Sleep Medicine

Sleep apnea and other types of sleep disorders appear to elevate the risk for some types of cancer, specifically prostate cancer, more so than others. But the overall risk can be highly variable, and some sleep problems were found to be associated with a lower risk for cancer and cancer-related death, an analysis of a large observational cohort study of cardiovascular patients found.

Results of the analysis were published online in the journal Cancer Epidemiology. Investigators analyzed the presence of sleep apnea and insomnia and cancer risk in more than 8,500 patients in the Cardiovascular Health Study (CHS). “The fact that we observed certain sleep problems, like apneas, to be associated with elevated risk of some cancers but not others reflects the fact that cancer is a heterogeneous disease,” senior author Amanda Phipps, PhD, said in an interview. Dr. Phipps is an associate professor of epidemiology at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle.
 

Variable cancer links

The researchers assessed sleep problems in two groups in the CHS: an incident cancer group of 3,930 patients and a cancer mortality group of 4,580 patients. Within those respective groups, the investigators identified 885 first-incident cancers and 804 cancer deaths with a median follow-up of 12 and 14 years. The average age of the study population was 73 years, and 57% were women.

Sleep apnea symptoms (SAS) were associated with a lower risk for incident cancers – a 16% lower baseline risk and a 24% lower time-dependent risk. The study showed no association between cancer incidence and daytime sleepiness and apneas.

However, there was a significantly elevated risk relationship between sleep problems and prostate cancer. A time-dependent analysis of apnea showed more than double the risk (hazard ratio, 2.34), and baseline snoring carried a 69% greater risk. There was also a dose-response relationship for baseline cumulative SAS, compared with not having symptoms: an HR of 1.30 for one symptom, and 2.22 for two or more symptoms.

Risks for lymphatic or hematopoietic cancers were also associated with baseline daytime sleepiness (HR, 1.81), but not with insomnia (HR, 0.54).

With regard to cancer mortality, the study found no relationship between sleep problems and cancer death. In fact, it found an overall inverse relationship with snoring (time-dependent HR, 0.73; cumulative average HR, 0.67) and baseline apnea (HR, 0.69). Likewise, patients reporting SAS had lower risks than those having no SAS: an HR of 0.90 for one symptom and 0.75 for multiple symptoms. No relationships were found between any insomnia symptom and cancer death.

“We know the pathways that lead to prostate cancer can be very different than the pathways that lead to colorectal cancer,” Dr. Phipps said. “What we don’t yet understand is why these associations differ or what mechanisms are responsible for these cancer site-specific associations.”
 

Need for sleep assessment

The findings don’t change much for how clinicians should evaluate cancer risks in patients with sleep problems, Dr. Phipps said. “Other studies have clearly demonstrated the implications that sleep apnea has for a variety of other important health conditions – such as cardiovascular disease – so there are already plenty of good reasons for clinicians to ask their patients about their sleep and to connect patients with resources for the diagnosis and treatment of sleep apnea,” she added. “This study provides another possible reason.”

These findings provide context for future studies of the relationship between sleep problems and cancer. “But, given that sleep is something we all do and given that sleep problems are so pervasive, it’s important that we keep trying to better understand this relationship,” Dr. Phipps said.

“My hope is that future cancer studies will build in more detailed, longitudinal information on sleep patterns to help us fill current gaps in knowledge.”

Dr. Phipps has disclosed no relevant financial relationships.

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

Sleep apnea and other types of sleep disorders appear to elevate the risk for some types of cancer, specifically prostate cancer, more so than others. But the overall risk can be highly variable, and some sleep problems were found to be associated with a lower risk for cancer and cancer-related death, an analysis of a large observational cohort study of cardiovascular patients found.

Results of the analysis were published online in the journal Cancer Epidemiology. Investigators analyzed the presence of sleep apnea and insomnia and cancer risk in more than 8,500 patients in the Cardiovascular Health Study (CHS). “The fact that we observed certain sleep problems, like apneas, to be associated with elevated risk of some cancers but not others reflects the fact that cancer is a heterogeneous disease,” senior author Amanda Phipps, PhD, said in an interview. Dr. Phipps is an associate professor of epidemiology at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle.
 

Variable cancer links

The researchers assessed sleep problems in two groups in the CHS: an incident cancer group of 3,930 patients and a cancer mortality group of 4,580 patients. Within those respective groups, the investigators identified 885 first-incident cancers and 804 cancer deaths with a median follow-up of 12 and 14 years. The average age of the study population was 73 years, and 57% were women.

Sleep apnea symptoms (SAS) were associated with a lower risk for incident cancers – a 16% lower baseline risk and a 24% lower time-dependent risk. The study showed no association between cancer incidence and daytime sleepiness and apneas.

However, there was a significantly elevated risk relationship between sleep problems and prostate cancer. A time-dependent analysis of apnea showed more than double the risk (hazard ratio, 2.34), and baseline snoring carried a 69% greater risk. There was also a dose-response relationship for baseline cumulative SAS, compared with not having symptoms: an HR of 1.30 for one symptom, and 2.22 for two or more symptoms.

Risks for lymphatic or hematopoietic cancers were also associated with baseline daytime sleepiness (HR, 1.81), but not with insomnia (HR, 0.54).

With regard to cancer mortality, the study found no relationship between sleep problems and cancer death. In fact, it found an overall inverse relationship with snoring (time-dependent HR, 0.73; cumulative average HR, 0.67) and baseline apnea (HR, 0.69). Likewise, patients reporting SAS had lower risks than those having no SAS: an HR of 0.90 for one symptom and 0.75 for multiple symptoms. No relationships were found between any insomnia symptom and cancer death.

“We know the pathways that lead to prostate cancer can be very different than the pathways that lead to colorectal cancer,” Dr. Phipps said. “What we don’t yet understand is why these associations differ or what mechanisms are responsible for these cancer site-specific associations.”
 

Need for sleep assessment

The findings don’t change much for how clinicians should evaluate cancer risks in patients with sleep problems, Dr. Phipps said. “Other studies have clearly demonstrated the implications that sleep apnea has for a variety of other important health conditions – such as cardiovascular disease – so there are already plenty of good reasons for clinicians to ask their patients about their sleep and to connect patients with resources for the diagnosis and treatment of sleep apnea,” she added. “This study provides another possible reason.”

These findings provide context for future studies of the relationship between sleep problems and cancer. “But, given that sleep is something we all do and given that sleep problems are so pervasive, it’s important that we keep trying to better understand this relationship,” Dr. Phipps said.

“My hope is that future cancer studies will build in more detailed, longitudinal information on sleep patterns to help us fill current gaps in knowledge.”

Dr. Phipps has disclosed no relevant financial relationships.

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

Sleep apnea and other types of sleep disorders appear to elevate the risk for some types of cancer, specifically prostate cancer, more so than others. But the overall risk can be highly variable, and some sleep problems were found to be associated with a lower risk for cancer and cancer-related death, an analysis of a large observational cohort study of cardiovascular patients found.

Results of the analysis were published online in the journal Cancer Epidemiology. Investigators analyzed the presence of sleep apnea and insomnia and cancer risk in more than 8,500 patients in the Cardiovascular Health Study (CHS). “The fact that we observed certain sleep problems, like apneas, to be associated with elevated risk of some cancers but not others reflects the fact that cancer is a heterogeneous disease,” senior author Amanda Phipps, PhD, said in an interview. Dr. Phipps is an associate professor of epidemiology at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle.
 

Variable cancer links

The researchers assessed sleep problems in two groups in the CHS: an incident cancer group of 3,930 patients and a cancer mortality group of 4,580 patients. Within those respective groups, the investigators identified 885 first-incident cancers and 804 cancer deaths with a median follow-up of 12 and 14 years. The average age of the study population was 73 years, and 57% were women.

Sleep apnea symptoms (SAS) were associated with a lower risk for incident cancers – a 16% lower baseline risk and a 24% lower time-dependent risk. The study showed no association between cancer incidence and daytime sleepiness and apneas.

However, there was a significantly elevated risk relationship between sleep problems and prostate cancer. A time-dependent analysis of apnea showed more than double the risk (hazard ratio, 2.34), and baseline snoring carried a 69% greater risk. There was also a dose-response relationship for baseline cumulative SAS, compared with not having symptoms: an HR of 1.30 for one symptom, and 2.22 for two or more symptoms.

Risks for lymphatic or hematopoietic cancers were also associated with baseline daytime sleepiness (HR, 1.81), but not with insomnia (HR, 0.54).

With regard to cancer mortality, the study found no relationship between sleep problems and cancer death. In fact, it found an overall inverse relationship with snoring (time-dependent HR, 0.73; cumulative average HR, 0.67) and baseline apnea (HR, 0.69). Likewise, patients reporting SAS had lower risks than those having no SAS: an HR of 0.90 for one symptom and 0.75 for multiple symptoms. No relationships were found between any insomnia symptom and cancer death.

“We know the pathways that lead to prostate cancer can be very different than the pathways that lead to colorectal cancer,” Dr. Phipps said. “What we don’t yet understand is why these associations differ or what mechanisms are responsible for these cancer site-specific associations.”
 

Need for sleep assessment

The findings don’t change much for how clinicians should evaluate cancer risks in patients with sleep problems, Dr. Phipps said. “Other studies have clearly demonstrated the implications that sleep apnea has for a variety of other important health conditions – such as cardiovascular disease – so there are already plenty of good reasons for clinicians to ask their patients about their sleep and to connect patients with resources for the diagnosis and treatment of sleep apnea,” she added. “This study provides another possible reason.”

These findings provide context for future studies of the relationship between sleep problems and cancer. “But, given that sleep is something we all do and given that sleep problems are so pervasive, it’s important that we keep trying to better understand this relationship,” Dr. Phipps said.

“My hope is that future cancer studies will build in more detailed, longitudinal information on sleep patterns to help us fill current gaps in knowledge.”

Dr. Phipps has disclosed no relevant financial relationships.

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

Going to bed later than usual and/or getting a poor night’s sleep are both associated with impaired glycemic response to breakfast the following morning in healthy adults, according to a multiple test-meal challenge study conducted over 14 days.

“Our data suggest that sleep duration, efficiency, and midpoint are important determinants of postprandial glycemic control at a population level,” Neil Tsereteli, MD, Lund University Diabetes Centre, Malmo, Sweden, and colleagues wrote in their article, published online Nov. 30, 2021, in Diabetologia.

“And [the results] suggest that one-size-fits-all sleep recommendations are suboptimal, particularly in the context of postprandial glycemic control, a key component of diabetes prevention,” they added.
 

Prior research on sleep quality and control of glucose lacking

Diet, exercise, and sleep are fundamental components of a healthy lifestyle; however, the role that sleep plays in affecting blood glucose control in generally healthy people has been studied little so far, the researchers wrote.

Sleep disorders can act as a measure of general health as they often occur alongside other health problems. Sleep quality also has a direct causal effect on many conditions such as cardiovascular disease, obesity, and type 2 diabetes. And disturbed sleep caused by conditions such as obstructive sleep apnea is associated with the prevalence of type 2 diabetes and risk of associated complications.

This and other evidence suggest a strong link between glucose regulation and the quality and duration of sleep.

Dr. Tsereteli and colleagues set out to examine this further in the Personalized Responses to Dietary Composition Trial 1, which involved 953 healthy adults who consumed standardized meals over 2 weeks in a clinic setting and at home.

“The meals were consumed either for breakfast or lunch in a randomized meal order and consisted of eight different standardized meals,”  the researchers wrote.

Activity and sleep were monitored using a wearable device with an accelerometer. Postprandial blood glucose levels were measured using a continuous glucose monitor.

Sleep variables including quality, duration, and timing and their impact on glycemic response to breakfast the following morning, and were compared between participants and within each individual.
 

Better sleep efficiency, better glucose control

The study found that, although there was no significant association between length of sleep period and postmeal glycemic response, there was a significant interaction when the nutritional content of the breakfast meal was also considered.

Longer sleep periods were associated with lower blood glucose following high-carbohydrate and high-fat breakfasts, indicating better blood glucose control.

Additionally, the researchers observed a within-person effect in which a study participant who slept for longer than they typically would was likely to have reduced postprandial blood glucose following a high-carbohydrate or high-fat breakfast the next day.

The authors also found a significant link between sleep efficiency (ratio of time asleep to total length of sleep period) and glycemic control. When a participant slept more efficiently than usual, their postprandial blood glucose also tended to be lower than usual.

“This effect was largely driven by sleep onset (going to bed later) rather than sleep offset (waking up later),” Dr. Tsereteli and colleagues noted.
 

Sleep a key pillar of health

Asked whether these particular sleep effects might be exacerbated in patients with diabetes, senior author Paul Franks, MD, also from the Lund University Diabetes Centre, felt they could not meaningfully extrapolate results to people with diabetes, given that many take glucose-lowering medications.

“However, it is likely that these results would be similar or exacerbated in people with prediabetes, as glucose fluctuations in this subgroup of patients are generally greater than in people with normoglycemia,” he noted in an interview.

“Sleep is a key pillar of health, and focusing on both sleep and diet is key for healthy blood glucose control,” he added.

“Compensating for a bad night’s sleep by consuming a very sugary breakfast or energy drinks is likely to be especially detrimental for blood glucose control,” Dr. Franks said.

The study was funded by Lund University. Dr. Tsereteli and Dr. Franks reported no relevant financial relationships.

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

Going to bed later than usual and/or getting a poor night’s sleep are both associated with impaired glycemic response to breakfast the following morning in healthy adults, according to a multiple test-meal challenge study conducted over 14 days.

“Our data suggest that sleep duration, efficiency, and midpoint are important determinants of postprandial glycemic control at a population level,” Neil Tsereteli, MD, Lund University Diabetes Centre, Malmo, Sweden, and colleagues wrote in their article, published online Nov. 30, 2021, in Diabetologia.

“And [the results] suggest that one-size-fits-all sleep recommendations are suboptimal, particularly in the context of postprandial glycemic control, a key component of diabetes prevention,” they added.
 

Prior research on sleep quality and control of glucose lacking

Diet, exercise, and sleep are fundamental components of a healthy lifestyle; however, the role that sleep plays in affecting blood glucose control in generally healthy people has been studied little so far, the researchers wrote.

Sleep disorders can act as a measure of general health as they often occur alongside other health problems. Sleep quality also has a direct causal effect on many conditions such as cardiovascular disease, obesity, and type 2 diabetes. And disturbed sleep caused by conditions such as obstructive sleep apnea is associated with the prevalence of type 2 diabetes and risk of associated complications.

This and other evidence suggest a strong link between glucose regulation and the quality and duration of sleep.

Dr. Tsereteli and colleagues set out to examine this further in the Personalized Responses to Dietary Composition Trial 1, which involved 953 healthy adults who consumed standardized meals over 2 weeks in a clinic setting and at home.

“The meals were consumed either for breakfast or lunch in a randomized meal order and consisted of eight different standardized meals,”  the researchers wrote.

Activity and sleep were monitored using a wearable device with an accelerometer. Postprandial blood glucose levels were measured using a continuous glucose monitor.

Sleep variables including quality, duration, and timing and their impact on glycemic response to breakfast the following morning, and were compared between participants and within each individual.
 

Better sleep efficiency, better glucose control

The study found that, although there was no significant association between length of sleep period and postmeal glycemic response, there was a significant interaction when the nutritional content of the breakfast meal was also considered.

Longer sleep periods were associated with lower blood glucose following high-carbohydrate and high-fat breakfasts, indicating better blood glucose control.

Additionally, the researchers observed a within-person effect in which a study participant who slept for longer than they typically would was likely to have reduced postprandial blood glucose following a high-carbohydrate or high-fat breakfast the next day.

The authors also found a significant link between sleep efficiency (ratio of time asleep to total length of sleep period) and glycemic control. When a participant slept more efficiently than usual, their postprandial blood glucose also tended to be lower than usual.

“This effect was largely driven by sleep onset (going to bed later) rather than sleep offset (waking up later),” Dr. Tsereteli and colleagues noted.
 

Sleep a key pillar of health

Asked whether these particular sleep effects might be exacerbated in patients with diabetes, senior author Paul Franks, MD, also from the Lund University Diabetes Centre, felt they could not meaningfully extrapolate results to people with diabetes, given that many take glucose-lowering medications.

“However, it is likely that these results would be similar or exacerbated in people with prediabetes, as glucose fluctuations in this subgroup of patients are generally greater than in people with normoglycemia,” he noted in an interview.

“Sleep is a key pillar of health, and focusing on both sleep and diet is key for healthy blood glucose control,” he added.

“Compensating for a bad night’s sleep by consuming a very sugary breakfast or energy drinks is likely to be especially detrimental for blood glucose control,” Dr. Franks said.

The study was funded by Lund University. Dr. Tsereteli and Dr. Franks reported no relevant financial relationships.

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

Going to bed later than usual and/or getting a poor night’s sleep are both associated with impaired glycemic response to breakfast the following morning in healthy adults, according to a multiple test-meal challenge study conducted over 14 days.

“Our data suggest that sleep duration, efficiency, and midpoint are important determinants of postprandial glycemic control at a population level,” Neil Tsereteli, MD, Lund University Diabetes Centre, Malmo, Sweden, and colleagues wrote in their article, published online Nov. 30, 2021, in Diabetologia.

“And [the results] suggest that one-size-fits-all sleep recommendations are suboptimal, particularly in the context of postprandial glycemic control, a key component of diabetes prevention,” they added.
 

Prior research on sleep quality and control of glucose lacking

Diet, exercise, and sleep are fundamental components of a healthy lifestyle; however, the role that sleep plays in affecting blood glucose control in generally healthy people has been studied little so far, the researchers wrote.

Sleep disorders can act as a measure of general health as they often occur alongside other health problems. Sleep quality also has a direct causal effect on many conditions such as cardiovascular disease, obesity, and type 2 diabetes. And disturbed sleep caused by conditions such as obstructive sleep apnea is associated with the prevalence of type 2 diabetes and risk of associated complications.

This and other evidence suggest a strong link between glucose regulation and the quality and duration of sleep.

Dr. Tsereteli and colleagues set out to examine this further in the Personalized Responses to Dietary Composition Trial 1, which involved 953 healthy adults who consumed standardized meals over 2 weeks in a clinic setting and at home.

“The meals were consumed either for breakfast or lunch in a randomized meal order and consisted of eight different standardized meals,”  the researchers wrote.

Activity and sleep were monitored using a wearable device with an accelerometer. Postprandial blood glucose levels were measured using a continuous glucose monitor.

Sleep variables including quality, duration, and timing and their impact on glycemic response to breakfast the following morning, and were compared between participants and within each individual.
 

Better sleep efficiency, better glucose control

The study found that, although there was no significant association between length of sleep period and postmeal glycemic response, there was a significant interaction when the nutritional content of the breakfast meal was also considered.

Longer sleep periods were associated with lower blood glucose following high-carbohydrate and high-fat breakfasts, indicating better blood glucose control.

Additionally, the researchers observed a within-person effect in which a study participant who slept for longer than they typically would was likely to have reduced postprandial blood glucose following a high-carbohydrate or high-fat breakfast the next day.

The authors also found a significant link between sleep efficiency (ratio of time asleep to total length of sleep period) and glycemic control. When a participant slept more efficiently than usual, their postprandial blood glucose also tended to be lower than usual.

“This effect was largely driven by sleep onset (going to bed later) rather than sleep offset (waking up later),” Dr. Tsereteli and colleagues noted.
 

Sleep a key pillar of health

Asked whether these particular sleep effects might be exacerbated in patients with diabetes, senior author Paul Franks, MD, also from the Lund University Diabetes Centre, felt they could not meaningfully extrapolate results to people with diabetes, given that many take glucose-lowering medications.

“However, it is likely that these results would be similar or exacerbated in people with prediabetes, as glucose fluctuations in this subgroup of patients are generally greater than in people with normoglycemia,” he noted in an interview.

“Sleep is a key pillar of health, and focusing on both sleep and diet is key for healthy blood glucose control,” he added.

“Compensating for a bad night’s sleep by consuming a very sugary breakfast or energy drinks is likely to be especially detrimental for blood glucose control,” Dr. Franks said.

The study was funded by Lund University. Dr. Tsereteli and Dr. Franks reported no relevant financial relationships.

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

Cognitive-behavioral therapy (CBT) is linked to a significantly reduced risk of depression in patients with insomnia, new research shows.

Insomnia affects over 50% of older adults, and insomnia contributes to a twofold greater risk for major depression, investigators noted.

“We show that by treating insomnia with a simple behavioral approach called Cognitive Behavioral Therapy for Insomnia, or CBT-I, you can reduce the likelihood of developing depression by over 50%,” lead author Michael R. Irwin, MD, Cousins Distinguished Professor of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, said in an interview.

The study is unique in that the treatment “is not just reducing depression, it’s preventing depression,” Dr. Irwin added.

The findings were published online Nov. 24 in JAMA Psychiatry.
 

Primary outcome met

The study included 291 patients aged 60 years and older (mean age, 70 years; 58% women) with confirmed insomnia disorder and no major depression within the previous 12 months.

All were randomly assigned to receive either CBT-I or Sleep Education Therapy (SET).

CBT-I is a first-line treatment for insomnia that includes five components: cognitive therapy targeting dysfunctional thoughts about sleep, stimulus control, sleep restriction, sleep hygiene, and relaxation.

SET provides information on behavioral and environmental factors contributing to poor sleep. While sleep education provides tips on improving sleep, CBT-I helps patients implement those changes and behaviors, Dr. Irwin noted.

Both interventions were delivered by trained personnel in weekly 120-minute group sessions for 2 months, consistent with the format and duration of most CBT-I trials.

The primary outcome was time to incident or recurrent major depressive disorder as diagnosed by the Structured Clinical Interview of the DSM-5 every 6 months during 36 months of follow-up. A monthly Patient Health Questionnaire 9 (PHQ-9) was used to screen for depressive symptoms.

Results showed depression occurred in 12.2% of the CBT-I group versus 25.9% of the SET group. The hazard ratio (HR) for depression in the CBT-I group compared with the SET group was 0.51 (95% confidence interval, 0.29-0.88; P = .02). The number needed to treat to prevent incident or recurrent depression was 7.3.

After adjustment for factors affecting depression risk such as sex, educational level, income, comorbidity, and history of depression, the HR for depression in the CBT-I group versus the SET group was 0.45 (95% CI, 0.23-0.86; P = .02).

Treatment with CBT-I yielded an annual 4.1% incidence of depression, which is similar to the population rate and half the rate in SET, which was 8.6%.
 

‘Remission is key’

The secondary outcome was sustained remission of insomnia disorder. The investigators found a greater proportion of the CBT-I group than the SET group achieved remission after treatment (50.7% vs. 37.7%; 95% CI, 0.10-0.93; P = .02).

“Remission is really key to the benefits that we’re seeing,” said Dr. Irwin.

Inflammation may explain why insomnia raises the risk for depression, he noted. “We know sleep disturbance can lead to inflammation and we also know inflammation can produce depression,” Dr. Irwin said.

It is also possible insomnia leads to an impaired pleasure or reward system, which is linked to depression, he added.

The authors noted that because insomnia is associated with suicidal ideation and dementia, CBT-I may reduce risk for suicide or cognitive decline.

While 8-week CBT-I treatments are readily available, “unfortunately, most clinicians will prescribe medications,” said Dr. Irwin. He noted that in older adults, drugs are linked to adverse events such as falls and cognitive problems.

These new results “really argue that psychology and psychiatry need to be fully integrated into what we call collaborative care models,” Dr. Irwin said.

There were no adverse events during treatment, and none of the serious events that occurred during follow-up were attributed to the trial.
 

Convincing argument?

Commenting on the findings for this news organization, Philip R. Muskin, MD, professor of psychiatry at Columbia University Irving Medical Center, New York, said the study was “nicely written” and the authors put forward “a very convincing argument” for CBT-I to prevent depression.

“It’s eye opening in that it’s a robust study; it’s carefully done; subjects were followed for a long period of time, and it’s an accessible treatment,” said Dr. Muskin, who was not involved with the research.

The study also shows “it’s possible to intervene in something we know is a risk factor in elderly people,” he added. “We think of older people as being less malleable to these kinds of things, but they’re not. They clearly participated, and there wasn’t a huge dropout rate.”

Dr. Muskin noted that less than half of the older participants were married or had a partner. He would have liked more information on this status because being widowed or divorced, as well as when this life change occurred, could affect vulnerability to depression.

The authors of an accompanying editorial called the study “seminal,” and noted that insomnia treatment possibly preventing depressive disorders is a “major finding.”

Proving this preventive strategy is effective in older adults will be important because “insomnia and depression are highly prevalent in this population and the uptake of both preventive and treatment services is low,” wrote Pim Cuijpers, PhD, department of clinical, neuro, and developmental psychology, Amsterdam Public Health Research Institute, and Charles F. Reynolds III, MD, department of psychiatry, University of Pittsburgh.

If the reduced rates of depression observed in the study could be generalized to the total population with insomnia, “the incidence of major depression could be reduced considerably,” they wrote.

“Can we prevent depression through interventions aimed at procrastination in college students, interventions aimed at perfectionism in perinatal women, stress management training for employees, social skills training in adolescents?” they asked.

This approach to preventing depressive disorders “offers all kinds of new opportunities to develop and test indirect interventions” for problems that are significantly associated with the onset of depression, the editorialists wrote.

The study was funded by a grant from the National Institute on Aging to the University of California, which partially supported the authors’ salaries. Dr. Irwin, Dr. Muskin, and Dr. Cuijpers have reported no relevant financial relationships. Dr. Reynolds reported being coinventor of the Pittsburgh Sleep Quality Index, for which he receives royalties.

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

Cognitive-behavioral therapy (CBT) is linked to a significantly reduced risk of depression in patients with insomnia, new research shows.

Insomnia affects over 50% of older adults, and insomnia contributes to a twofold greater risk for major depression, investigators noted.

“We show that by treating insomnia with a simple behavioral approach called Cognitive Behavioral Therapy for Insomnia, or CBT-I, you can reduce the likelihood of developing depression by over 50%,” lead author Michael R. Irwin, MD, Cousins Distinguished Professor of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, said in an interview.

The study is unique in that the treatment “is not just reducing depression, it’s preventing depression,” Dr. Irwin added.

The findings were published online Nov. 24 in JAMA Psychiatry.
 

Primary outcome met

The study included 291 patients aged 60 years and older (mean age, 70 years; 58% women) with confirmed insomnia disorder and no major depression within the previous 12 months.

All were randomly assigned to receive either CBT-I or Sleep Education Therapy (SET).

CBT-I is a first-line treatment for insomnia that includes five components: cognitive therapy targeting dysfunctional thoughts about sleep, stimulus control, sleep restriction, sleep hygiene, and relaxation.

SET provides information on behavioral and environmental factors contributing to poor sleep. While sleep education provides tips on improving sleep, CBT-I helps patients implement those changes and behaviors, Dr. Irwin noted.

Both interventions were delivered by trained personnel in weekly 120-minute group sessions for 2 months, consistent with the format and duration of most CBT-I trials.

The primary outcome was time to incident or recurrent major depressive disorder as diagnosed by the Structured Clinical Interview of the DSM-5 every 6 months during 36 months of follow-up. A monthly Patient Health Questionnaire 9 (PHQ-9) was used to screen for depressive symptoms.

Results showed depression occurred in 12.2% of the CBT-I group versus 25.9% of the SET group. The hazard ratio (HR) for depression in the CBT-I group compared with the SET group was 0.51 (95% confidence interval, 0.29-0.88; P = .02). The number needed to treat to prevent incident or recurrent depression was 7.3.

After adjustment for factors affecting depression risk such as sex, educational level, income, comorbidity, and history of depression, the HR for depression in the CBT-I group versus the SET group was 0.45 (95% CI, 0.23-0.86; P = .02).

Treatment with CBT-I yielded an annual 4.1% incidence of depression, which is similar to the population rate and half the rate in SET, which was 8.6%.
 

‘Remission is key’

The secondary outcome was sustained remission of insomnia disorder. The investigators found a greater proportion of the CBT-I group than the SET group achieved remission after treatment (50.7% vs. 37.7%; 95% CI, 0.10-0.93; P = .02).

“Remission is really key to the benefits that we’re seeing,” said Dr. Irwin.

Inflammation may explain why insomnia raises the risk for depression, he noted. “We know sleep disturbance can lead to inflammation and we also know inflammation can produce depression,” Dr. Irwin said.

It is also possible insomnia leads to an impaired pleasure or reward system, which is linked to depression, he added.

The authors noted that because insomnia is associated with suicidal ideation and dementia, CBT-I may reduce risk for suicide or cognitive decline.

While 8-week CBT-I treatments are readily available, “unfortunately, most clinicians will prescribe medications,” said Dr. Irwin. He noted that in older adults, drugs are linked to adverse events such as falls and cognitive problems.

These new results “really argue that psychology and psychiatry need to be fully integrated into what we call collaborative care models,” Dr. Irwin said.

There were no adverse events during treatment, and none of the serious events that occurred during follow-up were attributed to the trial.
 

Convincing argument?

Commenting on the findings for this news organization, Philip R. Muskin, MD, professor of psychiatry at Columbia University Irving Medical Center, New York, said the study was “nicely written” and the authors put forward “a very convincing argument” for CBT-I to prevent depression.

“It’s eye opening in that it’s a robust study; it’s carefully done; subjects were followed for a long period of time, and it’s an accessible treatment,” said Dr. Muskin, who was not involved with the research.

The study also shows “it’s possible to intervene in something we know is a risk factor in elderly people,” he added. “We think of older people as being less malleable to these kinds of things, but they’re not. They clearly participated, and there wasn’t a huge dropout rate.”

Dr. Muskin noted that less than half of the older participants were married or had a partner. He would have liked more information on this status because being widowed or divorced, as well as when this life change occurred, could affect vulnerability to depression.

The authors of an accompanying editorial called the study “seminal,” and noted that insomnia treatment possibly preventing depressive disorders is a “major finding.”

Proving this preventive strategy is effective in older adults will be important because “insomnia and depression are highly prevalent in this population and the uptake of both preventive and treatment services is low,” wrote Pim Cuijpers, PhD, department of clinical, neuro, and developmental psychology, Amsterdam Public Health Research Institute, and Charles F. Reynolds III, MD, department of psychiatry, University of Pittsburgh.

If the reduced rates of depression observed in the study could be generalized to the total population with insomnia, “the incidence of major depression could be reduced considerably,” they wrote.

“Can we prevent depression through interventions aimed at procrastination in college students, interventions aimed at perfectionism in perinatal women, stress management training for employees, social skills training in adolescents?” they asked.

This approach to preventing depressive disorders “offers all kinds of new opportunities to develop and test indirect interventions” for problems that are significantly associated with the onset of depression, the editorialists wrote.

The study was funded by a grant from the National Institute on Aging to the University of California, which partially supported the authors’ salaries. Dr. Irwin, Dr. Muskin, and Dr. Cuijpers have reported no relevant financial relationships. Dr. Reynolds reported being coinventor of the Pittsburgh Sleep Quality Index, for which he receives royalties.

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

Cognitive-behavioral therapy (CBT) is linked to a significantly reduced risk of depression in patients with insomnia, new research shows.

Insomnia affects over 50% of older adults, and insomnia contributes to a twofold greater risk for major depression, investigators noted.

“We show that by treating insomnia with a simple behavioral approach called Cognitive Behavioral Therapy for Insomnia, or CBT-I, you can reduce the likelihood of developing depression by over 50%,” lead author Michael R. Irwin, MD, Cousins Distinguished Professor of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, said in an interview.

The study is unique in that the treatment “is not just reducing depression, it’s preventing depression,” Dr. Irwin added.

The findings were published online Nov. 24 in JAMA Psychiatry.
 

Primary outcome met

The study included 291 patients aged 60 years and older (mean age, 70 years; 58% women) with confirmed insomnia disorder and no major depression within the previous 12 months.

All were randomly assigned to receive either CBT-I or Sleep Education Therapy (SET).

CBT-I is a first-line treatment for insomnia that includes five components: cognitive therapy targeting dysfunctional thoughts about sleep, stimulus control, sleep restriction, sleep hygiene, and relaxation.

SET provides information on behavioral and environmental factors contributing to poor sleep. While sleep education provides tips on improving sleep, CBT-I helps patients implement those changes and behaviors, Dr. Irwin noted.

Both interventions were delivered by trained personnel in weekly 120-minute group sessions for 2 months, consistent with the format and duration of most CBT-I trials.

The primary outcome was time to incident or recurrent major depressive disorder as diagnosed by the Structured Clinical Interview of the DSM-5 every 6 months during 36 months of follow-up. A monthly Patient Health Questionnaire 9 (PHQ-9) was used to screen for depressive symptoms.

Results showed depression occurred in 12.2% of the CBT-I group versus 25.9% of the SET group. The hazard ratio (HR) for depression in the CBT-I group compared with the SET group was 0.51 (95% confidence interval, 0.29-0.88; P = .02). The number needed to treat to prevent incident or recurrent depression was 7.3.

After adjustment for factors affecting depression risk such as sex, educational level, income, comorbidity, and history of depression, the HR for depression in the CBT-I group versus the SET group was 0.45 (95% CI, 0.23-0.86; P = .02).

Treatment with CBT-I yielded an annual 4.1% incidence of depression, which is similar to the population rate and half the rate in SET, which was 8.6%.
 

‘Remission is key’

The secondary outcome was sustained remission of insomnia disorder. The investigators found a greater proportion of the CBT-I group than the SET group achieved remission after treatment (50.7% vs. 37.7%; 95% CI, 0.10-0.93; P = .02).

“Remission is really key to the benefits that we’re seeing,” said Dr. Irwin.

Inflammation may explain why insomnia raises the risk for depression, he noted. “We know sleep disturbance can lead to inflammation and we also know inflammation can produce depression,” Dr. Irwin said.

It is also possible insomnia leads to an impaired pleasure or reward system, which is linked to depression, he added.

The authors noted that because insomnia is associated with suicidal ideation and dementia, CBT-I may reduce risk for suicide or cognitive decline.

While 8-week CBT-I treatments are readily available, “unfortunately, most clinicians will prescribe medications,” said Dr. Irwin. He noted that in older adults, drugs are linked to adverse events such as falls and cognitive problems.

These new results “really argue that psychology and psychiatry need to be fully integrated into what we call collaborative care models,” Dr. Irwin said.

There were no adverse events during treatment, and none of the serious events that occurred during follow-up were attributed to the trial.
 

Convincing argument?

Commenting on the findings for this news organization, Philip R. Muskin, MD, professor of psychiatry at Columbia University Irving Medical Center, New York, said the study was “nicely written” and the authors put forward “a very convincing argument” for CBT-I to prevent depression.

“It’s eye opening in that it’s a robust study; it’s carefully done; subjects were followed for a long period of time, and it’s an accessible treatment,” said Dr. Muskin, who was not involved with the research.

The study also shows “it’s possible to intervene in something we know is a risk factor in elderly people,” he added. “We think of older people as being less malleable to these kinds of things, but they’re not. They clearly participated, and there wasn’t a huge dropout rate.”

Dr. Muskin noted that less than half of the older participants were married or had a partner. He would have liked more information on this status because being widowed or divorced, as well as when this life change occurred, could affect vulnerability to depression.

The authors of an accompanying editorial called the study “seminal,” and noted that insomnia treatment possibly preventing depressive disorders is a “major finding.”

Proving this preventive strategy is effective in older adults will be important because “insomnia and depression are highly prevalent in this population and the uptake of both preventive and treatment services is low,” wrote Pim Cuijpers, PhD, department of clinical, neuro, and developmental psychology, Amsterdam Public Health Research Institute, and Charles F. Reynolds III, MD, department of psychiatry, University of Pittsburgh.

If the reduced rates of depression observed in the study could be generalized to the total population with insomnia, “the incidence of major depression could be reduced considerably,” they wrote.

“Can we prevent depression through interventions aimed at procrastination in college students, interventions aimed at perfectionism in perinatal women, stress management training for employees, social skills training in adolescents?” they asked.

This approach to preventing depressive disorders “offers all kinds of new opportunities to develop and test indirect interventions” for problems that are significantly associated with the onset of depression, the editorialists wrote.

The study was funded by a grant from the National Institute on Aging to the University of California, which partially supported the authors’ salaries. Dr. Irwin, Dr. Muskin, and Dr. Cuijpers have reported no relevant financial relationships. Dr. Reynolds reported being coinventor of the Pittsburgh Sleep Quality Index, for which he receives royalties.

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

A growing trend of off-label, low-dose antipsychotic prescribing to treat disorders such as anxiety and insomnia has been tied to an increased risk of cardiometabolic death, new research shows.

Investigators studied data from large Swedish registries on over 420,000 individuals without previous psychotic, bipolar, or cardiometabolic disorders and found that off-label treatment with olanzapine or quetiapine for 6 to 12 months – even at a low dose – was associated with an almost twofold higher risk of cardiometabolic mortality, compared to no treatment. The risk remained elevated after 12 months, but the finding was not deemed significant.

“Clinicians should be made aware that low-dose treatment with these drugs is probably not a harmless choice for insomnia and anxiety, and while they have the benefit of not being addictive and [are] seemingly effective, they might come at a cost of shortening patients’ life span,” study investigator Jonas Berge, MD, PhD, associate professor and resident psychiatrist, Lund University, Sweden, said in an interview.

“Clinicians should take this information into account when prescribing the drugs and also monitor the patients with regular physical examinations and blood tests in the same way as when treating patients with psychosis with higher doses of these drugs,” he said.

The study was published online Nov. 9 in the Journal of Psychiatric Research.
 

A growing trend

Use of low-dose antipsychotics to treat a variety of psychiatric and behavioral disturbances, including anxiety, insomnia, and agitation, has “surged in popularity,” the authors wrote.

Quetiapine and olanzapine “rank as two of the most frequently prescribed second-generation antipsychotics and, next to clozapine, are considered to exhort the highest risk for cardiometabolic sequelae, including components of metabolic syndrome,” they added.

Previous research examining the association between second-generation antipsychotics and placebo has either not focused on cardiometabolic-specific causes or has examined only cohorts with severe mental illness, so those findings “do not necessarily generalize to others treated off-label,” they noted.

“The motivation for the study came from my work as a psychiatrist, in which I’ve noticed that the off-label use of these medications [olanzapine and quetiapine] for anxiety and insomnia seems highly prevalent, and that many patients seem to gain a lot of weight, despite low doses,” Dr. Berge said.

There is “evidence to suggest that clinicians may underappreciate cardiometabolic risks owing to antipsychotic treatment, as routine screening is often incomplete or inconsistent,” the authors noted.

“To do a risk-benefit analysis of these drugs in low doses, the risks involved – as well as the effects, of course – need to be studied,” Dr. Berge stated.

To investigate the question, the researchers turned to three large cross-linked Swedish registers: the National Patient Register, containing demographic and medical data; the Prescribed Drug Register; and the Cause of Death Register.

They identified all individuals aged 18 years and older with at least one psychiatric visit (inpatient or outpatient) between July 1, 2006, and Dec. 31, 2016, to see how many were prescribed low-dose olanzapine or quetiapine (defined as ≤ 5 mg/day of olanzapine or olanzapine equivalent [OE]), which was used as a proxy marker for off-label treatment, since this dose is considered subtherapeutic for severe mental illness.

They calculated two time-dependent variables – cumulative dose and past annual average dose – and then used those to compute three different exposure valuables: those treated with low-dose OE; cumulative exposure (i.e., period treated with an average 5 mg/day); and a continuous variable “corresponding to each year exposed OE 5 mg/day.”

The primary outcome was set as mortality from cardiometabolic-related disorders, while secondary outcomes were disease-specific and all-cause mortality.
 

‘Weak’ association

The final cohort consisted of 428,525 individuals (mean [SD] age, 36.8 [15.4] years, 52.7% female) at baseline, with observation taking place over a mean of 4.8 years [range, 1 day to 10.5 years]) or a total of over 2 million (2,062,241) person-years.

Of the cohort, 4.3% (n = 18,317) had at least two prescriptions for either olanzapine or quetiapine (although subsequently, 86.5% were censored for exceeding the average OE dose of 5 mg/day).

By the end of the study, 3.1% of the cohort had died during the observation time, and of these, 69.5% were from disease-specific causes, while close to one-fifth (19.5%) were from cardiometabolic-specific causes.

On the whole, treatment status (i.e., treated vs. untreated) was not significantly associated with cardiometabolic mortality (adjusted hazard ratio [HR], .86 [95% confidence interval, 0.64-1.15]; P = .307).

Compared to no treatment, treatment with olanzapine or quetiapine for less than 6 months was significantly associated with a reduced risk of cardiovascular mortality (adjusted HR, .56 [.37 – .87]; P = .010). On the other hand, treatment for 6-12 months was significantly associated with an almost twofold increased risk (adjusted HR, 1.89 [1.22-2.92]; P = .004). The increased risk continued beyond 12 months, although the difference no longer remained significant.

“In the subgroup analysis consisting of individuals who had ever been treated with olanzapine/quetiapine, starting at the date of their first prescription, the hazard for cardiometabolic mortality increased significantly by 45% (6%-99%; P = .019) for every year exposed to an average 5 mg/day,” the authors reported.

The authors concluded that the association between low-dose olanzapine/quetiapine treatment and cardiometabolic mortality was present, but “weak.”

The hazard for disease-specific mortality also significantly increased with each year exposed to an average of 5 mg/day of OE (HR, 1.24 [1.03-1.50]; P = .026).

Treatment status similarly was associated with all-cause mortality (HR, 1.16 [1.03-1.30]; P = .012), although the increased hazard for all-cause mortality with each year of exposure was not considered significant.

“The findings of this study are consistent with the hypothesis that continuous low-dose treatment with these drugs is associated with increased cardiometabolic mortality, but the results are somewhat divergent and not conclusive, so more research is needed,” Dr. Berge said.
 

Seek alternatives

Commenting on the study for this news organization, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the Mood Disorders Psychopharmacology Unit, called it a “timely paper” and “an important concept [because] low-doses of these antipsychotics are frequently prescribed across America and there has been less data on the safety [of these antipsychotics at lower doses].”

Dr. McIntyre, chairman and executive director of the Brain and Cognitive Discover Foundation, Toronto, who was not involved with the study, said that this “important report reminds us that there are metabolic safety concerns, even at low doses, where these medications are often used off label.”

He advised clinicians to “seek alternatives, and alternatives that are on-label, for conditions like anxiety and sleep disturbances.”

This work was supported by the South Region Board ALF, Sweden. Dr. Berge and coauthors have disclosed no relevant financial relationships. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation; and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is CEO of AltMed.

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

A growing trend of off-label, low-dose antipsychotic prescribing to treat disorders such as anxiety and insomnia has been tied to an increased risk of cardiometabolic death, new research shows.

Investigators studied data from large Swedish registries on over 420,000 individuals without previous psychotic, bipolar, or cardiometabolic disorders and found that off-label treatment with olanzapine or quetiapine for 6 to 12 months – even at a low dose – was associated with an almost twofold higher risk of cardiometabolic mortality, compared to no treatment. The risk remained elevated after 12 months, but the finding was not deemed significant.

“Clinicians should be made aware that low-dose treatment with these drugs is probably not a harmless choice for insomnia and anxiety, and while they have the benefit of not being addictive and [are] seemingly effective, they might come at a cost of shortening patients’ life span,” study investigator Jonas Berge, MD, PhD, associate professor and resident psychiatrist, Lund University, Sweden, said in an interview.

“Clinicians should take this information into account when prescribing the drugs and also monitor the patients with regular physical examinations and blood tests in the same way as when treating patients with psychosis with higher doses of these drugs,” he said.

The study was published online Nov. 9 in the Journal of Psychiatric Research.
 

A growing trend

Use of low-dose antipsychotics to treat a variety of psychiatric and behavioral disturbances, including anxiety, insomnia, and agitation, has “surged in popularity,” the authors wrote.

Quetiapine and olanzapine “rank as two of the most frequently prescribed second-generation antipsychotics and, next to clozapine, are considered to exhort the highest risk for cardiometabolic sequelae, including components of metabolic syndrome,” they added.

Previous research examining the association between second-generation antipsychotics and placebo has either not focused on cardiometabolic-specific causes or has examined only cohorts with severe mental illness, so those findings “do not necessarily generalize to others treated off-label,” they noted.

“The motivation for the study came from my work as a psychiatrist, in which I’ve noticed that the off-label use of these medications [olanzapine and quetiapine] for anxiety and insomnia seems highly prevalent, and that many patients seem to gain a lot of weight, despite low doses,” Dr. Berge said.

There is “evidence to suggest that clinicians may underappreciate cardiometabolic risks owing to antipsychotic treatment, as routine screening is often incomplete or inconsistent,” the authors noted.

“To do a risk-benefit analysis of these drugs in low doses, the risks involved – as well as the effects, of course – need to be studied,” Dr. Berge stated.

To investigate the question, the researchers turned to three large cross-linked Swedish registers: the National Patient Register, containing demographic and medical data; the Prescribed Drug Register; and the Cause of Death Register.

They identified all individuals aged 18 years and older with at least one psychiatric visit (inpatient or outpatient) between July 1, 2006, and Dec. 31, 2016, to see how many were prescribed low-dose olanzapine or quetiapine (defined as ≤ 5 mg/day of olanzapine or olanzapine equivalent [OE]), which was used as a proxy marker for off-label treatment, since this dose is considered subtherapeutic for severe mental illness.

They calculated two time-dependent variables – cumulative dose and past annual average dose – and then used those to compute three different exposure valuables: those treated with low-dose OE; cumulative exposure (i.e., period treated with an average 5 mg/day); and a continuous variable “corresponding to each year exposed OE 5 mg/day.”

The primary outcome was set as mortality from cardiometabolic-related disorders, while secondary outcomes were disease-specific and all-cause mortality.
 

‘Weak’ association

The final cohort consisted of 428,525 individuals (mean [SD] age, 36.8 [15.4] years, 52.7% female) at baseline, with observation taking place over a mean of 4.8 years [range, 1 day to 10.5 years]) or a total of over 2 million (2,062,241) person-years.

Of the cohort, 4.3% (n = 18,317) had at least two prescriptions for either olanzapine or quetiapine (although subsequently, 86.5% were censored for exceeding the average OE dose of 5 mg/day).

By the end of the study, 3.1% of the cohort had died during the observation time, and of these, 69.5% were from disease-specific causes, while close to one-fifth (19.5%) were from cardiometabolic-specific causes.

On the whole, treatment status (i.e., treated vs. untreated) was not significantly associated with cardiometabolic mortality (adjusted hazard ratio [HR], .86 [95% confidence interval, 0.64-1.15]; P = .307).

Compared to no treatment, treatment with olanzapine or quetiapine for less than 6 months was significantly associated with a reduced risk of cardiovascular mortality (adjusted HR, .56 [.37 – .87]; P = .010). On the other hand, treatment for 6-12 months was significantly associated with an almost twofold increased risk (adjusted HR, 1.89 [1.22-2.92]; P = .004). The increased risk continued beyond 12 months, although the difference no longer remained significant.

“In the subgroup analysis consisting of individuals who had ever been treated with olanzapine/quetiapine, starting at the date of their first prescription, the hazard for cardiometabolic mortality increased significantly by 45% (6%-99%; P = .019) for every year exposed to an average 5 mg/day,” the authors reported.

The authors concluded that the association between low-dose olanzapine/quetiapine treatment and cardiometabolic mortality was present, but “weak.”

The hazard for disease-specific mortality also significantly increased with each year exposed to an average of 5 mg/day of OE (HR, 1.24 [1.03-1.50]; P = .026).

Treatment status similarly was associated with all-cause mortality (HR, 1.16 [1.03-1.30]; P = .012), although the increased hazard for all-cause mortality with each year of exposure was not considered significant.

“The findings of this study are consistent with the hypothesis that continuous low-dose treatment with these drugs is associated with increased cardiometabolic mortality, but the results are somewhat divergent and not conclusive, so more research is needed,” Dr. Berge said.
 

Seek alternatives

Commenting on the study for this news organization, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the Mood Disorders Psychopharmacology Unit, called it a “timely paper” and “an important concept [because] low-doses of these antipsychotics are frequently prescribed across America and there has been less data on the safety [of these antipsychotics at lower doses].”

Dr. McIntyre, chairman and executive director of the Brain and Cognitive Discover Foundation, Toronto, who was not involved with the study, said that this “important report reminds us that there are metabolic safety concerns, even at low doses, where these medications are often used off label.”

He advised clinicians to “seek alternatives, and alternatives that are on-label, for conditions like anxiety and sleep disturbances.”

This work was supported by the South Region Board ALF, Sweden. Dr. Berge and coauthors have disclosed no relevant financial relationships. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation; and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is CEO of AltMed.

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

A growing trend of off-label, low-dose antipsychotic prescribing to treat disorders such as anxiety and insomnia has been tied to an increased risk of cardiometabolic death, new research shows.

Investigators studied data from large Swedish registries on over 420,000 individuals without previous psychotic, bipolar, or cardiometabolic disorders and found that off-label treatment with olanzapine or quetiapine for 6 to 12 months – even at a low dose – was associated with an almost twofold higher risk of cardiometabolic mortality, compared to no treatment. The risk remained elevated after 12 months, but the finding was not deemed significant.

“Clinicians should be made aware that low-dose treatment with these drugs is probably not a harmless choice for insomnia and anxiety, and while they have the benefit of not being addictive and [are] seemingly effective, they might come at a cost of shortening patients’ life span,” study investigator Jonas Berge, MD, PhD, associate professor and resident psychiatrist, Lund University, Sweden, said in an interview.

“Clinicians should take this information into account when prescribing the drugs and also monitor the patients with regular physical examinations and blood tests in the same way as when treating patients with psychosis with higher doses of these drugs,” he said.

The study was published online Nov. 9 in the Journal of Psychiatric Research.
 

A growing trend

Use of low-dose antipsychotics to treat a variety of psychiatric and behavioral disturbances, including anxiety, insomnia, and agitation, has “surged in popularity,” the authors wrote.

Quetiapine and olanzapine “rank as two of the most frequently prescribed second-generation antipsychotics and, next to clozapine, are considered to exhort the highest risk for cardiometabolic sequelae, including components of metabolic syndrome,” they added.

Previous research examining the association between second-generation antipsychotics and placebo has either not focused on cardiometabolic-specific causes or has examined only cohorts with severe mental illness, so those findings “do not necessarily generalize to others treated off-label,” they noted.

“The motivation for the study came from my work as a psychiatrist, in which I’ve noticed that the off-label use of these medications [olanzapine and quetiapine] for anxiety and insomnia seems highly prevalent, and that many patients seem to gain a lot of weight, despite low doses,” Dr. Berge said.

There is “evidence to suggest that clinicians may underappreciate cardiometabolic risks owing to antipsychotic treatment, as routine screening is often incomplete or inconsistent,” the authors noted.

“To do a risk-benefit analysis of these drugs in low doses, the risks involved – as well as the effects, of course – need to be studied,” Dr. Berge stated.

To investigate the question, the researchers turned to three large cross-linked Swedish registers: the National Patient Register, containing demographic and medical data; the Prescribed Drug Register; and the Cause of Death Register.

They identified all individuals aged 18 years and older with at least one psychiatric visit (inpatient or outpatient) between July 1, 2006, and Dec. 31, 2016, to see how many were prescribed low-dose olanzapine or quetiapine (defined as ≤ 5 mg/day of olanzapine or olanzapine equivalent [OE]), which was used as a proxy marker for off-label treatment, since this dose is considered subtherapeutic for severe mental illness.

They calculated two time-dependent variables – cumulative dose and past annual average dose – and then used those to compute three different exposure valuables: those treated with low-dose OE; cumulative exposure (i.e., period treated with an average 5 mg/day); and a continuous variable “corresponding to each year exposed OE 5 mg/day.”

The primary outcome was set as mortality from cardiometabolic-related disorders, while secondary outcomes were disease-specific and all-cause mortality.
 

‘Weak’ association

The final cohort consisted of 428,525 individuals (mean [SD] age, 36.8 [15.4] years, 52.7% female) at baseline, with observation taking place over a mean of 4.8 years [range, 1 day to 10.5 years]) or a total of over 2 million (2,062,241) person-years.

Of the cohort, 4.3% (n = 18,317) had at least two prescriptions for either olanzapine or quetiapine (although subsequently, 86.5% were censored for exceeding the average OE dose of 5 mg/day).

By the end of the study, 3.1% of the cohort had died during the observation time, and of these, 69.5% were from disease-specific causes, while close to one-fifth (19.5%) were from cardiometabolic-specific causes.

On the whole, treatment status (i.e., treated vs. untreated) was not significantly associated with cardiometabolic mortality (adjusted hazard ratio [HR], .86 [95% confidence interval, 0.64-1.15]; P = .307).

Compared to no treatment, treatment with olanzapine or quetiapine for less than 6 months was significantly associated with a reduced risk of cardiovascular mortality (adjusted HR, .56 [.37 – .87]; P = .010). On the other hand, treatment for 6-12 months was significantly associated with an almost twofold increased risk (adjusted HR, 1.89 [1.22-2.92]; P = .004). The increased risk continued beyond 12 months, although the difference no longer remained significant.

“In the subgroup analysis consisting of individuals who had ever been treated with olanzapine/quetiapine, starting at the date of their first prescription, the hazard for cardiometabolic mortality increased significantly by 45% (6%-99%; P = .019) for every year exposed to an average 5 mg/day,” the authors reported.

The authors concluded that the association between low-dose olanzapine/quetiapine treatment and cardiometabolic mortality was present, but “weak.”

The hazard for disease-specific mortality also significantly increased with each year exposed to an average of 5 mg/day of OE (HR, 1.24 [1.03-1.50]; P = .026).

Treatment status similarly was associated with all-cause mortality (HR, 1.16 [1.03-1.30]; P = .012), although the increased hazard for all-cause mortality with each year of exposure was not considered significant.

“The findings of this study are consistent with the hypothesis that continuous low-dose treatment with these drugs is associated with increased cardiometabolic mortality, but the results are somewhat divergent and not conclusive, so more research is needed,” Dr. Berge said.
 

Seek alternatives

Commenting on the study for this news organization, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the Mood Disorders Psychopharmacology Unit, called it a “timely paper” and “an important concept [because] low-doses of these antipsychotics are frequently prescribed across America and there has been less data on the safety [of these antipsychotics at lower doses].”

Dr. McIntyre, chairman and executive director of the Brain and Cognitive Discover Foundation, Toronto, who was not involved with the study, said that this “important report reminds us that there are metabolic safety concerns, even at low doses, where these medications are often used off label.”

He advised clinicians to “seek alternatives, and alternatives that are on-label, for conditions like anxiety and sleep disturbances.”

This work was supported by the South Region Board ALF, Sweden. Dr. Berge and coauthors have disclosed no relevant financial relationships. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation; and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is CEO of AltMed.

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

The negative emotions stemming from teens’ involvement with social media have been grabbing the headlines. But adults may also be experiencing depression because of their use of social media, suggests a new study.

Use of social media has been linked to increased anxiety and depression, as well as reduced well-being in adolescents and young adults, but similar associations in older adults have not been well studied, and longitudinal data are lacking, Ron H. Perlis, MD, of Massachusetts General Hospital, Boston, and colleagues wrote in their paper, which was published in JAMA Network Open.

To examine the association between social media use and depressive symptoms in older adults, the researchers reviewed data from 13 waves of an internet survey conducted each month between May 2020 and May 2021. The survey respondents included individuals aged 18 years and older, with a mean age of 56 years.

In the study the researchers analyzed responses from 5,395 individuals aged 18 years and older, with a mean age of 56 years. The study participants had minimal or no depressive symptoms at baseline, according to scores on the nine-item Patient Health Questionnaire (PHQ-9).

Overall, 8.9% of the respondents reported a worsening of 5 points or more on the PHQ-9 score on a follow-up survey, which was the primary outcome. Participants who reported using social media platforms Snapchat, Facebook, or TikTok were significantly more likely to report increased depressive symptoms, compared with those who did not report use of social media. The fully adjusted odds ratio was largest for Snapchat (aOR, 1.53), followed by Facebook (aOR, 1.42), and TikTok (aOR, 1.39).

Incorporating recent television and internet news terms, such as COVID-19, changed the association for Snapchat, for which the aOR decreased from 1.53 to 1.12 when news source terms were included in the survey. TikTok and Facebook associations remained similar.

When the results were further stratified by age, use of TikTok and Snapchat was associated with depressive symptoms in those aged 35 years and older, but not in those younger than 35 years. However, the opposite pattern emerged for Facebook; use was associated with depressive symptoms for individuals younger than 35 years, but not in those aged 35 years and older (aOR, 2.60 vs. aOR, 1.12).

The association between increased self-reported depressive symptoms and use of certain social media platforms was not impacted by baseline social support or face-to-face interactions, the researchers noted.
 

Family physician was surprised results weren’t more significant

In the current study, “I was honestly surprised the results weren’t more significant,” Mary Ann Dakkak, MD, of Boston University said in an interview. “That said, social media uses during the COVID pandemic may have been a necessary social outlet and form of connection for many people who were otherwise isolated.”

To still see a significant increase in depression when social media could have been a positive force may suggest a heavier impact during “normal” times, she added.

“It is not surprising that what we see in youth is shown among adults,” noted Dr. Dakkak, who was not involved with this study. “I always tell my patients that what is good for their children is good for the adults too, and vice versa.

“We expect to see outcomes of this on youth and adults who have been more isolated, who have used more screen time for learning, work, connection and boredom, in the near future,” she said. “The complex nature of why social media may have been used more heavily for connection during a time when in-person meetings were not possible may be a heavy confounder as the typical profile of heavy social media users may have differed during the COVID shutdowns.”
 

Psychiatrist: Balance benefits of social media with mental health risks

The current study was likely conducted before the recent news on “hidden” Facebook data and the implications that Facebook knew it was contributing to worsened mental health in teens, particularly around self-esteem, Jessica “Jessi” Gold, MD, a psychiatrist at Washington University, St. Louis, said in an interview.

“If you look more specifically at other studies, however, the data around social media and mental health is constantly varied, with some showing benefits and some showing negatives, and none conclusively suggesting either way,” said Dr. Gold, who also was not involved with the new research. “More data are needed, especially longitudinally and on a broader age group, to understand social media’s impact on mental health over time.

“It is also even more important in the wake of COVID-19, as so many people have turned to social media as a primary source of social support and connection, and are using it even more than before,” she emphasized.

In the current study, “I think the most interesting information is that, for TikTok and Snapchat, the effects seemed to be more pronounced in those older than 35 years who used social media,” said Dr. Gold.

What this study leaves unanswered is “whether people who might develop depression are simply more prone to use social media in the first place, such as to seek out social support,” Dr. Gold said. “Also, we don’t know anything about how long they are using social media or what they are using it for, which to me is important for understanding more about the nuance of the relationship with mental health and social media.”
 

Experts advise clinicians to discuss social media with patients

This new research suggests that clinicians should be talking to their patients about how social media impacts their emotional reactions, as well as their sleep, Dr. Gold said.

“Patients should be asking themselves how they are feeling when they are on social media and not using it before sleep. They should also be considering time limits and how to effectively use social media while taking care of their mental health,” she said. This conversation between clinician and patient should be had with any patient of any age, who uses social media, not only with teenagers.

“This is also a conversation about moderation, and knowing that individuals may feel they benefit from social media, that they should balance these benefits with potential mental health risks,” she said.

“Studies such as this one shed light onto why social media consumption should be at least a point of discussion with our patients,” said Dr. Dakkak.

She advised clinicians to ask and listen to patients and their families when it comes to screen time habits. “Whenever I see a patient with mood symptoms, I ask about their habits – eating, sleeping, socializing, screen time – including phone time. I ask about the family dynamics around screen time.

“I’ve added screen time to my adolescent assessment. Discussing safe use of cell phones and social media can have a significant impact on adolescent behavior and wellbeing, and parents are very thankful for the help,” she said. “This study encourages us to add screen time to the assessments we do at all adult ages, especially if mood symptoms exist,” Dr. Dakkak emphasized.
 

Suggestions for future research

Dr. Dakkak added that more areas for research include the differences in the impact of social media use on content creators versus content consumers. Also, “I would like to see research using the real data of use, the times of use, interruptions in sleep and use, possible confounding variables to include exercise, presence of intimate relationship and school/job performance.”

Given the many confounding variables, more controlled studies are needed to examine mental health outcomes in use, how long people use social media, and the impact of interventions such as time limits, Dr. Gold said.

“We can’t ignore the benefits of social media, such as helping those with social anxiety, finding peer support, and normalizing mental health, and those factors need to be studied and measured more effectively as well, she said.
 

Take-home message

It is important to recognize that the current study represents a correlation, not causality, said Dr. Gold. In addressing the issues of how social media impact mental health, “as always, the hardest thing is that many people get their news from social media, and often get social support from social media, so there has to be a balance of not removing social media completely, but of helping people see how it affects their mental health and how to find balance.”

The study findings were limited by several factors, including the inability to control for all potential confounders, the inability to assess the nature of social media use, and the lack of dose-response data, the researchers noted. Although the surveys in the current study were not specific to COVID-19, the effects of social media on depression may be specific to the content, and the findings may not generalize beyond the COVID-19 pandemic period.

Approximately two-thirds (66%) of the study participants identified as female, and 76% as White; 11% as Black; 6% as Asian; 5% as Hispanic; and 2% as American Indian or Alaska Native, Pacific Islander or Native Hawaiian, or other.

The National Institute of Mental Health provided a grant for the study to Dr. Pelis, who disclosed consulting fees from various companies and equity in Psy Therapeutics. The study’s lead author also serves as associate editor for JAMA Network Open, but was not involved in the decision process for publication of this study. Dr. Gold disclosed conducting a conference for Johnson & Johnson about social media and health care workers, and was on the advisory council.

The negative emotions stemming from teens’ involvement with social media have been grabbing the headlines. But adults may also be experiencing depression because of their use of social media, suggests a new study.

Use of social media has been linked to increased anxiety and depression, as well as reduced well-being in adolescents and young adults, but similar associations in older adults have not been well studied, and longitudinal data are lacking, Ron H. Perlis, MD, of Massachusetts General Hospital, Boston, and colleagues wrote in their paper, which was published in JAMA Network Open.

To examine the association between social media use and depressive symptoms in older adults, the researchers reviewed data from 13 waves of an internet survey conducted each month between May 2020 and May 2021. The survey respondents included individuals aged 18 years and older, with a mean age of 56 years.

In the study the researchers analyzed responses from 5,395 individuals aged 18 years and older, with a mean age of 56 years. The study participants had minimal or no depressive symptoms at baseline, according to scores on the nine-item Patient Health Questionnaire (PHQ-9).

Overall, 8.9% of the respondents reported a worsening of 5 points or more on the PHQ-9 score on a follow-up survey, which was the primary outcome. Participants who reported using social media platforms Snapchat, Facebook, or TikTok were significantly more likely to report increased depressive symptoms, compared with those who did not report use of social media. The fully adjusted odds ratio was largest for Snapchat (aOR, 1.53), followed by Facebook (aOR, 1.42), and TikTok (aOR, 1.39).

Incorporating recent television and internet news terms, such as COVID-19, changed the association for Snapchat, for which the aOR decreased from 1.53 to 1.12 when news source terms were included in the survey. TikTok and Facebook associations remained similar.

When the results were further stratified by age, use of TikTok and Snapchat was associated with depressive symptoms in those aged 35 years and older, but not in those younger than 35 years. However, the opposite pattern emerged for Facebook; use was associated with depressive symptoms for individuals younger than 35 years, but not in those aged 35 years and older (aOR, 2.60 vs. aOR, 1.12).

The association between increased self-reported depressive symptoms and use of certain social media platforms was not impacted by baseline social support or face-to-face interactions, the researchers noted.
 

Family physician was surprised results weren’t more significant

In the current study, “I was honestly surprised the results weren’t more significant,” Mary Ann Dakkak, MD, of Boston University said in an interview. “That said, social media uses during the COVID pandemic may have been a necessary social outlet and form of connection for many people who were otherwise isolated.”

To still see a significant increase in depression when social media could have been a positive force may suggest a heavier impact during “normal” times, she added.

“It is not surprising that what we see in youth is shown among adults,” noted Dr. Dakkak, who was not involved with this study. “I always tell my patients that what is good for their children is good for the adults too, and vice versa.

“We expect to see outcomes of this on youth and adults who have been more isolated, who have used more screen time for learning, work, connection and boredom, in the near future,” she said. “The complex nature of why social media may have been used more heavily for connection during a time when in-person meetings were not possible may be a heavy confounder as the typical profile of heavy social media users may have differed during the COVID shutdowns.”
 

Psychiatrist: Balance benefits of social media with mental health risks

The current study was likely conducted before the recent news on “hidden” Facebook data and the implications that Facebook knew it was contributing to worsened mental health in teens, particularly around self-esteem, Jessica “Jessi” Gold, MD, a psychiatrist at Washington University, St. Louis, said in an interview.

“If you look more specifically at other studies, however, the data around social media and mental health is constantly varied, with some showing benefits and some showing negatives, and none conclusively suggesting either way,” said Dr. Gold, who also was not involved with the new research. “More data are needed, especially longitudinally and on a broader age group, to understand social media’s impact on mental health over time.

“It is also even more important in the wake of COVID-19, as so many people have turned to social media as a primary source of social support and connection, and are using it even more than before,” she emphasized.

In the current study, “I think the most interesting information is that, for TikTok and Snapchat, the effects seemed to be more pronounced in those older than 35 years who used social media,” said Dr. Gold.

What this study leaves unanswered is “whether people who might develop depression are simply more prone to use social media in the first place, such as to seek out social support,” Dr. Gold said. “Also, we don’t know anything about how long they are using social media or what they are using it for, which to me is important for understanding more about the nuance of the relationship with mental health and social media.”
 

Experts advise clinicians to discuss social media with patients

This new research suggests that clinicians should be talking to their patients about how social media impacts their emotional reactions, as well as their sleep, Dr. Gold said.

“Patients should be asking themselves how they are feeling when they are on social media and not using it before sleep. They should also be considering time limits and how to effectively use social media while taking care of their mental health,” she said. This conversation between clinician and patient should be had with any patient of any age, who uses social media, not only with teenagers.

“This is also a conversation about moderation, and knowing that individuals may feel they benefit from social media, that they should balance these benefits with potential mental health risks,” she said.

“Studies such as this one shed light onto why social media consumption should be at least a point of discussion with our patients,” said Dr. Dakkak.

She advised clinicians to ask and listen to patients and their families when it comes to screen time habits. “Whenever I see a patient with mood symptoms, I ask about their habits – eating, sleeping, socializing, screen time – including phone time. I ask about the family dynamics around screen time.

“I’ve added screen time to my adolescent assessment. Discussing safe use of cell phones and social media can have a significant impact on adolescent behavior and wellbeing, and parents are very thankful for the help,” she said. “This study encourages us to add screen time to the assessments we do at all adult ages, especially if mood symptoms exist,” Dr. Dakkak emphasized.
 

Suggestions for future research

Dr. Dakkak added that more areas for research include the differences in the impact of social media use on content creators versus content consumers. Also, “I would like to see research using the real data of use, the times of use, interruptions in sleep and use, possible confounding variables to include exercise, presence of intimate relationship and school/job performance.”

Given the many confounding variables, more controlled studies are needed to examine mental health outcomes in use, how long people use social media, and the impact of interventions such as time limits, Dr. Gold said.

“We can’t ignore the benefits of social media, such as helping those with social anxiety, finding peer support, and normalizing mental health, and those factors need to be studied and measured more effectively as well, she said.
 

Take-home message

It is important to recognize that the current study represents a correlation, not causality, said Dr. Gold. In addressing the issues of how social media impact mental health, “as always, the hardest thing is that many people get their news from social media, and often get social support from social media, so there has to be a balance of not removing social media completely, but of helping people see how it affects their mental health and how to find balance.”

The study findings were limited by several factors, including the inability to control for all potential confounders, the inability to assess the nature of social media use, and the lack of dose-response data, the researchers noted. Although the surveys in the current study were not specific to COVID-19, the effects of social media on depression may be specific to the content, and the findings may not generalize beyond the COVID-19 pandemic period.

Approximately two-thirds (66%) of the study participants identified as female, and 76% as White; 11% as Black; 6% as Asian; 5% as Hispanic; and 2% as American Indian or Alaska Native, Pacific Islander or Native Hawaiian, or other.

The National Institute of Mental Health provided a grant for the study to Dr. Pelis, who disclosed consulting fees from various companies and equity in Psy Therapeutics. The study’s lead author also serves as associate editor for JAMA Network Open, but was not involved in the decision process for publication of this study. Dr. Gold disclosed conducting a conference for Johnson & Johnson about social media and health care workers, and was on the advisory council.

The negative emotions stemming from teens’ involvement with social media have been grabbing the headlines. But adults may also be experiencing depression because of their use of social media, suggests a new study.

Use of social media has been linked to increased anxiety and depression, as well as reduced well-being in adolescents and young adults, but similar associations in older adults have not been well studied, and longitudinal data are lacking, Ron H. Perlis, MD, of Massachusetts General Hospital, Boston, and colleagues wrote in their paper, which was published in JAMA Network Open.

To examine the association between social media use and depressive symptoms in older adults, the researchers reviewed data from 13 waves of an internet survey conducted each month between May 2020 and May 2021. The survey respondents included individuals aged 18 years and older, with a mean age of 56 years.

In the study the researchers analyzed responses from 5,395 individuals aged 18 years and older, with a mean age of 56 years. The study participants had minimal or no depressive symptoms at baseline, according to scores on the nine-item Patient Health Questionnaire (PHQ-9).

Overall, 8.9% of the respondents reported a worsening of 5 points or more on the PHQ-9 score on a follow-up survey, which was the primary outcome. Participants who reported using social media platforms Snapchat, Facebook, or TikTok were significantly more likely to report increased depressive symptoms, compared with those who did not report use of social media. The fully adjusted odds ratio was largest for Snapchat (aOR, 1.53), followed by Facebook (aOR, 1.42), and TikTok (aOR, 1.39).

Incorporating recent television and internet news terms, such as COVID-19, changed the association for Snapchat, for which the aOR decreased from 1.53 to 1.12 when news source terms were included in the survey. TikTok and Facebook associations remained similar.

When the results were further stratified by age, use of TikTok and Snapchat was associated with depressive symptoms in those aged 35 years and older, but not in those younger than 35 years. However, the opposite pattern emerged for Facebook; use was associated with depressive symptoms for individuals younger than 35 years, but not in those aged 35 years and older (aOR, 2.60 vs. aOR, 1.12).

The association between increased self-reported depressive symptoms and use of certain social media platforms was not impacted by baseline social support or face-to-face interactions, the researchers noted.
 

Family physician was surprised results weren’t more significant

In the current study, “I was honestly surprised the results weren’t more significant,” Mary Ann Dakkak, MD, of Boston University said in an interview. “That said, social media uses during the COVID pandemic may have been a necessary social outlet and form of connection for many people who were otherwise isolated.”

To still see a significant increase in depression when social media could have been a positive force may suggest a heavier impact during “normal” times, she added.

“It is not surprising that what we see in youth is shown among adults,” noted Dr. Dakkak, who was not involved with this study. “I always tell my patients that what is good for their children is good for the adults too, and vice versa.

“We expect to see outcomes of this on youth and adults who have been more isolated, who have used more screen time for learning, work, connection and boredom, in the near future,” she said. “The complex nature of why social media may have been used more heavily for connection during a time when in-person meetings were not possible may be a heavy confounder as the typical profile of heavy social media users may have differed during the COVID shutdowns.”
 

Psychiatrist: Balance benefits of social media with mental health risks

The current study was likely conducted before the recent news on “hidden” Facebook data and the implications that Facebook knew it was contributing to worsened mental health in teens, particularly around self-esteem, Jessica “Jessi” Gold, MD, a psychiatrist at Washington University, St. Louis, said in an interview.

“If you look more specifically at other studies, however, the data around social media and mental health is constantly varied, with some showing benefits and some showing negatives, and none conclusively suggesting either way,” said Dr. Gold, who also was not involved with the new research. “More data are needed, especially longitudinally and on a broader age group, to understand social media’s impact on mental health over time.

“It is also even more important in the wake of COVID-19, as so many people have turned to social media as a primary source of social support and connection, and are using it even more than before,” she emphasized.

In the current study, “I think the most interesting information is that, for TikTok and Snapchat, the effects seemed to be more pronounced in those older than 35 years who used social media,” said Dr. Gold.

What this study leaves unanswered is “whether people who might develop depression are simply more prone to use social media in the first place, such as to seek out social support,” Dr. Gold said. “Also, we don’t know anything about how long they are using social media or what they are using it for, which to me is important for understanding more about the nuance of the relationship with mental health and social media.”
 

Experts advise clinicians to discuss social media with patients

This new research suggests that clinicians should be talking to their patients about how social media impacts their emotional reactions, as well as their sleep, Dr. Gold said.

“Patients should be asking themselves how they are feeling when they are on social media and not using it before sleep. They should also be considering time limits and how to effectively use social media while taking care of their mental health,” she said. This conversation between clinician and patient should be had with any patient of any age, who uses social media, not only with teenagers.

“This is also a conversation about moderation, and knowing that individuals may feel they benefit from social media, that they should balance these benefits with potential mental health risks,” she said.

“Studies such as this one shed light onto why social media consumption should be at least a point of discussion with our patients,” said Dr. Dakkak.

She advised clinicians to ask and listen to patients and their families when it comes to screen time habits. “Whenever I see a patient with mood symptoms, I ask about their habits – eating, sleeping, socializing, screen time – including phone time. I ask about the family dynamics around screen time.

“I’ve added screen time to my adolescent assessment. Discussing safe use of cell phones and social media can have a significant impact on adolescent behavior and wellbeing, and parents are very thankful for the help,” she said. “This study encourages us to add screen time to the assessments we do at all adult ages, especially if mood symptoms exist,” Dr. Dakkak emphasized.
 

Suggestions for future research

Dr. Dakkak added that more areas for research include the differences in the impact of social media use on content creators versus content consumers. Also, “I would like to see research using the real data of use, the times of use, interruptions in sleep and use, possible confounding variables to include exercise, presence of intimate relationship and school/job performance.”

Given the many confounding variables, more controlled studies are needed to examine mental health outcomes in use, how long people use social media, and the impact of interventions such as time limits, Dr. Gold said.

“We can’t ignore the benefits of social media, such as helping those with social anxiety, finding peer support, and normalizing mental health, and those factors need to be studied and measured more effectively as well, she said.
 

Take-home message

It is important to recognize that the current study represents a correlation, not causality, said Dr. Gold. In addressing the issues of how social media impact mental health, “as always, the hardest thing is that many people get their news from social media, and often get social support from social media, so there has to be a balance of not removing social media completely, but of helping people see how it affects their mental health and how to find balance.”

The study findings were limited by several factors, including the inability to control for all potential confounders, the inability to assess the nature of social media use, and the lack of dose-response data, the researchers noted. Although the surveys in the current study were not specific to COVID-19, the effects of social media on depression may be specific to the content, and the findings may not generalize beyond the COVID-19 pandemic period.

Approximately two-thirds (66%) of the study participants identified as female, and 76% as White; 11% as Black; 6% as Asian; 5% as Hispanic; and 2% as American Indian or Alaska Native, Pacific Islander or Native Hawaiian, or other.

The National Institute of Mental Health provided a grant for the study to Dr. Pelis, who disclosed consulting fees from various companies and equity in Psy Therapeutics. The study’s lead author also serves as associate editor for JAMA Network Open, but was not involved in the decision process for publication of this study. Dr. Gold disclosed conducting a conference for Johnson & Johnson about social media and health care workers, and was on the advisory council.

Treatment with intravenous ferric carboxymaltose significantly improved symptoms in restless legs syndrome (RLS) patients with iron-deficiency anemia (IDA), data from 29 adults show.

RLS occurs among individuals with normal iron but is at least six times higher among individuals with IDA, Hyoeun Bae, MD, of Keimyung University, Daegu, South Korea, and colleagues wrote. Previous studies have explored iron treatments for RLS patients with IDA, however, guidelines for treatment have not yet been published.

In a study published in Sleep Medicine, the researchers randomized 29 RLS patients with IDA to either 1,500 mg IV ferric carboxymaltose (FCM) or placebo for a short-term period of 6 weeks, followed by a phase 2 study for responders that lasted for 52 weeks. Baseline characteristics, including age, gender, iron parameters, and sleep and mood scales were similar between the groups.

At 6 weeks, patients in the FCM group showed significant improvement in RLS symptom severity based on changes from baseline International Restless Legs Syndrome Study Group scale (IRLS) scores, compared with placebo patients (–13.47 vs. 1.36, P < .001). A secondary outcome of sleep quality also improved significantly in the FCM group, compared with the placebo group.

After 6 weeks, 11 of the 14 patients in the placebo group also received 1,500 mg FCM for an open-label study. These patients also showed significant improvement in IRLS scores from baseline to 6 weeks.

All 23 responders from the short-term studies (13 who received FCM initially and 10 from the postplacebo group) enrolled in a phase 2 long-term study that lasted for 52 weeks; 14 of these completed the full 52-week study period.

Overall, 61% of participants in phase 2 of the study remained off their RLS medications at 52 weeks, and no serious adverse events were reported during the study period. Of these, 10 received one additional dose of FCM and 4 received more than one additional dose. The median change in IRLS score at 4 weeks after treatment was –4.00, compared with the score prior to treatment.

The study is the first of its design to show benefits of intravenous iron therapy for RLS in patients with IDA, the researchers said, noting that the findings of improved, but not cured, RLS symptoms might suggest that more than 1,500 mg of iron is needed to fully treat RLS in this patient population. “A second interpretation is that the RLS and IDA were separate events: a patient with idiopathic RLS who subsequently developed anemia,” they said. “Treating the IDA might improve symptoms but may not eliminate the symptoms.”

The study findings were limited by several factors, including the relatively small study population and inability to know the time frame for the development of IDA, the researchers noted. However, the results support the use of intravenous iron therapy for relief of RLS in IDA patients.

“Since IDA could result in epigenetic changes leading to irreversible state of RLS, then urgent and adequate management of the IDA in RLS patients would seem a very prudent and important clinical approach to this specific clinical condition,” they concluded.

The study received no outside funding. The researchers had no disclosures.

Treatment with intravenous ferric carboxymaltose significantly improved symptoms in restless legs syndrome (RLS) patients with iron-deficiency anemia (IDA), data from 29 adults show.

RLS occurs among individuals with normal iron but is at least six times higher among individuals with IDA, Hyoeun Bae, MD, of Keimyung University, Daegu, South Korea, and colleagues wrote. Previous studies have explored iron treatments for RLS patients with IDA, however, guidelines for treatment have not yet been published.

In a study published in Sleep Medicine, the researchers randomized 29 RLS patients with IDA to either 1,500 mg IV ferric carboxymaltose (FCM) or placebo for a short-term period of 6 weeks, followed by a phase 2 study for responders that lasted for 52 weeks. Baseline characteristics, including age, gender, iron parameters, and sleep and mood scales were similar between the groups.

At 6 weeks, patients in the FCM group showed significant improvement in RLS symptom severity based on changes from baseline International Restless Legs Syndrome Study Group scale (IRLS) scores, compared with placebo patients (–13.47 vs. 1.36, P < .001). A secondary outcome of sleep quality also improved significantly in the FCM group, compared with the placebo group.

After 6 weeks, 11 of the 14 patients in the placebo group also received 1,500 mg FCM for an open-label study. These patients also showed significant improvement in IRLS scores from baseline to 6 weeks.

All 23 responders from the short-term studies (13 who received FCM initially and 10 from the postplacebo group) enrolled in a phase 2 long-term study that lasted for 52 weeks; 14 of these completed the full 52-week study period.

Overall, 61% of participants in phase 2 of the study remained off their RLS medications at 52 weeks, and no serious adverse events were reported during the study period. Of these, 10 received one additional dose of FCM and 4 received more than one additional dose. The median change in IRLS score at 4 weeks after treatment was –4.00, compared with the score prior to treatment.

The study is the first of its design to show benefits of intravenous iron therapy for RLS in patients with IDA, the researchers said, noting that the findings of improved, but not cured, RLS symptoms might suggest that more than 1,500 mg of iron is needed to fully treat RLS in this patient population. “A second interpretation is that the RLS and IDA were separate events: a patient with idiopathic RLS who subsequently developed anemia,” they said. “Treating the IDA might improve symptoms but may not eliminate the symptoms.”

The study findings were limited by several factors, including the relatively small study population and inability to know the time frame for the development of IDA, the researchers noted. However, the results support the use of intravenous iron therapy for relief of RLS in IDA patients.

“Since IDA could result in epigenetic changes leading to irreversible state of RLS, then urgent and adequate management of the IDA in RLS patients would seem a very prudent and important clinical approach to this specific clinical condition,” they concluded.

The study received no outside funding. The researchers had no disclosures.

Treatment with intravenous ferric carboxymaltose significantly improved symptoms in restless legs syndrome (RLS) patients with iron-deficiency anemia (IDA), data from 29 adults show.

RLS occurs among individuals with normal iron but is at least six times higher among individuals with IDA, Hyoeun Bae, MD, of Keimyung University, Daegu, South Korea, and colleagues wrote. Previous studies have explored iron treatments for RLS patients with IDA, however, guidelines for treatment have not yet been published.

In a study published in Sleep Medicine, the researchers randomized 29 RLS patients with IDA to either 1,500 mg IV ferric carboxymaltose (FCM) or placebo for a short-term period of 6 weeks, followed by a phase 2 study for responders that lasted for 52 weeks. Baseline characteristics, including age, gender, iron parameters, and sleep and mood scales were similar between the groups.

At 6 weeks, patients in the FCM group showed significant improvement in RLS symptom severity based on changes from baseline International Restless Legs Syndrome Study Group scale (IRLS) scores, compared with placebo patients (–13.47 vs. 1.36, P < .001). A secondary outcome of sleep quality also improved significantly in the FCM group, compared with the placebo group.

After 6 weeks, 11 of the 14 patients in the placebo group also received 1,500 mg FCM for an open-label study. These patients also showed significant improvement in IRLS scores from baseline to 6 weeks.

All 23 responders from the short-term studies (13 who received FCM initially and 10 from the postplacebo group) enrolled in a phase 2 long-term study that lasted for 52 weeks; 14 of these completed the full 52-week study period.

Overall, 61% of participants in phase 2 of the study remained off their RLS medications at 52 weeks, and no serious adverse events were reported during the study period. Of these, 10 received one additional dose of FCM and 4 received more than one additional dose. The median change in IRLS score at 4 weeks after treatment was –4.00, compared with the score prior to treatment.

The study is the first of its design to show benefits of intravenous iron therapy for RLS in patients with IDA, the researchers said, noting that the findings of improved, but not cured, RLS symptoms might suggest that more than 1,500 mg of iron is needed to fully treat RLS in this patient population. “A second interpretation is that the RLS and IDA were separate events: a patient with idiopathic RLS who subsequently developed anemia,” they said. “Treating the IDA might improve symptoms but may not eliminate the symptoms.”

The study findings were limited by several factors, including the relatively small study population and inability to know the time frame for the development of IDA, the researchers noted. However, the results support the use of intravenous iron therapy for relief of RLS in IDA patients.

“Since IDA could result in epigenetic changes leading to irreversible state of RLS, then urgent and adequate management of the IDA in RLS patients would seem a very prudent and important clinical approach to this specific clinical condition,” they concluded.

The study received no outside funding. The researchers had no disclosures.

In men with a normal waist circumference, obstructive sleep apnea (OSA) metrics were positively associated with serum triglycerides, according to results of a study published in Nature and Science of Sleep (2021:13 1771-82).

Layla B. Guscoth, MD, of the South Australian Health and Medical Research Institute and Faculty of Health and Medical Sciences, University of Adelaide, Australia, and colleagues assessed unselected male community-dwelling participants in the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) and the Florey Adelaide Male Aging Study (FAMAS) studies.

They examined the association of OSA and nocturnal hypoxemia with serum lipid profiles, and suggested that the cardiometabolic risk profiles of healthy weight individuals with OSA require clinical attention, according to the researchers.

The partial or complete obstruction of upper airways found in the OSA syndrome results in intermittent hypoxia, accompanied variably by sleep fragmentation and daytime sleepiness. While the prevalence of moderate to severe OSA was 49.7% in the Swiss HypnoLaus cohort, it was 74.7% in men aged 40 or older (or having OSA syndrome according to ICD-3 criteria). Dr. Guscoth and colleagues point out, however, that OSA is frequently underdiagnosed or unrecognized in clinical settings, and that OSA has been implicated in development of cardiovascular conditions. Furthermore, the nocturnal hypoxemia resulting from OSA during rapid eye movement (REM) sleep is longitudinally associated with cardiovascular disease and its risk factors (hypertension, insulin resistance, metabolic syndrome and carotid atherosclerosis).
 

Study details

Prior research suggests that intermittent hypoxemia activates the sympathetic nervous system, increases oxidative stress and systemic inflammation, and that when chronic, reduces clearance of triglyceride-rich lipoproteins and inhibits adipose tissue lipoprotein lipase activity. To clarify inconsistent results in studies investigating potential OSA-dyslipidemia associations, and to confirm research suggesting an independent association with severe OSA (apnea-hypopnea index [AHI] ≥ 30/h), the authors conducted analyses stratified by waist circumference to observe an obesity-independent association between OSA metrics and dyslipidemia.

The investigators assessed 753 MAILES participants (mean age 60.8 years) who underwent full in-home polysomnography (Embletta X100). They looked at triglycerides, high- (HDL) and low-density lipoprotein (LDL), total cholesterol, associations between lipids and continuous measures of nocturnal hypoxemia (oxygen desaturation index [ODI], AHI, and REM-AHI), and adjusted for chronic conditions, risk behavior, and sociodemographic factors.

Mean waist circumference was 99.3 cm and OSA (AHI ≥ 10) prevalence was 52.6%. No significant associations were found between OSA metrics and lipid measures in an overall analysis, nor in a sensitivity analysis excluding lipid-lowering therapies.

In a covariate adjusted analysis stratified according to waist circumference (< 95 cm, 95-100 cm, > 100 cm) to minimize the contribution of obesity to hypertriglyceridemia, triglyceride levels were positively associated with AHI, ODI and REM-AHI in the participants with a waist circumference < 95 cm (P < .05), but not in participants with waist circumferences of 95-100 cm or > 100 cm.
 

Worse during REM

The authors observed also that OSA during REM sleep is marked by longer obstructive events with greater oxygen desaturations. Obstructive events during REM sleep, research has shown, may be more harmful than obstructive events during non-REM sleep with respect to hypertension, cardiovascular disease, and glycemic control in type 2 diabetes.

Looking at clinical categories of OSA, Dr. Guscoth and colleagues found that severe OSA was significantly associated with higher likelihood of triglyceride levels ≥ 1.7 mmol/L (odds ratio, 4.1, 95% confidence interval, 1.1-15.5, P = .039). Analysis according to waist circumference confirmed the relationship only among men with waist circumference < 95 cm.
 

Clinical concern

“We therefore suggest that with our data unstratified by weight circumference, metabolic derangements associated with insulin resistance induced by intermittent hypoxia due to OSA cannot be separated from the predominant effect of visceral obesity. When stratified by weight circumference, our data show that these derangements in triglycerides are observed only in lean participants where obesity does not have a dominant effect,” the researchers concluded.

“These findings of high prevalence of metabolic risk in lean patients with OSA, I find very worrying,” coauthor Sarah Appleton, PhD, Flinders Medical Center, Adelaide, Australia, said in an interview. She cited a study showing a 61% risk of dyslipidemia in lean patients with OSA (AHI > 5/hr, body mass index < 25 kg/m², and waist < 80 cm in women, < 90 cm in men), and two of three metabolic syndrome components in 64%. “Annual fasting blood tests would identify metabolic problems such as elevated fasting glucose and triglyceride levels,” she noted.

This work was supported by a National Health and Medical Research Council of Australia Project Grant (627227), the Hospital Research Foundation and ResMed Foundation. There were no relevant conflicts reported.

In men with a normal waist circumference, obstructive sleep apnea (OSA) metrics were positively associated with serum triglycerides, according to results of a study published in Nature and Science of Sleep (2021:13 1771-82).

Layla B. Guscoth, MD, of the South Australian Health and Medical Research Institute and Faculty of Health and Medical Sciences, University of Adelaide, Australia, and colleagues assessed unselected male community-dwelling participants in the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) and the Florey Adelaide Male Aging Study (FAMAS) studies.

They examined the association of OSA and nocturnal hypoxemia with serum lipid profiles, and suggested that the cardiometabolic risk profiles of healthy weight individuals with OSA require clinical attention, according to the researchers.

The partial or complete obstruction of upper airways found in the OSA syndrome results in intermittent hypoxia, accompanied variably by sleep fragmentation and daytime sleepiness. While the prevalence of moderate to severe OSA was 49.7% in the Swiss HypnoLaus cohort, it was 74.7% in men aged 40 or older (or having OSA syndrome according to ICD-3 criteria). Dr. Guscoth and colleagues point out, however, that OSA is frequently underdiagnosed or unrecognized in clinical settings, and that OSA has been implicated in development of cardiovascular conditions. Furthermore, the nocturnal hypoxemia resulting from OSA during rapid eye movement (REM) sleep is longitudinally associated with cardiovascular disease and its risk factors (hypertension, insulin resistance, metabolic syndrome and carotid atherosclerosis).
 

Study details

Prior research suggests that intermittent hypoxemia activates the sympathetic nervous system, increases oxidative stress and systemic inflammation, and that when chronic, reduces clearance of triglyceride-rich lipoproteins and inhibits adipose tissue lipoprotein lipase activity. To clarify inconsistent results in studies investigating potential OSA-dyslipidemia associations, and to confirm research suggesting an independent association with severe OSA (apnea-hypopnea index [AHI] ≥ 30/h), the authors conducted analyses stratified by waist circumference to observe an obesity-independent association between OSA metrics and dyslipidemia.

The investigators assessed 753 MAILES participants (mean age 60.8 years) who underwent full in-home polysomnography (Embletta X100). They looked at triglycerides, high- (HDL) and low-density lipoprotein (LDL), total cholesterol, associations between lipids and continuous measures of nocturnal hypoxemia (oxygen desaturation index [ODI], AHI, and REM-AHI), and adjusted for chronic conditions, risk behavior, and sociodemographic factors.

Mean waist circumference was 99.3 cm and OSA (AHI ≥ 10) prevalence was 52.6%. No significant associations were found between OSA metrics and lipid measures in an overall analysis, nor in a sensitivity analysis excluding lipid-lowering therapies.

In a covariate adjusted analysis stratified according to waist circumference (< 95 cm, 95-100 cm, > 100 cm) to minimize the contribution of obesity to hypertriglyceridemia, triglyceride levels were positively associated with AHI, ODI and REM-AHI in the participants with a waist circumference < 95 cm (P < .05), but not in participants with waist circumferences of 95-100 cm or > 100 cm.
 

Worse during REM

The authors observed also that OSA during REM sleep is marked by longer obstructive events with greater oxygen desaturations. Obstructive events during REM sleep, research has shown, may be more harmful than obstructive events during non-REM sleep with respect to hypertension, cardiovascular disease, and glycemic control in type 2 diabetes.

Looking at clinical categories of OSA, Dr. Guscoth and colleagues found that severe OSA was significantly associated with higher likelihood of triglyceride levels ≥ 1.7 mmol/L (odds ratio, 4.1, 95% confidence interval, 1.1-15.5, P = .039). Analysis according to waist circumference confirmed the relationship only among men with waist circumference < 95 cm.
 

Clinical concern

“We therefore suggest that with our data unstratified by weight circumference, metabolic derangements associated with insulin resistance induced by intermittent hypoxia due to OSA cannot be separated from the predominant effect of visceral obesity. When stratified by weight circumference, our data show that these derangements in triglycerides are observed only in lean participants where obesity does not have a dominant effect,” the researchers concluded.

“These findings of high prevalence of metabolic risk in lean patients with OSA, I find very worrying,” coauthor Sarah Appleton, PhD, Flinders Medical Center, Adelaide, Australia, said in an interview. She cited a study showing a 61% risk of dyslipidemia in lean patients with OSA (AHI > 5/hr, body mass index < 25 kg/m², and waist < 80 cm in women, < 90 cm in men), and two of three metabolic syndrome components in 64%. “Annual fasting blood tests would identify metabolic problems such as elevated fasting glucose and triglyceride levels,” she noted.

This work was supported by a National Health and Medical Research Council of Australia Project Grant (627227), the Hospital Research Foundation and ResMed Foundation. There were no relevant conflicts reported.

In men with a normal waist circumference, obstructive sleep apnea (OSA) metrics were positively associated with serum triglycerides, according to results of a study published in Nature and Science of Sleep (2021:13 1771-82).

Layla B. Guscoth, MD, of the South Australian Health and Medical Research Institute and Faculty of Health and Medical Sciences, University of Adelaide, Australia, and colleagues assessed unselected male community-dwelling participants in the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) and the Florey Adelaide Male Aging Study (FAMAS) studies.

They examined the association of OSA and nocturnal hypoxemia with serum lipid profiles, and suggested that the cardiometabolic risk profiles of healthy weight individuals with OSA require clinical attention, according to the researchers.

The partial or complete obstruction of upper airways found in the OSA syndrome results in intermittent hypoxia, accompanied variably by sleep fragmentation and daytime sleepiness. While the prevalence of moderate to severe OSA was 49.7% in the Swiss HypnoLaus cohort, it was 74.7% in men aged 40 or older (or having OSA syndrome according to ICD-3 criteria). Dr. Guscoth and colleagues point out, however, that OSA is frequently underdiagnosed or unrecognized in clinical settings, and that OSA has been implicated in development of cardiovascular conditions. Furthermore, the nocturnal hypoxemia resulting from OSA during rapid eye movement (REM) sleep is longitudinally associated with cardiovascular disease and its risk factors (hypertension, insulin resistance, metabolic syndrome and carotid atherosclerosis).
 

Study details

Prior research suggests that intermittent hypoxemia activates the sympathetic nervous system, increases oxidative stress and systemic inflammation, and that when chronic, reduces clearance of triglyceride-rich lipoproteins and inhibits adipose tissue lipoprotein lipase activity. To clarify inconsistent results in studies investigating potential OSA-dyslipidemia associations, and to confirm research suggesting an independent association with severe OSA (apnea-hypopnea index [AHI] ≥ 30/h), the authors conducted analyses stratified by waist circumference to observe an obesity-independent association between OSA metrics and dyslipidemia.

The investigators assessed 753 MAILES participants (mean age 60.8 years) who underwent full in-home polysomnography (Embletta X100). They looked at triglycerides, high- (HDL) and low-density lipoprotein (LDL), total cholesterol, associations between lipids and continuous measures of nocturnal hypoxemia (oxygen desaturation index [ODI], AHI, and REM-AHI), and adjusted for chronic conditions, risk behavior, and sociodemographic factors.

Mean waist circumference was 99.3 cm and OSA (AHI ≥ 10) prevalence was 52.6%. No significant associations were found between OSA metrics and lipid measures in an overall analysis, nor in a sensitivity analysis excluding lipid-lowering therapies.

In a covariate adjusted analysis stratified according to waist circumference (< 95 cm, 95-100 cm, > 100 cm) to minimize the contribution of obesity to hypertriglyceridemia, triglyceride levels were positively associated with AHI, ODI and REM-AHI in the participants with a waist circumference < 95 cm (P < .05), but not in participants with waist circumferences of 95-100 cm or > 100 cm.
 

Worse during REM

The authors observed also that OSA during REM sleep is marked by longer obstructive events with greater oxygen desaturations. Obstructive events during REM sleep, research has shown, may be more harmful than obstructive events during non-REM sleep with respect to hypertension, cardiovascular disease, and glycemic control in type 2 diabetes.

Looking at clinical categories of OSA, Dr. Guscoth and colleagues found that severe OSA was significantly associated with higher likelihood of triglyceride levels ≥ 1.7 mmol/L (odds ratio, 4.1, 95% confidence interval, 1.1-15.5, P = .039). Analysis according to waist circumference confirmed the relationship only among men with waist circumference < 95 cm.
 

Clinical concern

“We therefore suggest that with our data unstratified by weight circumference, metabolic derangements associated with insulin resistance induced by intermittent hypoxia due to OSA cannot be separated from the predominant effect of visceral obesity. When stratified by weight circumference, our data show that these derangements in triglycerides are observed only in lean participants where obesity does not have a dominant effect,” the researchers concluded.

“These findings of high prevalence of metabolic risk in lean patients with OSA, I find very worrying,” coauthor Sarah Appleton, PhD, Flinders Medical Center, Adelaide, Australia, said in an interview. She cited a study showing a 61% risk of dyslipidemia in lean patients with OSA (AHI > 5/hr, body mass index < 25 kg/m², and waist < 80 cm in women, < 90 cm in men), and two of three metabolic syndrome components in 64%. “Annual fasting blood tests would identify metabolic problems such as elevated fasting glucose and triglyceride levels,” she noted.

This work was supported by a National Health and Medical Research Council of Australia Project Grant (627227), the Hospital Research Foundation and ResMed Foundation. There were no relevant conflicts reported.

Obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse resulting in intermittent hypoxemia and hypercapnia, large intrathoracic pressure swings, and cortical arousals. The rate of apneas and hypopneas observed during sleep, the apnea-hypopnea index (AHI), has been used for decades to diagnose OSA and to classify its severity. Despite the wide acceptance of this metric by the sleep medicine community, clinical research has found poor correlations between the AHI- and OSA-related complications or symptoms. We have come to learn that the AHI is an oversimplification of a complex and diverse disease process. (Punjabi. Chest. 2016;149[1]:16-9).

The most important features of a disease metric are reliability, and the ability to predict clinically relevant outcomes. The reliability of the AHI has been in question due to substantial night-to-night variability that can lead to missed diagnosis and disease severity misclassification (Dzierzewski et al. J Clin Sleep Med. 2020;16[4]:539-44). Furthermore, the AHI fails to reflect some important physiologic derangements resulting from respiratory events. Apart from imperfectly set thresholds for scoring, it disregards the depth and the duration of ventilatory disturbances. For example, a hypopnea lasting 30 seconds and resulting in a decrease of 10% in oxyhemoglobin saturation is considered equivalent to a hypopnea lasting 10 seconds and resulting in a decrease of 4% in oxyhemoglobin saturation. The AHI also assumes that apneas and hypopneas are equal in their biological effects regardless of when they occur during sleep (NREM vs REM), despite reports suggesting that the sequalae of OSA are sleep-stage dependent (Varga, Mokhlesi. Sleep Breath. 2019;23[2]:413-23). This is further complicated by the varying hypopnea definitions and the difficulties in differentiating obstructive vs central hypopneas. It is doubtful that these events, which differ in mechanism, would result in similar outcomes.
 

Over the past decade, our understanding of the different pathophysiological mechanisms leading to OSA has grown substantially, suggesting the need for a phenotype-specific treatment approach (Zinchuk, Yaggi. Chest. 2020;157[2]:403-20). The reliance on a single metric that does not capture this heterogeneity may prove detrimental to our therapeutic efforts. One extremely important dimension that is missed by the AHI is the patient. Individual response to airway obstruction varies with age, genetics, gender, and comorbidities, among other things. This may explain the difference in symptoms and outcomes experienced by patients with the same AHI. During the era of precision medicine, the concept of defining a clinical condition by a single test result, without regard to patient characteristics, is antiquated.

Several studies have attempted to propose complementary metrics that may better characterize OSA and predict outcomes. The hypoxic burden has gained a lot of attention as it is generally felt that hypoxemia is a major factor contributing to the pathogenesis of OSA-related comorbidities. Azarbarzin, et al. reported a hypoxic burden metric by measuring the area under the oxygen desaturation curve during a respiratory event (Azarbarzin et al. Eur Heart J. 2019;40[14]:1149-57). It factors the length and depth of the desaturations into a single value that expresses the average desaturation burden per hour of sleep time. The hypoxic burden was independently predictive of cardiovascular mortality in two large cohorts. Interestingly, the AHI did not have such an association. Similarly, another novel proposed parameter, the oxygen desaturation rate (ODR), outperformed the AHI in predicting cardiovascular outcomes in severe OSA patients (Wang et al. J Clin Sleep Med. 2020;16[7]:1055-62). The ODR measures the speed of an oxygen desaturation during an apnea event. Subjects with a faster ODR were found to have higher blood pressure values and variability. The authors hypothesized that slower desaturations generate hypoxemia-conditioning that may protect from exaggerated hemodynamic changes. These findings of novel hypoxemia metrics, albeit having their own limitations, recapitulate the need to move beyond the AHI to characterize OSA.

The apnea-hypopnea event duration is another overlooked feature that may impact OSA outcomes. Butler, et al. demonstrated that shorter event duration predicted a higher all-cause mortality over and beyond that predicted by AHI (Butler et al. Am J Respir Crit Care Med. 2019;199[7]:903-12). These results contrast views that early arousals in response to respiratory events may improve outcomes as they reflect a protective mechanism to prevent further hypoxemia and sympatho-excitation. For example, Ma, et al. found that higher percentage of total sleep time spent in apnea/hypopnea (AHT%) predicted worse daytime sleepiness to a higher degree than standard AHI (Ma et al. Sci Rep. 2021;11[1]:4702). However, shorter event duration may represent lower arousal thresholds (increased excitability), and ventilatory control instability (higher loop gain), predisposing patients to augmented sympathetic activity. Along similar lines, the intensity of respiratory-related arousals (as measured by EEG wavelet transformation) was found to be independent of preceding respiratory stimulus, with higher arousal intensity levels correlating with higher respiratory and heart rate responses (Amatoury et al. Sleep. 2016;39[12]:2091-100). The contribution of arousals to OSA morbidity is of particular importance for women in whom long-term outcomes of elevated AHI are poorly understood. Bearing in mind the differences in the metrics used, these results underscore the role of event duration and arousability in the pathogenesis of OSA-related morbidity.

The AHI is certainly an important piece of data that is informative and somewhat predictive. However, when used as a sole disease-defining metric, it has yielded disappointing results, especially after OSA treatment trials failed to show cardiovascular benefits despite therapies achieving a low residual AHI. As we aim to achieve a more personalized approach for diagnosing and treating OSA, we need to explore beyond the concept of a single metric to define a heterogenous and complex disorder. Instead of relying on the frequency of respiratory events, it is time to use complementary polysomnographic data that better reflect the origin and systemic effects of these disturbances. Machine-learning methods may offer sophisticated approaches to identifying polysomnographic patterns for future research. Clinical characteristics will also likely need to be considered in OSA severity scales. The identification of symptom subtypes or blood biomarkers may help identify patient groups who may be impacted differently by OSA, and consequently have a different treatment response (Malhotra et al. Sleep. 2021;44[7]:zsab030).

Almost half a century has lapsed since the original descriptions of OSA. Since then, our understanding of the disorder has improved greatly, with much still to be discovered, but our method of disease capture is unwavering. Future research requires a focus on novel measures aimed at identifying OSA endophenotypes, which will transform our understanding of disease traits and propel us into personalized therapies.
 

Dr. Mansour is Assistant Professor of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University School of Medicine, Durham, North Carolina. Dr. Won is Associate Professor of Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine; and VA Connecticut Healthcare System, West Haven, Connecticut.

Obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse resulting in intermittent hypoxemia and hypercapnia, large intrathoracic pressure swings, and cortical arousals. The rate of apneas and hypopneas observed during sleep, the apnea-hypopnea index (AHI), has been used for decades to diagnose OSA and to classify its severity. Despite the wide acceptance of this metric by the sleep medicine community, clinical research has found poor correlations between the AHI- and OSA-related complications or symptoms. We have come to learn that the AHI is an oversimplification of a complex and diverse disease process. (Punjabi. Chest. 2016;149[1]:16-9).

The most important features of a disease metric are reliability, and the ability to predict clinically relevant outcomes. The reliability of the AHI has been in question due to substantial night-to-night variability that can lead to missed diagnosis and disease severity misclassification (Dzierzewski et al. J Clin Sleep Med. 2020;16[4]:539-44). Furthermore, the AHI fails to reflect some important physiologic derangements resulting from respiratory events. Apart from imperfectly set thresholds for scoring, it disregards the depth and the duration of ventilatory disturbances. For example, a hypopnea lasting 30 seconds and resulting in a decrease of 10% in oxyhemoglobin saturation is considered equivalent to a hypopnea lasting 10 seconds and resulting in a decrease of 4% in oxyhemoglobin saturation. The AHI also assumes that apneas and hypopneas are equal in their biological effects regardless of when they occur during sleep (NREM vs REM), despite reports suggesting that the sequalae of OSA are sleep-stage dependent (Varga, Mokhlesi. Sleep Breath. 2019;23[2]:413-23). This is further complicated by the varying hypopnea definitions and the difficulties in differentiating obstructive vs central hypopneas. It is doubtful that these events, which differ in mechanism, would result in similar outcomes.
 

Over the past decade, our understanding of the different pathophysiological mechanisms leading to OSA has grown substantially, suggesting the need for a phenotype-specific treatment approach (Zinchuk, Yaggi. Chest. 2020;157[2]:403-20). The reliance on a single metric that does not capture this heterogeneity may prove detrimental to our therapeutic efforts. One extremely important dimension that is missed by the AHI is the patient. Individual response to airway obstruction varies with age, genetics, gender, and comorbidities, among other things. This may explain the difference in symptoms and outcomes experienced by patients with the same AHI. During the era of precision medicine, the concept of defining a clinical condition by a single test result, without regard to patient characteristics, is antiquated.

Several studies have attempted to propose complementary metrics that may better characterize OSA and predict outcomes. The hypoxic burden has gained a lot of attention as it is generally felt that hypoxemia is a major factor contributing to the pathogenesis of OSA-related comorbidities. Azarbarzin, et al. reported a hypoxic burden metric by measuring the area under the oxygen desaturation curve during a respiratory event (Azarbarzin et al. Eur Heart J. 2019;40[14]:1149-57). It factors the length and depth of the desaturations into a single value that expresses the average desaturation burden per hour of sleep time. The hypoxic burden was independently predictive of cardiovascular mortality in two large cohorts. Interestingly, the AHI did not have such an association. Similarly, another novel proposed parameter, the oxygen desaturation rate (ODR), outperformed the AHI in predicting cardiovascular outcomes in severe OSA patients (Wang et al. J Clin Sleep Med. 2020;16[7]:1055-62). The ODR measures the speed of an oxygen desaturation during an apnea event. Subjects with a faster ODR were found to have higher blood pressure values and variability. The authors hypothesized that slower desaturations generate hypoxemia-conditioning that may protect from exaggerated hemodynamic changes. These findings of novel hypoxemia metrics, albeit having their own limitations, recapitulate the need to move beyond the AHI to characterize OSA.

The apnea-hypopnea event duration is another overlooked feature that may impact OSA outcomes. Butler, et al. demonstrated that shorter event duration predicted a higher all-cause mortality over and beyond that predicted by AHI (Butler et al. Am J Respir Crit Care Med. 2019;199[7]:903-12). These results contrast views that early arousals in response to respiratory events may improve outcomes as they reflect a protective mechanism to prevent further hypoxemia and sympatho-excitation. For example, Ma, et al. found that higher percentage of total sleep time spent in apnea/hypopnea (AHT%) predicted worse daytime sleepiness to a higher degree than standard AHI (Ma et al. Sci Rep. 2021;11[1]:4702). However, shorter event duration may represent lower arousal thresholds (increased excitability), and ventilatory control instability (higher loop gain), predisposing patients to augmented sympathetic activity. Along similar lines, the intensity of respiratory-related arousals (as measured by EEG wavelet transformation) was found to be independent of preceding respiratory stimulus, with higher arousal intensity levels correlating with higher respiratory and heart rate responses (Amatoury et al. Sleep. 2016;39[12]:2091-100). The contribution of arousals to OSA morbidity is of particular importance for women in whom long-term outcomes of elevated AHI are poorly understood. Bearing in mind the differences in the metrics used, these results underscore the role of event duration and arousability in the pathogenesis of OSA-related morbidity.

The AHI is certainly an important piece of data that is informative and somewhat predictive. However, when used as a sole disease-defining metric, it has yielded disappointing results, especially after OSA treatment trials failed to show cardiovascular benefits despite therapies achieving a low residual AHI. As we aim to achieve a more personalized approach for diagnosing and treating OSA, we need to explore beyond the concept of a single metric to define a heterogenous and complex disorder. Instead of relying on the frequency of respiratory events, it is time to use complementary polysomnographic data that better reflect the origin and systemic effects of these disturbances. Machine-learning methods may offer sophisticated approaches to identifying polysomnographic patterns for future research. Clinical characteristics will also likely need to be considered in OSA severity scales. The identification of symptom subtypes or blood biomarkers may help identify patient groups who may be impacted differently by OSA, and consequently have a different treatment response (Malhotra et al. Sleep. 2021;44[7]:zsab030).

Almost half a century has lapsed since the original descriptions of OSA. Since then, our understanding of the disorder has improved greatly, with much still to be discovered, but our method of disease capture is unwavering. Future research requires a focus on novel measures aimed at identifying OSA endophenotypes, which will transform our understanding of disease traits and propel us into personalized therapies.
 

Dr. Mansour is Assistant Professor of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University School of Medicine, Durham, North Carolina. Dr. Won is Associate Professor of Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine; and VA Connecticut Healthcare System, West Haven, Connecticut.

Obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse resulting in intermittent hypoxemia and hypercapnia, large intrathoracic pressure swings, and cortical arousals. The rate of apneas and hypopneas observed during sleep, the apnea-hypopnea index (AHI), has been used for decades to diagnose OSA and to classify its severity. Despite the wide acceptance of this metric by the sleep medicine community, clinical research has found poor correlations between the AHI- and OSA-related complications or symptoms. We have come to learn that the AHI is an oversimplification of a complex and diverse disease process. (Punjabi. Chest. 2016;149[1]:16-9).

The most important features of a disease metric are reliability, and the ability to predict clinically relevant outcomes. The reliability of the AHI has been in question due to substantial night-to-night variability that can lead to missed diagnosis and disease severity misclassification (Dzierzewski et al. J Clin Sleep Med. 2020;16[4]:539-44). Furthermore, the AHI fails to reflect some important physiologic derangements resulting from respiratory events. Apart from imperfectly set thresholds for scoring, it disregards the depth and the duration of ventilatory disturbances. For example, a hypopnea lasting 30 seconds and resulting in a decrease of 10% in oxyhemoglobin saturation is considered equivalent to a hypopnea lasting 10 seconds and resulting in a decrease of 4% in oxyhemoglobin saturation. The AHI also assumes that apneas and hypopneas are equal in their biological effects regardless of when they occur during sleep (NREM vs REM), despite reports suggesting that the sequalae of OSA are sleep-stage dependent (Varga, Mokhlesi. Sleep Breath. 2019;23[2]:413-23). This is further complicated by the varying hypopnea definitions and the difficulties in differentiating obstructive vs central hypopneas. It is doubtful that these events, which differ in mechanism, would result in similar outcomes.
 

Over the past decade, our understanding of the different pathophysiological mechanisms leading to OSA has grown substantially, suggesting the need for a phenotype-specific treatment approach (Zinchuk, Yaggi. Chest. 2020;157[2]:403-20). The reliance on a single metric that does not capture this heterogeneity may prove detrimental to our therapeutic efforts. One extremely important dimension that is missed by the AHI is the patient. Individual response to airway obstruction varies with age, genetics, gender, and comorbidities, among other things. This may explain the difference in symptoms and outcomes experienced by patients with the same AHI. During the era of precision medicine, the concept of defining a clinical condition by a single test result, without regard to patient characteristics, is antiquated.

Several studies have attempted to propose complementary metrics that may better characterize OSA and predict outcomes. The hypoxic burden has gained a lot of attention as it is generally felt that hypoxemia is a major factor contributing to the pathogenesis of OSA-related comorbidities. Azarbarzin, et al. reported a hypoxic burden metric by measuring the area under the oxygen desaturation curve during a respiratory event (Azarbarzin et al. Eur Heart J. 2019;40[14]:1149-57). It factors the length and depth of the desaturations into a single value that expresses the average desaturation burden per hour of sleep time. The hypoxic burden was independently predictive of cardiovascular mortality in two large cohorts. Interestingly, the AHI did not have such an association. Similarly, another novel proposed parameter, the oxygen desaturation rate (ODR), outperformed the AHI in predicting cardiovascular outcomes in severe OSA patients (Wang et al. J Clin Sleep Med. 2020;16[7]:1055-62). The ODR measures the speed of an oxygen desaturation during an apnea event. Subjects with a faster ODR were found to have higher blood pressure values and variability. The authors hypothesized that slower desaturations generate hypoxemia-conditioning that may protect from exaggerated hemodynamic changes. These findings of novel hypoxemia metrics, albeit having their own limitations, recapitulate the need to move beyond the AHI to characterize OSA.

The apnea-hypopnea event duration is another overlooked feature that may impact OSA outcomes. Butler, et al. demonstrated that shorter event duration predicted a higher all-cause mortality over and beyond that predicted by AHI (Butler et al. Am J Respir Crit Care Med. 2019;199[7]:903-12). These results contrast views that early arousals in response to respiratory events may improve outcomes as they reflect a protective mechanism to prevent further hypoxemia and sympatho-excitation. For example, Ma, et al. found that higher percentage of total sleep time spent in apnea/hypopnea (AHT%) predicted worse daytime sleepiness to a higher degree than standard AHI (Ma et al. Sci Rep. 2021;11[1]:4702). However, shorter event duration may represent lower arousal thresholds (increased excitability), and ventilatory control instability (higher loop gain), predisposing patients to augmented sympathetic activity. Along similar lines, the intensity of respiratory-related arousals (as measured by EEG wavelet transformation) was found to be independent of preceding respiratory stimulus, with higher arousal intensity levels correlating with higher respiratory and heart rate responses (Amatoury et al. Sleep. 2016;39[12]:2091-100). The contribution of arousals to OSA morbidity is of particular importance for women in whom long-term outcomes of elevated AHI are poorly understood. Bearing in mind the differences in the metrics used, these results underscore the role of event duration and arousability in the pathogenesis of OSA-related morbidity.

The AHI is certainly an important piece of data that is informative and somewhat predictive. However, when used as a sole disease-defining metric, it has yielded disappointing results, especially after OSA treatment trials failed to show cardiovascular benefits despite therapies achieving a low residual AHI. As we aim to achieve a more personalized approach for diagnosing and treating OSA, we need to explore beyond the concept of a single metric to define a heterogenous and complex disorder. Instead of relying on the frequency of respiratory events, it is time to use complementary polysomnographic data that better reflect the origin and systemic effects of these disturbances. Machine-learning methods may offer sophisticated approaches to identifying polysomnographic patterns for future research. Clinical characteristics will also likely need to be considered in OSA severity scales. The identification of symptom subtypes or blood biomarkers may help identify patient groups who may be impacted differently by OSA, and consequently have a different treatment response (Malhotra et al. Sleep. 2021;44[7]:zsab030).

Almost half a century has lapsed since the original descriptions of OSA. Since then, our understanding of the disorder has improved greatly, with much still to be discovered, but our method of disease capture is unwavering. Future research requires a focus on novel measures aimed at identifying OSA endophenotypes, which will transform our understanding of disease traits and propel us into personalized therapies.
 

Dr. Mansour is Assistant Professor of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University School of Medicine, Durham, North Carolina. Dr. Won is Associate Professor of Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine; and VA Connecticut Healthcare System, West Haven, Connecticut.

THE CASE

A 49-year-old man with chronic insomnia was referred to the pharmacist authors (LF and DP) to initiate and manage the tapering of nightly zolpidem use. Per chart review, the patient had complaints of insomnia for more than 30 years. His care had been transferred to a Nebraska clinic 5 years earlier, with a medication list that included zolpidem controlled release (CR) 12.5 mg nightly. Since then, multiple interventions to achieve cessation had been tried, including counseling on sleep hygiene, adjunct antidepressant use, and abrupt discontinuation. Each of these methods was unsuccessful. So, his family physician (SS) reached out to the pharmacist authors (LF and DP).

THE APPROACH

Due to the patient’s long history of zolpidem use, a lack of literature on the topic, and worry for withdrawal symptoms, a taper schedule was designed utilizing various benzodiazepine taper resources for guidance. The proposed taper utilized 5-mg immediate release (IR) tablets to ensure ease of tapering. The taper ranged from 20% to 43% weekly reductions based on the ability to split the zolpidem tablet in half.

DISCUSSION

Zolpidem is a sedative-hypnotic medication indicated for the treatment of insomnia when used at therapeutic dosing (ie, 5 to 10 mg nightly). Anecdotal efficacy, accompanied by weak chronic insomnia guideline recommendations, has led prescribers to use zolpidem as a chronic medication to treat insomnia.^1,2 There is evidence of dependence and possible seizures from supratherapeutic zolpidem doses in the hundreds of milligrams, raising safety concerns regarding abuse, dependence, and withdrawal seizures in chronic use.^2,3

Additionally, there is limited evidence regarding the appropriate process of discontinuing zolpidem after chronic use.² Often a taper schedule—similar to those used with benzodiazepine medications—is used as a reference for discontinuation.¹ The hypothetical goal of a taper is to prevent withdrawal effects such as rebound insomnia, anxiety, palpitations, and seizures.³ However, an extended taper may not actually be necessary with chronic zolpidem patients.

Tapering with minimal adverse effects

Pharmacokinetic and pharmacodynamic studies have suggested minimal, if not complete, absence of rebound or withdrawal effects with short-term zolpidem use.⁴ The same appears to be true of patients with long-term use. In a study, Roehrs and colleagues⁵ explored whether long-term treatment (defined as 8 months) caused rebound insomnia upon abrupt withdrawal. The investigators concluded that people with primary insomnia do not experience rebound insomnia or withdrawal symptoms with chronic, therapeutic dosing.

This case documents a successfully accelerated taper for a patient with a chronic history (> 5 years) of zolpidem use.

Another study involving 92 elderly patients on long-term treatment of zolpidem (defined as > 1 month, with average around 9.9 ± 6.2 years) experienced only 1 or 2 nights of rebound insomnia during a month-long taper.^1,6 Following that, they experienced improvements in initiation and staying asleep.

A possible explanation for the lack of dependence or withdrawal symptoms in patients chronically treated with zolpidem is the pharmacokinetic profile. While the selectivity of the binding sites differentiates this medication from benzodiazepines, the additional fact of a short half-life, and no repeated dosing throughout the day, likely limit the risk of experiencing withdrawal symptoms.¹ The daily periods of minimal zolpidem exposure in the body may limit the amount of physical dependence.

Continue to: Discontinuation of zolpidem

Discontinuation of zolpidem

The 49-year-old man had a history of failed abrupt discontinuation of zolpidem in the past (without noted withdrawal symptoms). Thus, various benzodiazepine taper resources were consulted to develop a taper schedule.

We switched our patient from the zolpidem CR 12.5 mg nightly to 10 mg of the IR formulation, and the pharmacists proposed 20% to 43% weekly decreases in dosing based on dosage strengths. At the initial 3-day follow-up (having taken 10 mg nightly for 3 days), the patient reported a quicker onset of sleep but an inability to sleep through the night. The patient denied withdrawal symptoms or any significant impact to his daily routines. These results encouraged a progression to the next step of the taper. For the next 9 days, the patient took 5 mg nightly, rather than the pharmacist-advised dosing of alternating 5 mg and 10 mg nightly, and reported similar outcomes at his next visit.

This success led to the discontinuation of scheduled zolpidem. The patient was also given a prescription of 2.5 mg, as needed, if insomnia rebounded. No adverse effects were noted despite the accelerated taper. Based on patient response and motivation, the taper had progressed more quickly than scheduled, resulting in 3 days of 10 mg, 9 days of 5 mg, and 1 final day of 2.5 mg that was used when the patient had trouble falling asleep. At the 6-month follow-up, the patient informed the physician that he had neither experienced insomnia nor used any further medication.

THE TAKEAWAY

This case documents a successfully accelerated taper for a patient with a chronic history (> 5 years) of zolpidem use. Although withdrawal is often patient specific, this case suggests the risk is low despite the chronic usage. This further adds to the literature suggesting against the need for an extended taper, and possibly a taper at all, when using recommended doses of chronic zolpidem. This is a significant difference compared to past practices that drew from literature-based benzodiazepine tapers.⁶ This case serves as an observational point of reference for clinicians who are assisting patients with chronic zolpidem tapers.

CORRESPONDENCE
Logan Franck, PharmD, 986145 Nebraska Medical Center, Omaha, NE 68198-6145; [email protected]

THE CASE

A 49-year-old man with chronic insomnia was referred to the pharmacist authors (LF and DP) to initiate and manage the tapering of nightly zolpidem use. Per chart review, the patient had complaints of insomnia for more than 30 years. His care had been transferred to a Nebraska clinic 5 years earlier, with a medication list that included zolpidem controlled release (CR) 12.5 mg nightly. Since then, multiple interventions to achieve cessation had been tried, including counseling on sleep hygiene, adjunct antidepressant use, and abrupt discontinuation. Each of these methods was unsuccessful. So, his family physician (SS) reached out to the pharmacist authors (LF and DP).

THE APPROACH

Due to the patient’s long history of zolpidem use, a lack of literature on the topic, and worry for withdrawal symptoms, a taper schedule was designed utilizing various benzodiazepine taper resources for guidance. The proposed taper utilized 5-mg immediate release (IR) tablets to ensure ease of tapering. The taper ranged from 20% to 43% weekly reductions based on the ability to split the zolpidem tablet in half.

DISCUSSION

Zolpidem is a sedative-hypnotic medication indicated for the treatment of insomnia when used at therapeutic dosing (ie, 5 to 10 mg nightly). Anecdotal efficacy, accompanied by weak chronic insomnia guideline recommendations, has led prescribers to use zolpidem as a chronic medication to treat insomnia.^1,2 There is evidence of dependence and possible seizures from supratherapeutic zolpidem doses in the hundreds of milligrams, raising safety concerns regarding abuse, dependence, and withdrawal seizures in chronic use.^2,3

Additionally, there is limited evidence regarding the appropriate process of discontinuing zolpidem after chronic use.² Often a taper schedule—similar to those used with benzodiazepine medications—is used as a reference for discontinuation.¹ The hypothetical goal of a taper is to prevent withdrawal effects such as rebound insomnia, anxiety, palpitations, and seizures.³ However, an extended taper may not actually be necessary with chronic zolpidem patients.

Tapering with minimal adverse effects

Pharmacokinetic and pharmacodynamic studies have suggested minimal, if not complete, absence of rebound or withdrawal effects with short-term zolpidem use.⁴ The same appears to be true of patients with long-term use. In a study, Roehrs and colleagues⁵ explored whether long-term treatment (defined as 8 months) caused rebound insomnia upon abrupt withdrawal. The investigators concluded that people with primary insomnia do not experience rebound insomnia or withdrawal symptoms with chronic, therapeutic dosing.

This case documents a successfully accelerated taper for a patient with a chronic history (> 5 years) of zolpidem use.

Another study involving 92 elderly patients on long-term treatment of zolpidem (defined as > 1 month, with average around 9.9 ± 6.2 years) experienced only 1 or 2 nights of rebound insomnia during a month-long taper.^1,6 Following that, they experienced improvements in initiation and staying asleep.

A possible explanation for the lack of dependence or withdrawal symptoms in patients chronically treated with zolpidem is the pharmacokinetic profile. While the selectivity of the binding sites differentiates this medication from benzodiazepines, the additional fact of a short half-life, and no repeated dosing throughout the day, likely limit the risk of experiencing withdrawal symptoms.¹ The daily periods of minimal zolpidem exposure in the body may limit the amount of physical dependence.

Continue to: Discontinuation of zolpidem

Discontinuation of zolpidem

The 49-year-old man had a history of failed abrupt discontinuation of zolpidem in the past (without noted withdrawal symptoms). Thus, various benzodiazepine taper resources were consulted to develop a taper schedule.

We switched our patient from the zolpidem CR 12.5 mg nightly to 10 mg of the IR formulation, and the pharmacists proposed 20% to 43% weekly decreases in dosing based on dosage strengths. At the initial 3-day follow-up (having taken 10 mg nightly for 3 days), the patient reported a quicker onset of sleep but an inability to sleep through the night. The patient denied withdrawal symptoms or any significant impact to his daily routines. These results encouraged a progression to the next step of the taper. For the next 9 days, the patient took 5 mg nightly, rather than the pharmacist-advised dosing of alternating 5 mg and 10 mg nightly, and reported similar outcomes at his next visit.

This success led to the discontinuation of scheduled zolpidem. The patient was also given a prescription of 2.5 mg, as needed, if insomnia rebounded. No adverse effects were noted despite the accelerated taper. Based on patient response and motivation, the taper had progressed more quickly than scheduled, resulting in 3 days of 10 mg, 9 days of 5 mg, and 1 final day of 2.5 mg that was used when the patient had trouble falling asleep. At the 6-month follow-up, the patient informed the physician that he had neither experienced insomnia nor used any further medication.

THE TAKEAWAY

This case documents a successfully accelerated taper for a patient with a chronic history (> 5 years) of zolpidem use. Although withdrawal is often patient specific, this case suggests the risk is low despite the chronic usage. This further adds to the literature suggesting against the need for an extended taper, and possibly a taper at all, when using recommended doses of chronic zolpidem. This is a significant difference compared to past practices that drew from literature-based benzodiazepine tapers.⁶ This case serves as an observational point of reference for clinicians who are assisting patients with chronic zolpidem tapers.

CORRESPONDENCE
Logan Franck, PharmD, 986145 Nebraska Medical Center, Omaha, NE 68198-6145; [email protected]

THE CASE

A 49-year-old man with chronic insomnia was referred to the pharmacist authors (LF and DP) to initiate and manage the tapering of nightly zolpidem use. Per chart review, the patient had complaints of insomnia for more than 30 years. His care had been transferred to a Nebraska clinic 5 years earlier, with a medication list that included zolpidem controlled release (CR) 12.5 mg nightly. Since then, multiple interventions to achieve cessation had been tried, including counseling on sleep hygiene, adjunct antidepressant use, and abrupt discontinuation. Each of these methods was unsuccessful. So, his family physician (SS) reached out to the pharmacist authors (LF and DP).

THE APPROACH

Due to the patient’s long history of zolpidem use, a lack of literature on the topic, and worry for withdrawal symptoms, a taper schedule was designed utilizing various benzodiazepine taper resources for guidance. The proposed taper utilized 5-mg immediate release (IR) tablets to ensure ease of tapering. The taper ranged from 20% to 43% weekly reductions based on the ability to split the zolpidem tablet in half.

DISCUSSION

Zolpidem is a sedative-hypnotic medication indicated for the treatment of insomnia when used at therapeutic dosing (ie, 5 to 10 mg nightly). Anecdotal efficacy, accompanied by weak chronic insomnia guideline recommendations, has led prescribers to use zolpidem as a chronic medication to treat insomnia.^1,2 There is evidence of dependence and possible seizures from supratherapeutic zolpidem doses in the hundreds of milligrams, raising safety concerns regarding abuse, dependence, and withdrawal seizures in chronic use.^2,3

Additionally, there is limited evidence regarding the appropriate process of discontinuing zolpidem after chronic use.² Often a taper schedule—similar to those used with benzodiazepine medications—is used as a reference for discontinuation.¹ The hypothetical goal of a taper is to prevent withdrawal effects such as rebound insomnia, anxiety, palpitations, and seizures.³ However, an extended taper may not actually be necessary with chronic zolpidem patients.

Tapering with minimal adverse effects

Pharmacokinetic and pharmacodynamic studies have suggested minimal, if not complete, absence of rebound or withdrawal effects with short-term zolpidem use.⁴ The same appears to be true of patients with long-term use. In a study, Roehrs and colleagues⁵ explored whether long-term treatment (defined as 8 months) caused rebound insomnia upon abrupt withdrawal. The investigators concluded that people with primary insomnia do not experience rebound insomnia or withdrawal symptoms with chronic, therapeutic dosing.

This case documents a successfully accelerated taper for a patient with a chronic history (> 5 years) of zolpidem use.

Another study involving 92 elderly patients on long-term treatment of zolpidem (defined as > 1 month, with average around 9.9 ± 6.2 years) experienced only 1 or 2 nights of rebound insomnia during a month-long taper.^1,6 Following that, they experienced improvements in initiation and staying asleep.

A possible explanation for the lack of dependence or withdrawal symptoms in patients chronically treated with zolpidem is the pharmacokinetic profile. While the selectivity of the binding sites differentiates this medication from benzodiazepines, the additional fact of a short half-life, and no repeated dosing throughout the day, likely limit the risk of experiencing withdrawal symptoms.¹ The daily periods of minimal zolpidem exposure in the body may limit the amount of physical dependence.

Continue to: Discontinuation of zolpidem

Discontinuation of zolpidem

The 49-year-old man had a history of failed abrupt discontinuation of zolpidem in the past (without noted withdrawal symptoms). Thus, various benzodiazepine taper resources were consulted to develop a taper schedule.

We switched our patient from the zolpidem CR 12.5 mg nightly to 10 mg of the IR formulation, and the pharmacists proposed 20% to 43% weekly decreases in dosing based on dosage strengths. At the initial 3-day follow-up (having taken 10 mg nightly for 3 days), the patient reported a quicker onset of sleep but an inability to sleep through the night. The patient denied withdrawal symptoms or any significant impact to his daily routines. These results encouraged a progression to the next step of the taper. For the next 9 days, the patient took 5 mg nightly, rather than the pharmacist-advised dosing of alternating 5 mg and 10 mg nightly, and reported similar outcomes at his next visit.

This success led to the discontinuation of scheduled zolpidem. The patient was also given a prescription of 2.5 mg, as needed, if insomnia rebounded. No adverse effects were noted despite the accelerated taper. Based on patient response and motivation, the taper had progressed more quickly than scheduled, resulting in 3 days of 10 mg, 9 days of 5 mg, and 1 final day of 2.5 mg that was used when the patient had trouble falling asleep. At the 6-month follow-up, the patient informed the physician that he had neither experienced insomnia nor used any further medication.

THE TAKEAWAY

This case documents a successfully accelerated taper for a patient with a chronic history (> 5 years) of zolpidem use. Although withdrawal is often patient specific, this case suggests the risk is low despite the chronic usage. This further adds to the literature suggesting against the need for an extended taper, and possibly a taper at all, when using recommended doses of chronic zolpidem. This is a significant difference compared to past practices that drew from literature-based benzodiazepine tapers.⁶ This case serves as an observational point of reference for clinicians who are assisting patients with chronic zolpidem tapers.

CORRESPONDENCE
Logan Franck, PharmD, 986145 Nebraska Medical Center, Omaha, NE 68198-6145; [email protected]

When the COVID-19 pandemic engulfed the nation well over a year ago, Rebecca Hendrickson, MD, PhD, immersed herself in the shell-shocking revelations that clinicians began posting on social media. The accounts offered just a snapshot of the pandemic’s heavy psychological toll, and Dr. Hendrickson, a psychiatrist at the University of Washington in Seattle and an expert in posttraumatic stress disorder (PTSD), wanted to know more.

xavierarnau/Getty Images

She and her colleagues devised a survey to assess the impact of several pandemic-related factors, including increased work hours, social distancing restrictions, and lack of adequate personal protective equipment.

What began as a survey of health care workers soon expanded in scope. Of the more than 600 survey respondents to date, health care workers account for about 60%, while the rest are first responders – police officers, firefighters, paramedics, and emergency medical technicians – and nonclinical personnel, such as security guards and office staff, in health care settings. The respondents range in age from 19 to 72, and hail from all regions of the country.

“Our findings were really striking,” Dr. Hendrickson said, “including very high rates of thoughts of suicide and thoughts of leaving one’s current field, which were both strongly linked to COVID-19–related occupational stress exposure.”

The distress stemmed from a multitude of factors. Among the most demoralizing: witnessing patients die in isolation and being stretched thin to provide optimal care for all patients amid an unrelenting onslaught of COVID-19 cases, she said. For some health care workers, living in the garage or basement – to avoid infecting family members with the virus – also wore on their psyches.

Of all health care workers in the study, more than three-quarters reported symptoms that fell within the clinical range for depression (76%) and anxiety (78%). More than 25% noted that they had lost a family member or close colleague to the virus.

Dr. Hendrickson, who works with military veterans at the VA Puget Sound Hospital System’s Mental Illness Research, Education, and Clinical Center and its PTSD outpatient clinic, hadn’t expected the experience of loss to be so pervasive. She said the sheer number of people who “crossed the threshold” into despair concerned her deeply.
 

Signs and symptoms of PTSD

PTSD’s prevalence among health care workers has always been variable, said Jessica Gold, MD, assistant professor and director of wellness, engagement, and outreach in the department of psychiatry at Washington University in St. Louis.

As a psychiatrist who sees health care workers in her clinical practice, Dr. Gold has noted poor baseline mental health, including depression and trauma. Significant data have pointed to a relatively higher suicide rate among physicians than among the general population. These problems have been compounded by COVID-19.

“It has been an unrelenting series of new stressors,” she said, citing lack of resources; a feeling of being unable to help; and the high frequency of risk of death to patients, family and friends, and the caregivers themselves as just as few examples. “It is very likely going to increase our baseline trauma, and honestly, I don’t know that we can predict how. To me, trauma has no real timeline and can show up months or even years after the pandemic.”

PTSD can manifest itself in health care workers in several different ways. A few commonalities Dr. Gold has observed are sleep disruption (including insomnia and nightmares), work avoidance by taking disability or quitting, irritability or other changes in mood, trouble concentrating, and hypervigilance.

She said she has seen physical manifestations of trauma – such as body pain, stomachaches, and teeth grinding, which “you might not realize are at all related to trauma but ultimately are.” Sometimes, she added, “people have panic attacks on the way to work or right when they get to work, or are thinking about work.”

Dr. Gold noted that different types of treatment, such as cognitive-behavioral therapy and eye movement desensitization and reprocessing (EMDR), can be effective for PTSD. Medication is often necessary because of comorbid anxiety, depression, or eating disorders, said Dr. Gold, who is conducting a study on the pandemic’s effects on medical students.
 

The difficulties in isolating COVID-19 as a contributor

Not all researchers are convinced that a causal relationship has been established between the pandemic and worsening mental health among those in the health care sector.

With provider burnout being a long-standing concern in medicine, Ankur A. Butala, MD, assistant professor of neurology, psychiatry, and behavioral sciences at the Johns Hopkins University, Baltimore, said he remains a bit skeptical that acute stressors during the pandemic amounted to a uniquely potent driving force that can be extrapolated and quantified in a study.

“It’s hard to interpret a chronic, rolling, ongoing trauma like COVID-19 against tools or scales developed to investigate symptoms from a singular and acute trauma, like a school shooting or a [military] firefight,” Dr. Butala said.

In addition, he noted a reluctance to generalizing results from a study in which participants were recruited via social media as opposed to research methods involving more rigorous selection protocols.

Although Dr. Hendrickson acknowledged the study’s limitations, she said her team nonetheless found strong correlations between COVID-19-related stressors and self-reported struggles in completing work-related tasks, as well as increasing thoughts of leaving one’s current field. They adjusted for previous lifetime trauma exposure, age, gender, and a personal history of contracting COVID-19.

The underlying premise of the study could be confirmed with repeated surveys over time, Dr. Butala said, as the COVID-19 pandemic evolves and the vaccination effort unfolds.

Follow-up surveys are being sent to participants every 2 weeks and every 3 months to gauge their mood, for a total follow-up period of 9 months per individual. New participants are still welcome. “We will continue to enroll as long as it seems relevant,” Dr. Hendrickson said.

Carol S. North, MD, MPE, who has added to the growing research on the pandemic’s toll on mental health, noted that because symptom scales do not provide psychiatric diagnoses, it is difficult to attribute the prevalence of psychiatric disorders to the pandemic. Dr. North is chair and professor of crisis psychiatry at UT Southwestern Medical Center in Dallas, and director of the program in trauma and disaster at VA North Texas Health Care System.

The DSM-5 criteria exclude naturally occurring illness, such as a virus (even during a pandemic) as a qualifying trauma for the diagnosis of PTSD. According to current criteria by the American Psychiatric Association, COVID-19 and the pandemic are not defined as trauma, Dr. North said, while noting that “just because it’s not trauma or PTSD does not mean that the pandemic should be discounted as not stressful; people are finding it very stressful.”

Identifying the exact source of distress would still be difficult, Dr. North said, as the pandemic has produced severe economic consequences and prolonged social isolation, as well as occurring alongside nationwide protests over racial and ethnic divisions. Studies to date haven’t effectively separated out for these stressors, making it impossible to weigh their relative impact.

Furthermore, “most of us face many other stressors in our daily lives, such as grief, losses, broken relationships, and personal failures,” she said. “All of these may contribute to psychological distress, and research is needed to determine how much was a product of the virus, other aspects of the pandemic, or unrelated life stressors.”
 

A rallying cry for new interventions

Despite such doubts, a growing number of studies are reporting that health care workers and first responders are experiencing intensified PTSD, depression, anxiety, and insomnia as a result of the pandemic, said Hrayr Pierre Attarian, MD, professor of neurology at Northwestern University, Chicago. These results should act as a rallying cry for implementing more policies tailored to prevent burnout, he said.

“What we are seeing during this terrible pandemic is burnout on steroids,” said Dr. Attarian, medical director of Northwestern’s Center for Sleep Disorders. There are already high burnout rates, “so this should be doubly important.”

Rooting out this problem starts at the institutional level, but merely advising providers to “be well” wouldn’t make inroads. “There needs to be fluid dialogue between health care workers and the leadership,” he said.

Among his proposed remedies: Access to confidential and free mental health resources, increased administrative support, flexible hours, respect for work-life balance, and forgiveness for occasional errors that don’t result in harm.

“Sometimes even the perception that a mistake has been made is taken as proof of guilt,” Dr. Attarian said. “It is not conducive to wellness. Extra income does not replace a nurturing work environment.”

Furthermore, “as a profession, we must stop glorifying ‘overwork.’ We must stop wearing ‘lack of sleep’ as badge of honor,” he said. “Sleep is a biological imperative like self-preservation, hunger, and thirst. When we don’t sleep anxiety, pain, and depression get amplified. Our perception of distress is off, as is our judgment.”

The Federation of State Physician Health Programs provides a directory that physicians can use for referrals to confidential consultation or treatment.

Christopher Bundy, MD, MPH, executive medical director of Washington Physicians Health Program in Seattle, has been following Dr. Hendrickson’s longitudinal study with keen interest. As president of the Federation of State Physician Health Programs, he hopes to translate the findings into practice.

“Obviously, the COVID-19 pandemic has been a ‘black swan’ in terms of workforce sustainability issues,” Dr. Bundy said, citing “high rates of burnout, disillusionment, and dissatisfaction.” He sees some similarities with his former role in treating war veterans.

“The invisible wounds of combat, the psychological scars don’t really become apparent until after you’re out of the war zone,” said Dr. Bundy, clinical associate professor of psychiatry at the University of Washington.

Likewise, he expects the “emotional chickens will come home to roost as the pandemic subsides.” Until then, “people are just focused on survival, and in doing their jobs and protecting their patients.” Eventually, “their own wounds inside the pandemic will take hold.”
 

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

When the COVID-19 pandemic engulfed the nation well over a year ago, Rebecca Hendrickson, MD, PhD, immersed herself in the shell-shocking revelations that clinicians began posting on social media. The accounts offered just a snapshot of the pandemic’s heavy psychological toll, and Dr. Hendrickson, a psychiatrist at the University of Washington in Seattle and an expert in posttraumatic stress disorder (PTSD), wanted to know more.

xavierarnau/Getty Images

She and her colleagues devised a survey to assess the impact of several pandemic-related factors, including increased work hours, social distancing restrictions, and lack of adequate personal protective equipment.

What began as a survey of health care workers soon expanded in scope. Of the more than 600 survey respondents to date, health care workers account for about 60%, while the rest are first responders – police officers, firefighters, paramedics, and emergency medical technicians – and nonclinical personnel, such as security guards and office staff, in health care settings. The respondents range in age from 19 to 72, and hail from all regions of the country.

“Our findings were really striking,” Dr. Hendrickson said, “including very high rates of thoughts of suicide and thoughts of leaving one’s current field, which were both strongly linked to COVID-19–related occupational stress exposure.”

The distress stemmed from a multitude of factors. Among the most demoralizing: witnessing patients die in isolation and being stretched thin to provide optimal care for all patients amid an unrelenting onslaught of COVID-19 cases, she said. For some health care workers, living in the garage or basement – to avoid infecting family members with the virus – also wore on their psyches.

Of all health care workers in the study, more than three-quarters reported symptoms that fell within the clinical range for depression (76%) and anxiety (78%). More than 25% noted that they had lost a family member or close colleague to the virus.

Dr. Hendrickson, who works with military veterans at the VA Puget Sound Hospital System’s Mental Illness Research, Education, and Clinical Center and its PTSD outpatient clinic, hadn’t expected the experience of loss to be so pervasive. She said the sheer number of people who “crossed the threshold” into despair concerned her deeply.
 

Signs and symptoms of PTSD

PTSD’s prevalence among health care workers has always been variable, said Jessica Gold, MD, assistant professor and director of wellness, engagement, and outreach in the department of psychiatry at Washington University in St. Louis.

As a psychiatrist who sees health care workers in her clinical practice, Dr. Gold has noted poor baseline mental health, including depression and trauma. Significant data have pointed to a relatively higher suicide rate among physicians than among the general population. These problems have been compounded by COVID-19.

“It has been an unrelenting series of new stressors,” she said, citing lack of resources; a feeling of being unable to help; and the high frequency of risk of death to patients, family and friends, and the caregivers themselves as just as few examples. “It is very likely going to increase our baseline trauma, and honestly, I don’t know that we can predict how. To me, trauma has no real timeline and can show up months or even years after the pandemic.”

PTSD can manifest itself in health care workers in several different ways. A few commonalities Dr. Gold has observed are sleep disruption (including insomnia and nightmares), work avoidance by taking disability or quitting, irritability or other changes in mood, trouble concentrating, and hypervigilance.

She said she has seen physical manifestations of trauma – such as body pain, stomachaches, and teeth grinding, which “you might not realize are at all related to trauma but ultimately are.” Sometimes, she added, “people have panic attacks on the way to work or right when they get to work, or are thinking about work.”

Dr. Gold noted that different types of treatment, such as cognitive-behavioral therapy and eye movement desensitization and reprocessing (EMDR), can be effective for PTSD. Medication is often necessary because of comorbid anxiety, depression, or eating disorders, said Dr. Gold, who is conducting a study on the pandemic’s effects on medical students.
 

The difficulties in isolating COVID-19 as a contributor

Not all researchers are convinced that a causal relationship has been established between the pandemic and worsening mental health among those in the health care sector.

With provider burnout being a long-standing concern in medicine, Ankur A. Butala, MD, assistant professor of neurology, psychiatry, and behavioral sciences at the Johns Hopkins University, Baltimore, said he remains a bit skeptical that acute stressors during the pandemic amounted to a uniquely potent driving force that can be extrapolated and quantified in a study.

“It’s hard to interpret a chronic, rolling, ongoing trauma like COVID-19 against tools or scales developed to investigate symptoms from a singular and acute trauma, like a school shooting or a [military] firefight,” Dr. Butala said.

In addition, he noted a reluctance to generalizing results from a study in which participants were recruited via social media as opposed to research methods involving more rigorous selection protocols.

Although Dr. Hendrickson acknowledged the study’s limitations, she said her team nonetheless found strong correlations between COVID-19-related stressors and self-reported struggles in completing work-related tasks, as well as increasing thoughts of leaving one’s current field. They adjusted for previous lifetime trauma exposure, age, gender, and a personal history of contracting COVID-19.

The underlying premise of the study could be confirmed with repeated surveys over time, Dr. Butala said, as the COVID-19 pandemic evolves and the vaccination effort unfolds.

Follow-up surveys are being sent to participants every 2 weeks and every 3 months to gauge their mood, for a total follow-up period of 9 months per individual. New participants are still welcome. “We will continue to enroll as long as it seems relevant,” Dr. Hendrickson said.

Carol S. North, MD, MPE, who has added to the growing research on the pandemic’s toll on mental health, noted that because symptom scales do not provide psychiatric diagnoses, it is difficult to attribute the prevalence of psychiatric disorders to the pandemic. Dr. North is chair and professor of crisis psychiatry at UT Southwestern Medical Center in Dallas, and director of the program in trauma and disaster at VA North Texas Health Care System.

The DSM-5 criteria exclude naturally occurring illness, such as a virus (even during a pandemic) as a qualifying trauma for the diagnosis of PTSD. According to current criteria by the American Psychiatric Association, COVID-19 and the pandemic are not defined as trauma, Dr. North said, while noting that “just because it’s not trauma or PTSD does not mean that the pandemic should be discounted as not stressful; people are finding it very stressful.”

Identifying the exact source of distress would still be difficult, Dr. North said, as the pandemic has produced severe economic consequences and prolonged social isolation, as well as occurring alongside nationwide protests over racial and ethnic divisions. Studies to date haven’t effectively separated out for these stressors, making it impossible to weigh their relative impact.

Furthermore, “most of us face many other stressors in our daily lives, such as grief, losses, broken relationships, and personal failures,” she said. “All of these may contribute to psychological distress, and research is needed to determine how much was a product of the virus, other aspects of the pandemic, or unrelated life stressors.”
 

A rallying cry for new interventions

Despite such doubts, a growing number of studies are reporting that health care workers and first responders are experiencing intensified PTSD, depression, anxiety, and insomnia as a result of the pandemic, said Hrayr Pierre Attarian, MD, professor of neurology at Northwestern University, Chicago. These results should act as a rallying cry for implementing more policies tailored to prevent burnout, he said.

“What we are seeing during this terrible pandemic is burnout on steroids,” said Dr. Attarian, medical director of Northwestern’s Center for Sleep Disorders. There are already high burnout rates, “so this should be doubly important.”

Rooting out this problem starts at the institutional level, but merely advising providers to “be well” wouldn’t make inroads. “There needs to be fluid dialogue between health care workers and the leadership,” he said.

Among his proposed remedies: Access to confidential and free mental health resources, increased administrative support, flexible hours, respect for work-life balance, and forgiveness for occasional errors that don’t result in harm.

“Sometimes even the perception that a mistake has been made is taken as proof of guilt,” Dr. Attarian said. “It is not conducive to wellness. Extra income does not replace a nurturing work environment.”

Furthermore, “as a profession, we must stop glorifying ‘overwork.’ We must stop wearing ‘lack of sleep’ as badge of honor,” he said. “Sleep is a biological imperative like self-preservation, hunger, and thirst. When we don’t sleep anxiety, pain, and depression get amplified. Our perception of distress is off, as is our judgment.”

The Federation of State Physician Health Programs provides a directory that physicians can use for referrals to confidential consultation or treatment.

Christopher Bundy, MD, MPH, executive medical director of Washington Physicians Health Program in Seattle, has been following Dr. Hendrickson’s longitudinal study with keen interest. As president of the Federation of State Physician Health Programs, he hopes to translate the findings into practice.

“Obviously, the COVID-19 pandemic has been a ‘black swan’ in terms of workforce sustainability issues,” Dr. Bundy said, citing “high rates of burnout, disillusionment, and dissatisfaction.” He sees some similarities with his former role in treating war veterans.

“The invisible wounds of combat, the psychological scars don’t really become apparent until after you’re out of the war zone,” said Dr. Bundy, clinical associate professor of psychiatry at the University of Washington.

Likewise, he expects the “emotional chickens will come home to roost as the pandemic subsides.” Until then, “people are just focused on survival, and in doing their jobs and protecting their patients.” Eventually, “their own wounds inside the pandemic will take hold.”
 

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

When the COVID-19 pandemic engulfed the nation well over a year ago, Rebecca Hendrickson, MD, PhD, immersed herself in the shell-shocking revelations that clinicians began posting on social media. The accounts offered just a snapshot of the pandemic’s heavy psychological toll, and Dr. Hendrickson, a psychiatrist at the University of Washington in Seattle and an expert in posttraumatic stress disorder (PTSD), wanted to know more.

xavierarnau/Getty Images

She and her colleagues devised a survey to assess the impact of several pandemic-related factors, including increased work hours, social distancing restrictions, and lack of adequate personal protective equipment.

What began as a survey of health care workers soon expanded in scope. Of the more than 600 survey respondents to date, health care workers account for about 60%, while the rest are first responders – police officers, firefighters, paramedics, and emergency medical technicians – and nonclinical personnel, such as security guards and office staff, in health care settings. The respondents range in age from 19 to 72, and hail from all regions of the country.

“Our findings were really striking,” Dr. Hendrickson said, “including very high rates of thoughts of suicide and thoughts of leaving one’s current field, which were both strongly linked to COVID-19–related occupational stress exposure.”

The distress stemmed from a multitude of factors. Among the most demoralizing: witnessing patients die in isolation and being stretched thin to provide optimal care for all patients amid an unrelenting onslaught of COVID-19 cases, she said. For some health care workers, living in the garage or basement – to avoid infecting family members with the virus – also wore on their psyches.

Of all health care workers in the study, more than three-quarters reported symptoms that fell within the clinical range for depression (76%) and anxiety (78%). More than 25% noted that they had lost a family member or close colleague to the virus.

Dr. Hendrickson, who works with military veterans at the VA Puget Sound Hospital System’s Mental Illness Research, Education, and Clinical Center and its PTSD outpatient clinic, hadn’t expected the experience of loss to be so pervasive. She said the sheer number of people who “crossed the threshold” into despair concerned her deeply.
 

Signs and symptoms of PTSD

PTSD’s prevalence among health care workers has always been variable, said Jessica Gold, MD, assistant professor and director of wellness, engagement, and outreach in the department of psychiatry at Washington University in St. Louis.

As a psychiatrist who sees health care workers in her clinical practice, Dr. Gold has noted poor baseline mental health, including depression and trauma. Significant data have pointed to a relatively higher suicide rate among physicians than among the general population. These problems have been compounded by COVID-19.

“It has been an unrelenting series of new stressors,” she said, citing lack of resources; a feeling of being unable to help; and the high frequency of risk of death to patients, family and friends, and the caregivers themselves as just as few examples. “It is very likely going to increase our baseline trauma, and honestly, I don’t know that we can predict how. To me, trauma has no real timeline and can show up months or even years after the pandemic.”

PTSD can manifest itself in health care workers in several different ways. A few commonalities Dr. Gold has observed are sleep disruption (including insomnia and nightmares), work avoidance by taking disability or quitting, irritability or other changes in mood, trouble concentrating, and hypervigilance.

She said she has seen physical manifestations of trauma – such as body pain, stomachaches, and teeth grinding, which “you might not realize are at all related to trauma but ultimately are.” Sometimes, she added, “people have panic attacks on the way to work or right when they get to work, or are thinking about work.”

Dr. Gold noted that different types of treatment, such as cognitive-behavioral therapy and eye movement desensitization and reprocessing (EMDR), can be effective for PTSD. Medication is often necessary because of comorbid anxiety, depression, or eating disorders, said Dr. Gold, who is conducting a study on the pandemic’s effects on medical students.
 

The difficulties in isolating COVID-19 as a contributor

Not all researchers are convinced that a causal relationship has been established between the pandemic and worsening mental health among those in the health care sector.

With provider burnout being a long-standing concern in medicine, Ankur A. Butala, MD, assistant professor of neurology, psychiatry, and behavioral sciences at the Johns Hopkins University, Baltimore, said he remains a bit skeptical that acute stressors during the pandemic amounted to a uniquely potent driving force that can be extrapolated and quantified in a study.

“It’s hard to interpret a chronic, rolling, ongoing trauma like COVID-19 against tools or scales developed to investigate symptoms from a singular and acute trauma, like a school shooting or a [military] firefight,” Dr. Butala said.

In addition, he noted a reluctance to generalizing results from a study in which participants were recruited via social media as opposed to research methods involving more rigorous selection protocols.

Although Dr. Hendrickson acknowledged the study’s limitations, she said her team nonetheless found strong correlations between COVID-19-related stressors and self-reported struggles in completing work-related tasks, as well as increasing thoughts of leaving one’s current field. They adjusted for previous lifetime trauma exposure, age, gender, and a personal history of contracting COVID-19.

The underlying premise of the study could be confirmed with repeated surveys over time, Dr. Butala said, as the COVID-19 pandemic evolves and the vaccination effort unfolds.

Follow-up surveys are being sent to participants every 2 weeks and every 3 months to gauge their mood, for a total follow-up period of 9 months per individual. New participants are still welcome. “We will continue to enroll as long as it seems relevant,” Dr. Hendrickson said.

Carol S. North, MD, MPE, who has added to the growing research on the pandemic’s toll on mental health, noted that because symptom scales do not provide psychiatric diagnoses, it is difficult to attribute the prevalence of psychiatric disorders to the pandemic. Dr. North is chair and professor of crisis psychiatry at UT Southwestern Medical Center in Dallas, and director of the program in trauma and disaster at VA North Texas Health Care System.

The DSM-5 criteria exclude naturally occurring illness, such as a virus (even during a pandemic) as a qualifying trauma for the diagnosis of PTSD. According to current criteria by the American Psychiatric Association, COVID-19 and the pandemic are not defined as trauma, Dr. North said, while noting that “just because it’s not trauma or PTSD does not mean that the pandemic should be discounted as not stressful; people are finding it very stressful.”

Identifying the exact source of distress would still be difficult, Dr. North said, as the pandemic has produced severe economic consequences and prolonged social isolation, as well as occurring alongside nationwide protests over racial and ethnic divisions. Studies to date haven’t effectively separated out for these stressors, making it impossible to weigh their relative impact.

Furthermore, “most of us face many other stressors in our daily lives, such as grief, losses, broken relationships, and personal failures,” she said. “All of these may contribute to psychological distress, and research is needed to determine how much was a product of the virus, other aspects of the pandemic, or unrelated life stressors.”
 

A rallying cry for new interventions

Despite such doubts, a growing number of studies are reporting that health care workers and first responders are experiencing intensified PTSD, depression, anxiety, and insomnia as a result of the pandemic, said Hrayr Pierre Attarian, MD, professor of neurology at Northwestern University, Chicago. These results should act as a rallying cry for implementing more policies tailored to prevent burnout, he said.

“What we are seeing during this terrible pandemic is burnout on steroids,” said Dr. Attarian, medical director of Northwestern’s Center for Sleep Disorders. There are already high burnout rates, “so this should be doubly important.”

Rooting out this problem starts at the institutional level, but merely advising providers to “be well” wouldn’t make inroads. “There needs to be fluid dialogue between health care workers and the leadership,” he said.

Among his proposed remedies: Access to confidential and free mental health resources, increased administrative support, flexible hours, respect for work-life balance, and forgiveness for occasional errors that don’t result in harm.

“Sometimes even the perception that a mistake has been made is taken as proof of guilt,” Dr. Attarian said. “It is not conducive to wellness. Extra income does not replace a nurturing work environment.”

Furthermore, “as a profession, we must stop glorifying ‘overwork.’ We must stop wearing ‘lack of sleep’ as badge of honor,” he said. “Sleep is a biological imperative like self-preservation, hunger, and thirst. When we don’t sleep anxiety, pain, and depression get amplified. Our perception of distress is off, as is our judgment.”

The Federation of State Physician Health Programs provides a directory that physicians can use for referrals to confidential consultation or treatment.

Christopher Bundy, MD, MPH, executive medical director of Washington Physicians Health Program in Seattle, has been following Dr. Hendrickson’s longitudinal study with keen interest. As president of the Federation of State Physician Health Programs, he hopes to translate the findings into practice.

“Obviously, the COVID-19 pandemic has been a ‘black swan’ in terms of workforce sustainability issues,” Dr. Bundy said, citing “high rates of burnout, disillusionment, and dissatisfaction.” He sees some similarities with his former role in treating war veterans.

“The invisible wounds of combat, the psychological scars don’t really become apparent until after you’re out of the war zone,” said Dr. Bundy, clinical associate professor of psychiatry at the University of Washington.

Likewise, he expects the “emotional chickens will come home to roost as the pandemic subsides.” Until then, “people are just focused on survival, and in doing their jobs and protecting their patients.” Eventually, “their own wounds inside the pandemic will take hold.”
 

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