibility that olfactory enrichment alone might improve brain function.”
 

Rose, orange, eucalyptus …

For the study, the researchers randomly assigned 43 older adults, aged 60-85 years, to receive either nightly exposure to essential oil scents delivered via a diffuser (n = 20; mean [SD] age, 70.1 [6.6] years) or to a sham control with only trace amounts of odorants (n = 23; mean age, 69.2 [7.1] years) for a period of 6 months.

The intervention group was exposed to a single odorant, delivered through a diffuser, for 2 hours nightly, rotating through seven pleasant aromas each week. They included rose, orange, eucalyptus, lemon, peppermint, rosemary, and lavender scents.

All participants completed a battery of tests at baseline, including the Mini-Mental State Examination (MMSE), which confirmed normal cognitive functioning. At baseline and after a 6-month follow-up, participants completed the Rey Auditory Verbal Learning Test (RAVLT) as well as three subsets of the Wechsler Adult Intelligence Scale–Third Edition (WAIS-III).

Olfactory system function was assessed using “Sniffin Sticks,” allowing the researchers to determine if olfactory enrichment enhanced olfactory performance.

Participants underwent fMRI at baseline and again at 6 months.

Brain imaging results showed a “clear, statistically significant 226% difference between enriched and control older adults in performance on the RAVLT, which evaluates learning and memory (timepoint × group interaction; F = 6.63; P = .02; Cohen’s d = 1.08; a “large effect size”).

They also found a significant change in the mean diffusivity of the left uncinate fasciculus in the enriched group compared with the controls (timepoint × group interaction; F = 4.39; P = .043; h 2 p = .101; a “medium-size effect”).

The uncinate fasciculus is a “major pathway” connecting the basolateral amygdala and the entorhinal cortex to the prefrontal cortex. This pathway deteriorates in aging and in AD and “has been suggested to play a role in mediating episodic memory, language, socio-emotional processing, and selecting among competing memories during retrieval.”

No significant differences were found between the groups in olfactory ability.

Limitations of the study include its small sample size. The investigators hope the findings will “stimulate larger scale clinical trials systematically testing the therapeutic efficacy of olfactory enrichment in treating memory loss in older adults.”
 

Exciting but preliminary

Commenting for this article, Donald Wilson, PhD, professor of child and adolescent psychiatry and of neuroscience and physiology, the Child Study Center, NYU Langone Medical Center, New York, said that multiple studies have “demonstrated that problems with sense of smell are associated with and sometimes can precede other symptoms for many disorders, including AD, Parkinson’s disease, and depression.”

Recent work has suggested that this relationship can be “bidirectional” – for example, losing one’s sense of smell might promote depression, while depressive disorder might lead to impaired smell, according to Dr. Wilson, also director and senior research scientist, the Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research. He was not involved with the study.

This “two-way interaction” may raise the possibility that “improving olfaction could impact nonolfactory disorders.”

This paper “brings together” previous research findings to show that odors during bedtime can improve some aspects of cognitive function and circuits that are known to be important for memory and cognition – which Dr. Wilson called “a very exciting, though relatively preliminary, finding.”

A caveat is that several measures of cognitive function were assessed and only one (verbal memory) showed clear improvement.

Nevertheless, there’s “very strong interest now in the olfactory and nonolfactory aspects of odor training and this training expands the training possibilities to sleep. This could be a powerful tool for cognitive improvement and/or rescue if follow-up studies support these findings,” Dr. Wilson said.

A version of this article appeared on Medscape.com.

Inhaling a pleasant aroma during sleep has been linked to a “dramatic” improvement in memory, early research suggests.

In a small, randomized controlled trial researchers found that when cognitively normal individuals were exposed to the scent of an essential oil for 2 hours every night over 6 months, they experienced a 226% improvement in memory compared with a control group who received only a trace amount of the diffused scent.

In addition, functional magnetic resonance imaging (fMRI) showed that those in the enriched group had improved functioning of the left uncinate fasciculus, an area of the brain linked to memory and cognition, which typically declines with age.

“To my knowledge, that level of [memory] improvement is far greater than anything that has been reported for healthy older adults and we also found a critical memory pathway in their brains improved to a similar extent relative to unenriched older adults,” senior investigator Michael Leon, PhD, professor emeritus, University of California, Irvine, said in an interview.

The study was published online in Frontiers of Neuroscience.
 

The brain’s “superhighway”

Olfactory enrichment “involves the daily exposure of individuals to multiple odorants” and has been shown in mouse models to improve memory and neurogenesis, the investigators noted.

A previous study showed that exposure to individual essential oils for 30 minutes a day over 3 months induced neurogenesis in the olfactory bulb and the hippocampus.

“The olfactory system is the only sense that has a direct ‘superhighway’ input to the memory centers areas of the brain; all the other senses have to reach those brain areas through what you might call the ‘side streets’ of the brain, and so consequently, they have much less impact on maintaining the health of those memory centers.”

When olfaction is compromised, “the memory centers of the brain start to deteriorate and, conversely, when people are given olfactory enrichment, their memory areas become larger and more functional,” he added.

Olfactory dysfunction is the first symptom of Alzheimer’s disease (AD) and is also found in virtually all neurological and psychiatric disorders.

“I’ve counted 68 of them – including anorexia, anxiety, [attention-deficit/hyperactivity disorder], depression, epilepsy, and stroke. In fact, by mid-life, your all-cause mortality can be predicted by your ability to smell things,” Dr. Leon said.

Dr. Leon and colleagues previously developed an effective treatment for autism using environmental enrichment that focused on odor stimulation, along with stimulating other senses. “We then considered the possibility that olfactory enrichment alone might improve brain function.”
 

Rose, orange, eucalyptus …

For the study, the researchers randomly assigned 43 older adults, aged 60-85 years, to receive either nightly exposure to essential oil scents delivered via a diffuser (n = 20; mean [SD] age, 70.1 [6.6] years) or to a sham control with only trace amounts of odorants (n = 23; mean age, 69.2 [7.1] years) for a period of 6 months.

The intervention group was exposed to a single odorant, delivered through a diffuser, for 2 hours nightly, rotating through seven pleasant aromas each week. They included rose, orange, eucalyptus, lemon, peppermint, rosemary, and lavender scents.

All participants completed a battery of tests at baseline, including the Mini-Mental State Examination (MMSE), which confirmed normal cognitive functioning. At baseline and after a 6-month follow-up, participants completed the Rey Auditory Verbal Learning Test (RAVLT) as well as three subsets of the Wechsler Adult Intelligence Scale–Third Edition (WAIS-III).

Olfactory system function was assessed using “Sniffin Sticks,” allowing the researchers to determine if olfactory enrichment enhanced olfactory performance.

Participants underwent fMRI at baseline and again at 6 months.

Brain imaging results showed a “clear, statistically significant 226% difference between enriched and control older adults in performance on the RAVLT, which evaluates learning and memory (timepoint × group interaction; F = 6.63; P = .02; Cohen’s d = 1.08; a “large effect size”).

They also found a significant change in the mean diffusivity of the left uncinate fasciculus in the enriched group compared with the controls (timepoint × group interaction; F = 4.39; P = .043; h 2 p = .101; a “medium-size effect”).

The uncinate fasciculus is a “major pathway” connecting the basolateral amygdala and the entorhinal cortex to the prefrontal cortex. This pathway deteriorates in aging and in AD and “has been suggested to play a role in mediating episodic memory, language, socio-emotional processing, and selecting among competing memories during retrieval.”

No significant differences were found between the groups in olfactory ability.

Limitations of the study include its small sample size. The investigators hope the findings will “stimulate larger scale clinical trials systematically testing the therapeutic efficacy of olfactory enrichment in treating memory loss in older adults.”
 

Exciting but preliminary

Commenting for this article, Donald Wilson, PhD, professor of child and adolescent psychiatry and of neuroscience and physiology, the Child Study Center, NYU Langone Medical Center, New York, said that multiple studies have “demonstrated that problems with sense of smell are associated with and sometimes can precede other symptoms for many disorders, including AD, Parkinson’s disease, and depression.”

Recent work has suggested that this relationship can be “bidirectional” – for example, losing one’s sense of smell might promote depression, while depressive disorder might lead to impaired smell, according to Dr. Wilson, also director and senior research scientist, the Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research. He was not involved with the study.

This “two-way interaction” may raise the possibility that “improving olfaction could impact nonolfactory disorders.”

This paper “brings together” previous research findings to show that odors during bedtime can improve some aspects of cognitive function and circuits that are known to be important for memory and cognition – which Dr. Wilson called “a very exciting, though relatively preliminary, finding.”

A caveat is that several measures of cognitive function were assessed and only one (verbal memory) showed clear improvement.

Nevertheless, there’s “very strong interest now in the olfactory and nonolfactory aspects of odor training and this training expands the training possibilities to sleep. This could be a powerful tool for cognitive improvement and/or rescue if follow-up studies support these findings,” Dr. Wilson said.

A version of this article appeared on Medscape.com.

Obstructive sleep apnea (OSA) affects roughly 1 billion people worldwide, according to a report by the American Academy of Sleep Medicine. Severe OSA has been associated with an elevated risk of all-cause and cardiovascular-specific mortality. Studies support an association between OSA and a host of comorbidities, including hypertension, stroke, atrial fibrillation, mood disorders, and neurocognitive outcomes. Undiagnosed and untreated OSA also has major economic and societal costs, reducing workplace productivity and increasing one’s risk of accidents both on the job and while driving.

Positive airway pressure (PAP) is widely considered the most effective treatment for OSA. The majority of patients tolerate CPAP: real-world estimates using international big data show good adherence in over 70% of patients. Robust evidence shows that PAP reduces snoring, decreases daytime sleepiness, and improves quality of life in a dose-dependent manner. Economic analyses have also found CPAP to be cost-effective (Streatfeild, et al. Sleep. 2019;42[12]:zsz181).

But what do we know about the impact of PAP on health outcomes? Perhaps the best studied outcome is cardiovascular disease. Results of observational trials have suggested that CPAP adherence was associated with survival (Pepin JL et al. Chest. 2022;161[6]:1657). However, it has been speculated that these findings may have been driven, at least in part, by the “healthy user effect.” This phenomenon refers to the tendency for people who engage in one health-promoting behavior (eg, CPAP adherence) to engage in another as well (eg, eating well, exercising, taking prescribed medications). When we observe that patients who use CPAP live longer, we must ask ourselves whether perhaps their better outcomes resulted from healthy habits in general, as opposed to their CPAP usage per se.

Randomization eliminates the potential for the healthy user effect, by assigning patients to a certain intervention as opposed to simply observing whether they choose to use it. And herein lies one of the great disappointments for our field over the past decade: multiple large-scale randomized controlled trials have failed to demonstrate that CPAP reduces cardiovascular mortality, even in patients with pre-existing CAD. The first two of these were the SAVE (Sleep Apnea Cardiovascular Endpoints) (McEvoy R, et al.  N Engl J Med. 2016;375[10]:919) and RICCADSA (Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA) (Peker Y, et al. Am J Respir Crit Care Med. 2016;194[5]:613) trials evaluating the effects of PAP on a composite endpoint that included cardiovascular death and nonfatal cardiovascular events. Both trials found no difference between PAP and control groups, leading to a conclusion that PAP did not prevent cardiovascular events in patients with moderate-to-severe OSA and established cardiovascular disease. The ISAAC study (Impact of Sleep Apnea syndrome in the evolution of Acute Coronary syndrome) also failed to show a benefit of CPAP for secondary prevention of cardiovascular events in patients with moderate to severe OSA.

These negative findings were echoed in a recent report by the Agency for Healthcare Research and Quality evaluating a variety of long-term health outcomes in obstructive sleep apnea. The authors stated that “RCTs do not provide evidence that CPAP prescription affects long-term, clinically important outcomes. Specifically, with low strength of evidence, RCTs do not demonstrate that CPAP affects all-cause mortality, various CV outcomes, clinically important changes in psychosocial measures, or other clinical events” (AHRQ, Project ID: SLPT0919, 12/1/2022).

What plausible explanations have been offered for these negative results? Perhaps trials were underpowered. Perhaps patients did not use PAP for a sufficient duration to achieve benefit (usage was under 3 hours in most studies). Perhaps the patients selected for these trials were at such low-risk of adverse outcomes in the first place that treating their OSA didn’t have much impact. Many trials have excluded sleepy patients due to ethical concerns about withholding treatment from this population. But this may have effectively excluded the patients most likely to benefit; in other studies, sleepy patients seem to experience the greatest cardiovascular risk reduction with CPAP. For example, a meta-analysis showed that CPAP is most strongly associated with blood pressure reduction in patients who are sleepy, compared with those with minimally symptomatic OSA (Bratton D, et al. Thorax. 2014;69[12]:1128). And, recent work suggests that even among non-sleepy patients, it might be possible to identify a subset who could benefit from CPAP. A recent analysis suggested that non-sleepy patients who exhibit a higher change in heart rate following a respiratory event may derive greater cardiovascular benefit from CPAP therapy (Azarbarzin, et al. Am J Respir Crit Care Med. 2022;206[6]:767).

We are moving toward a more personalized approach to characterizing OSA, which eventually may allow for more nuanced, individualized counseling rather than a “one-size -called-CPAP-fits-all” approach. Until we are there, a patient-centered approach that elicits the presence of sleep-related symptoms and daytime impairment, as opposed to isolated comorbidities, provides the most compelling justification for CPAP.

Obstructive sleep apnea (OSA) affects roughly 1 billion people worldwide, according to a report by the American Academy of Sleep Medicine. Severe OSA has been associated with an elevated risk of all-cause and cardiovascular-specific mortality. Studies support an association between OSA and a host of comorbidities, including hypertension, stroke, atrial fibrillation, mood disorders, and neurocognitive outcomes. Undiagnosed and untreated OSA also has major economic and societal costs, reducing workplace productivity and increasing one’s risk of accidents both on the job and while driving.

Positive airway pressure (PAP) is widely considered the most effective treatment for OSA. The majority of patients tolerate CPAP: real-world estimates using international big data show good adherence in over 70% of patients. Robust evidence shows that PAP reduces snoring, decreases daytime sleepiness, and improves quality of life in a dose-dependent manner. Economic analyses have also found CPAP to be cost-effective (Streatfeild, et al. Sleep. 2019;42[12]:zsz181).

But what do we know about the impact of PAP on health outcomes? Perhaps the best studied outcome is cardiovascular disease. Results of observational trials have suggested that CPAP adherence was associated with survival (Pepin JL et al. Chest. 2022;161[6]:1657). However, it has been speculated that these findings may have been driven, at least in part, by the “healthy user effect.” This phenomenon refers to the tendency for people who engage in one health-promoting behavior (eg, CPAP adherence) to engage in another as well (eg, eating well, exercising, taking prescribed medications). When we observe that patients who use CPAP live longer, we must ask ourselves whether perhaps their better outcomes resulted from healthy habits in general, as opposed to their CPAP usage per se.

Randomization eliminates the potential for the healthy user effect, by assigning patients to a certain intervention as opposed to simply observing whether they choose to use it. And herein lies one of the great disappointments for our field over the past decade: multiple large-scale randomized controlled trials have failed to demonstrate that CPAP reduces cardiovascular mortality, even in patients with pre-existing CAD. The first two of these were the SAVE (Sleep Apnea Cardiovascular Endpoints) (McEvoy R, et al.  N Engl J Med. 2016;375[10]:919) and RICCADSA (Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA) (Peker Y, et al. Am J Respir Crit Care Med. 2016;194[5]:613) trials evaluating the effects of PAP on a composite endpoint that included cardiovascular death and nonfatal cardiovascular events. Both trials found no difference between PAP and control groups, leading to a conclusion that PAP did not prevent cardiovascular events in patients with moderate-to-severe OSA and established cardiovascular disease. The ISAAC study (Impact of Sleep Apnea syndrome in the evolution of Acute Coronary syndrome) also failed to show a benefit of CPAP for secondary prevention of cardiovascular events in patients with moderate to severe OSA.

These negative findings were echoed in a recent report by the Agency for Healthcare Research and Quality evaluating a variety of long-term health outcomes in obstructive sleep apnea. The authors stated that “RCTs do not provide evidence that CPAP prescription affects long-term, clinically important outcomes. Specifically, with low strength of evidence, RCTs do not demonstrate that CPAP affects all-cause mortality, various CV outcomes, clinically important changes in psychosocial measures, or other clinical events” (AHRQ, Project ID: SLPT0919, 12/1/2022).

What plausible explanations have been offered for these negative results? Perhaps trials were underpowered. Perhaps patients did not use PAP for a sufficient duration to achieve benefit (usage was under 3 hours in most studies). Perhaps the patients selected for these trials were at such low-risk of adverse outcomes in the first place that treating their OSA didn’t have much impact. Many trials have excluded sleepy patients due to ethical concerns about withholding treatment from this population. But this may have effectively excluded the patients most likely to benefit; in other studies, sleepy patients seem to experience the greatest cardiovascular risk reduction with CPAP. For example, a meta-analysis showed that CPAP is most strongly associated with blood pressure reduction in patients who are sleepy, compared with those with minimally symptomatic OSA (Bratton D, et al. Thorax. 2014;69[12]:1128). And, recent work suggests that even among non-sleepy patients, it might be possible to identify a subset who could benefit from CPAP. A recent analysis suggested that non-sleepy patients who exhibit a higher change in heart rate following a respiratory event may derive greater cardiovascular benefit from CPAP therapy (Azarbarzin, et al. Am J Respir Crit Care Med. 2022;206[6]:767).

We are moving toward a more personalized approach to characterizing OSA, which eventually may allow for more nuanced, individualized counseling rather than a “one-size -called-CPAP-fits-all” approach. Until we are there, a patient-centered approach that elicits the presence of sleep-related symptoms and daytime impairment, as opposed to isolated comorbidities, provides the most compelling justification for CPAP.

Obstructive sleep apnea (OSA) affects roughly 1 billion people worldwide, according to a report by the American Academy of Sleep Medicine. Severe OSA has been associated with an elevated risk of all-cause and cardiovascular-specific mortality. Studies support an association between OSA and a host of comorbidities, including hypertension, stroke, atrial fibrillation, mood disorders, and neurocognitive outcomes. Undiagnosed and untreated OSA also has major economic and societal costs, reducing workplace productivity and increasing one’s risk of accidents both on the job and while driving.

Positive airway pressure (PAP) is widely considered the most effective treatment for OSA. The majority of patients tolerate CPAP: real-world estimates using international big data show good adherence in over 70% of patients. Robust evidence shows that PAP reduces snoring, decreases daytime sleepiness, and improves quality of life in a dose-dependent manner. Economic analyses have also found CPAP to be cost-effective (Streatfeild, et al. Sleep. 2019;42[12]:zsz181).

But what do we know about the impact of PAP on health outcomes? Perhaps the best studied outcome is cardiovascular disease. Results of observational trials have suggested that CPAP adherence was associated with survival (Pepin JL et al. Chest. 2022;161[6]:1657). However, it has been speculated that these findings may have been driven, at least in part, by the “healthy user effect.” This phenomenon refers to the tendency for people who engage in one health-promoting behavior (eg, CPAP adherence) to engage in another as well (eg, eating well, exercising, taking prescribed medications). When we observe that patients who use CPAP live longer, we must ask ourselves whether perhaps their better outcomes resulted from healthy habits in general, as opposed to their CPAP usage per se.

Randomization eliminates the potential for the healthy user effect, by assigning patients to a certain intervention as opposed to simply observing whether they choose to use it. And herein lies one of the great disappointments for our field over the past decade: multiple large-scale randomized controlled trials have failed to demonstrate that CPAP reduces cardiovascular mortality, even in patients with pre-existing CAD. The first two of these were the SAVE (Sleep Apnea Cardiovascular Endpoints) (McEvoy R, et al.  N Engl J Med. 2016;375[10]:919) and RICCADSA (Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA) (Peker Y, et al. Am J Respir Crit Care Med. 2016;194[5]:613) trials evaluating the effects of PAP on a composite endpoint that included cardiovascular death and nonfatal cardiovascular events. Both trials found no difference between PAP and control groups, leading to a conclusion that PAP did not prevent cardiovascular events in patients with moderate-to-severe OSA and established cardiovascular disease. The ISAAC study (Impact of Sleep Apnea syndrome in the evolution of Acute Coronary syndrome) also failed to show a benefit of CPAP for secondary prevention of cardiovascular events in patients with moderate to severe OSA.

These negative findings were echoed in a recent report by the Agency for Healthcare Research and Quality evaluating a variety of long-term health outcomes in obstructive sleep apnea. The authors stated that “RCTs do not provide evidence that CPAP prescription affects long-term, clinically important outcomes. Specifically, with low strength of evidence, RCTs do not demonstrate that CPAP affects all-cause mortality, various CV outcomes, clinically important changes in psychosocial measures, or other clinical events” (AHRQ, Project ID: SLPT0919, 12/1/2022).

What plausible explanations have been offered for these negative results? Perhaps trials were underpowered. Perhaps patients did not use PAP for a sufficient duration to achieve benefit (usage was under 3 hours in most studies). Perhaps the patients selected for these trials were at such low-risk of adverse outcomes in the first place that treating their OSA didn’t have much impact. Many trials have excluded sleepy patients due to ethical concerns about withholding treatment from this population. But this may have effectively excluded the patients most likely to benefit; in other studies, sleepy patients seem to experience the greatest cardiovascular risk reduction with CPAP. For example, a meta-analysis showed that CPAP is most strongly associated with blood pressure reduction in patients who are sleepy, compared with those with minimally symptomatic OSA (Bratton D, et al. Thorax. 2014;69[12]:1128). And, recent work suggests that even among non-sleepy patients, it might be possible to identify a subset who could benefit from CPAP. A recent analysis suggested that non-sleepy patients who exhibit a higher change in heart rate following a respiratory event may derive greater cardiovascular benefit from CPAP therapy (Azarbarzin, et al. Am J Respir Crit Care Med. 2022;206[6]:767).

We are moving toward a more personalized approach to characterizing OSA, which eventually may allow for more nuanced, individualized counseling rather than a “one-size -called-CPAP-fits-all” approach. Until we are there, a patient-centered approach that elicits the presence of sleep-related symptoms and daytime impairment, as opposed to isolated comorbidities, provides the most compelling justification for CPAP.

COVID-19’s increased demand on the mental health care delivery system led to expanded utilization of technology-based solutions, including digital tools to deliver care.¹ Technology-based solutions include both synchronous telehealth (eg, real-time interactive audio/video visits) and asynchronous tools such as smartphone applications (apps). Both real-time telehealth and apps continue to gain popularity. More than 10,000 mental health–related apps are available, and that number continues to rise.² Numerous web- or mobile-based apps are available to aid in the treatment of various psychiatric conditions, including generalized anxiety disorder (GAD), major depressive disorder, insomnia, and posttraumatic stress disorder (PTSD).

Clinicians may find it challenging to choose the best psychiatry-related apps to recommend to patients. This dilemma calls for an approach to help clinicians select apps that are safe and effective.² The American Psychiatric Association provides information to help mental health professionals navigate these issues and identify which aspects to consider when selecting an app for clinical use.³ The M-Health Index and Navigation Database also provides a set of objective evaluative criteria and offers guidance on choosing apps.⁴

In this article, we review 8 randomized controlled trials (RCTs) of mental health–related apps. We took several steps to ensure the RCTs we included were impactful and meaningful. First, we conducted a general search using mainstream search engines to assess which psychiatric apps were most popular for use in clinical practice. Using this list, we conducted a scholarly search engine query of RCTs using the name of the apps as a search parameter along with the following keywords: “mobile,” “web,” “applications,” and “psychiatry.” This search yielded approximately 50 results, which were narrowed down based on content and interest to a list of 8 articles (Table^5-12). These articles were then graded using the limitations of each study as the primary substrate for evaluation.

1. Linardon J, Shatte A, Rosato J, et al. Efficacy of a transdiagnostic cognitive-behavioral intervention for eating disorder psychopathology delivered through a smartphone app: a randomized controlled trial. Psychol Med. 2022;52(9):1679-1690. doi:10.1017/S0033291720003426

Many patients with eating disorders are unable to receive effective treatment due to problems with accessing health care. Smartphone apps may help bridge the treatment gap for patients in this position. Linardon et al⁵ developed an app that uses the principles of cognitive-behavioral therapy (CBT) for treating eating disorders and conducted this study to evaluate its effectiveness.

Study design

• This RCT assigned individuals who reported episodes of binge eating to a group that used a mobile app (n = 197) or to a waiting list (n = 195). At baseline, 42% of participants exhibited diagnostic-level symptoms of bulimia nervosa and 31% had symptoms of binge-eating disorder.
• Assessments took place at baseline, Week 4, and Week 8.
• The primary outcome was global levels of eating disorder psychopathology.
• Secondary outcomes were other eating disorder symptoms, impairment, and distress.

Outcomes

• Compared to the control group, participants who used the mobile app reported greater reductions in global eating disorder psychopathology (d = -0.80).
• Significant effects were also observed for secondary outcomes except compensatory behavior frequency.
• Overall, participants reported they were satisfied with the app.

Continue to: Conclusions/limitations

• Findings show this app could potentially be a cost-effective and easily accessible option for patients who cannot receive standard treatment for eating disorders.
• Limitations: The overall posttest attrition rate was 35%.

2. Christoforou M, Sáez Fonseca JA, Tsakanikos E. Two novel cognitive behavioral therapy–based mobile apps for agoraphobia: randomized controlled trial. J Med Internet Res. 2017;19(11):e398. doi:10.2196/jmir.7747

CBT is generally the most accepted first-line treatment for agoraphobia. However, numerous barriers to obtaining CBT can prevent successful treatment. Limited research has evaluated the efficacy of apps for treating agoraphobia. Christoforou et al⁶ conducted an RCT to determine the effectiveness of a self-guided smartphone app for improving agoraphobic symptoms, compared to a mobile app used to treat anxiety.

Study design

• Participants (N = 170) who self-identified as having agoraphobia were randomly assigned to use a smartphone app designed to target agoraphobia (Agoraphobia Free) or a smartphone app designed to help with symptoms of anxiety (Stress Free) for 12 weeks. Both apps were based on established cognitive behavioral principles.
• Assessment occurred at baseline, midpoint, and end point.
• The primary outcome was symptom severity as measured by the Panic and Agoraphobia Scale (PAS).

Outcomes

• Both groups experienced statistically significant improvements in symptom severity over time. The differences in PAS score were -5.97 (95% CI, -8.49 to -3.44, P < .001) for Agoraphobia Free and -6.35 (95% CI, -8.82 to -3.87, P < .001) for Stress Free.
• There were no significant between-group differences in symptom severity.

Continue to: Conclusions/limitations

• This study is the first RCT to show that patients with agoraphobia could benefit from mobile-based interventions.
• Limitations: There was no waitlist control group. Limited information was collected about participant characteristics; there were no data on comorbid disorders, other psychological or physiological treatments, or other demographic characteristics such as ethnicity or computer literacy.

3. Everitt N, Broadbent J, Richardson B, et al. Exploring the features of an app-based just-in-time intervention for depression. J Affect Disord. 2021;291:279-287. doi:10.1016/j.jad.2021.05.021

The apps MoodTracker, ImproveYourMood, and ImproveYourMood+ deliver content “just in time” (in response to acute negative symptoms) to help patients with depression. In an RCT, Everitt et al⁷ evaluated delivering acute care for depressive mood states via a smartphone app. They sought to delineate whether symptom improvement was due to microintervention content, mood augmentation, or just-in-time prompts to use content.

Study design

• Participants (N = 235) from the general population who said they wanted to improve their mood were randomly assigned to a waitlist control group (n = 55) or 1 of 3 intervention groups: MoodTracker (monitoring-only; n = 58), ImproveYourMood (monitoring and content; n = 62), or ImproveYourMood+ (monitoring, content, and prompts; n = 60).
• The microintervention content provided by these apps consisted of 4 audio files of brief (2- to 3-minute) mindfulness and relaxation exercises. Participants used the assigned app for 3 weeks.
• Depressive symptoms, anxiety symptoms, and negative automatic thoughts were assessed at baseline, immediately following the intervention, and 1 month after the intervention using the 9-item Patient Health Questionnaire (PHQ-9), 7-item GAD scale (GAD-7), and 8-item Automatic Thoughts Questionnaire, respectively.

Outcomes

• Compared to the waitlist control group, participants in the ImproveYourMood group showed greater declines in depressive symptoms and anxiety symptoms (at follow-up only), and negative automatic thoughts (at both postintervention and follow-up).
• Those in the ImproveYourMood+ group only showed significantly greater improvements for automatic negative thoughts (at postintervention).
• MoodTracker participants did not differ from waitlist controls for any variables at any timepoints.

Continue to: Conclusions/limitations

• This study suggests that using microinterventions in acute settings can effectively reduce depressive symptoms both as they occur, and 1 to 2 months later.
• Limitations: The study featured a naturalistic design, where participants self-selected whether they wanted to use the program. Participants did not complete eligibility assessments or receive compensation, and the study had high dropout rates, ranging from 20% for the waitlist control group to 67% for the ImproveYourMood+ group.

4. McLean C, Davis CA, Miller M, et al. The effects of an exposure-based mobile app on symptoms of posttraumatic stress disorder in veterans: pilot randomized controlled trial. JMIR Mhealth Uhealth. 2022;10(11):e38951. doi:10.2196/38951

Veterans with PTSD face barriers when receiving trauma-focused treatments such as exposure therapy or CBT. Smartphone apps may help veterans self-treat and self-manage their PTSD symptoms. McLean et al⁸ studied the efficacy of Renew, a smartphone app that uses exposure therapy and social support to treat PTSD.

Study design

• In this pilot RCT, 93 veterans with clinically significant PTSD symptoms were randomly assigned to use the Renew app with and without support from a research staff member (active use group) or to a waitlist (delayed use group) for 6 weeks.
• The PTSD Checklist for DSM-5 (PCL-5) was used to measure PTSD symptoms at preintervention, postintervention, and 6-week follow-up.
• Most participants (69%) were women, and the mean age was 49.

Outcomes

• Compared to the delayed use group, participants in the active use group experienced a larger decrease in PCL-5 score (-6.14 vs -1.84). However, this difference was not statistically significant (P = .29), and the effect size was small (d = -0.39).
• There was no difference in engagement with the app between participants who received support from a research staff member and those who did not receive such support.

Continue to: Conclusions/limitations

• Renew may show promise as a tool to reduce PTSD symptoms in veterans.
• Educating family and friends on how to best support a patient using a mobile mental health app may help improve the efficacy of Renew and increase app engagement.
• Limitations: Because the study was conducted in veterans, the results may not be generalizable to other populations. Because most data collection occurred during the first wave of the COVID-19 pandemic in the United States, COVID-19–related stress may have impacted PTSD symptoms, app engagement, or outcomes.

5. Graham AK, Greene CJ, Kwasny MJ, et al. Coached mobile app platform for the treatment of depression and anxiety among primary care patients: a randomized clinical trial. JAMA Psychiatry. 2020;77(9):906-914. doi:10.1001/jamapsychiatry.2020.1011

Many cases of depression and anxiety are initially treated in primary care settings. However, these settings may have limited resources and inadequate training, and mobile interventions might be helpful to augment patient care. Graham et al⁹ studied the mobile platform IntelliCare to determine its efficacy as a tool to be used in primary care settings to treat depression and anxiety.

Study design

• This RCT randomly assigned adult primary care patients (N = 146) who screened positive for depression on the PHQ-9 (score ≥10) or anxiety on the GAD-7 (score ≥8) to the coach-supported IntelliCare platform, which consisted of 5 clinically focused apps, or to a waitlist control group. Interventions were delivered over 8 weeks.
• Overall, 122 (83.6%) patients were diagnosed with depression and 131 (89.7%) were diagnosed with anxiety.
• The primary outcomes were changes in depression (as measured by change in PHQ-9 score) and anxiety (change in GAD-7 score) during the intervention period.

Outcomes

• Participants who used the IntelliCare platform had a greater reduction in depression and anxiety symptoms compared to waitlist controls, and changes were sustained over 2-month follow-up.
• The least square means (LSM) difference in depression scores at Week 4 was 2.91 (SE = 0.83; d = 0.43) and at Week 8 was 4.37 (SE = 0.83; d = 0.64). The LSM difference in anxiety scores at Week 4 was 2.51 (SE = 0.78; d = 0.41) and at Week 8 was 3.33 (SE = 0.76; d = 0.55).
• A median number of 93 and 98 sessions among participants with depression and anxiety were recorded, respectively, indicating high use of the IntelliCare platform.

Continue to: Conclusions/limitations

• The IntelliCare platform was shown to be effective in reducing depression and anxiety among primary care patients. Simple apps can be bundled together and used by patients in conjunction to treat their individual needs.
• Limitations: The study had a limited follow-up period and did not record participants’ use of other apps. Slightly more than one-half (56%) of participants were taking an antidepressant.

6. Wilhelm S, Weingarden H, Greenberg JL, et al. Efficacy of app-based cognitive behavioral therapy for body dysmorphic disorder with coach support: initial randomized controlled clinical trial. Psychother Psychosom. 2022;91(4):277-285. doi:10.1159/000524628

Body dysmorphic disorder (BDD) is a severe yet undertreated disorder. Apps can improve access to treatment for patients experiencing BDD. Wilhelm et al¹⁰ studied the usability and efficacy of a coach-supported app called Perspectives that was specifically designed for treating BDD. Perspectives provide CBT in 7 modules: psychoeducation, cognitive restructuring, exposure, response prevention, mindfulness, attention retraining, and relapse prevention.

Study design

• Adults (N = 80) with primary BDD were assigned to use the Perspectives app for 12 weeks or to a waitlist control group. Participants were predominately female (84%) and White (71%), with a mean age of 27.
• Coaches promoted engagement and answered questions via in-app messaging and phone calls.
• Blinded independent evaluators used the Yale-Brown Obsessive Compulsive Scale Modified for BDD (BDD-YBOCS) to measure BDD severity at baseline, midtreatment (Week 6), and end of treatment (Week 12).
• Secondary outcomes included BDD-related insight, depression, quality of life, and functioning. Various scales were used to measure these outcomes.

Outcomes

• In intent-to-treat analyses, patients who received CBT via the Perspectives app had significantly lower BDD severity at the end of treatment compared to the waitlist control group, with a mean (SD) BDD-YBOCS score of 16.8 (7.5) vs 26.7 (6.2), with P < .001 and d = 1.44.
• Slightly more than one-half (52%) of those who used Perspectives achieved full or partial remission, compared to 8% in the waitlist control group.

Continue to: Conclusions/limitations

• CBT delivered via the Perspectives app and a coach proved to be effective treatment for adults with BDD.
• Adoption of the application was relatively high; 86% of Perspectives users were very or mostly satisfied.
• Limitations: Because the participants in this study were predominantly female and White, the findings might not be generalizable to other populations.

7. Kuhn E, Miller KE, Puran D, et al. A pilot randomized controlled trial of the Insomnia Coach mobile app to assess its feasibility, acceptability, and potential efficacy. Behav Ther. 2022;53(3):440-457. doi:10.1016/j.beth.2021.11.003

Insomnia remains a substantial problem among military veterans. First-line treatments for the disorder are sleep hygiene modification and CBT. Access to CBT is limited, especially for veterans. Kuhn et al¹¹ studied the effectiveness of using Insomnia Coach, a CBT for insomnia–based app, to improve insomnia symptoms.

Study design

• Fifty US veterans who were mostly male (58%) with a mean age of 44.5 and moderate insomnia symptoms were randomized to use Insomnia Coach (n = 25) or to a waitlist control group (n = 25) for 6 weeks.
• All participants completed self-report measures and sleep diaries at baseline, posttreatment, and follow-up (12 weeks). Those who used the app (n = 15) completed a qualitative interview at posttreatment.

Outcomes

• At posttreatment, 28% of participants who used Insomnia Coach achieved clinically significant improvement, vs 4% of waitlist control participants. There was also a significant treatment effect on daytime sleep-related impairment (P = .044, d = -0.6).
• Additional treatment effects emerged at follow-up for insomnia severity, sleep onset latency, global sleep quality, and depression symptoms.
• Based on self-reports and qualitative interview responses, participants’ perceptions of Insomnia Coach were favorable. Three-fourths of participants used the app through 6 weeks and engaged with active elements.

Continue to: Conclusions/limitations

• Insomnia Coach may provide an accessible and convenient public health intervention for patients who aren’t receiving adequate care or CBT.
• Limitations: Because this study evaluated only veterans, the findings might not be generalizable to other populations.

8. Dahne J, Lejuez CW, Diaz VA, et al. Pilot randomized trial of a self-help behavioral activation mobile app for utilization in primary care. Behav Ther. 2019;50(4):817-827. doi:10.1016/j.beth.2018.12.003

Previous mobile technologies have shown the ability to treat depression in primary care settings. Moodivate is a self-help mobile app based on the Brief Behavioral Activation Treatment for Depression, which is an evidence-based treatment. This app is designed to help the user reengage in positive, nondepressed activities by identifying, scheduling, and completing activities. Dahne et al¹² investigated the feasibility and efficacy of Moodivate for depressive symptoms in primary care patients.

Study design

• Participants (N = 52) were recruited from primary care practices and randomized 2:2:1 to receive Moodivate, a CBT-based mobile app called MoodKit, or treatment as usual (no app). All participants had an initial PHQ-8 score >10.
• Participants completed assessments of depressive symptoms (PHQ-8) weekly for 8 weeks.
• App analytics data were captured to examine if the use of Moodivate was feasible. (Analytics were not available for MoodKit).

Outcomes

• Participants who used Moodivate had a mean (SD) of 46.76 (30.10) sessions throughout the trial, spent 3.50 (2.76) minutes using the app per session, and spent 120.76 (101.02) minutes using the app in total.
• Nearly 70% of Moodivate participants continued to use the app 1 month after trial enrollment and 50% at the end of the 8-week follow-up period.
• Compared to the treatment as usual group, participants who used Moodivate and those who used MoodKit experienced significant decreases in depressive symptoms over time.

Conclusions/limitations

• The results show that for primary care patients with depression, the use of Moodivate is feasible and may reduce depressive symptoms.
• Limitations: For the first 3 months of enrollment, patients who met diagnostic criteria for a current major depressive episode were excluded. This study did not assess duration of medication use (ie, whether a study participant was stabilized on medication or recently started taking a new medication) and therefore could not ascertain whether treatment gains were a result of the use of the app or of possible new medication use.

COVID-19’s increased demand on the mental health care delivery system led to expanded utilization of technology-based solutions, including digital tools to deliver care.¹ Technology-based solutions include both synchronous telehealth (eg, real-time interactive audio/video visits) and asynchronous tools such as smartphone applications (apps). Both real-time telehealth and apps continue to gain popularity. More than 10,000 mental health–related apps are available, and that number continues to rise.² Numerous web- or mobile-based apps are available to aid in the treatment of various psychiatric conditions, including generalized anxiety disorder (GAD), major depressive disorder, insomnia, and posttraumatic stress disorder (PTSD).

Clinicians may find it challenging to choose the best psychiatry-related apps to recommend to patients. This dilemma calls for an approach to help clinicians select apps that are safe and effective.² The American Psychiatric Association provides information to help mental health professionals navigate these issues and identify which aspects to consider when selecting an app for clinical use.³ The M-Health Index and Navigation Database also provides a set of objective evaluative criteria and offers guidance on choosing apps.⁴

In this article, we review 8 randomized controlled trials (RCTs) of mental health–related apps. We took several steps to ensure the RCTs we included were impactful and meaningful. First, we conducted a general search using mainstream search engines to assess which psychiatric apps were most popular for use in clinical practice. Using this list, we conducted a scholarly search engine query of RCTs using the name of the apps as a search parameter along with the following keywords: “mobile,” “web,” “applications,” and “psychiatry.” This search yielded approximately 50 results, which were narrowed down based on content and interest to a list of 8 articles (Table^5-12). These articles were then graded using the limitations of each study as the primary substrate for evaluation.

1. Linardon J, Shatte A, Rosato J, et al. Efficacy of a transdiagnostic cognitive-behavioral intervention for eating disorder psychopathology delivered through a smartphone app: a randomized controlled trial. Psychol Med. 2022;52(9):1679-1690. doi:10.1017/S0033291720003426

Many patients with eating disorders are unable to receive effective treatment due to problems with accessing health care. Smartphone apps may help bridge the treatment gap for patients in this position. Linardon et al⁵ developed an app that uses the principles of cognitive-behavioral therapy (CBT) for treating eating disorders and conducted this study to evaluate its effectiveness.

Study design

• This RCT assigned individuals who reported episodes of binge eating to a group that used a mobile app (n = 197) or to a waiting list (n = 195). At baseline, 42% of participants exhibited diagnostic-level symptoms of bulimia nervosa and 31% had symptoms of binge-eating disorder.
• Assessments took place at baseline, Week 4, and Week 8.
• The primary outcome was global levels of eating disorder psychopathology.
• Secondary outcomes were other eating disorder symptoms, impairment, and distress.

Outcomes

• Compared to the control group, participants who used the mobile app reported greater reductions in global eating disorder psychopathology (d = -0.80).
• Significant effects were also observed for secondary outcomes except compensatory behavior frequency.
• Overall, participants reported they were satisfied with the app.

Continue to: Conclusions/limitations

• Findings show this app could potentially be a cost-effective and easily accessible option for patients who cannot receive standard treatment for eating disorders.
• Limitations: The overall posttest attrition rate was 35%.

2. Christoforou M, Sáez Fonseca JA, Tsakanikos E. Two novel cognitive behavioral therapy–based mobile apps for agoraphobia: randomized controlled trial. J Med Internet Res. 2017;19(11):e398. doi:10.2196/jmir.7747

CBT is generally the most accepted first-line treatment for agoraphobia. However, numerous barriers to obtaining CBT can prevent successful treatment. Limited research has evaluated the efficacy of apps for treating agoraphobia. Christoforou et al⁶ conducted an RCT to determine the effectiveness of a self-guided smartphone app for improving agoraphobic symptoms, compared to a mobile app used to treat anxiety.

Study design

• Participants (N = 170) who self-identified as having agoraphobia were randomly assigned to use a smartphone app designed to target agoraphobia (Agoraphobia Free) or a smartphone app designed to help with symptoms of anxiety (Stress Free) for 12 weeks. Both apps were based on established cognitive behavioral principles.
• Assessment occurred at baseline, midpoint, and end point.
• The primary outcome was symptom severity as measured by the Panic and Agoraphobia Scale (PAS).

Outcomes

• Both groups experienced statistically significant improvements in symptom severity over time. The differences in PAS score were -5.97 (95% CI, -8.49 to -3.44, P < .001) for Agoraphobia Free and -6.35 (95% CI, -8.82 to -3.87, P < .001) for Stress Free.
• There were no significant between-group differences in symptom severity.

Continue to: Conclusions/limitations

• This study is the first RCT to show that patients with agoraphobia could benefit from mobile-based interventions.
• Limitations: There was no waitlist control group. Limited information was collected about participant characteristics; there were no data on comorbid disorders, other psychological or physiological treatments, or other demographic characteristics such as ethnicity or computer literacy.

3. Everitt N, Broadbent J, Richardson B, et al. Exploring the features of an app-based just-in-time intervention for depression. J Affect Disord. 2021;291:279-287. doi:10.1016/j.jad.2021.05.021

The apps MoodTracker, ImproveYourMood, and ImproveYourMood+ deliver content “just in time” (in response to acute negative symptoms) to help patients with depression. In an RCT, Everitt et al⁷ evaluated delivering acute care for depressive mood states via a smartphone app. They sought to delineate whether symptom improvement was due to microintervention content, mood augmentation, or just-in-time prompts to use content.

Study design

• Participants (N = 235) from the general population who said they wanted to improve their mood were randomly assigned to a waitlist control group (n = 55) or 1 of 3 intervention groups: MoodTracker (monitoring-only; n = 58), ImproveYourMood (monitoring and content; n = 62), or ImproveYourMood+ (monitoring, content, and prompts; n = 60).
• The microintervention content provided by these apps consisted of 4 audio files of brief (2- to 3-minute) mindfulness and relaxation exercises. Participants used the assigned app for 3 weeks.
• Depressive symptoms, anxiety symptoms, and negative automatic thoughts were assessed at baseline, immediately following the intervention, and 1 month after the intervention using the 9-item Patient Health Questionnaire (PHQ-9), 7-item GAD scale (GAD-7), and 8-item Automatic Thoughts Questionnaire, respectively.

Outcomes

• Compared to the waitlist control group, participants in the ImproveYourMood group showed greater declines in depressive symptoms and anxiety symptoms (at follow-up only), and negative automatic thoughts (at both postintervention and follow-up).
• Those in the ImproveYourMood+ group only showed significantly greater improvements for automatic negative thoughts (at postintervention).
• MoodTracker participants did not differ from waitlist controls for any variables at any timepoints.

Continue to: Conclusions/limitations

• This study suggests that using microinterventions in acute settings can effectively reduce depressive symptoms both as they occur, and 1 to 2 months later.
• Limitations: The study featured a naturalistic design, where participants self-selected whether they wanted to use the program. Participants did not complete eligibility assessments or receive compensation, and the study had high dropout rates, ranging from 20% for the waitlist control group to 67% for the ImproveYourMood+ group.

4. McLean C, Davis CA, Miller M, et al. The effects of an exposure-based mobile app on symptoms of posttraumatic stress disorder in veterans: pilot randomized controlled trial. JMIR Mhealth Uhealth. 2022;10(11):e38951. doi:10.2196/38951

Veterans with PTSD face barriers when receiving trauma-focused treatments such as exposure therapy or CBT. Smartphone apps may help veterans self-treat and self-manage their PTSD symptoms. McLean et al⁸ studied the efficacy of Renew, a smartphone app that uses exposure therapy and social support to treat PTSD.

Study design

• In this pilot RCT, 93 veterans with clinically significant PTSD symptoms were randomly assigned to use the Renew app with and without support from a research staff member (active use group) or to a waitlist (delayed use group) for 6 weeks.
• The PTSD Checklist for DSM-5 (PCL-5) was used to measure PTSD symptoms at preintervention, postintervention, and 6-week follow-up.
• Most participants (69%) were women, and the mean age was 49.

Outcomes

• Compared to the delayed use group, participants in the active use group experienced a larger decrease in PCL-5 score (-6.14 vs -1.84). However, this difference was not statistically significant (P = .29), and the effect size was small (d = -0.39).
• There was no difference in engagement with the app between participants who received support from a research staff member and those who did not receive such support.

Continue to: Conclusions/limitations

• Renew may show promise as a tool to reduce PTSD symptoms in veterans.
• Educating family and friends on how to best support a patient using a mobile mental health app may help improve the efficacy of Renew and increase app engagement.
• Limitations: Because the study was conducted in veterans, the results may not be generalizable to other populations. Because most data collection occurred during the first wave of the COVID-19 pandemic in the United States, COVID-19–related stress may have impacted PTSD symptoms, app engagement, or outcomes.

5. Graham AK, Greene CJ, Kwasny MJ, et al. Coached mobile app platform for the treatment of depression and anxiety among primary care patients: a randomized clinical trial. JAMA Psychiatry. 2020;77(9):906-914. doi:10.1001/jamapsychiatry.2020.1011

Many cases of depression and anxiety are initially treated in primary care settings. However, these settings may have limited resources and inadequate training, and mobile interventions might be helpful to augment patient care. Graham et al⁹ studied the mobile platform IntelliCare to determine its efficacy as a tool to be used in primary care settings to treat depression and anxiety.

Study design

• This RCT randomly assigned adult primary care patients (N = 146) who screened positive for depression on the PHQ-9 (score ≥10) or anxiety on the GAD-7 (score ≥8) to the coach-supported IntelliCare platform, which consisted of 5 clinically focused apps, or to a waitlist control group. Interventions were delivered over 8 weeks.
• Overall, 122 (83.6%) patients were diagnosed with depression and 131 (89.7%) were diagnosed with anxiety.
• The primary outcomes were changes in depression (as measured by change in PHQ-9 score) and anxiety (change in GAD-7 score) during the intervention period.

Outcomes

• Participants who used the IntelliCare platform had a greater reduction in depression and anxiety symptoms compared to waitlist controls, and changes were sustained over 2-month follow-up.
• The least square means (LSM) difference in depression scores at Week 4 was 2.91 (SE = 0.83; d = 0.43) and at Week 8 was 4.37 (SE = 0.83; d = 0.64). The LSM difference in anxiety scores at Week 4 was 2.51 (SE = 0.78; d = 0.41) and at Week 8 was 3.33 (SE = 0.76; d = 0.55).
• A median number of 93 and 98 sessions among participants with depression and anxiety were recorded, respectively, indicating high use of the IntelliCare platform.

Continue to: Conclusions/limitations

• The IntelliCare platform was shown to be effective in reducing depression and anxiety among primary care patients. Simple apps can be bundled together and used by patients in conjunction to treat their individual needs.
• Limitations: The study had a limited follow-up period and did not record participants’ use of other apps. Slightly more than one-half (56%) of participants were taking an antidepressant.

6. Wilhelm S, Weingarden H, Greenberg JL, et al. Efficacy of app-based cognitive behavioral therapy for body dysmorphic disorder with coach support: initial randomized controlled clinical trial. Psychother Psychosom. 2022;91(4):277-285. doi:10.1159/000524628

Body dysmorphic disorder (BDD) is a severe yet undertreated disorder. Apps can improve access to treatment for patients experiencing BDD. Wilhelm et al¹⁰ studied the usability and efficacy of a coach-supported app called Perspectives that was specifically designed for treating BDD. Perspectives provide CBT in 7 modules: psychoeducation, cognitive restructuring, exposure, response prevention, mindfulness, attention retraining, and relapse prevention.

Study design

• Adults (N = 80) with primary BDD were assigned to use the Perspectives app for 12 weeks or to a waitlist control group. Participants were predominately female (84%) and White (71%), with a mean age of 27.
• Coaches promoted engagement and answered questions via in-app messaging and phone calls.
• Blinded independent evaluators used the Yale-Brown Obsessive Compulsive Scale Modified for BDD (BDD-YBOCS) to measure BDD severity at baseline, midtreatment (Week 6), and end of treatment (Week 12).
• Secondary outcomes included BDD-related insight, depression, quality of life, and functioning. Various scales were used to measure these outcomes.

Outcomes

• In intent-to-treat analyses, patients who received CBT via the Perspectives app had significantly lower BDD severity at the end of treatment compared to the waitlist control group, with a mean (SD) BDD-YBOCS score of 16.8 (7.5) vs 26.7 (6.2), with P < .001 and d = 1.44.
• Slightly more than one-half (52%) of those who used Perspectives achieved full or partial remission, compared to 8% in the waitlist control group.

Continue to: Conclusions/limitations

• CBT delivered via the Perspectives app and a coach proved to be effective treatment for adults with BDD.
• Adoption of the application was relatively high; 86% of Perspectives users were very or mostly satisfied.
• Limitations: Because the participants in this study were predominantly female and White, the findings might not be generalizable to other populations.

7. Kuhn E, Miller KE, Puran D, et al. A pilot randomized controlled trial of the Insomnia Coach mobile app to assess its feasibility, acceptability, and potential efficacy. Behav Ther. 2022;53(3):440-457. doi:10.1016/j.beth.2021.11.003

Insomnia remains a substantial problem among military veterans. First-line treatments for the disorder are sleep hygiene modification and CBT. Access to CBT is limited, especially for veterans. Kuhn et al¹¹ studied the effectiveness of using Insomnia Coach, a CBT for insomnia–based app, to improve insomnia symptoms.

Study design

• Fifty US veterans who were mostly male (58%) with a mean age of 44.5 and moderate insomnia symptoms were randomized to use Insomnia Coach (n = 25) or to a waitlist control group (n = 25) for 6 weeks.
• All participants completed self-report measures and sleep diaries at baseline, posttreatment, and follow-up (12 weeks). Those who used the app (n = 15) completed a qualitative interview at posttreatment.

Outcomes

• At posttreatment, 28% of participants who used Insomnia Coach achieved clinically significant improvement, vs 4% of waitlist control participants. There was also a significant treatment effect on daytime sleep-related impairment (P = .044, d = -0.6).
• Additional treatment effects emerged at follow-up for insomnia severity, sleep onset latency, global sleep quality, and depression symptoms.
• Based on self-reports and qualitative interview responses, participants’ perceptions of Insomnia Coach were favorable. Three-fourths of participants used the app through 6 weeks and engaged with active elements.

Continue to: Conclusions/limitations

• Insomnia Coach may provide an accessible and convenient public health intervention for patients who aren’t receiving adequate care or CBT.
• Limitations: Because this study evaluated only veterans, the findings might not be generalizable to other populations.

8. Dahne J, Lejuez CW, Diaz VA, et al. Pilot randomized trial of a self-help behavioral activation mobile app for utilization in primary care. Behav Ther. 2019;50(4):817-827. doi:10.1016/j.beth.2018.12.003

Previous mobile technologies have shown the ability to treat depression in primary care settings. Moodivate is a self-help mobile app based on the Brief Behavioral Activation Treatment for Depression, which is an evidence-based treatment. This app is designed to help the user reengage in positive, nondepressed activities by identifying, scheduling, and completing activities. Dahne et al¹² investigated the feasibility and efficacy of Moodivate for depressive symptoms in primary care patients.

Study design

• Participants (N = 52) were recruited from primary care practices and randomized 2:2:1 to receive Moodivate, a CBT-based mobile app called MoodKit, or treatment as usual (no app). All participants had an initial PHQ-8 score >10.
• Participants completed assessments of depressive symptoms (PHQ-8) weekly for 8 weeks.
• App analytics data were captured to examine if the use of Moodivate was feasible. (Analytics were not available for MoodKit).

Outcomes

• Participants who used Moodivate had a mean (SD) of 46.76 (30.10) sessions throughout the trial, spent 3.50 (2.76) minutes using the app per session, and spent 120.76 (101.02) minutes using the app in total.
• Nearly 70% of Moodivate participants continued to use the app 1 month after trial enrollment and 50% at the end of the 8-week follow-up period.
• Compared to the treatment as usual group, participants who used Moodivate and those who used MoodKit experienced significant decreases in depressive symptoms over time.

Conclusions/limitations

• The results show that for primary care patients with depression, the use of Moodivate is feasible and may reduce depressive symptoms.
• Limitations: For the first 3 months of enrollment, patients who met diagnostic criteria for a current major depressive episode were excluded. This study did not assess duration of medication use (ie, whether a study participant was stabilized on medication or recently started taking a new medication) and therefore could not ascertain whether treatment gains were a result of the use of the app or of possible new medication use.

COVID-19’s increased demand on the mental health care delivery system led to expanded utilization of technology-based solutions, including digital tools to deliver care.¹ Technology-based solutions include both synchronous telehealth (eg, real-time interactive audio/video visits) and asynchronous tools such as smartphone applications (apps). Both real-time telehealth and apps continue to gain popularity. More than 10,000 mental health–related apps are available, and that number continues to rise.² Numerous web- or mobile-based apps are available to aid in the treatment of various psychiatric conditions, including generalized anxiety disorder (GAD), major depressive disorder, insomnia, and posttraumatic stress disorder (PTSD).

Clinicians may find it challenging to choose the best psychiatry-related apps to recommend to patients. This dilemma calls for an approach to help clinicians select apps that are safe and effective.² The American Psychiatric Association provides information to help mental health professionals navigate these issues and identify which aspects to consider when selecting an app for clinical use.³ The M-Health Index and Navigation Database also provides a set of objective evaluative criteria and offers guidance on choosing apps.⁴

In this article, we review 8 randomized controlled trials (RCTs) of mental health–related apps. We took several steps to ensure the RCTs we included were impactful and meaningful. First, we conducted a general search using mainstream search engines to assess which psychiatric apps were most popular for use in clinical practice. Using this list, we conducted a scholarly search engine query of RCTs using the name of the apps as a search parameter along with the following keywords: “mobile,” “web,” “applications,” and “psychiatry.” This search yielded approximately 50 results, which were narrowed down based on content and interest to a list of 8 articles (Table^5-12). These articles were then graded using the limitations of each study as the primary substrate for evaluation.

1. Linardon J, Shatte A, Rosato J, et al. Efficacy of a transdiagnostic cognitive-behavioral intervention for eating disorder psychopathology delivered through a smartphone app: a randomized controlled trial. Psychol Med. 2022;52(9):1679-1690. doi:10.1017/S0033291720003426

Many patients with eating disorders are unable to receive effective treatment due to problems with accessing health care. Smartphone apps may help bridge the treatment gap for patients in this position. Linardon et al⁵ developed an app that uses the principles of cognitive-behavioral therapy (CBT) for treating eating disorders and conducted this study to evaluate its effectiveness.

Study design

• This RCT assigned individuals who reported episodes of binge eating to a group that used a mobile app (n = 197) or to a waiting list (n = 195). At baseline, 42% of participants exhibited diagnostic-level symptoms of bulimia nervosa and 31% had symptoms of binge-eating disorder.
• Assessments took place at baseline, Week 4, and Week 8.
• The primary outcome was global levels of eating disorder psychopathology.
• Secondary outcomes were other eating disorder symptoms, impairment, and distress.

Outcomes

• Compared to the control group, participants who used the mobile app reported greater reductions in global eating disorder psychopathology (d = -0.80).
• Significant effects were also observed for secondary outcomes except compensatory behavior frequency.
• Overall, participants reported they were satisfied with the app.

Continue to: Conclusions/limitations

• Findings show this app could potentially be a cost-effective and easily accessible option for patients who cannot receive standard treatment for eating disorders.
• Limitations: The overall posttest attrition rate was 35%.

2. Christoforou M, Sáez Fonseca JA, Tsakanikos E. Two novel cognitive behavioral therapy–based mobile apps for agoraphobia: randomized controlled trial. J Med Internet Res. 2017;19(11):e398. doi:10.2196/jmir.7747

CBT is generally the most accepted first-line treatment for agoraphobia. However, numerous barriers to obtaining CBT can prevent successful treatment. Limited research has evaluated the efficacy of apps for treating agoraphobia. Christoforou et al⁶ conducted an RCT to determine the effectiveness of a self-guided smartphone app for improving agoraphobic symptoms, compared to a mobile app used to treat anxiety.

Study design

• Participants (N = 170) who self-identified as having agoraphobia were randomly assigned to use a smartphone app designed to target agoraphobia (Agoraphobia Free) or a smartphone app designed to help with symptoms of anxiety (Stress Free) for 12 weeks. Both apps were based on established cognitive behavioral principles.
• Assessment occurred at baseline, midpoint, and end point.
• The primary outcome was symptom severity as measured by the Panic and Agoraphobia Scale (PAS).

Outcomes

• Both groups experienced statistically significant improvements in symptom severity over time. The differences in PAS score were -5.97 (95% CI, -8.49 to -3.44, P < .001) for Agoraphobia Free and -6.35 (95% CI, -8.82 to -3.87, P < .001) for Stress Free.
• There were no significant between-group differences in symptom severity.

Continue to: Conclusions/limitations

• This study is the first RCT to show that patients with agoraphobia could benefit from mobile-based interventions.
• Limitations: There was no waitlist control group. Limited information was collected about participant characteristics; there were no data on comorbid disorders, other psychological or physiological treatments, or other demographic characteristics such as ethnicity or computer literacy.

3. Everitt N, Broadbent J, Richardson B, et al. Exploring the features of an app-based just-in-time intervention for depression. J Affect Disord. 2021;291:279-287. doi:10.1016/j.jad.2021.05.021

The apps MoodTracker, ImproveYourMood, and ImproveYourMood+ deliver content “just in time” (in response to acute negative symptoms) to help patients with depression. In an RCT, Everitt et al⁷ evaluated delivering acute care for depressive mood states via a smartphone app. They sought to delineate whether symptom improvement was due to microintervention content, mood augmentation, or just-in-time prompts to use content.

Study design

• Participants (N = 235) from the general population who said they wanted to improve their mood were randomly assigned to a waitlist control group (n = 55) or 1 of 3 intervention groups: MoodTracker (monitoring-only; n = 58), ImproveYourMood (monitoring and content; n = 62), or ImproveYourMood+ (monitoring, content, and prompts; n = 60).
• The microintervention content provided by these apps consisted of 4 audio files of brief (2- to 3-minute) mindfulness and relaxation exercises. Participants used the assigned app for 3 weeks.
• Depressive symptoms, anxiety symptoms, and negative automatic thoughts were assessed at baseline, immediately following the intervention, and 1 month after the intervention using the 9-item Patient Health Questionnaire (PHQ-9), 7-item GAD scale (GAD-7), and 8-item Automatic Thoughts Questionnaire, respectively.

Outcomes

• Compared to the waitlist control group, participants in the ImproveYourMood group showed greater declines in depressive symptoms and anxiety symptoms (at follow-up only), and negative automatic thoughts (at both postintervention and follow-up).
• Those in the ImproveYourMood+ group only showed significantly greater improvements for automatic negative thoughts (at postintervention).
• MoodTracker participants did not differ from waitlist controls for any variables at any timepoints.

Continue to: Conclusions/limitations

• This study suggests that using microinterventions in acute settings can effectively reduce depressive symptoms both as they occur, and 1 to 2 months later.
• Limitations: The study featured a naturalistic design, where participants self-selected whether they wanted to use the program. Participants did not complete eligibility assessments or receive compensation, and the study had high dropout rates, ranging from 20% for the waitlist control group to 67% for the ImproveYourMood+ group.

4. McLean C, Davis CA, Miller M, et al. The effects of an exposure-based mobile app on symptoms of posttraumatic stress disorder in veterans: pilot randomized controlled trial. JMIR Mhealth Uhealth. 2022;10(11):e38951. doi:10.2196/38951

Veterans with PTSD face barriers when receiving trauma-focused treatments such as exposure therapy or CBT. Smartphone apps may help veterans self-treat and self-manage their PTSD symptoms. McLean et al⁸ studied the efficacy of Renew, a smartphone app that uses exposure therapy and social support to treat PTSD.

Study design

• In this pilot RCT, 93 veterans with clinically significant PTSD symptoms were randomly assigned to use the Renew app with and without support from a research staff member (active use group) or to a waitlist (delayed use group) for 6 weeks.
• The PTSD Checklist for DSM-5 (PCL-5) was used to measure PTSD symptoms at preintervention, postintervention, and 6-week follow-up.
• Most participants (69%) were women, and the mean age was 49.

Outcomes

• Compared to the delayed use group, participants in the active use group experienced a larger decrease in PCL-5 score (-6.14 vs -1.84). However, this difference was not statistically significant (P = .29), and the effect size was small (d = -0.39).
• There was no difference in engagement with the app between participants who received support from a research staff member and those who did not receive such support.

Continue to: Conclusions/limitations

• Renew may show promise as a tool to reduce PTSD symptoms in veterans.
• Educating family and friends on how to best support a patient using a mobile mental health app may help improve the efficacy of Renew and increase app engagement.
• Limitations: Because the study was conducted in veterans, the results may not be generalizable to other populations. Because most data collection occurred during the first wave of the COVID-19 pandemic in the United States, COVID-19–related stress may have impacted PTSD symptoms, app engagement, or outcomes.

5. Graham AK, Greene CJ, Kwasny MJ, et al. Coached mobile app platform for the treatment of depression and anxiety among primary care patients: a randomized clinical trial. JAMA Psychiatry. 2020;77(9):906-914. doi:10.1001/jamapsychiatry.2020.1011

Many cases of depression and anxiety are initially treated in primary care settings. However, these settings may have limited resources and inadequate training, and mobile interventions might be helpful to augment patient care. Graham et al⁹ studied the mobile platform IntelliCare to determine its efficacy as a tool to be used in primary care settings to treat depression and anxiety.

Study design

• This RCT randomly assigned adult primary care patients (N = 146) who screened positive for depression on the PHQ-9 (score ≥10) or anxiety on the GAD-7 (score ≥8) to the coach-supported IntelliCare platform, which consisted of 5 clinically focused apps, or to a waitlist control group. Interventions were delivered over 8 weeks.
• Overall, 122 (83.6%) patients were diagnosed with depression and 131 (89.7%) were diagnosed with anxiety.
• The primary outcomes were changes in depression (as measured by change in PHQ-9 score) and anxiety (change in GAD-7 score) during the intervention period.

Outcomes

• Participants who used the IntelliCare platform had a greater reduction in depression and anxiety symptoms compared to waitlist controls, and changes were sustained over 2-month follow-up.
• The least square means (LSM) difference in depression scores at Week 4 was 2.91 (SE = 0.83; d = 0.43) and at Week 8 was 4.37 (SE = 0.83; d = 0.64). The LSM difference in anxiety scores at Week 4 was 2.51 (SE = 0.78; d = 0.41) and at Week 8 was 3.33 (SE = 0.76; d = 0.55).
• A median number of 93 and 98 sessions among participants with depression and anxiety were recorded, respectively, indicating high use of the IntelliCare platform.

Continue to: Conclusions/limitations

• The IntelliCare platform was shown to be effective in reducing depression and anxiety among primary care patients. Simple apps can be bundled together and used by patients in conjunction to treat their individual needs.
• Limitations: The study had a limited follow-up period and did not record participants’ use of other apps. Slightly more than one-half (56%) of participants were taking an antidepressant.

6. Wilhelm S, Weingarden H, Greenberg JL, et al. Efficacy of app-based cognitive behavioral therapy for body dysmorphic disorder with coach support: initial randomized controlled clinical trial. Psychother Psychosom. 2022;91(4):277-285. doi:10.1159/000524628

Body dysmorphic disorder (BDD) is a severe yet undertreated disorder. Apps can improve access to treatment for patients experiencing BDD. Wilhelm et al¹⁰ studied the usability and efficacy of a coach-supported app called Perspectives that was specifically designed for treating BDD. Perspectives provide CBT in 7 modules: psychoeducation, cognitive restructuring, exposure, response prevention, mindfulness, attention retraining, and relapse prevention.

Study design

• Adults (N = 80) with primary BDD were assigned to use the Perspectives app for 12 weeks or to a waitlist control group. Participants were predominately female (84%) and White (71%), with a mean age of 27.
• Coaches promoted engagement and answered questions via in-app messaging and phone calls.
• Blinded independent evaluators used the Yale-Brown Obsessive Compulsive Scale Modified for BDD (BDD-YBOCS) to measure BDD severity at baseline, midtreatment (Week 6), and end of treatment (Week 12).
• Secondary outcomes included BDD-related insight, depression, quality of life, and functioning. Various scales were used to measure these outcomes.

Outcomes

• In intent-to-treat analyses, patients who received CBT via the Perspectives app had significantly lower BDD severity at the end of treatment compared to the waitlist control group, with a mean (SD) BDD-YBOCS score of 16.8 (7.5) vs 26.7 (6.2), with P < .001 and d = 1.44.
• Slightly more than one-half (52%) of those who used Perspectives achieved full or partial remission, compared to 8% in the waitlist control group.

Continue to: Conclusions/limitations

• CBT delivered via the Perspectives app and a coach proved to be effective treatment for adults with BDD.
• Adoption of the application was relatively high; 86% of Perspectives users were very or mostly satisfied.
• Limitations: Because the participants in this study were predominantly female and White, the findings might not be generalizable to other populations.

7. Kuhn E, Miller KE, Puran D, et al. A pilot randomized controlled trial of the Insomnia Coach mobile app to assess its feasibility, acceptability, and potential efficacy. Behav Ther. 2022;53(3):440-457. doi:10.1016/j.beth.2021.11.003

Insomnia remains a substantial problem among military veterans. First-line treatments for the disorder are sleep hygiene modification and CBT. Access to CBT is limited, especially for veterans. Kuhn et al¹¹ studied the effectiveness of using Insomnia Coach, a CBT for insomnia–based app, to improve insomnia symptoms.

Study design

• Fifty US veterans who were mostly male (58%) with a mean age of 44.5 and moderate insomnia symptoms were randomized to use Insomnia Coach (n = 25) or to a waitlist control group (n = 25) for 6 weeks.
• All participants completed self-report measures and sleep diaries at baseline, posttreatment, and follow-up (12 weeks). Those who used the app (n = 15) completed a qualitative interview at posttreatment.

Outcomes

• At posttreatment, 28% of participants who used Insomnia Coach achieved clinically significant improvement, vs 4% of waitlist control participants. There was also a significant treatment effect on daytime sleep-related impairment (P = .044, d = -0.6).
• Additional treatment effects emerged at follow-up for insomnia severity, sleep onset latency, global sleep quality, and depression symptoms.
• Based on self-reports and qualitative interview responses, participants’ perceptions of Insomnia Coach were favorable. Three-fourths of participants used the app through 6 weeks and engaged with active elements.

Continue to: Conclusions/limitations

• Insomnia Coach may provide an accessible and convenient public health intervention for patients who aren’t receiving adequate care or CBT.
• Limitations: Because this study evaluated only veterans, the findings might not be generalizable to other populations.

8. Dahne J, Lejuez CW, Diaz VA, et al. Pilot randomized trial of a self-help behavioral activation mobile app for utilization in primary care. Behav Ther. 2019;50(4):817-827. doi:10.1016/j.beth.2018.12.003

Previous mobile technologies have shown the ability to treat depression in primary care settings. Moodivate is a self-help mobile app based on the Brief Behavioral Activation Treatment for Depression, which is an evidence-based treatment. This app is designed to help the user reengage in positive, nondepressed activities by identifying, scheduling, and completing activities. Dahne et al¹² investigated the feasibility and efficacy of Moodivate for depressive symptoms in primary care patients.

Study design

• Participants (N = 52) were recruited from primary care practices and randomized 2:2:1 to receive Moodivate, a CBT-based mobile app called MoodKit, or treatment as usual (no app). All participants had an initial PHQ-8 score >10.
• Participants completed assessments of depressive symptoms (PHQ-8) weekly for 8 weeks.
• App analytics data were captured to examine if the use of Moodivate was feasible. (Analytics were not available for MoodKit).

Outcomes

• Participants who used Moodivate had a mean (SD) of 46.76 (30.10) sessions throughout the trial, spent 3.50 (2.76) minutes using the app per session, and spent 120.76 (101.02) minutes using the app in total.
• Nearly 70% of Moodivate participants continued to use the app 1 month after trial enrollment and 50% at the end of the 8-week follow-up period.
• Compared to the treatment as usual group, participants who used Moodivate and those who used MoodKit experienced significant decreases in depressive symptoms over time.

Conclusions/limitations

• The results show that for primary care patients with depression, the use of Moodivate is feasible and may reduce depressive symptoms.
• Limitations: For the first 3 months of enrollment, patients who met diagnostic criteria for a current major depressive episode were excluded. This study did not assess duration of medication use (ie, whether a study participant was stabilized on medication or recently started taking a new medication) and therefore could not ascertain whether treatment gains were a result of the use of the app or of possible new medication use.