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Schizophrenia meds a key contributor to cognitive impairment
Anticholinergic medication burden from antipsychotics, antidepressants, and other psychotropics has a cumulative effect of worsening cognitive function in patients with schizophrenia, new research indicates.
“The link between long-term use of anticholinergic medications and cognitive impairment is well-known and growing,” lead researcher Yash Joshi, MD, department of psychiatry, University of California, San Diego, said in an interview.
“While this association is relevant for everyone, it is particularly important for those living with schizophrenia, who often struggle with cognitive difficulties conferred by the illness itself,” said Dr. Joshi.
“Brain health in schizophrenia is a game of inches, and even small negative effects on cognitive functioning through anticholinergic medication burden may have large impacts on patients’ lives,” he added.
The study was published online May 14 in the American Journal of Psychiatry.
‘Striking’ results
Dr. Joshi and colleagues set out to comprehensively characterize how the cumulative anticholinergic burden from different classes of medications affect cognition in patients with schizophrenia.
They assessed medical records, including all prescribed medications, for 1,120 adults with a diagnosis of schizophrenia or schizoaffective disorder.
For each participant, prescribed medications were rated and summed using a modified anticholinergic cognitive burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB).
The investigators found that 63% of participants had an ACB score of at least 3, which is “striking,” said Dr. Joshi, given that previous studies have shown that an ACB score of 3 in a healthy, older adult is associated with cognitive dysfunction and a 50% increased risk of developing dementia.
About one-quarter of participants had an ACB score of 6 or higher.
Yet, these high ACB scores are not hard to achieve in routine psychiatric care, the researchers note.
For example, a patient taking olanzapine daily to ease symptoms of psychosis would have an ACB score of 3; if hydroxyzine was added for anxiety or insomnia, the patient’s ACB score would rise to 6, they point out.
Lightening the load
Antipsychotics contributed more than half of the anticholinergic burden, while traditional anticholinergics, antidepressants, mood stabilizers, and benzodiazepines accounted for the remainder.
“It is easy even for well-meaning clinicians to inadvertently contribute to anticholinergic medication burden through routine and appropriate care. The unique finding here is that this burden comes from medications we don’t usually think of as typical anticholinergic agents,” senior author Gregory Light, PhD, with University of California, San Diego, said in a news release.
Anticholinergic medication burden was significantly associated with generalized impairments in cognitive functioning across all cognitive domains on the PCNB with comparable magnitude and after controlling for multiple proxies of functioning or disease severity.
Higher anticholinergic medication burden was associated with worse cognitive performance. The PCNB global cognitive averages for none, low, average, high, and very high anticholinergic burdens were, respectively (in z values), -0.51, -0.70, -0.85, -0.96, and -1.15.
The results suggest “total cumulative anticholinergic burden – rather than anticholinergic burden attributable to a specific antipsychotic or psychotropic medication class – is a key contributor to cognitive impairment in schizophrenia,” the researchers write.
“The results imply that if it is clinically safe and practical,” said Dr. Joshi.
“This may be accomplished by reducing overall polypharmacy or transitioning to equivalent medications with lower overall anticholinergic burden. While ‘traditional’ anticholinergic medications should always be scrutinized, all medications should be carefully evaluated to understand whether they contribute to cumulative anticholinergic medication burden,” he added.
Confirmatory findings
Commenting on the study for this news organization, Jessica Gannon, MD, assistant professor of psychiatry, University of Pittsburgh, said the author’s findings “aren’t surprising, but the work that they did was pretty comprehensive [and] further fleshed out some of our concerns about the impact of anticholinergics on cognitive function in patients with schizophrenia.”
“We certainly have to use some of these medications for patients, like antipsychotics that do have some anticholinergic burden associated with them. We don’t really have other options,” Dr. Gannon said.
“But certainly I think this calls us to be better stewards of medication in general. And when we prescribe for comorbid conditions, like depression and anxiety, we should be careful in our prescribing practices, try not to prescribe an anticholinergic medication, and, if they have been prescribed, to deprescribe them,” Dr. Gannon added.
The study was supported by grants from the National Institute of Mental Health; the Sidney R. Baer, Jr. Foundation; the Brain and Behavior Research Foundation; the VISN-22 Mental Illness Research, Education, and Clinical Center; and the Department of Veterans Affairs. Dr. Joshi and Dr. Gannon have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Anticholinergic medication burden from antipsychotics, antidepressants, and other psychotropics has a cumulative effect of worsening cognitive function in patients with schizophrenia, new research indicates.
“The link between long-term use of anticholinergic medications and cognitive impairment is well-known and growing,” lead researcher Yash Joshi, MD, department of psychiatry, University of California, San Diego, said in an interview.
“While this association is relevant for everyone, it is particularly important for those living with schizophrenia, who often struggle with cognitive difficulties conferred by the illness itself,” said Dr. Joshi.
“Brain health in schizophrenia is a game of inches, and even small negative effects on cognitive functioning through anticholinergic medication burden may have large impacts on patients’ lives,” he added.
The study was published online May 14 in the American Journal of Psychiatry.
‘Striking’ results
Dr. Joshi and colleagues set out to comprehensively characterize how the cumulative anticholinergic burden from different classes of medications affect cognition in patients with schizophrenia.
They assessed medical records, including all prescribed medications, for 1,120 adults with a diagnosis of schizophrenia or schizoaffective disorder.
For each participant, prescribed medications were rated and summed using a modified anticholinergic cognitive burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB).
The investigators found that 63% of participants had an ACB score of at least 3, which is “striking,” said Dr. Joshi, given that previous studies have shown that an ACB score of 3 in a healthy, older adult is associated with cognitive dysfunction and a 50% increased risk of developing dementia.
About one-quarter of participants had an ACB score of 6 or higher.
Yet, these high ACB scores are not hard to achieve in routine psychiatric care, the researchers note.
For example, a patient taking olanzapine daily to ease symptoms of psychosis would have an ACB score of 3; if hydroxyzine was added for anxiety or insomnia, the patient’s ACB score would rise to 6, they point out.
Lightening the load
Antipsychotics contributed more than half of the anticholinergic burden, while traditional anticholinergics, antidepressants, mood stabilizers, and benzodiazepines accounted for the remainder.
“It is easy even for well-meaning clinicians to inadvertently contribute to anticholinergic medication burden through routine and appropriate care. The unique finding here is that this burden comes from medications we don’t usually think of as typical anticholinergic agents,” senior author Gregory Light, PhD, with University of California, San Diego, said in a news release.
Anticholinergic medication burden was significantly associated with generalized impairments in cognitive functioning across all cognitive domains on the PCNB with comparable magnitude and after controlling for multiple proxies of functioning or disease severity.
Higher anticholinergic medication burden was associated with worse cognitive performance. The PCNB global cognitive averages for none, low, average, high, and very high anticholinergic burdens were, respectively (in z values), -0.51, -0.70, -0.85, -0.96, and -1.15.
The results suggest “total cumulative anticholinergic burden – rather than anticholinergic burden attributable to a specific antipsychotic or psychotropic medication class – is a key contributor to cognitive impairment in schizophrenia,” the researchers write.
“The results imply that if it is clinically safe and practical,” said Dr. Joshi.
“This may be accomplished by reducing overall polypharmacy or transitioning to equivalent medications with lower overall anticholinergic burden. While ‘traditional’ anticholinergic medications should always be scrutinized, all medications should be carefully evaluated to understand whether they contribute to cumulative anticholinergic medication burden,” he added.
Confirmatory findings
Commenting on the study for this news organization, Jessica Gannon, MD, assistant professor of psychiatry, University of Pittsburgh, said the author’s findings “aren’t surprising, but the work that they did was pretty comprehensive [and] further fleshed out some of our concerns about the impact of anticholinergics on cognitive function in patients with schizophrenia.”
“We certainly have to use some of these medications for patients, like antipsychotics that do have some anticholinergic burden associated with them. We don’t really have other options,” Dr. Gannon said.
“But certainly I think this calls us to be better stewards of medication in general. And when we prescribe for comorbid conditions, like depression and anxiety, we should be careful in our prescribing practices, try not to prescribe an anticholinergic medication, and, if they have been prescribed, to deprescribe them,” Dr. Gannon added.
The study was supported by grants from the National Institute of Mental Health; the Sidney R. Baer, Jr. Foundation; the Brain and Behavior Research Foundation; the VISN-22 Mental Illness Research, Education, and Clinical Center; and the Department of Veterans Affairs. Dr. Joshi and Dr. Gannon have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Anticholinergic medication burden from antipsychotics, antidepressants, and other psychotropics has a cumulative effect of worsening cognitive function in patients with schizophrenia, new research indicates.
“The link between long-term use of anticholinergic medications and cognitive impairment is well-known and growing,” lead researcher Yash Joshi, MD, department of psychiatry, University of California, San Diego, said in an interview.
“While this association is relevant for everyone, it is particularly important for those living with schizophrenia, who often struggle with cognitive difficulties conferred by the illness itself,” said Dr. Joshi.
“Brain health in schizophrenia is a game of inches, and even small negative effects on cognitive functioning through anticholinergic medication burden may have large impacts on patients’ lives,” he added.
The study was published online May 14 in the American Journal of Psychiatry.
‘Striking’ results
Dr. Joshi and colleagues set out to comprehensively characterize how the cumulative anticholinergic burden from different classes of medications affect cognition in patients with schizophrenia.
They assessed medical records, including all prescribed medications, for 1,120 adults with a diagnosis of schizophrenia or schizoaffective disorder.
For each participant, prescribed medications were rated and summed using a modified anticholinergic cognitive burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB).
The investigators found that 63% of participants had an ACB score of at least 3, which is “striking,” said Dr. Joshi, given that previous studies have shown that an ACB score of 3 in a healthy, older adult is associated with cognitive dysfunction and a 50% increased risk of developing dementia.
About one-quarter of participants had an ACB score of 6 or higher.
Yet, these high ACB scores are not hard to achieve in routine psychiatric care, the researchers note.
For example, a patient taking olanzapine daily to ease symptoms of psychosis would have an ACB score of 3; if hydroxyzine was added for anxiety or insomnia, the patient’s ACB score would rise to 6, they point out.
Lightening the load
Antipsychotics contributed more than half of the anticholinergic burden, while traditional anticholinergics, antidepressants, mood stabilizers, and benzodiazepines accounted for the remainder.
“It is easy even for well-meaning clinicians to inadvertently contribute to anticholinergic medication burden through routine and appropriate care. The unique finding here is that this burden comes from medications we don’t usually think of as typical anticholinergic agents,” senior author Gregory Light, PhD, with University of California, San Diego, said in a news release.
Anticholinergic medication burden was significantly associated with generalized impairments in cognitive functioning across all cognitive domains on the PCNB with comparable magnitude and after controlling for multiple proxies of functioning or disease severity.
Higher anticholinergic medication burden was associated with worse cognitive performance. The PCNB global cognitive averages for none, low, average, high, and very high anticholinergic burdens were, respectively (in z values), -0.51, -0.70, -0.85, -0.96, and -1.15.
The results suggest “total cumulative anticholinergic burden – rather than anticholinergic burden attributable to a specific antipsychotic or psychotropic medication class – is a key contributor to cognitive impairment in schizophrenia,” the researchers write.
“The results imply that if it is clinically safe and practical,” said Dr. Joshi.
“This may be accomplished by reducing overall polypharmacy or transitioning to equivalent medications with lower overall anticholinergic burden. While ‘traditional’ anticholinergic medications should always be scrutinized, all medications should be carefully evaluated to understand whether they contribute to cumulative anticholinergic medication burden,” he added.
Confirmatory findings
Commenting on the study for this news organization, Jessica Gannon, MD, assistant professor of psychiatry, University of Pittsburgh, said the author’s findings “aren’t surprising, but the work that they did was pretty comprehensive [and] further fleshed out some of our concerns about the impact of anticholinergics on cognitive function in patients with schizophrenia.”
“We certainly have to use some of these medications for patients, like antipsychotics that do have some anticholinergic burden associated with them. We don’t really have other options,” Dr. Gannon said.
“But certainly I think this calls us to be better stewards of medication in general. And when we prescribe for comorbid conditions, like depression and anxiety, we should be careful in our prescribing practices, try not to prescribe an anticholinergic medication, and, if they have been prescribed, to deprescribe them,” Dr. Gannon added.
The study was supported by grants from the National Institute of Mental Health; the Sidney R. Baer, Jr. Foundation; the Brain and Behavior Research Foundation; the VISN-22 Mental Illness Research, Education, and Clinical Center; and the Department of Veterans Affairs. Dr. Joshi and Dr. Gannon have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sleep Medicine A Special Report
Sleep Medicine A Special Report
- MOBILE PHONE RELIANCE
How it’s linked to young adults’ sleep problems in two studies - OBSTRUCTIVE SLEEP APNEA
New research validates phenotypes in Latinos - DEMENTIA
Papers show associations between disease and sleep therapies
Sleep Medicine A Special Report
- MOBILE PHONE RELIANCE
How it’s linked to young adults’ sleep problems in two studies - OBSTRUCTIVE SLEEP APNEA
New research validates phenotypes in Latinos - DEMENTIA
Papers show associations between disease and sleep therapies
Sleep Medicine A Special Report
- MOBILE PHONE RELIANCE
How it’s linked to young adults’ sleep problems in two studies - OBSTRUCTIVE SLEEP APNEA
New research validates phenotypes in Latinos - DEMENTIA
Papers show associations between disease and sleep therapies
Psychiatric fallout from long-COVID: How to prepare
As mounting evidence points to a significant psychiatric component of COVID-19, experts are concerned about an influx of survivors presenting with persistent mental health problems and how best to prepare.
Clinicians should be aware that patients who have had COVID frequently develop psychiatric symptoms, Silvia S. Martins, MD, PhD, associate professor of epidemiology, Columbia University, New York, said in an interview.
“There should be more screening of all patients recovering from a COVID infection for anxiety, posttraumatic stress disorder, and depression, as well as referral to services, including psychotherapy, and medication as needed,” said Dr. Martins, who, along with colleagues, uncovered a high rate of these symptoms in patients who had the disease.
The COVID-19 pandemic has taken an enormous social, emotional, and public health toll. It has disrupted lives and caused stress, fear, and uncertainty about loss of health and income, not to mention forced isolation.
In addition, a significant number of patients who contract COVID-19 continue to have symptoms after the acute phase of the illness. This post-COVID, or “long-haul,” syndrome isn’t well defined; experts cite a range of symptoms that persist for weeks or months.
These ongoing symptoms can include cough, fatigue, and chronic pain, as well as psychiatric complaints. As reported by this news organization, an observational study of more than 230,000 U.S. patient health records revealed that one in three COVID-19 survivors received a psychiatric or neurologic diagnosis within 6 months of contracting the virus.
The most common psychiatric diagnoses were anxiety disorders, mood disorders, substance misuse disorders, and insomnia.
Significant symptoms even in mild cases
Another study showed that even those with mild COVID-19 may experience psychiatric symptoms independently of previous psychiatric diagnoses. Results revealed that 26% of the sample of almost 900 patients reported depression, 22% reported anxiety, and 17% reported symptoms of posttraumatic stress 2 months after testing positive for the virus. This finding is important because the majority of individuals who contract COVID-19 have a mild case.
“We saw very high levels of clinically significant depression, anxiety, and posttraumatic stress symptoms in people who had mild disease,” study investigator João Mauricio Castaldelli-Maia, MD, PhD, postdoctoral fellow, department of epidemiology, Columbia University, said in an interview.
He attributed these symptoms in part to long periods of isolation, even from relatives in the same household, in cramped spaces typical of large cities such as São Paulo.
Social isolation can have a huge impact on persons who depend on social connections and relationships, Vivian Pender, MD, president of the American Psychiatric Association and clinical professor of psychiatry, Weill Cornell Medical Center, New York, said in an interview.
“The fact that we have not been able to see our colleagues, our friends, our family, and in the case of psychiatrists, even our patients has taken a toll on everyone, and that leads to more stress, more anxiety,” she said.
National surveys show that psychiatric symptoms occur after acute COVID. One survey revealed that over 50% of 3,900 respondents who had COVID reported having at least moderate symptoms of major depression.
Unique depression subtype?
Another survey, slated for publication later this year, shows that lead investigator Roy Perlis, MD, professor of psychiatry, Harvard Medical School, Boston, said in an interview.
This might suggest a neurobiological element. Researchers are speculating as to whether lingering psychiatric problems that occur after having COVID are linked to the psychosocial impact of the disease or to pathological processes, such as inflammation, that affect the brain.
Although rates of post-COVID psychiatric symptoms vary from study to study, “they seem to be pretty enduring,” noted Faith Gunning, PhD, vice chair of research, department of psychology, Weill Cornell Medicine, who specializes in clinical neuropsychology.
“So they’re not just a brief response” to getting sick, a fact that points to the possible need for treatment, she told this news organization. “In some of the work that’s starting to emerge, it does appear that the symptoms persist, at least for a relatively large subset of individuals.”
Although depression typically affects twice as many women as men, these new surveys show that, after COVID, “that difference is not so distinct,” said Dr. Gunning.
It’s unclear why this is, but it could be cause by financial stresses that may affect men to a greater extent, she added. “There is so much we’re still learning.”
Increased suicide risk?
Other researchers, including Leo Sher, MD, professor of psychiatry, Icahn School of Medicine at Mount Sinai, and director of inpatient psychiatry, James J. Peters Veterans Affairs Medical Center, both in New York, are concerned that higher rates of psychiatric symptoms among patients with long-haul COVID raise the risk for suicidal ideation and behavior.
Studies of suicidality in COVID-19 survivors “are urgently needed,” said Dr. Sher in an article published in the Monthly Journal of the Association of Physicians.
“We need to study what factors may increase suicide risk among the COVID-19 survivors during and after the recovery. We also need to investigate whether there is a long-term increased suicide risk among COVID-19 survivors,” Dr. Sher said.
COVID-19 is not unique among viral respiratory diseases in being associated with long-term mental health problems. Research shows that survivors of the 2003 outbreak of severe acute respiratory syndrome experienced increased psychological distress that persisted for at least a year, as did patients who in 2015 had Middle East respiratory syndrome coronavirus (MERS-CoV).
Some experts believe clinicians should screen patients for mental health symptoms after the acute phase of COVID and offer early and prolonged care.
“Early mental health intervention such as psychotherapy and supportive groups could play an important role in preventing incident mental health problems for post-COVID sufferers,” said Dr. Castaldelli-Maia.
A version of this article first appeared on Medscape.com.
As mounting evidence points to a significant psychiatric component of COVID-19, experts are concerned about an influx of survivors presenting with persistent mental health problems and how best to prepare.
Clinicians should be aware that patients who have had COVID frequently develop psychiatric symptoms, Silvia S. Martins, MD, PhD, associate professor of epidemiology, Columbia University, New York, said in an interview.
“There should be more screening of all patients recovering from a COVID infection for anxiety, posttraumatic stress disorder, and depression, as well as referral to services, including psychotherapy, and medication as needed,” said Dr. Martins, who, along with colleagues, uncovered a high rate of these symptoms in patients who had the disease.
The COVID-19 pandemic has taken an enormous social, emotional, and public health toll. It has disrupted lives and caused stress, fear, and uncertainty about loss of health and income, not to mention forced isolation.
In addition, a significant number of patients who contract COVID-19 continue to have symptoms after the acute phase of the illness. This post-COVID, or “long-haul,” syndrome isn’t well defined; experts cite a range of symptoms that persist for weeks or months.
These ongoing symptoms can include cough, fatigue, and chronic pain, as well as psychiatric complaints. As reported by this news organization, an observational study of more than 230,000 U.S. patient health records revealed that one in three COVID-19 survivors received a psychiatric or neurologic diagnosis within 6 months of contracting the virus.
The most common psychiatric diagnoses were anxiety disorders, mood disorders, substance misuse disorders, and insomnia.
Significant symptoms even in mild cases
Another study showed that even those with mild COVID-19 may experience psychiatric symptoms independently of previous psychiatric diagnoses. Results revealed that 26% of the sample of almost 900 patients reported depression, 22% reported anxiety, and 17% reported symptoms of posttraumatic stress 2 months after testing positive for the virus. This finding is important because the majority of individuals who contract COVID-19 have a mild case.
“We saw very high levels of clinically significant depression, anxiety, and posttraumatic stress symptoms in people who had mild disease,” study investigator João Mauricio Castaldelli-Maia, MD, PhD, postdoctoral fellow, department of epidemiology, Columbia University, said in an interview.
He attributed these symptoms in part to long periods of isolation, even from relatives in the same household, in cramped spaces typical of large cities such as São Paulo.
Social isolation can have a huge impact on persons who depend on social connections and relationships, Vivian Pender, MD, president of the American Psychiatric Association and clinical professor of psychiatry, Weill Cornell Medical Center, New York, said in an interview.
“The fact that we have not been able to see our colleagues, our friends, our family, and in the case of psychiatrists, even our patients has taken a toll on everyone, and that leads to more stress, more anxiety,” she said.
National surveys show that psychiatric symptoms occur after acute COVID. One survey revealed that over 50% of 3,900 respondents who had COVID reported having at least moderate symptoms of major depression.
Unique depression subtype?
Another survey, slated for publication later this year, shows that lead investigator Roy Perlis, MD, professor of psychiatry, Harvard Medical School, Boston, said in an interview.
This might suggest a neurobiological element. Researchers are speculating as to whether lingering psychiatric problems that occur after having COVID are linked to the psychosocial impact of the disease or to pathological processes, such as inflammation, that affect the brain.
Although rates of post-COVID psychiatric symptoms vary from study to study, “they seem to be pretty enduring,” noted Faith Gunning, PhD, vice chair of research, department of psychology, Weill Cornell Medicine, who specializes in clinical neuropsychology.
“So they’re not just a brief response” to getting sick, a fact that points to the possible need for treatment, she told this news organization. “In some of the work that’s starting to emerge, it does appear that the symptoms persist, at least for a relatively large subset of individuals.”
Although depression typically affects twice as many women as men, these new surveys show that, after COVID, “that difference is not so distinct,” said Dr. Gunning.
It’s unclear why this is, but it could be cause by financial stresses that may affect men to a greater extent, she added. “There is so much we’re still learning.”
Increased suicide risk?
Other researchers, including Leo Sher, MD, professor of psychiatry, Icahn School of Medicine at Mount Sinai, and director of inpatient psychiatry, James J. Peters Veterans Affairs Medical Center, both in New York, are concerned that higher rates of psychiatric symptoms among patients with long-haul COVID raise the risk for suicidal ideation and behavior.
Studies of suicidality in COVID-19 survivors “are urgently needed,” said Dr. Sher in an article published in the Monthly Journal of the Association of Physicians.
“We need to study what factors may increase suicide risk among the COVID-19 survivors during and after the recovery. We also need to investigate whether there is a long-term increased suicide risk among COVID-19 survivors,” Dr. Sher said.
COVID-19 is not unique among viral respiratory diseases in being associated with long-term mental health problems. Research shows that survivors of the 2003 outbreak of severe acute respiratory syndrome experienced increased psychological distress that persisted for at least a year, as did patients who in 2015 had Middle East respiratory syndrome coronavirus (MERS-CoV).
Some experts believe clinicians should screen patients for mental health symptoms after the acute phase of COVID and offer early and prolonged care.
“Early mental health intervention such as psychotherapy and supportive groups could play an important role in preventing incident mental health problems for post-COVID sufferers,” said Dr. Castaldelli-Maia.
A version of this article first appeared on Medscape.com.
As mounting evidence points to a significant psychiatric component of COVID-19, experts are concerned about an influx of survivors presenting with persistent mental health problems and how best to prepare.
Clinicians should be aware that patients who have had COVID frequently develop psychiatric symptoms, Silvia S. Martins, MD, PhD, associate professor of epidemiology, Columbia University, New York, said in an interview.
“There should be more screening of all patients recovering from a COVID infection for anxiety, posttraumatic stress disorder, and depression, as well as referral to services, including psychotherapy, and medication as needed,” said Dr. Martins, who, along with colleagues, uncovered a high rate of these symptoms in patients who had the disease.
The COVID-19 pandemic has taken an enormous social, emotional, and public health toll. It has disrupted lives and caused stress, fear, and uncertainty about loss of health and income, not to mention forced isolation.
In addition, a significant number of patients who contract COVID-19 continue to have symptoms after the acute phase of the illness. This post-COVID, or “long-haul,” syndrome isn’t well defined; experts cite a range of symptoms that persist for weeks or months.
These ongoing symptoms can include cough, fatigue, and chronic pain, as well as psychiatric complaints. As reported by this news organization, an observational study of more than 230,000 U.S. patient health records revealed that one in three COVID-19 survivors received a psychiatric or neurologic diagnosis within 6 months of contracting the virus.
The most common psychiatric diagnoses were anxiety disorders, mood disorders, substance misuse disorders, and insomnia.
Significant symptoms even in mild cases
Another study showed that even those with mild COVID-19 may experience psychiatric symptoms independently of previous psychiatric diagnoses. Results revealed that 26% of the sample of almost 900 patients reported depression, 22% reported anxiety, and 17% reported symptoms of posttraumatic stress 2 months after testing positive for the virus. This finding is important because the majority of individuals who contract COVID-19 have a mild case.
“We saw very high levels of clinically significant depression, anxiety, and posttraumatic stress symptoms in people who had mild disease,” study investigator João Mauricio Castaldelli-Maia, MD, PhD, postdoctoral fellow, department of epidemiology, Columbia University, said in an interview.
He attributed these symptoms in part to long periods of isolation, even from relatives in the same household, in cramped spaces typical of large cities such as São Paulo.
Social isolation can have a huge impact on persons who depend on social connections and relationships, Vivian Pender, MD, president of the American Psychiatric Association and clinical professor of psychiatry, Weill Cornell Medical Center, New York, said in an interview.
“The fact that we have not been able to see our colleagues, our friends, our family, and in the case of psychiatrists, even our patients has taken a toll on everyone, and that leads to more stress, more anxiety,” she said.
National surveys show that psychiatric symptoms occur after acute COVID. One survey revealed that over 50% of 3,900 respondents who had COVID reported having at least moderate symptoms of major depression.
Unique depression subtype?
Another survey, slated for publication later this year, shows that lead investigator Roy Perlis, MD, professor of psychiatry, Harvard Medical School, Boston, said in an interview.
This might suggest a neurobiological element. Researchers are speculating as to whether lingering psychiatric problems that occur after having COVID are linked to the psychosocial impact of the disease or to pathological processes, such as inflammation, that affect the brain.
Although rates of post-COVID psychiatric symptoms vary from study to study, “they seem to be pretty enduring,” noted Faith Gunning, PhD, vice chair of research, department of psychology, Weill Cornell Medicine, who specializes in clinical neuropsychology.
“So they’re not just a brief response” to getting sick, a fact that points to the possible need for treatment, she told this news organization. “In some of the work that’s starting to emerge, it does appear that the symptoms persist, at least for a relatively large subset of individuals.”
Although depression typically affects twice as many women as men, these new surveys show that, after COVID, “that difference is not so distinct,” said Dr. Gunning.
It’s unclear why this is, but it could be cause by financial stresses that may affect men to a greater extent, she added. “There is so much we’re still learning.”
Increased suicide risk?
Other researchers, including Leo Sher, MD, professor of psychiatry, Icahn School of Medicine at Mount Sinai, and director of inpatient psychiatry, James J. Peters Veterans Affairs Medical Center, both in New York, are concerned that higher rates of psychiatric symptoms among patients with long-haul COVID raise the risk for suicidal ideation and behavior.
Studies of suicidality in COVID-19 survivors “are urgently needed,” said Dr. Sher in an article published in the Monthly Journal of the Association of Physicians.
“We need to study what factors may increase suicide risk among the COVID-19 survivors during and after the recovery. We also need to investigate whether there is a long-term increased suicide risk among COVID-19 survivors,” Dr. Sher said.
COVID-19 is not unique among viral respiratory diseases in being associated with long-term mental health problems. Research shows that survivors of the 2003 outbreak of severe acute respiratory syndrome experienced increased psychological distress that persisted for at least a year, as did patients who in 2015 had Middle East respiratory syndrome coronavirus (MERS-CoV).
Some experts believe clinicians should screen patients for mental health symptoms after the acute phase of COVID and offer early and prolonged care.
“Early mental health intervention such as psychotherapy and supportive groups could play an important role in preventing incident mental health problems for post-COVID sufferers,” said Dr. Castaldelli-Maia.
A version of this article first appeared on Medscape.com.
Obstructive sleep apnea linked to COVID-19 risk
Greater severity of obstructive sleep apnea (OSA) is associated with a higher risk of contracting COVID-19, and positive airway pressure (PAP) treatment may counter that risk, according to a retrospective analysis from the records of Kaiser Permanente Southern California.
OSA patients often worry that PAP therapy might increase risk of severe COVID-19, said Dennis Hwang, MD, who presented the study at the American Thoracic Society’s virtual international conference (Abstract A1108). But the findings should be reassuring. “If you have obstructive sleep apnea, and you’re supposed to be using PAP, we recommend that you continue using PAP. It’s good for your overall wellness and reducing the risk of cardiovascular disease, but as it relates to COVID-19, it’s possible that it could protect. And there doesn’t appear to be any risk of increased severity of illness (with use of PAP),” Dr. Hwang said in an interview. He is medical director of sleep medicine for Kaiser Permanente San Bernardino County and cochair of sleep medicine for Kaiser Southern California.
He noted that the retrospective nature of the study makes it difficult to pin down whether PAP therapy is truly protective, “but I think there’s enough that we’ve been able conceptually to understand, to suggest that a direct causative relationship is possible,” said Dr. Hwang.
The results may imply that OSA patients should pay special attention to their OSA when there’s concern about exposure to an infectious agent like SARS-CoV-2. “The intermittent hypoxia at night, which can linger over to the day as increased sympathetic activity, increased heart rate. All of these are stresses to the body. So if you’re going to get infected, you want to start at a healthier level. You want to eliminate your sleep apnea to help reduce your risk of morbidity,” said Esra Tasali, MD, who was asked to comment on the study. Dr. Tasali is associate professor of medicine at the University of Chicago, and director of the Sleep Research Center there.
During the Q&A session after the talk, audience members asked about the timing of PAP use during COVID-19 infection, for example how often it was used during the asymptomatic phase of infection and if PAP has a positive effect. The data were not available, but “I think that the way to go is to understand this chronology,” said Dr. Tasali.
The researchers examined records between 2015 and 2020, using sleep study data, remotely collected daily PAP data, and electronic health records, all from Kaiser Permanente Southern California. Included subjects were adults who had enrolled before Feb. 1, 2020, and had sleep diagnostic or PAP data on record by March 1, 2020. The researchers analyzed PAP adherence between March 1, 2020, and the time of COVID-19 diagnosis, or until the study ended on July 31, 2020.
Patients were defined as being untreated (< 2 hours/night PAP), moderately treated (2-3.9 hours/night), or well treated (4 or more hours/night). Apnea hypopnea index (AHI) was used to determine severity. The analysis included 81,932 patients (39.8% were women, mean age was 54.0 years, 9.9% were Black, and 34.5% were Hispanic). A total of 1.7% of subjects without OSA experienced COVID-19 infection, compared to 1.8% with OSA; 0.3% with OSA were hospitalized and 0.07% underwent intensive care or died.
There were some differences between the two groups. The non-USA population was younger (mean age 47.0 vs. 54.5 years), was less likely to be men (44% vs. 60.3%), had a lower mean body mass index (30.4 vs. 34.3), had fewer comorbidities according to the Charleston Comorbidity Index (1.3 vs. 2.0), and were less likely to have hypertension (5.6% vs. 12.4%; P < .0001 for all).
Infection rates were higher in patients with more severe OSA. The rates in untreated mild, moderate, and severe OSA were 2%, 2%, and 2.4% respectively. The rate among all treated patients was 1.4% (P < .0001). Infection rates also dropped among patients with better treatment: untreated, 2.1%; moderately treated, 1.7%; and well treated, 1.3% (P < .0001).
Not having OSA was associated with a lower infection risk than was having OSA (odds ratio [OR], 0.82; 95% confidence interval, 0.70-0.96). Compared to untreated patients, there was lower infection risk in the moderately treated (OR, 0.82; 95% CI, 0.65-1.03) and well treated (OR, 0.68; 95% CI, 0.59-0.79) groups. Higher infection rates were associated with obesity, higher Charlson Comorbidity score (> 2; OR, 1.29; 95% CI, 1.09-1.53), Black (OR, 1.51; 95% CI, 1.24-1.84) and Hispanic ethnicities (OR, 2.23; 95% CI, 1.96-2.54), and Medicaid enrollment. Increasing age was associated with lower risk of infection, with each 5-year increment linked to reduced risk (OR, 0.88; 95% CI, 0.86-0.90). Dr. Hwang suggested that the age association may be because older individuals were more likely to follow social distancing and other precautions.
A multivariate analysis found that OSA was associated with infection risk according to OSA severity, including mild (OR, 1.21; 95% CI, 1.01-1.44), and moderate to severe (OR, 1.27; 95% CI, 1.07-1.51). There was no association between hospitalization rate or ICU admission/death and presence of OSA or PAP adherence in the data presented, but Dr. Hwang said that an updated analysis suggests that OSA may be associated with a risk of greater COVID-19 severity.
The control group was composed of individuals who had undergone sleep testing, but found to not have OSA. Still, they aren’t necessarily representative of the general population, since symptoms likely drove them to testing. A high percentage were also obese, and the average BMI was 30. “It’s certainly not a ‘normal population,’ but the advantage of what we did in terms of using this control group is that they underwent sleep testing, so they were proven to have no obstructive sleep apnea, whereas if we used a general population, we just don’t know,” said Dr. Hwang.
The study received technical and data support from Somnoware, and was funded by Kaiser Permanente. Dr. Tasali has no relevant financial disclosures.
Greater severity of obstructive sleep apnea (OSA) is associated with a higher risk of contracting COVID-19, and positive airway pressure (PAP) treatment may counter that risk, according to a retrospective analysis from the records of Kaiser Permanente Southern California.
OSA patients often worry that PAP therapy might increase risk of severe COVID-19, said Dennis Hwang, MD, who presented the study at the American Thoracic Society’s virtual international conference (Abstract A1108). But the findings should be reassuring. “If you have obstructive sleep apnea, and you’re supposed to be using PAP, we recommend that you continue using PAP. It’s good for your overall wellness and reducing the risk of cardiovascular disease, but as it relates to COVID-19, it’s possible that it could protect. And there doesn’t appear to be any risk of increased severity of illness (with use of PAP),” Dr. Hwang said in an interview. He is medical director of sleep medicine for Kaiser Permanente San Bernardino County and cochair of sleep medicine for Kaiser Southern California.
He noted that the retrospective nature of the study makes it difficult to pin down whether PAP therapy is truly protective, “but I think there’s enough that we’ve been able conceptually to understand, to suggest that a direct causative relationship is possible,” said Dr. Hwang.
The results may imply that OSA patients should pay special attention to their OSA when there’s concern about exposure to an infectious agent like SARS-CoV-2. “The intermittent hypoxia at night, which can linger over to the day as increased sympathetic activity, increased heart rate. All of these are stresses to the body. So if you’re going to get infected, you want to start at a healthier level. You want to eliminate your sleep apnea to help reduce your risk of morbidity,” said Esra Tasali, MD, who was asked to comment on the study. Dr. Tasali is associate professor of medicine at the University of Chicago, and director of the Sleep Research Center there.
During the Q&A session after the talk, audience members asked about the timing of PAP use during COVID-19 infection, for example how often it was used during the asymptomatic phase of infection and if PAP has a positive effect. The data were not available, but “I think that the way to go is to understand this chronology,” said Dr. Tasali.
The researchers examined records between 2015 and 2020, using sleep study data, remotely collected daily PAP data, and electronic health records, all from Kaiser Permanente Southern California. Included subjects were adults who had enrolled before Feb. 1, 2020, and had sleep diagnostic or PAP data on record by March 1, 2020. The researchers analyzed PAP adherence between March 1, 2020, and the time of COVID-19 diagnosis, or until the study ended on July 31, 2020.
Patients were defined as being untreated (< 2 hours/night PAP), moderately treated (2-3.9 hours/night), or well treated (4 or more hours/night). Apnea hypopnea index (AHI) was used to determine severity. The analysis included 81,932 patients (39.8% were women, mean age was 54.0 years, 9.9% were Black, and 34.5% were Hispanic). A total of 1.7% of subjects without OSA experienced COVID-19 infection, compared to 1.8% with OSA; 0.3% with OSA were hospitalized and 0.07% underwent intensive care or died.
There were some differences between the two groups. The non-USA population was younger (mean age 47.0 vs. 54.5 years), was less likely to be men (44% vs. 60.3%), had a lower mean body mass index (30.4 vs. 34.3), had fewer comorbidities according to the Charleston Comorbidity Index (1.3 vs. 2.0), and were less likely to have hypertension (5.6% vs. 12.4%; P < .0001 for all).
Infection rates were higher in patients with more severe OSA. The rates in untreated mild, moderate, and severe OSA were 2%, 2%, and 2.4% respectively. The rate among all treated patients was 1.4% (P < .0001). Infection rates also dropped among patients with better treatment: untreated, 2.1%; moderately treated, 1.7%; and well treated, 1.3% (P < .0001).
Not having OSA was associated with a lower infection risk than was having OSA (odds ratio [OR], 0.82; 95% confidence interval, 0.70-0.96). Compared to untreated patients, there was lower infection risk in the moderately treated (OR, 0.82; 95% CI, 0.65-1.03) and well treated (OR, 0.68; 95% CI, 0.59-0.79) groups. Higher infection rates were associated with obesity, higher Charlson Comorbidity score (> 2; OR, 1.29; 95% CI, 1.09-1.53), Black (OR, 1.51; 95% CI, 1.24-1.84) and Hispanic ethnicities (OR, 2.23; 95% CI, 1.96-2.54), and Medicaid enrollment. Increasing age was associated with lower risk of infection, with each 5-year increment linked to reduced risk (OR, 0.88; 95% CI, 0.86-0.90). Dr. Hwang suggested that the age association may be because older individuals were more likely to follow social distancing and other precautions.
A multivariate analysis found that OSA was associated with infection risk according to OSA severity, including mild (OR, 1.21; 95% CI, 1.01-1.44), and moderate to severe (OR, 1.27; 95% CI, 1.07-1.51). There was no association between hospitalization rate or ICU admission/death and presence of OSA or PAP adherence in the data presented, but Dr. Hwang said that an updated analysis suggests that OSA may be associated with a risk of greater COVID-19 severity.
The control group was composed of individuals who had undergone sleep testing, but found to not have OSA. Still, they aren’t necessarily representative of the general population, since symptoms likely drove them to testing. A high percentage were also obese, and the average BMI was 30. “It’s certainly not a ‘normal population,’ but the advantage of what we did in terms of using this control group is that they underwent sleep testing, so they were proven to have no obstructive sleep apnea, whereas if we used a general population, we just don’t know,” said Dr. Hwang.
The study received technical and data support from Somnoware, and was funded by Kaiser Permanente. Dr. Tasali has no relevant financial disclosures.
Greater severity of obstructive sleep apnea (OSA) is associated with a higher risk of contracting COVID-19, and positive airway pressure (PAP) treatment may counter that risk, according to a retrospective analysis from the records of Kaiser Permanente Southern California.
OSA patients often worry that PAP therapy might increase risk of severe COVID-19, said Dennis Hwang, MD, who presented the study at the American Thoracic Society’s virtual international conference (Abstract A1108). But the findings should be reassuring. “If you have obstructive sleep apnea, and you’re supposed to be using PAP, we recommend that you continue using PAP. It’s good for your overall wellness and reducing the risk of cardiovascular disease, but as it relates to COVID-19, it’s possible that it could protect. And there doesn’t appear to be any risk of increased severity of illness (with use of PAP),” Dr. Hwang said in an interview. He is medical director of sleep medicine for Kaiser Permanente San Bernardino County and cochair of sleep medicine for Kaiser Southern California.
He noted that the retrospective nature of the study makes it difficult to pin down whether PAP therapy is truly protective, “but I think there’s enough that we’ve been able conceptually to understand, to suggest that a direct causative relationship is possible,” said Dr. Hwang.
The results may imply that OSA patients should pay special attention to their OSA when there’s concern about exposure to an infectious agent like SARS-CoV-2. “The intermittent hypoxia at night, which can linger over to the day as increased sympathetic activity, increased heart rate. All of these are stresses to the body. So if you’re going to get infected, you want to start at a healthier level. You want to eliminate your sleep apnea to help reduce your risk of morbidity,” said Esra Tasali, MD, who was asked to comment on the study. Dr. Tasali is associate professor of medicine at the University of Chicago, and director of the Sleep Research Center there.
During the Q&A session after the talk, audience members asked about the timing of PAP use during COVID-19 infection, for example how often it was used during the asymptomatic phase of infection and if PAP has a positive effect. The data were not available, but “I think that the way to go is to understand this chronology,” said Dr. Tasali.
The researchers examined records between 2015 and 2020, using sleep study data, remotely collected daily PAP data, and electronic health records, all from Kaiser Permanente Southern California. Included subjects were adults who had enrolled before Feb. 1, 2020, and had sleep diagnostic or PAP data on record by March 1, 2020. The researchers analyzed PAP adherence between March 1, 2020, and the time of COVID-19 diagnosis, or until the study ended on July 31, 2020.
Patients were defined as being untreated (< 2 hours/night PAP), moderately treated (2-3.9 hours/night), or well treated (4 or more hours/night). Apnea hypopnea index (AHI) was used to determine severity. The analysis included 81,932 patients (39.8% were women, mean age was 54.0 years, 9.9% were Black, and 34.5% were Hispanic). A total of 1.7% of subjects without OSA experienced COVID-19 infection, compared to 1.8% with OSA; 0.3% with OSA were hospitalized and 0.07% underwent intensive care or died.
There were some differences between the two groups. The non-USA population was younger (mean age 47.0 vs. 54.5 years), was less likely to be men (44% vs. 60.3%), had a lower mean body mass index (30.4 vs. 34.3), had fewer comorbidities according to the Charleston Comorbidity Index (1.3 vs. 2.0), and were less likely to have hypertension (5.6% vs. 12.4%; P < .0001 for all).
Infection rates were higher in patients with more severe OSA. The rates in untreated mild, moderate, and severe OSA were 2%, 2%, and 2.4% respectively. The rate among all treated patients was 1.4% (P < .0001). Infection rates also dropped among patients with better treatment: untreated, 2.1%; moderately treated, 1.7%; and well treated, 1.3% (P < .0001).
Not having OSA was associated with a lower infection risk than was having OSA (odds ratio [OR], 0.82; 95% confidence interval, 0.70-0.96). Compared to untreated patients, there was lower infection risk in the moderately treated (OR, 0.82; 95% CI, 0.65-1.03) and well treated (OR, 0.68; 95% CI, 0.59-0.79) groups. Higher infection rates were associated with obesity, higher Charlson Comorbidity score (> 2; OR, 1.29; 95% CI, 1.09-1.53), Black (OR, 1.51; 95% CI, 1.24-1.84) and Hispanic ethnicities (OR, 2.23; 95% CI, 1.96-2.54), and Medicaid enrollment. Increasing age was associated with lower risk of infection, with each 5-year increment linked to reduced risk (OR, 0.88; 95% CI, 0.86-0.90). Dr. Hwang suggested that the age association may be because older individuals were more likely to follow social distancing and other precautions.
A multivariate analysis found that OSA was associated with infection risk according to OSA severity, including mild (OR, 1.21; 95% CI, 1.01-1.44), and moderate to severe (OR, 1.27; 95% CI, 1.07-1.51). There was no association between hospitalization rate or ICU admission/death and presence of OSA or PAP adherence in the data presented, but Dr. Hwang said that an updated analysis suggests that OSA may be associated with a risk of greater COVID-19 severity.
The control group was composed of individuals who had undergone sleep testing, but found to not have OSA. Still, they aren’t necessarily representative of the general population, since symptoms likely drove them to testing. A high percentage were also obese, and the average BMI was 30. “It’s certainly not a ‘normal population,’ but the advantage of what we did in terms of using this control group is that they underwent sleep testing, so they were proven to have no obstructive sleep apnea, whereas if we used a general population, we just don’t know,” said Dr. Hwang.
The study received technical and data support from Somnoware, and was funded by Kaiser Permanente. Dr. Tasali has no relevant financial disclosures.
FROM ATS 2021
APA, AMA, others move to stop insurer from overturning mental health claims ruling
The American Psychiatric Association has joined with the American Medical Association and other medical societies to oppose United Behavioral Health’s (UBH) request that a court throw out a ruling that found the insurer unfairly denied tens of thousands of claims for mental health and substance use disorder services.
Wit v. United Behavioral Health, in litigation since 2014, is being closely watched by clinicians, patients, providers, and attorneys.
Reena Kapoor, MD, chair of the APA’s Committee on Judicial Action, said in an interview that the APA is hopeful that “whatever the court says about UBH should be applicable to all insurance companies that are providing employer-sponsored health benefits.”
In a friend of the court (amicus curiae) brief, the APA, AMA, the California Medical Association, Southern California Psychiatric Society, Northern California Psychiatric Society, Orange County Psychiatric Society, Central California Psychiatric Society, and San Diego Psychiatric Society argue that “despite the availability of professionally developed, evidence-based guidelines embodying generally accepted standards of care for mental health and substance use disorders, managed care organizations commonly base coverage decisions on internally developed ‘level of care guidelines’ that are inappropriately restrictive.”
The guidelines “may lead to denial of coverage for treatment that is recommended by a patient’s physician and even cut off coverage when treatment is already being delivered,” said the groups.
The U.S. Department of Labor also filed a brief in support of the plaintiffs who are suing UBH. Those individuals suffered injury when they were denied coverage, said the federal agency, which regulates employer-sponsored insurance plans.
California Attorney General Rob Bonta also made an amicus filing supporting the plaintiffs.
“When insurers limit access to this critical care, they leave Californians who need it feeling as if they have no other option than to try to cope alone,” said Mr. Bonta in a statement.
‘Discrimination must end’
Mr. Bonta said he agreed with a 2019 ruling by the U.S. District Court for the Northern District of California that UBH had violated its fiduciary duties by wrongfully using its internally developed coverage determination guidelines and level of care guidelines to deny care.
The court also found that UBH’s medically necessary criteria meant that only “acute” episodes would be covered. Instead, said the court last November, chronic and comorbid conditions should always be treated, according to Maureen Gammon and Kathleen Rosenow of Willis Towers Watson, a risk advisor.
In November, the same Northern California District Court ruled on the remedies it would require of United, including that the insurer reprocess more than 67,000 claims. UBH was also barred indefinitely from using any of its guidelines to make coverage determinations. Instead, it was ordered to make determinations “consistent with generally accepted standards of care,” and consistent with state laws.
The District Court denied a request by UBH to put a hold on the claims reprocessing until it appealed the overall case. But the Ninth Circuit Court of Appeals in February granted that request.
Then, in March, United appealed the District Court’s overall ruling, claiming that the plaintiffs had not proven harm.
The U.S. Chamber of Commerce has filed a brief in support of United, agreeing with its arguments.
However, the APA and other clinician groups said there is no question of harm.
“Failure to provide appropriate levels of care for treatment of mental illness and substance use disorders leads to relapse, overdose, transmission of infectious diseases, and death,” said APA CEO and Medical Director Saul Levin, MD, MPA, in a statement.
APA President Vivian Pender, MD, said guidelines that “are overly focused on stabilizing acute symptoms of mental health and substance use disorders” are not treating the underlying disease. “When the injury is physical, insurers treat the underlying disease and not just the symptoms. Discrimination against patients with mental illness must end,” she said.
No court has ever recognized the type of claims reprocessing ordered by the District Court judge, said attorneys Nathaniel Cohen and Joseph Laska of Manatt, Phelps & Phillips, in an analysis of the case.
Mr. Cohen and Mr. Laska write. “Practitioners, health plans, and health insurers would be wise to track UBH’s long-awaited appeal to the Ninth Circuit.”
This article first appeared on Medscape.com.
The American Psychiatric Association has joined with the American Medical Association and other medical societies to oppose United Behavioral Health’s (UBH) request that a court throw out a ruling that found the insurer unfairly denied tens of thousands of claims for mental health and substance use disorder services.
Wit v. United Behavioral Health, in litigation since 2014, is being closely watched by clinicians, patients, providers, and attorneys.
Reena Kapoor, MD, chair of the APA’s Committee on Judicial Action, said in an interview that the APA is hopeful that “whatever the court says about UBH should be applicable to all insurance companies that are providing employer-sponsored health benefits.”
In a friend of the court (amicus curiae) brief, the APA, AMA, the California Medical Association, Southern California Psychiatric Society, Northern California Psychiatric Society, Orange County Psychiatric Society, Central California Psychiatric Society, and San Diego Psychiatric Society argue that “despite the availability of professionally developed, evidence-based guidelines embodying generally accepted standards of care for mental health and substance use disorders, managed care organizations commonly base coverage decisions on internally developed ‘level of care guidelines’ that are inappropriately restrictive.”
The guidelines “may lead to denial of coverage for treatment that is recommended by a patient’s physician and even cut off coverage when treatment is already being delivered,” said the groups.
The U.S. Department of Labor also filed a brief in support of the plaintiffs who are suing UBH. Those individuals suffered injury when they were denied coverage, said the federal agency, which regulates employer-sponsored insurance plans.
California Attorney General Rob Bonta also made an amicus filing supporting the plaintiffs.
“When insurers limit access to this critical care, they leave Californians who need it feeling as if they have no other option than to try to cope alone,” said Mr. Bonta in a statement.
‘Discrimination must end’
Mr. Bonta said he agreed with a 2019 ruling by the U.S. District Court for the Northern District of California that UBH had violated its fiduciary duties by wrongfully using its internally developed coverage determination guidelines and level of care guidelines to deny care.
The court also found that UBH’s medically necessary criteria meant that only “acute” episodes would be covered. Instead, said the court last November, chronic and comorbid conditions should always be treated, according to Maureen Gammon and Kathleen Rosenow of Willis Towers Watson, a risk advisor.
In November, the same Northern California District Court ruled on the remedies it would require of United, including that the insurer reprocess more than 67,000 claims. UBH was also barred indefinitely from using any of its guidelines to make coverage determinations. Instead, it was ordered to make determinations “consistent with generally accepted standards of care,” and consistent with state laws.
The District Court denied a request by UBH to put a hold on the claims reprocessing until it appealed the overall case. But the Ninth Circuit Court of Appeals in February granted that request.
Then, in March, United appealed the District Court’s overall ruling, claiming that the plaintiffs had not proven harm.
The U.S. Chamber of Commerce has filed a brief in support of United, agreeing with its arguments.
However, the APA and other clinician groups said there is no question of harm.
“Failure to provide appropriate levels of care for treatment of mental illness and substance use disorders leads to relapse, overdose, transmission of infectious diseases, and death,” said APA CEO and Medical Director Saul Levin, MD, MPA, in a statement.
APA President Vivian Pender, MD, said guidelines that “are overly focused on stabilizing acute symptoms of mental health and substance use disorders” are not treating the underlying disease. “When the injury is physical, insurers treat the underlying disease and not just the symptoms. Discrimination against patients with mental illness must end,” she said.
No court has ever recognized the type of claims reprocessing ordered by the District Court judge, said attorneys Nathaniel Cohen and Joseph Laska of Manatt, Phelps & Phillips, in an analysis of the case.
Mr. Cohen and Mr. Laska write. “Practitioners, health plans, and health insurers would be wise to track UBH’s long-awaited appeal to the Ninth Circuit.”
This article first appeared on Medscape.com.
The American Psychiatric Association has joined with the American Medical Association and other medical societies to oppose United Behavioral Health’s (UBH) request that a court throw out a ruling that found the insurer unfairly denied tens of thousands of claims for mental health and substance use disorder services.
Wit v. United Behavioral Health, in litigation since 2014, is being closely watched by clinicians, patients, providers, and attorneys.
Reena Kapoor, MD, chair of the APA’s Committee on Judicial Action, said in an interview that the APA is hopeful that “whatever the court says about UBH should be applicable to all insurance companies that are providing employer-sponsored health benefits.”
In a friend of the court (amicus curiae) brief, the APA, AMA, the California Medical Association, Southern California Psychiatric Society, Northern California Psychiatric Society, Orange County Psychiatric Society, Central California Psychiatric Society, and San Diego Psychiatric Society argue that “despite the availability of professionally developed, evidence-based guidelines embodying generally accepted standards of care for mental health and substance use disorders, managed care organizations commonly base coverage decisions on internally developed ‘level of care guidelines’ that are inappropriately restrictive.”
The guidelines “may lead to denial of coverage for treatment that is recommended by a patient’s physician and even cut off coverage when treatment is already being delivered,” said the groups.
The U.S. Department of Labor also filed a brief in support of the plaintiffs who are suing UBH. Those individuals suffered injury when they were denied coverage, said the federal agency, which regulates employer-sponsored insurance plans.
California Attorney General Rob Bonta also made an amicus filing supporting the plaintiffs.
“When insurers limit access to this critical care, they leave Californians who need it feeling as if they have no other option than to try to cope alone,” said Mr. Bonta in a statement.
‘Discrimination must end’
Mr. Bonta said he agreed with a 2019 ruling by the U.S. District Court for the Northern District of California that UBH had violated its fiduciary duties by wrongfully using its internally developed coverage determination guidelines and level of care guidelines to deny care.
The court also found that UBH’s medically necessary criteria meant that only “acute” episodes would be covered. Instead, said the court last November, chronic and comorbid conditions should always be treated, according to Maureen Gammon and Kathleen Rosenow of Willis Towers Watson, a risk advisor.
In November, the same Northern California District Court ruled on the remedies it would require of United, including that the insurer reprocess more than 67,000 claims. UBH was also barred indefinitely from using any of its guidelines to make coverage determinations. Instead, it was ordered to make determinations “consistent with generally accepted standards of care,” and consistent with state laws.
The District Court denied a request by UBH to put a hold on the claims reprocessing until it appealed the overall case. But the Ninth Circuit Court of Appeals in February granted that request.
Then, in March, United appealed the District Court’s overall ruling, claiming that the plaintiffs had not proven harm.
The U.S. Chamber of Commerce has filed a brief in support of United, agreeing with its arguments.
However, the APA and other clinician groups said there is no question of harm.
“Failure to provide appropriate levels of care for treatment of mental illness and substance use disorders leads to relapse, overdose, transmission of infectious diseases, and death,” said APA CEO and Medical Director Saul Levin, MD, MPA, in a statement.
APA President Vivian Pender, MD, said guidelines that “are overly focused on stabilizing acute symptoms of mental health and substance use disorders” are not treating the underlying disease. “When the injury is physical, insurers treat the underlying disease and not just the symptoms. Discrimination against patients with mental illness must end,” she said.
No court has ever recognized the type of claims reprocessing ordered by the District Court judge, said attorneys Nathaniel Cohen and Joseph Laska of Manatt, Phelps & Phillips, in an analysis of the case.
Mr. Cohen and Mr. Laska write. “Practitioners, health plans, and health insurers would be wise to track UBH’s long-awaited appeal to the Ninth Circuit.”
This article first appeared on Medscape.com.
OSA: Heart rate change may signal CPAP benefit
Some nonsleepy patients with coronary artery disease and obstructive sleep apnea (OSA) may receive cardiovascular benefit from continuous positive airway pressure (CPAP) therapy, according to a post hoc analysis of the RICCADSA clinical trial. That study found no benefit among patients overall, but the new analysis found that patients whose heart rate increases (delta heart rate, or dHR) more than average during apnea or hypopnea experienced fewer cardiovascular or cerebrovascular events during apnea or hypopnea when treated with CPAP.
Although RICCADSA showed no benefit, an analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) and the Sleep Heart Health Study (SHHS) cohorts found that elevated pulse rate response to respiratory events was associated with greater risk of cardiovascular disease (CVD) morbidity and mortality. But the effect was seen only in nonsleepy patients. “We hypothesized that pulse rate response to apneas would predict which patients with OSA may most benefit from CPAP treatment. Now, our study suggests that there is, in fact, a subgroup of nonsleepy patients with OSA for whom CPAP could provide a reduction in risk, specifically those with a higher pulse rate response to their respiratory events,” Ali Azarbarzin, PhD, said in an interview.
Dr. Azarbarzin presented the study at the American Thoracic Society’s virtual international conference (Abstract A1103). He is in the division of sleep and circadian disorders at Brigham and Women’s Hospital, and is assistant professor of medicine at Harvard Medical School, both in Boston.
The study is in line with recent efforts to subgroup OSA patients to determine which are at higher risk of cardiovascular events and other complications, and which are most likely to respond to treatment, according to Esra Tasali, MD, of the University of Chicago, who moderated the session where the study was presented. “The field is really urgently in need of coming up with new methods, and I think this study is getting a handle on that,” said Dr. Tasali in an interview.
“I think that this is really pointing toward a new area that the whole (sleep field) is moving toward, which is better phenotyping of sleep apnea so that we can come up with more personalized treatments,” said Dr. Tasali.
The patients who appeared to gain a cardiovascular benefit from CPAP represented about 16% of trial participants. Dr. Azarbarzin refrained from making clinical recommendations, citing the need for more data. The team next plans to reproduce the findings in additional, larger trials such as the SAVE and ISAACC trials. “Ultimately, our goal is to confirm our findings in a future randomized controlled trial of CPAP by enrolling participants based on their pulse rate response,” said Dr. Azarbarzin.
The RICCADSA study was a single center randomized, controlled trial with 226 patients with coronary artery disease and OSA who were randomized to CPAP or no CPAP treatment. In the overall population, CPAP treatment was not associated with a statistically significant change in repeat revascularization, myocardial infarction, stroke, or cardiovascular mortality (hazard ratio [HR], 0.79; P = .435). That study assumed that the effect of OSA on CVD is similar across all subgroups of dHR.
The mean increase in heart rate was 7.1 beats per minute (BPM; standard deviation, 3.7). Each standard deviation increase in dHR was linked to greater CVD risk (HR, 1.45; P = .029). For each standard deviation decrease in dHR, treatment with CPAP decreased the CVD risk (HR, 0.54; P = .043).
For patients with a low dHR of 4 BPM, the hazard ratio for CVD was 0.8 with no CPAP treatment and 1.2 for CPAP treatment. For those at the mean value of 7 BPM, the HRs were 1.1 and 0.9 respectively. For those with a high dHR, (10 BPM), the hazard ratio was 1.6 without treatment and 0.7 with CPAP.
“We modeled delta heart rate interaction with CPAP, which was significant. What this means is that for someone with a mean delta heart rate of 7 beats per minute, the risk reduction (with CPAP) is similar to what RICCADSA reported. But if you look at those with high delta heart rate, the risk reduction was significantly larger. It was actually a more than 50% reduction of risk with CPAP treatment,” said Dr. Azarbarzin.
Dr. Azarbarzin has consulted for Somnifix and Apnimed and has received grants from Somnifix. Dr. Tasali has no relevant financial disclosures.
Some nonsleepy patients with coronary artery disease and obstructive sleep apnea (OSA) may receive cardiovascular benefit from continuous positive airway pressure (CPAP) therapy, according to a post hoc analysis of the RICCADSA clinical trial. That study found no benefit among patients overall, but the new analysis found that patients whose heart rate increases (delta heart rate, or dHR) more than average during apnea or hypopnea experienced fewer cardiovascular or cerebrovascular events during apnea or hypopnea when treated with CPAP.
Although RICCADSA showed no benefit, an analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) and the Sleep Heart Health Study (SHHS) cohorts found that elevated pulse rate response to respiratory events was associated with greater risk of cardiovascular disease (CVD) morbidity and mortality. But the effect was seen only in nonsleepy patients. “We hypothesized that pulse rate response to apneas would predict which patients with OSA may most benefit from CPAP treatment. Now, our study suggests that there is, in fact, a subgroup of nonsleepy patients with OSA for whom CPAP could provide a reduction in risk, specifically those with a higher pulse rate response to their respiratory events,” Ali Azarbarzin, PhD, said in an interview.
Dr. Azarbarzin presented the study at the American Thoracic Society’s virtual international conference (Abstract A1103). He is in the division of sleep and circadian disorders at Brigham and Women’s Hospital, and is assistant professor of medicine at Harvard Medical School, both in Boston.
The study is in line with recent efforts to subgroup OSA patients to determine which are at higher risk of cardiovascular events and other complications, and which are most likely to respond to treatment, according to Esra Tasali, MD, of the University of Chicago, who moderated the session where the study was presented. “The field is really urgently in need of coming up with new methods, and I think this study is getting a handle on that,” said Dr. Tasali in an interview.
“I think that this is really pointing toward a new area that the whole (sleep field) is moving toward, which is better phenotyping of sleep apnea so that we can come up with more personalized treatments,” said Dr. Tasali.
The patients who appeared to gain a cardiovascular benefit from CPAP represented about 16% of trial participants. Dr. Azarbarzin refrained from making clinical recommendations, citing the need for more data. The team next plans to reproduce the findings in additional, larger trials such as the SAVE and ISAACC trials. “Ultimately, our goal is to confirm our findings in a future randomized controlled trial of CPAP by enrolling participants based on their pulse rate response,” said Dr. Azarbarzin.
The RICCADSA study was a single center randomized, controlled trial with 226 patients with coronary artery disease and OSA who were randomized to CPAP or no CPAP treatment. In the overall population, CPAP treatment was not associated with a statistically significant change in repeat revascularization, myocardial infarction, stroke, or cardiovascular mortality (hazard ratio [HR], 0.79; P = .435). That study assumed that the effect of OSA on CVD is similar across all subgroups of dHR.
The mean increase in heart rate was 7.1 beats per minute (BPM; standard deviation, 3.7). Each standard deviation increase in dHR was linked to greater CVD risk (HR, 1.45; P = .029). For each standard deviation decrease in dHR, treatment with CPAP decreased the CVD risk (HR, 0.54; P = .043).
For patients with a low dHR of 4 BPM, the hazard ratio for CVD was 0.8 with no CPAP treatment and 1.2 for CPAP treatment. For those at the mean value of 7 BPM, the HRs were 1.1 and 0.9 respectively. For those with a high dHR, (10 BPM), the hazard ratio was 1.6 without treatment and 0.7 with CPAP.
“We modeled delta heart rate interaction with CPAP, which was significant. What this means is that for someone with a mean delta heart rate of 7 beats per minute, the risk reduction (with CPAP) is similar to what RICCADSA reported. But if you look at those with high delta heart rate, the risk reduction was significantly larger. It was actually a more than 50% reduction of risk with CPAP treatment,” said Dr. Azarbarzin.
Dr. Azarbarzin has consulted for Somnifix and Apnimed and has received grants from Somnifix. Dr. Tasali has no relevant financial disclosures.
Some nonsleepy patients with coronary artery disease and obstructive sleep apnea (OSA) may receive cardiovascular benefit from continuous positive airway pressure (CPAP) therapy, according to a post hoc analysis of the RICCADSA clinical trial. That study found no benefit among patients overall, but the new analysis found that patients whose heart rate increases (delta heart rate, or dHR) more than average during apnea or hypopnea experienced fewer cardiovascular or cerebrovascular events during apnea or hypopnea when treated with CPAP.
Although RICCADSA showed no benefit, an analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) and the Sleep Heart Health Study (SHHS) cohorts found that elevated pulse rate response to respiratory events was associated with greater risk of cardiovascular disease (CVD) morbidity and mortality. But the effect was seen only in nonsleepy patients. “We hypothesized that pulse rate response to apneas would predict which patients with OSA may most benefit from CPAP treatment. Now, our study suggests that there is, in fact, a subgroup of nonsleepy patients with OSA for whom CPAP could provide a reduction in risk, specifically those with a higher pulse rate response to their respiratory events,” Ali Azarbarzin, PhD, said in an interview.
Dr. Azarbarzin presented the study at the American Thoracic Society’s virtual international conference (Abstract A1103). He is in the division of sleep and circadian disorders at Brigham and Women’s Hospital, and is assistant professor of medicine at Harvard Medical School, both in Boston.
The study is in line with recent efforts to subgroup OSA patients to determine which are at higher risk of cardiovascular events and other complications, and which are most likely to respond to treatment, according to Esra Tasali, MD, of the University of Chicago, who moderated the session where the study was presented. “The field is really urgently in need of coming up with new methods, and I think this study is getting a handle on that,” said Dr. Tasali in an interview.
“I think that this is really pointing toward a new area that the whole (sleep field) is moving toward, which is better phenotyping of sleep apnea so that we can come up with more personalized treatments,” said Dr. Tasali.
The patients who appeared to gain a cardiovascular benefit from CPAP represented about 16% of trial participants. Dr. Azarbarzin refrained from making clinical recommendations, citing the need for more data. The team next plans to reproduce the findings in additional, larger trials such as the SAVE and ISAACC trials. “Ultimately, our goal is to confirm our findings in a future randomized controlled trial of CPAP by enrolling participants based on their pulse rate response,” said Dr. Azarbarzin.
The RICCADSA study was a single center randomized, controlled trial with 226 patients with coronary artery disease and OSA who were randomized to CPAP or no CPAP treatment. In the overall population, CPAP treatment was not associated with a statistically significant change in repeat revascularization, myocardial infarction, stroke, or cardiovascular mortality (hazard ratio [HR], 0.79; P = .435). That study assumed that the effect of OSA on CVD is similar across all subgroups of dHR.
The mean increase in heart rate was 7.1 beats per minute (BPM; standard deviation, 3.7). Each standard deviation increase in dHR was linked to greater CVD risk (HR, 1.45; P = .029). For each standard deviation decrease in dHR, treatment with CPAP decreased the CVD risk (HR, 0.54; P = .043).
For patients with a low dHR of 4 BPM, the hazard ratio for CVD was 0.8 with no CPAP treatment and 1.2 for CPAP treatment. For those at the mean value of 7 BPM, the HRs were 1.1 and 0.9 respectively. For those with a high dHR, (10 BPM), the hazard ratio was 1.6 without treatment and 0.7 with CPAP.
“We modeled delta heart rate interaction with CPAP, which was significant. What this means is that for someone with a mean delta heart rate of 7 beats per minute, the risk reduction (with CPAP) is similar to what RICCADSA reported. But if you look at those with high delta heart rate, the risk reduction was significantly larger. It was actually a more than 50% reduction of risk with CPAP treatment,” said Dr. Azarbarzin.
Dr. Azarbarzin has consulted for Somnifix and Apnimed and has received grants from Somnifix. Dr. Tasali has no relevant financial disclosures.
FROM ATS 2021
Long-term use of prescription sleep meds unsupported by new research
a new study shows.
“While there are good data from [randomized, controlled trials] that these medications improve sleep disturbances in the short term,” few studies have examined whether they provide long-term benefits, stated the authors of the paper, which was published in BMJ Open.
“The current observational study does not support use of sleep medications over the long term, as there were no self-reported differences at 1 or 2 years of follow-up comparing sleep medication users with nonusers,” author Daniel H. Solomon, MD, MPH, from Brigham and Women’s Hospital, Boston, and colleagues wrote.
Women included in the analysis were drawn from the Study of Women’s Health Across the Nation (SWAN), an ongoing multicenter, longitudinal study examining women during the menopausal transition. The average age of the women included in the cohort was 49.5 years and approximately half were White. All women reported a sleep disturbance on at least 3 nights per week during a 2-week interval. At follow up, women were asked to use a Likert scale to rate three aspects of sleep: difficulty initiating sleep, frequent awakening, and waking up early. On the scale, 1 represented having no difficulties on any nights, 3 represented having difficulties 1-2 nights per week, and 5 represented having difficulty 5-7 nights per week.
Women already using prescription sleep medication at their baseline visit were excluded from the study. Medications used included benzodiazepines, selective BZD receptor agonists, and other hypnotics.
Over the 21 years of follow-up in the SWAN study (1995-2016), Dr. Solomon and colleagues identified 238 women using sleep medication and these were compared with a cohort of 447 propensity score–matched non–sleep medication uses. Overall, the 685 women included were similar in characteristics to each other as well as to the other potentially eligible women not included in the analysis.
Sleep disturbance patterns compared
At baseline, sleep disturbance patterns were similar between the two groups. Among medication users, the mean score for difficulty initiating sleep was 2.7 (95% confidence interval, 2.5-2.9), waking frequently 3.8 (95% CI, 3.6-3.9), and waking early 2.9 (95% CI, 2.7-3.1). Among the nonusers, the baseline scores were 2.6 (95% CI, 2.5-2.7), 3.7 (95% CI, 3.6-3.8), and 2.7 (95% CI, 2.5-2.8), respectively. After 1 year, there was no statistically significant difference in scores between the two groups. The average ratings for medication users were 2.6 (95% CI, 2.3-2.8) for difficulty initiating sleep, 3.8 (95% CI, 3.6-4.0) for waking frequently, and 2.8 (95% CI, 2.6-3.0) for waking early.
Average ratings among nonusers were 2.3 (95% CI, 2.2-2.4), 3.5 (95% CI, 3.3-3.6), and 2.5 (95% CI, 2.3-2.6), respectively.
After 2 years, there were still no statistically significant reductions in sleep disturbances among those taking prescription sleep medications, compared with those not taking medication.
The researchers noted that approximately half of the women in this cohort were current or past tobacco users and that 20% were moderate to heavy alcohol users.
More work-up, not more medication, needed
The study authors acknowledged the limitations of an observational study and noted that, since participants only reported medication use and sleep disturbances at annual visits, they did not know whether patients’ medication use was intermittent or of any interim outcomes. Additionally, the authors pointed out that those classified as “nonusers” may have been using over-the-counter medication.
“Investigations should look at detailed-use patterns, on a daily or weekly basis, with frequent outcomes data,” Dr. Solomon said in an interview. “While our data shed new light on chronic use, we only had data collected on an annual basis; daily or weekly data would provide more granular information.”
Regarding clinician prescribing practices, Dr. Solomon said, “short-term, intermittent use can be helpful, but use these agents sparingly” and “educate patients that chronic regular use of medications for sleep is not associated with improvement in sleep disturbances.”
Commenting on the study, Andrea Matsumura, MD, a sleep specialist at the Oregon Clinic in Portland, echoed this sentiment: “When someone says they are having trouble sleeping this is the tip of the iceberg and it warrants an evaluation to determine if someone has a breathing disorder, a circadian disorder, a life situation, or a type of insomnia that is driving the sleeplessness.”
“I think this study supports what we all should know,” Dr. Matsumura concluded. “Sleep aids are not meant to be used long term” and should not be used for longer than 2 weeks without further work-up.
Funding for this study was provided through a grant from the National Institutes of Health. Dr. Solomon has received salary support from research grants to Brigham and Women’s Hospital for unrelated work from AbbVie, Amgen, Corrona, Genentech and Pfizer. The other authors and Dr. Matsumura have reported no relevant financial relationships.
a new study shows.
“While there are good data from [randomized, controlled trials] that these medications improve sleep disturbances in the short term,” few studies have examined whether they provide long-term benefits, stated the authors of the paper, which was published in BMJ Open.
“The current observational study does not support use of sleep medications over the long term, as there were no self-reported differences at 1 or 2 years of follow-up comparing sleep medication users with nonusers,” author Daniel H. Solomon, MD, MPH, from Brigham and Women’s Hospital, Boston, and colleagues wrote.
Women included in the analysis were drawn from the Study of Women’s Health Across the Nation (SWAN), an ongoing multicenter, longitudinal study examining women during the menopausal transition. The average age of the women included in the cohort was 49.5 years and approximately half were White. All women reported a sleep disturbance on at least 3 nights per week during a 2-week interval. At follow up, women were asked to use a Likert scale to rate three aspects of sleep: difficulty initiating sleep, frequent awakening, and waking up early. On the scale, 1 represented having no difficulties on any nights, 3 represented having difficulties 1-2 nights per week, and 5 represented having difficulty 5-7 nights per week.
Women already using prescription sleep medication at their baseline visit were excluded from the study. Medications used included benzodiazepines, selective BZD receptor agonists, and other hypnotics.
Over the 21 years of follow-up in the SWAN study (1995-2016), Dr. Solomon and colleagues identified 238 women using sleep medication and these were compared with a cohort of 447 propensity score–matched non–sleep medication uses. Overall, the 685 women included were similar in characteristics to each other as well as to the other potentially eligible women not included in the analysis.
Sleep disturbance patterns compared
At baseline, sleep disturbance patterns were similar between the two groups. Among medication users, the mean score for difficulty initiating sleep was 2.7 (95% confidence interval, 2.5-2.9), waking frequently 3.8 (95% CI, 3.6-3.9), and waking early 2.9 (95% CI, 2.7-3.1). Among the nonusers, the baseline scores were 2.6 (95% CI, 2.5-2.7), 3.7 (95% CI, 3.6-3.8), and 2.7 (95% CI, 2.5-2.8), respectively. After 1 year, there was no statistically significant difference in scores between the two groups. The average ratings for medication users were 2.6 (95% CI, 2.3-2.8) for difficulty initiating sleep, 3.8 (95% CI, 3.6-4.0) for waking frequently, and 2.8 (95% CI, 2.6-3.0) for waking early.
Average ratings among nonusers were 2.3 (95% CI, 2.2-2.4), 3.5 (95% CI, 3.3-3.6), and 2.5 (95% CI, 2.3-2.6), respectively.
After 2 years, there were still no statistically significant reductions in sleep disturbances among those taking prescription sleep medications, compared with those not taking medication.
The researchers noted that approximately half of the women in this cohort were current or past tobacco users and that 20% were moderate to heavy alcohol users.
More work-up, not more medication, needed
The study authors acknowledged the limitations of an observational study and noted that, since participants only reported medication use and sleep disturbances at annual visits, they did not know whether patients’ medication use was intermittent or of any interim outcomes. Additionally, the authors pointed out that those classified as “nonusers” may have been using over-the-counter medication.
“Investigations should look at detailed-use patterns, on a daily or weekly basis, with frequent outcomes data,” Dr. Solomon said in an interview. “While our data shed new light on chronic use, we only had data collected on an annual basis; daily or weekly data would provide more granular information.”
Regarding clinician prescribing practices, Dr. Solomon said, “short-term, intermittent use can be helpful, but use these agents sparingly” and “educate patients that chronic regular use of medications for sleep is not associated with improvement in sleep disturbances.”
Commenting on the study, Andrea Matsumura, MD, a sleep specialist at the Oregon Clinic in Portland, echoed this sentiment: “When someone says they are having trouble sleeping this is the tip of the iceberg and it warrants an evaluation to determine if someone has a breathing disorder, a circadian disorder, a life situation, or a type of insomnia that is driving the sleeplessness.”
“I think this study supports what we all should know,” Dr. Matsumura concluded. “Sleep aids are not meant to be used long term” and should not be used for longer than 2 weeks without further work-up.
Funding for this study was provided through a grant from the National Institutes of Health. Dr. Solomon has received salary support from research grants to Brigham and Women’s Hospital for unrelated work from AbbVie, Amgen, Corrona, Genentech and Pfizer. The other authors and Dr. Matsumura have reported no relevant financial relationships.
a new study shows.
“While there are good data from [randomized, controlled trials] that these medications improve sleep disturbances in the short term,” few studies have examined whether they provide long-term benefits, stated the authors of the paper, which was published in BMJ Open.
“The current observational study does not support use of sleep medications over the long term, as there were no self-reported differences at 1 or 2 years of follow-up comparing sleep medication users with nonusers,” author Daniel H. Solomon, MD, MPH, from Brigham and Women’s Hospital, Boston, and colleagues wrote.
Women included in the analysis were drawn from the Study of Women’s Health Across the Nation (SWAN), an ongoing multicenter, longitudinal study examining women during the menopausal transition. The average age of the women included in the cohort was 49.5 years and approximately half were White. All women reported a sleep disturbance on at least 3 nights per week during a 2-week interval. At follow up, women were asked to use a Likert scale to rate three aspects of sleep: difficulty initiating sleep, frequent awakening, and waking up early. On the scale, 1 represented having no difficulties on any nights, 3 represented having difficulties 1-2 nights per week, and 5 represented having difficulty 5-7 nights per week.
Women already using prescription sleep medication at their baseline visit were excluded from the study. Medications used included benzodiazepines, selective BZD receptor agonists, and other hypnotics.
Over the 21 years of follow-up in the SWAN study (1995-2016), Dr. Solomon and colleagues identified 238 women using sleep medication and these were compared with a cohort of 447 propensity score–matched non–sleep medication uses. Overall, the 685 women included were similar in characteristics to each other as well as to the other potentially eligible women not included in the analysis.
Sleep disturbance patterns compared
At baseline, sleep disturbance patterns were similar between the two groups. Among medication users, the mean score for difficulty initiating sleep was 2.7 (95% confidence interval, 2.5-2.9), waking frequently 3.8 (95% CI, 3.6-3.9), and waking early 2.9 (95% CI, 2.7-3.1). Among the nonusers, the baseline scores were 2.6 (95% CI, 2.5-2.7), 3.7 (95% CI, 3.6-3.8), and 2.7 (95% CI, 2.5-2.8), respectively. After 1 year, there was no statistically significant difference in scores between the two groups. The average ratings for medication users were 2.6 (95% CI, 2.3-2.8) for difficulty initiating sleep, 3.8 (95% CI, 3.6-4.0) for waking frequently, and 2.8 (95% CI, 2.6-3.0) for waking early.
Average ratings among nonusers were 2.3 (95% CI, 2.2-2.4), 3.5 (95% CI, 3.3-3.6), and 2.5 (95% CI, 2.3-2.6), respectively.
After 2 years, there were still no statistically significant reductions in sleep disturbances among those taking prescription sleep medications, compared with those not taking medication.
The researchers noted that approximately half of the women in this cohort were current or past tobacco users and that 20% were moderate to heavy alcohol users.
More work-up, not more medication, needed
The study authors acknowledged the limitations of an observational study and noted that, since participants only reported medication use and sleep disturbances at annual visits, they did not know whether patients’ medication use was intermittent or of any interim outcomes. Additionally, the authors pointed out that those classified as “nonusers” may have been using over-the-counter medication.
“Investigations should look at detailed-use patterns, on a daily or weekly basis, with frequent outcomes data,” Dr. Solomon said in an interview. “While our data shed new light on chronic use, we only had data collected on an annual basis; daily or weekly data would provide more granular information.”
Regarding clinician prescribing practices, Dr. Solomon said, “short-term, intermittent use can be helpful, but use these agents sparingly” and “educate patients that chronic regular use of medications for sleep is not associated with improvement in sleep disturbances.”
Commenting on the study, Andrea Matsumura, MD, a sleep specialist at the Oregon Clinic in Portland, echoed this sentiment: “When someone says they are having trouble sleeping this is the tip of the iceberg and it warrants an evaluation to determine if someone has a breathing disorder, a circadian disorder, a life situation, or a type of insomnia that is driving the sleeplessness.”
“I think this study supports what we all should know,” Dr. Matsumura concluded. “Sleep aids are not meant to be used long term” and should not be used for longer than 2 weeks without further work-up.
Funding for this study was provided through a grant from the National Institutes of Health. Dr. Solomon has received salary support from research grants to Brigham and Women’s Hospital for unrelated work from AbbVie, Amgen, Corrona, Genentech and Pfizer. The other authors and Dr. Matsumura have reported no relevant financial relationships.
FROM BMJ OPEN
Obstructive sleep apnea and COVID-19
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused by the novel coronavirus of the year 2019 (COVID-19) has had a major impact on global health and economy. United States reported a total caseload of 28,998,834 patients and total mortality of 525,031 as of March 2021 (NPR.org; worldometer. Accessed March 8, 2021). The beginning of 2021 ushered positivity with the development of multiple highly effective SARS-CoV-2 vaccines. Although the medical world has gained much knowledge about this deadly disease, there are many unknowns and still much to be learned.
Two early landmark studies from Italy (Lombardy) and United States (New York City area) provided initial insight on comorbid conditions associated with increased risk of severe COVID-19 infection (Richardson S, et al. JAMA. 2020;323[20]:2052; Grasselli G, et al. JAMA Intern Med. 2020;180[10]:1345). In the United States cohort, hypertension (HTN), obesity, and diabetes (DM) were independent risk factors for severe disease, while in the Italy cohort, older age, male, COPD, hypercholesterolemia, and diabetes were independent risk factors for increased mortality. Obstructive sleep apnea (OSA) was not mentioned as a comorbid risk factor.
There is much speculation regarding OSA as an independent risk factor for severe COVID-19 infection. OSA is a common sleep-related breathing disorder with increased prevalence in men, older age, and higher body mass index (BMI); and OSA is associated with hypertension, obesity, and diabetes, all of which are risk factors for severe COVID-19. Because of the shared similarities in pathophysiology between OSA and COVID-19 (Tufik S, et al. J Clin Sleep Med. 2020;16[8]:1425), and shared comorbid conditions associated with increased risk of severe COVID-19 disease, OSA has been suggested as an independent risk factor for unfavorable COVID-19-related outcomes.
SARS-CoV-2 triggers a severe inflammatory response involving type-II pneumocytes and angiotensin-converting enzyme 2 pathway. OSA is characterized by intermittent hypoxia and sleep fragmentation, leading to a cascade of systemic inflammatory response involving oxidative stress, pro-inflammatory cytokines, endothelial dysfunction, and consequent cardiovascular injury (Jose RJ, et al. Lancet Respir Med. 2020;8[6]:e46; Saxena K, et al. Sleep Medicine. 2021;79:223). In this regard, OSA may contribute to COVID-19 “cytokine storm” by causing or exacerbating endothelial dysfunction, inflammation, and oxidative stress.
Multiple studies have recently been published on the impact of OSA on COVID-19 outcomes. The Coronavirus SARS-CoV-2 and Diabetes Outcomes (CORONADO) study was one of the initial studies that analyzed the relationship between OSA and COVID-19-related outcomes. This was a multicenter observational study involving diabetic patients hospitalized with COVID-19. The primary outcome was mechanical ventilation and/or death within 7 days of admission. Multivariate adjustment showed that age, BMI, and OSA, among other factors, were independently associated with risk of death on day 7 (Cariou B, et al. Diabetologia. 2020;63[8]:1500). Strausz and colleagues also evaluated OSA as an independent risk factor for severe COVID-19 in a large registry of hospital discharge patients (FinnGen study). The authors reported that although the risk of contracting COVID-19 was the same for patients with or without OSA, after adjusting for age, sex, and BMI, OSA was associated with higher risk of hospitalization (Strausz S, et al. BMJ Open Resp Res. 2021;8:e000845). Similar findings were confirmed by the Maas et al. study, which utilized a large socioeconomically diverse database composed of 10 hospital systems. Diagnoses and outcomes were identified by ICD-10 coding and medical record data. After adjustments for diabetes, HTN, and BMI, OSA conferred an eight-fold risk for COVID-19 infection, was associated with increased risk of hospitalization, and doubled the risk of developing respiratory failure (Maas MB, et al. Sleep Breath. 2020 Sep; 29:1-3. doi: 10.1007/s11325-020-02203-0).
Peker and colleagues conducted a prospective multicenter observational study comparing clinical outcomes of severe COVID-19 infection in patients with low vs high pretest probability of having OSA based on the Berlin questionnaire. The authors reported a clinically significant risk of poorer clinical outcomes in the high pretest probability OSA group after adjustments for age, sex, and comorbidities (Peker Y, et al. Ann Am Thorac Soc. 2021. Feb 17. doi: 10.1513/AnnalsATS.202011-1409OC). A timely meta-analysis including 21 studies (19 with retrospective design) with 54,276 COVID-19 patients and 4,640 OSA patients concluded poor composite outcomes including severe COVID-19, intensive care unit admission, mechanical ventilatory support, and death in association with OSA (OR – 1.72 95% CI 1.55-1.91, P< .00001). In patients with obesity, OSA is a highly prevalent co-morbid condition. BMI, however, was not adjusted in this model (Hariyanto TI, et al. Sleep Med. 2021. doi: 10.1016/j.sleep.2021.03.029).
Other studies have concluded the opposite with OSA not being an independent risk factor for severe COVID-19 infection. Cade and colleagues conducted a retrospective analysis from a comprehensive electronic health dataset using ICD codes to identify OSA patients with severe COVID-19 infection. A significant association between OSA and COVID-19 death was noted after adjustment for demographics (ethnicity, age, sex). However, when fully adjusted for demographics, BMI, asthma, COPD, HTN, or DM, OSA was not an independent risk factor for COVID-19-related mortality and hospitalization (Cade BE, et al. Am J Respir Crit Care Med. 2020;202[10]:1462). The FinnGen study (Strausz et al.) was part of a meta-analysis examining the association between OSA and severe COVID-19 with and without adjustments for BMI. This meta-analysis consisted of 15,835 COVID-19 patients including 1,294 with OSA. The authors found that OSA was a risk factor with a two-fold increased risk of severe COVID-19 infection (OR = 2.37, P = .021). However, after adjustments were made for BMI, this finding lost statistical significance (OR=1.55, P=.13) (Strausz S, et al. BMJ Open Resp Res. 2021;8:e000845).
It is worth noting that a majority of studies identified OSA by indirect and imperfect methods through chart review, ICD codes, and databases. Confirmed OSA based on formal testing with a sleep study in COVID-19 patients remains a challenge. Perhaps well performed screening questionnaires, such as STOP-Bang, Berlin, or NoSAS, can be utilized as was the case in one study. It is also unclear if outcomes of COVID-19 infection differ in patients with treated or untreated OSA, as raised by the CORONADO study. A recent cross-sectional telephone interview survey of patients with confirmed OSA in Iran alluded to higher prevalence of COVID-19 in patients with severe OSA with suggestion of lower prevalence in patients who were currently receiving OSA treatment with positive airway pressure (PAP) therapy (Najafi A, et al. Sleep Health. 2021 Feb;7[1]:14). This is a crucial question as PAP therapy is considered an aerosol-generating procedure (Lance CG. Cleve Clin J Med. 2020 May 5. doi: 10.3949/ccjm.87a.ccc003). Studies have suggested continued use of PAP therapy with additional measures to mitigate the spread of virus, since failure to use PAP could be deleterious to the patient’s quality of life. Interestingly, PAP adherence seemed to have improved during the pandemic as evidenced by a telephonic survey done in New York City that showed 88% of patients with OSA used a PAP device consistently (Attias D, et al. Eur Respir J. 2020 Jul 30;56[1]:2001607. doi: 10.1183/13993003.01607-2020).
In summary, the jury is still out on whether OSA is a facilitator for viral replication, or an independent risk factor for poor prognosis related to COVID-19 infection, or has no clinical relevance to COVID-19. COVID-19 and OSA share comorbidities and pathways leading to a systemic inflammatory cascade. Theoretically, it would make sense that OSA is a risk factor for severe COVID-19 infection; however, it remains to be proven. The recent studies are limited by retrospective and observational nature, imprecise OSA classification/diagnostic criteria, and confounded by difficult to control variables. Further research is needed to expand our understanding of OSA -induced intermittent hypoxemia, inflammation, and endothelial dysfunction that may play a role in COVID-19 morbidity and mortality. Until we have more clarity, close monitoring of OSA patients infected with COVID-19 is recommended along with implementation of safe protocols for continuation of PAP usage during the infectious phase. Identifying underlying comorbid conditions that contribute to worsening of a COVID-19 infectious course is a crucial step in improving clinical outcomes.
Dr. Sahni is Assistant Professor of Clinical Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago. Dr. Cao is Clinical Associate Professor, Division of Sleep Medicine and Division of Neuromuscular Medicine, Department of Psychiatry and Department of Neurology, Stanford (Calif.) University.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused by the novel coronavirus of the year 2019 (COVID-19) has had a major impact on global health and economy. United States reported a total caseload of 28,998,834 patients and total mortality of 525,031 as of March 2021 (NPR.org; worldometer. Accessed March 8, 2021). The beginning of 2021 ushered positivity with the development of multiple highly effective SARS-CoV-2 vaccines. Although the medical world has gained much knowledge about this deadly disease, there are many unknowns and still much to be learned.
Two early landmark studies from Italy (Lombardy) and United States (New York City area) provided initial insight on comorbid conditions associated with increased risk of severe COVID-19 infection (Richardson S, et al. JAMA. 2020;323[20]:2052; Grasselli G, et al. JAMA Intern Med. 2020;180[10]:1345). In the United States cohort, hypertension (HTN), obesity, and diabetes (DM) were independent risk factors for severe disease, while in the Italy cohort, older age, male, COPD, hypercholesterolemia, and diabetes were independent risk factors for increased mortality. Obstructive sleep apnea (OSA) was not mentioned as a comorbid risk factor.
There is much speculation regarding OSA as an independent risk factor for severe COVID-19 infection. OSA is a common sleep-related breathing disorder with increased prevalence in men, older age, and higher body mass index (BMI); and OSA is associated with hypertension, obesity, and diabetes, all of which are risk factors for severe COVID-19. Because of the shared similarities in pathophysiology between OSA and COVID-19 (Tufik S, et al. J Clin Sleep Med. 2020;16[8]:1425), and shared comorbid conditions associated with increased risk of severe COVID-19 disease, OSA has been suggested as an independent risk factor for unfavorable COVID-19-related outcomes.
SARS-CoV-2 triggers a severe inflammatory response involving type-II pneumocytes and angiotensin-converting enzyme 2 pathway. OSA is characterized by intermittent hypoxia and sleep fragmentation, leading to a cascade of systemic inflammatory response involving oxidative stress, pro-inflammatory cytokines, endothelial dysfunction, and consequent cardiovascular injury (Jose RJ, et al. Lancet Respir Med. 2020;8[6]:e46; Saxena K, et al. Sleep Medicine. 2021;79:223). In this regard, OSA may contribute to COVID-19 “cytokine storm” by causing or exacerbating endothelial dysfunction, inflammation, and oxidative stress.
Multiple studies have recently been published on the impact of OSA on COVID-19 outcomes. The Coronavirus SARS-CoV-2 and Diabetes Outcomes (CORONADO) study was one of the initial studies that analyzed the relationship between OSA and COVID-19-related outcomes. This was a multicenter observational study involving diabetic patients hospitalized with COVID-19. The primary outcome was mechanical ventilation and/or death within 7 days of admission. Multivariate adjustment showed that age, BMI, and OSA, among other factors, were independently associated with risk of death on day 7 (Cariou B, et al. Diabetologia. 2020;63[8]:1500). Strausz and colleagues also evaluated OSA as an independent risk factor for severe COVID-19 in a large registry of hospital discharge patients (FinnGen study). The authors reported that although the risk of contracting COVID-19 was the same for patients with or without OSA, after adjusting for age, sex, and BMI, OSA was associated with higher risk of hospitalization (Strausz S, et al. BMJ Open Resp Res. 2021;8:e000845). Similar findings were confirmed by the Maas et al. study, which utilized a large socioeconomically diverse database composed of 10 hospital systems. Diagnoses and outcomes were identified by ICD-10 coding and medical record data. After adjustments for diabetes, HTN, and BMI, OSA conferred an eight-fold risk for COVID-19 infection, was associated with increased risk of hospitalization, and doubled the risk of developing respiratory failure (Maas MB, et al. Sleep Breath. 2020 Sep; 29:1-3. doi: 10.1007/s11325-020-02203-0).
Peker and colleagues conducted a prospective multicenter observational study comparing clinical outcomes of severe COVID-19 infection in patients with low vs high pretest probability of having OSA based on the Berlin questionnaire. The authors reported a clinically significant risk of poorer clinical outcomes in the high pretest probability OSA group after adjustments for age, sex, and comorbidities (Peker Y, et al. Ann Am Thorac Soc. 2021. Feb 17. doi: 10.1513/AnnalsATS.202011-1409OC). A timely meta-analysis including 21 studies (19 with retrospective design) with 54,276 COVID-19 patients and 4,640 OSA patients concluded poor composite outcomes including severe COVID-19, intensive care unit admission, mechanical ventilatory support, and death in association with OSA (OR – 1.72 95% CI 1.55-1.91, P< .00001). In patients with obesity, OSA is a highly prevalent co-morbid condition. BMI, however, was not adjusted in this model (Hariyanto TI, et al. Sleep Med. 2021. doi: 10.1016/j.sleep.2021.03.029).
Other studies have concluded the opposite with OSA not being an independent risk factor for severe COVID-19 infection. Cade and colleagues conducted a retrospective analysis from a comprehensive electronic health dataset using ICD codes to identify OSA patients with severe COVID-19 infection. A significant association between OSA and COVID-19 death was noted after adjustment for demographics (ethnicity, age, sex). However, when fully adjusted for demographics, BMI, asthma, COPD, HTN, or DM, OSA was not an independent risk factor for COVID-19-related mortality and hospitalization (Cade BE, et al. Am J Respir Crit Care Med. 2020;202[10]:1462). The FinnGen study (Strausz et al.) was part of a meta-analysis examining the association between OSA and severe COVID-19 with and without adjustments for BMI. This meta-analysis consisted of 15,835 COVID-19 patients including 1,294 with OSA. The authors found that OSA was a risk factor with a two-fold increased risk of severe COVID-19 infection (OR = 2.37, P = .021). However, after adjustments were made for BMI, this finding lost statistical significance (OR=1.55, P=.13) (Strausz S, et al. BMJ Open Resp Res. 2021;8:e000845).
It is worth noting that a majority of studies identified OSA by indirect and imperfect methods through chart review, ICD codes, and databases. Confirmed OSA based on formal testing with a sleep study in COVID-19 patients remains a challenge. Perhaps well performed screening questionnaires, such as STOP-Bang, Berlin, or NoSAS, can be utilized as was the case in one study. It is also unclear if outcomes of COVID-19 infection differ in patients with treated or untreated OSA, as raised by the CORONADO study. A recent cross-sectional telephone interview survey of patients with confirmed OSA in Iran alluded to higher prevalence of COVID-19 in patients with severe OSA with suggestion of lower prevalence in patients who were currently receiving OSA treatment with positive airway pressure (PAP) therapy (Najafi A, et al. Sleep Health. 2021 Feb;7[1]:14). This is a crucial question as PAP therapy is considered an aerosol-generating procedure (Lance CG. Cleve Clin J Med. 2020 May 5. doi: 10.3949/ccjm.87a.ccc003). Studies have suggested continued use of PAP therapy with additional measures to mitigate the spread of virus, since failure to use PAP could be deleterious to the patient’s quality of life. Interestingly, PAP adherence seemed to have improved during the pandemic as evidenced by a telephonic survey done in New York City that showed 88% of patients with OSA used a PAP device consistently (Attias D, et al. Eur Respir J. 2020 Jul 30;56[1]:2001607. doi: 10.1183/13993003.01607-2020).
In summary, the jury is still out on whether OSA is a facilitator for viral replication, or an independent risk factor for poor prognosis related to COVID-19 infection, or has no clinical relevance to COVID-19. COVID-19 and OSA share comorbidities and pathways leading to a systemic inflammatory cascade. Theoretically, it would make sense that OSA is a risk factor for severe COVID-19 infection; however, it remains to be proven. The recent studies are limited by retrospective and observational nature, imprecise OSA classification/diagnostic criteria, and confounded by difficult to control variables. Further research is needed to expand our understanding of OSA -induced intermittent hypoxemia, inflammation, and endothelial dysfunction that may play a role in COVID-19 morbidity and mortality. Until we have more clarity, close monitoring of OSA patients infected with COVID-19 is recommended along with implementation of safe protocols for continuation of PAP usage during the infectious phase. Identifying underlying comorbid conditions that contribute to worsening of a COVID-19 infectious course is a crucial step in improving clinical outcomes.
Dr. Sahni is Assistant Professor of Clinical Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago. Dr. Cao is Clinical Associate Professor, Division of Sleep Medicine and Division of Neuromuscular Medicine, Department of Psychiatry and Department of Neurology, Stanford (Calif.) University.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused by the novel coronavirus of the year 2019 (COVID-19) has had a major impact on global health and economy. United States reported a total caseload of 28,998,834 patients and total mortality of 525,031 as of March 2021 (NPR.org; worldometer. Accessed March 8, 2021). The beginning of 2021 ushered positivity with the development of multiple highly effective SARS-CoV-2 vaccines. Although the medical world has gained much knowledge about this deadly disease, there are many unknowns and still much to be learned.
Two early landmark studies from Italy (Lombardy) and United States (New York City area) provided initial insight on comorbid conditions associated with increased risk of severe COVID-19 infection (Richardson S, et al. JAMA. 2020;323[20]:2052; Grasselli G, et al. JAMA Intern Med. 2020;180[10]:1345). In the United States cohort, hypertension (HTN), obesity, and diabetes (DM) were independent risk factors for severe disease, while in the Italy cohort, older age, male, COPD, hypercholesterolemia, and diabetes were independent risk factors for increased mortality. Obstructive sleep apnea (OSA) was not mentioned as a comorbid risk factor.
There is much speculation regarding OSA as an independent risk factor for severe COVID-19 infection. OSA is a common sleep-related breathing disorder with increased prevalence in men, older age, and higher body mass index (BMI); and OSA is associated with hypertension, obesity, and diabetes, all of which are risk factors for severe COVID-19. Because of the shared similarities in pathophysiology between OSA and COVID-19 (Tufik S, et al. J Clin Sleep Med. 2020;16[8]:1425), and shared comorbid conditions associated with increased risk of severe COVID-19 disease, OSA has been suggested as an independent risk factor for unfavorable COVID-19-related outcomes.
SARS-CoV-2 triggers a severe inflammatory response involving type-II pneumocytes and angiotensin-converting enzyme 2 pathway. OSA is characterized by intermittent hypoxia and sleep fragmentation, leading to a cascade of systemic inflammatory response involving oxidative stress, pro-inflammatory cytokines, endothelial dysfunction, and consequent cardiovascular injury (Jose RJ, et al. Lancet Respir Med. 2020;8[6]:e46; Saxena K, et al. Sleep Medicine. 2021;79:223). In this regard, OSA may contribute to COVID-19 “cytokine storm” by causing or exacerbating endothelial dysfunction, inflammation, and oxidative stress.
Multiple studies have recently been published on the impact of OSA on COVID-19 outcomes. The Coronavirus SARS-CoV-2 and Diabetes Outcomes (CORONADO) study was one of the initial studies that analyzed the relationship between OSA and COVID-19-related outcomes. This was a multicenter observational study involving diabetic patients hospitalized with COVID-19. The primary outcome was mechanical ventilation and/or death within 7 days of admission. Multivariate adjustment showed that age, BMI, and OSA, among other factors, were independently associated with risk of death on day 7 (Cariou B, et al. Diabetologia. 2020;63[8]:1500). Strausz and colleagues also evaluated OSA as an independent risk factor for severe COVID-19 in a large registry of hospital discharge patients (FinnGen study). The authors reported that although the risk of contracting COVID-19 was the same for patients with or without OSA, after adjusting for age, sex, and BMI, OSA was associated with higher risk of hospitalization (Strausz S, et al. BMJ Open Resp Res. 2021;8:e000845). Similar findings were confirmed by the Maas et al. study, which utilized a large socioeconomically diverse database composed of 10 hospital systems. Diagnoses and outcomes were identified by ICD-10 coding and medical record data. After adjustments for diabetes, HTN, and BMI, OSA conferred an eight-fold risk for COVID-19 infection, was associated with increased risk of hospitalization, and doubled the risk of developing respiratory failure (Maas MB, et al. Sleep Breath. 2020 Sep; 29:1-3. doi: 10.1007/s11325-020-02203-0).
Peker and colleagues conducted a prospective multicenter observational study comparing clinical outcomes of severe COVID-19 infection in patients with low vs high pretest probability of having OSA based on the Berlin questionnaire. The authors reported a clinically significant risk of poorer clinical outcomes in the high pretest probability OSA group after adjustments for age, sex, and comorbidities (Peker Y, et al. Ann Am Thorac Soc. 2021. Feb 17. doi: 10.1513/AnnalsATS.202011-1409OC). A timely meta-analysis including 21 studies (19 with retrospective design) with 54,276 COVID-19 patients and 4,640 OSA patients concluded poor composite outcomes including severe COVID-19, intensive care unit admission, mechanical ventilatory support, and death in association with OSA (OR – 1.72 95% CI 1.55-1.91, P< .00001). In patients with obesity, OSA is a highly prevalent co-morbid condition. BMI, however, was not adjusted in this model (Hariyanto TI, et al. Sleep Med. 2021. doi: 10.1016/j.sleep.2021.03.029).
Other studies have concluded the opposite with OSA not being an independent risk factor for severe COVID-19 infection. Cade and colleagues conducted a retrospective analysis from a comprehensive electronic health dataset using ICD codes to identify OSA patients with severe COVID-19 infection. A significant association between OSA and COVID-19 death was noted after adjustment for demographics (ethnicity, age, sex). However, when fully adjusted for demographics, BMI, asthma, COPD, HTN, or DM, OSA was not an independent risk factor for COVID-19-related mortality and hospitalization (Cade BE, et al. Am J Respir Crit Care Med. 2020;202[10]:1462). The FinnGen study (Strausz et al.) was part of a meta-analysis examining the association between OSA and severe COVID-19 with and without adjustments for BMI. This meta-analysis consisted of 15,835 COVID-19 patients including 1,294 with OSA. The authors found that OSA was a risk factor with a two-fold increased risk of severe COVID-19 infection (OR = 2.37, P = .021). However, after adjustments were made for BMI, this finding lost statistical significance (OR=1.55, P=.13) (Strausz S, et al. BMJ Open Resp Res. 2021;8:e000845).
It is worth noting that a majority of studies identified OSA by indirect and imperfect methods through chart review, ICD codes, and databases. Confirmed OSA based on formal testing with a sleep study in COVID-19 patients remains a challenge. Perhaps well performed screening questionnaires, such as STOP-Bang, Berlin, or NoSAS, can be utilized as was the case in one study. It is also unclear if outcomes of COVID-19 infection differ in patients with treated or untreated OSA, as raised by the CORONADO study. A recent cross-sectional telephone interview survey of patients with confirmed OSA in Iran alluded to higher prevalence of COVID-19 in patients with severe OSA with suggestion of lower prevalence in patients who were currently receiving OSA treatment with positive airway pressure (PAP) therapy (Najafi A, et al. Sleep Health. 2021 Feb;7[1]:14). This is a crucial question as PAP therapy is considered an aerosol-generating procedure (Lance CG. Cleve Clin J Med. 2020 May 5. doi: 10.3949/ccjm.87a.ccc003). Studies have suggested continued use of PAP therapy with additional measures to mitigate the spread of virus, since failure to use PAP could be deleterious to the patient’s quality of life. Interestingly, PAP adherence seemed to have improved during the pandemic as evidenced by a telephonic survey done in New York City that showed 88% of patients with OSA used a PAP device consistently (Attias D, et al. Eur Respir J. 2020 Jul 30;56[1]:2001607. doi: 10.1183/13993003.01607-2020).
In summary, the jury is still out on whether OSA is a facilitator for viral replication, or an independent risk factor for poor prognosis related to COVID-19 infection, or has no clinical relevance to COVID-19. COVID-19 and OSA share comorbidities and pathways leading to a systemic inflammatory cascade. Theoretically, it would make sense that OSA is a risk factor for severe COVID-19 infection; however, it remains to be proven. The recent studies are limited by retrospective and observational nature, imprecise OSA classification/diagnostic criteria, and confounded by difficult to control variables. Further research is needed to expand our understanding of OSA -induced intermittent hypoxemia, inflammation, and endothelial dysfunction that may play a role in COVID-19 morbidity and mortality. Until we have more clarity, close monitoring of OSA patients infected with COVID-19 is recommended along with implementation of safe protocols for continuation of PAP usage during the infectious phase. Identifying underlying comorbid conditions that contribute to worsening of a COVID-19 infectious course is a crucial step in improving clinical outcomes.
Dr. Sahni is Assistant Professor of Clinical Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago. Dr. Cao is Clinical Associate Professor, Division of Sleep Medicine and Division of Neuromuscular Medicine, Department of Psychiatry and Department of Neurology, Stanford (Calif.) University.
Once-nightly sodium oxybate agent effective in narcolepsy
, new research suggests. Top-line results from the phase 3 REST-ON trial released earlier this year showed that the agent known as FT218 (Avadel Pharmaceuticals) met all three of its coprimary efficacy endpoints at all three doses assessed (6 g, 7.5 g, and 9 g). Patients receiving the drug showed significantly greater improvements on the Maintenance of Wakefulness Test (MWT), the Clinical Global Impression of Improvement (CGI-I), and mean weekly attacks of cataplexy, compared with those who received placebo.
The new analyses, which focused on key secondary outcomes, showed that all three doses of the novel agent were associated with significant improvements in sleep quality, refreshing nature of sleep, sleep paralysis, disturbed nocturnal sleep, and scores on the Epworth Sleepiness Scale (ESS).
Principal investigator Michael J. Thorpy, MD, director of the Sleep-Wake Disorders Center at the Montefiore Medical Center, New York, said in a news release that the results represent “the promise of a potential new treatment strategy for physicians and patients.”
“I am particularly impressed by the consistency of results as early as 3 weeks with only a 6-g dose,” he added.
Dr. Thorpy, who is also a professor of neurology at the Albert Einstein College of Medicine, noted that the new formulation will be more convenient for patients. “The advantage of this medication is its once-nightly formulation, so patients don’t need to awaken during the night and can actually have a better night’s sleep,” he said.
Dr. Thorpy presented the study findings at the 2021 annual meeting of the American Academy of Neurology.
FT218 is currently under review by the U.S. Food and Drug Administration, which has set Oct. 15 as the Prescription Drug User Fee Act target date.
Forced awakening
Sodium oxybate was first approved by the FDA in 2002 to treat cataplexy in adults with narcolepsy and was expanded in 2005 to also treat excessive daytime sleepiness (EDS). That formulation is indicated for twice-nightly administration, with the second dose taken 2.5-4 hours after the first.
“The need for forced awakening to take the second dose ... may result in noncompliance, which may lead to reduced efficacy and/or mistimed doses,” the investigators noted.
FT218 is a modified-release version of sodium oxybate. A single 6-g dose of the investigational agent “has shown bioequivalent exposure to twice-nightly immediate-release [sodium oxybate] given as two 3-g doses,” wrote the researchers.
It also currently has Orphan Drug Designation from the FDA for the treatment of narcolepsy.
The randomized, double-blind, placebo-controlled, multicenter REST-ON study was conducted from November 2016 to March 2020 and included patients 16 years or older who had narcolepsy type 1 or type 2.
Patients received the active treatment (n = 107; mean age, 30.9 years; 64.5% women) or placebo (n = 105; mean age, 31.6 years; 71.4% women) according to a four-period forced uptitration dosing schedule of 4.5 g for 1 week, 6 g for 2 weeks, 7.5 g for 5 weeks, and 9 g for 5 weeks.
Secondary outcome measures included the ESS, sleep quality/refreshing nature of sleep on a visual analog scale, sleep paralysis and hypnagogic hallucinations on a sleep symptoms diary, disturbed nocturnal sleep on polysomnographic measures, and number of arousals as defined per the American Academy of Sleep Medicine Score Manual.
Reports of adverse events (AEs) were collected from time of informed consent until 7 days after the last dose received.
Improvement across doses
Results showed that, compared with placebo, improvement in disturbed nocturnal sleep from baseline was significantly greater for the active treatment at 6 g at week 3 (mean between-group difference, –11; P < .001), at 7.5 g at week 8 (mean difference, –17.7; P < .001), and at 9 g at week 13 (mean difference, –22.6; P < .001).
The mean difference between the three doses and placebo for reduction in number of arousals was –11.3 (P < .05), –19.4 (P < .001), and –23.7 (P < .001), respectively. And the 6 g at week 3, 7.5 g at week 8, and 9 g at week 13 doses showed significant (P < .001) improvements versus placebo on the ESS (mean difference, –2.1, –3.2, and –3.9, respectively).
All three doses also showed significant improvement in sleep quality and refreshing nature of sleep (P < .001 for all comparisons), as well as improvement of sleep paralysis (P = .04, P = .02, and P = .04, respectively).
There were no significant differences between FT218 and placebo for improvement in hypnagogic hallucinations. Dr. Thorpy noted that the number of patients with baseline hallucinations “was relatively small,” which may have led to this finding. “Had there been a much larger population with hallucinations, I suspect that we would have seen a statistically significant improvement there as well,” he said.
Generally well tolerated
The investigators noted that FT218 was “generally well tolerated, and the most common adverse reactions were well-known and established sodium oxybate adverse reactions.”
Treatment-related AEs that occurred in more than 2% of the patients receiving FT218 included nausea, dizziness, enuresis, headache, decreased appetite, and vomiting.
Seven serious AEs were reported, including five in those assigned to the active treatment. This included one case each of diabetes inadequate control, paresthesia, perirectal abscess, hypertension, and suicidal ideation. Only the case of suicidal ideation was considered to be a treatment-related AE.
The investigators noted that, although they have not yet delved into subgroup analysis to look for differences among sex, age, or race, they plan to do so in the future.
Overall, the results indicate that “FT218 is an effective agent not only for the major symptoms of sleepiness and cataplexy, but also the quality of sleep at night,” said Dr. Thorpy.
Asked whether he thinks the FDA will approve the drug, he said that it should be “straightforward” because it’s just a different formulation of an already-approved agent. “I very much expect there will not be any problems in this medication being approved,” Dr. Thorpy said.
Benefits ‘sleep architecture’
Commenting on the findings, Logan Schneider, MD, codirector of the Stanford/VA Alzheimer’s Center and clinical assistant professor at the Stanford Sleep Center, Redwood City, Calif., said that the investigators’ focus on these secondary outcomes “was really worthwhile.”
Dr. Schneider, who was not involved in the research, noted that, because the study only included patients with narcolepsy, the results can’t be extrapolated to groups who have other sleep disorders.
Still, “it is worthwhile now to expand beyond the two primary symptoms that are, in my consideration, life threatening: daytime sleepiness and cataplexy. We should also address more of the quality of life and other aspects of narcolepsy, including disturbed nocturnal sleep and sleep quality issues related to that,” he said.
“Being able to address those aspects and say, ‘I have a therapy that clearly helps the multidimensionality of our patients’ is very vindicating,” Dr. Schneider noted.
He was also impressed with the various measures the researchers used, rather than relying just on patient reports, “which are subject to recollection difficulties. This was a nice way to quantify possibly as a diagnostic marker the underlying disruption of sleep, as well as a possible treatment marker to show how well a therapy works.”
“It actually shows a beneficial effect on sleep architecture,” Dr. Schneider said.
The study was funded by Avadel Pharmaceuticals. Dr. Thorpy is a consultant/advisory board member for Avadel, Axsome, Balance Therapeutics, Eisai, Harmony Biosciences, Jazz Pharmaceuticals, NLS Pharmaceuticals, Suven Life Sciences, and Takeda Pharmaceutical. Dr. Schneider reports being an adviser and/or on the speakers’ bureau for similar drugs by Jazz Pharmaceuticals and Harmony Biosciences.
A version of this article first appeared on Medscape.com.
, new research suggests. Top-line results from the phase 3 REST-ON trial released earlier this year showed that the agent known as FT218 (Avadel Pharmaceuticals) met all three of its coprimary efficacy endpoints at all three doses assessed (6 g, 7.5 g, and 9 g). Patients receiving the drug showed significantly greater improvements on the Maintenance of Wakefulness Test (MWT), the Clinical Global Impression of Improvement (CGI-I), and mean weekly attacks of cataplexy, compared with those who received placebo.
The new analyses, which focused on key secondary outcomes, showed that all three doses of the novel agent were associated with significant improvements in sleep quality, refreshing nature of sleep, sleep paralysis, disturbed nocturnal sleep, and scores on the Epworth Sleepiness Scale (ESS).
Principal investigator Michael J. Thorpy, MD, director of the Sleep-Wake Disorders Center at the Montefiore Medical Center, New York, said in a news release that the results represent “the promise of a potential new treatment strategy for physicians and patients.”
“I am particularly impressed by the consistency of results as early as 3 weeks with only a 6-g dose,” he added.
Dr. Thorpy, who is also a professor of neurology at the Albert Einstein College of Medicine, noted that the new formulation will be more convenient for patients. “The advantage of this medication is its once-nightly formulation, so patients don’t need to awaken during the night and can actually have a better night’s sleep,” he said.
Dr. Thorpy presented the study findings at the 2021 annual meeting of the American Academy of Neurology.
FT218 is currently under review by the U.S. Food and Drug Administration, which has set Oct. 15 as the Prescription Drug User Fee Act target date.
Forced awakening
Sodium oxybate was first approved by the FDA in 2002 to treat cataplexy in adults with narcolepsy and was expanded in 2005 to also treat excessive daytime sleepiness (EDS). That formulation is indicated for twice-nightly administration, with the second dose taken 2.5-4 hours after the first.
“The need for forced awakening to take the second dose ... may result in noncompliance, which may lead to reduced efficacy and/or mistimed doses,” the investigators noted.
FT218 is a modified-release version of sodium oxybate. A single 6-g dose of the investigational agent “has shown bioequivalent exposure to twice-nightly immediate-release [sodium oxybate] given as two 3-g doses,” wrote the researchers.
It also currently has Orphan Drug Designation from the FDA for the treatment of narcolepsy.
The randomized, double-blind, placebo-controlled, multicenter REST-ON study was conducted from November 2016 to March 2020 and included patients 16 years or older who had narcolepsy type 1 or type 2.
Patients received the active treatment (n = 107; mean age, 30.9 years; 64.5% women) or placebo (n = 105; mean age, 31.6 years; 71.4% women) according to a four-period forced uptitration dosing schedule of 4.5 g for 1 week, 6 g for 2 weeks, 7.5 g for 5 weeks, and 9 g for 5 weeks.
Secondary outcome measures included the ESS, sleep quality/refreshing nature of sleep on a visual analog scale, sleep paralysis and hypnagogic hallucinations on a sleep symptoms diary, disturbed nocturnal sleep on polysomnographic measures, and number of arousals as defined per the American Academy of Sleep Medicine Score Manual.
Reports of adverse events (AEs) were collected from time of informed consent until 7 days after the last dose received.
Improvement across doses
Results showed that, compared with placebo, improvement in disturbed nocturnal sleep from baseline was significantly greater for the active treatment at 6 g at week 3 (mean between-group difference, –11; P < .001), at 7.5 g at week 8 (mean difference, –17.7; P < .001), and at 9 g at week 13 (mean difference, –22.6; P < .001).
The mean difference between the three doses and placebo for reduction in number of arousals was –11.3 (P < .05), –19.4 (P < .001), and –23.7 (P < .001), respectively. And the 6 g at week 3, 7.5 g at week 8, and 9 g at week 13 doses showed significant (P < .001) improvements versus placebo on the ESS (mean difference, –2.1, –3.2, and –3.9, respectively).
All three doses also showed significant improvement in sleep quality and refreshing nature of sleep (P < .001 for all comparisons), as well as improvement of sleep paralysis (P = .04, P = .02, and P = .04, respectively).
There were no significant differences between FT218 and placebo for improvement in hypnagogic hallucinations. Dr. Thorpy noted that the number of patients with baseline hallucinations “was relatively small,” which may have led to this finding. “Had there been a much larger population with hallucinations, I suspect that we would have seen a statistically significant improvement there as well,” he said.
Generally well tolerated
The investigators noted that FT218 was “generally well tolerated, and the most common adverse reactions were well-known and established sodium oxybate adverse reactions.”
Treatment-related AEs that occurred in more than 2% of the patients receiving FT218 included nausea, dizziness, enuresis, headache, decreased appetite, and vomiting.
Seven serious AEs were reported, including five in those assigned to the active treatment. This included one case each of diabetes inadequate control, paresthesia, perirectal abscess, hypertension, and suicidal ideation. Only the case of suicidal ideation was considered to be a treatment-related AE.
The investigators noted that, although they have not yet delved into subgroup analysis to look for differences among sex, age, or race, they plan to do so in the future.
Overall, the results indicate that “FT218 is an effective agent not only for the major symptoms of sleepiness and cataplexy, but also the quality of sleep at night,” said Dr. Thorpy.
Asked whether he thinks the FDA will approve the drug, he said that it should be “straightforward” because it’s just a different formulation of an already-approved agent. “I very much expect there will not be any problems in this medication being approved,” Dr. Thorpy said.
Benefits ‘sleep architecture’
Commenting on the findings, Logan Schneider, MD, codirector of the Stanford/VA Alzheimer’s Center and clinical assistant professor at the Stanford Sleep Center, Redwood City, Calif., said that the investigators’ focus on these secondary outcomes “was really worthwhile.”
Dr. Schneider, who was not involved in the research, noted that, because the study only included patients with narcolepsy, the results can’t be extrapolated to groups who have other sleep disorders.
Still, “it is worthwhile now to expand beyond the two primary symptoms that are, in my consideration, life threatening: daytime sleepiness and cataplexy. We should also address more of the quality of life and other aspects of narcolepsy, including disturbed nocturnal sleep and sleep quality issues related to that,” he said.
“Being able to address those aspects and say, ‘I have a therapy that clearly helps the multidimensionality of our patients’ is very vindicating,” Dr. Schneider noted.
He was also impressed with the various measures the researchers used, rather than relying just on patient reports, “which are subject to recollection difficulties. This was a nice way to quantify possibly as a diagnostic marker the underlying disruption of sleep, as well as a possible treatment marker to show how well a therapy works.”
“It actually shows a beneficial effect on sleep architecture,” Dr. Schneider said.
The study was funded by Avadel Pharmaceuticals. Dr. Thorpy is a consultant/advisory board member for Avadel, Axsome, Balance Therapeutics, Eisai, Harmony Biosciences, Jazz Pharmaceuticals, NLS Pharmaceuticals, Suven Life Sciences, and Takeda Pharmaceutical. Dr. Schneider reports being an adviser and/or on the speakers’ bureau for similar drugs by Jazz Pharmaceuticals and Harmony Biosciences.
A version of this article first appeared on Medscape.com.
, new research suggests. Top-line results from the phase 3 REST-ON trial released earlier this year showed that the agent known as FT218 (Avadel Pharmaceuticals) met all three of its coprimary efficacy endpoints at all three doses assessed (6 g, 7.5 g, and 9 g). Patients receiving the drug showed significantly greater improvements on the Maintenance of Wakefulness Test (MWT), the Clinical Global Impression of Improvement (CGI-I), and mean weekly attacks of cataplexy, compared with those who received placebo.
The new analyses, which focused on key secondary outcomes, showed that all three doses of the novel agent were associated with significant improvements in sleep quality, refreshing nature of sleep, sleep paralysis, disturbed nocturnal sleep, and scores on the Epworth Sleepiness Scale (ESS).
Principal investigator Michael J. Thorpy, MD, director of the Sleep-Wake Disorders Center at the Montefiore Medical Center, New York, said in a news release that the results represent “the promise of a potential new treatment strategy for physicians and patients.”
“I am particularly impressed by the consistency of results as early as 3 weeks with only a 6-g dose,” he added.
Dr. Thorpy, who is also a professor of neurology at the Albert Einstein College of Medicine, noted that the new formulation will be more convenient for patients. “The advantage of this medication is its once-nightly formulation, so patients don’t need to awaken during the night and can actually have a better night’s sleep,” he said.
Dr. Thorpy presented the study findings at the 2021 annual meeting of the American Academy of Neurology.
FT218 is currently under review by the U.S. Food and Drug Administration, which has set Oct. 15 as the Prescription Drug User Fee Act target date.
Forced awakening
Sodium oxybate was first approved by the FDA in 2002 to treat cataplexy in adults with narcolepsy and was expanded in 2005 to also treat excessive daytime sleepiness (EDS). That formulation is indicated for twice-nightly administration, with the second dose taken 2.5-4 hours after the first.
“The need for forced awakening to take the second dose ... may result in noncompliance, which may lead to reduced efficacy and/or mistimed doses,” the investigators noted.
FT218 is a modified-release version of sodium oxybate. A single 6-g dose of the investigational agent “has shown bioequivalent exposure to twice-nightly immediate-release [sodium oxybate] given as two 3-g doses,” wrote the researchers.
It also currently has Orphan Drug Designation from the FDA for the treatment of narcolepsy.
The randomized, double-blind, placebo-controlled, multicenter REST-ON study was conducted from November 2016 to March 2020 and included patients 16 years or older who had narcolepsy type 1 or type 2.
Patients received the active treatment (n = 107; mean age, 30.9 years; 64.5% women) or placebo (n = 105; mean age, 31.6 years; 71.4% women) according to a four-period forced uptitration dosing schedule of 4.5 g for 1 week, 6 g for 2 weeks, 7.5 g for 5 weeks, and 9 g for 5 weeks.
Secondary outcome measures included the ESS, sleep quality/refreshing nature of sleep on a visual analog scale, sleep paralysis and hypnagogic hallucinations on a sleep symptoms diary, disturbed nocturnal sleep on polysomnographic measures, and number of arousals as defined per the American Academy of Sleep Medicine Score Manual.
Reports of adverse events (AEs) were collected from time of informed consent until 7 days after the last dose received.
Improvement across doses
Results showed that, compared with placebo, improvement in disturbed nocturnal sleep from baseline was significantly greater for the active treatment at 6 g at week 3 (mean between-group difference, –11; P < .001), at 7.5 g at week 8 (mean difference, –17.7; P < .001), and at 9 g at week 13 (mean difference, –22.6; P < .001).
The mean difference between the three doses and placebo for reduction in number of arousals was –11.3 (P < .05), –19.4 (P < .001), and –23.7 (P < .001), respectively. And the 6 g at week 3, 7.5 g at week 8, and 9 g at week 13 doses showed significant (P < .001) improvements versus placebo on the ESS (mean difference, –2.1, –3.2, and –3.9, respectively).
All three doses also showed significant improvement in sleep quality and refreshing nature of sleep (P < .001 for all comparisons), as well as improvement of sleep paralysis (P = .04, P = .02, and P = .04, respectively).
There were no significant differences between FT218 and placebo for improvement in hypnagogic hallucinations. Dr. Thorpy noted that the number of patients with baseline hallucinations “was relatively small,” which may have led to this finding. “Had there been a much larger population with hallucinations, I suspect that we would have seen a statistically significant improvement there as well,” he said.
Generally well tolerated
The investigators noted that FT218 was “generally well tolerated, and the most common adverse reactions were well-known and established sodium oxybate adverse reactions.”
Treatment-related AEs that occurred in more than 2% of the patients receiving FT218 included nausea, dizziness, enuresis, headache, decreased appetite, and vomiting.
Seven serious AEs were reported, including five in those assigned to the active treatment. This included one case each of diabetes inadequate control, paresthesia, perirectal abscess, hypertension, and suicidal ideation. Only the case of suicidal ideation was considered to be a treatment-related AE.
The investigators noted that, although they have not yet delved into subgroup analysis to look for differences among sex, age, or race, they plan to do so in the future.
Overall, the results indicate that “FT218 is an effective agent not only for the major symptoms of sleepiness and cataplexy, but also the quality of sleep at night,” said Dr. Thorpy.
Asked whether he thinks the FDA will approve the drug, he said that it should be “straightforward” because it’s just a different formulation of an already-approved agent. “I very much expect there will not be any problems in this medication being approved,” Dr. Thorpy said.
Benefits ‘sleep architecture’
Commenting on the findings, Logan Schneider, MD, codirector of the Stanford/VA Alzheimer’s Center and clinical assistant professor at the Stanford Sleep Center, Redwood City, Calif., said that the investigators’ focus on these secondary outcomes “was really worthwhile.”
Dr. Schneider, who was not involved in the research, noted that, because the study only included patients with narcolepsy, the results can’t be extrapolated to groups who have other sleep disorders.
Still, “it is worthwhile now to expand beyond the two primary symptoms that are, in my consideration, life threatening: daytime sleepiness and cataplexy. We should also address more of the quality of life and other aspects of narcolepsy, including disturbed nocturnal sleep and sleep quality issues related to that,” he said.
“Being able to address those aspects and say, ‘I have a therapy that clearly helps the multidimensionality of our patients’ is very vindicating,” Dr. Schneider noted.
He was also impressed with the various measures the researchers used, rather than relying just on patient reports, “which are subject to recollection difficulties. This was a nice way to quantify possibly as a diagnostic marker the underlying disruption of sleep, as well as a possible treatment marker to show how well a therapy works.”
“It actually shows a beneficial effect on sleep architecture,” Dr. Schneider said.
The study was funded by Avadel Pharmaceuticals. Dr. Thorpy is a consultant/advisory board member for Avadel, Axsome, Balance Therapeutics, Eisai, Harmony Biosciences, Jazz Pharmaceuticals, NLS Pharmaceuticals, Suven Life Sciences, and Takeda Pharmaceutical. Dr. Schneider reports being an adviser and/or on the speakers’ bureau for similar drugs by Jazz Pharmaceuticals and Harmony Biosciences.
A version of this article first appeared on Medscape.com.
FROM AAN 2021
Insomnia? Referral, drugs not usually needed
Too often, medications are the treatment of choice, and when used long term they can perpetuate a problematic cycle, said Dr. Lettieri, professor in pulmonary, critical care, and sleep medicine at Johns Hopkins University, Baltimore.
However, medications alone won’t work without other behavior modifications and they come with potential side effects, he said in his talk. Prescription medications typically don’t treat the cause of the insomnia, just the symptoms.
“In the 15 years I’ve been practicing sleep medicine, I can honestly say I only have a handful of patients that I treat with long-term pharmacotherapy,” Dr. Lettieri said.
He said he typically uses pharmacotherapy only when conservative measures have failed or to help jump-start patients to behavior modifications.
Restricted sleep is a good place to start for chronic insomnia, he continued.
Physicians should ask patients the latest time they can wake up to make it to school, work, etc. If that time is 6 a.m., the goal is to move bedtime back to 10 p.m.–11 p.m. If the patient, however, is unable to sleep until 12:30 a.m., move bedtime there, he said.
Though the 5.5-hour window is not ideal, it’s better to get into bed when ready for sleep. From there, try to get the patient to move bedtime back 15 minutes each week as they train themselves to fall asleep earlier, he said.
“I promise you this works in the majority of patients and doesn’t require any medication. You can also accomplish this with one or two office visits, so it is not a huge drain on resources,” he said.
Sleep specialists in short supply
Cognitive-behavioral therapy (CBT) is “without question the best way to treat chronic insomnia and it’s recommended as first-line therapy by all published guidelines,” Dr. Lettieri said.
He defined chronic insomnia as happening most nights over at least 3 months. It affects twice as many women as men.
CBT offers a formalized way of changing sleep patterns with the help of an expert in sleep behavior disorders. It combines cognitive therapies with education about sleep and stimulus control and uses techniques such as mindfulness and relaxation.
However, most programs take 4-8 sessions with a sleep medicine provider and are usually not covered by insurance. In addition, the number of insomnia specialists is not nearly adequate to meet demand, he added.
Online and mobile-platform CBT programs are widely effective, Dr. Lettieri said. Many are free and all are convenient for patients to use. He said many of his patients use Sleepio, but many other online programs are effective.
“You can provide sufficient therapy for many of your patients and reserve CBT for patients who can’t be fixed with more conservative measures,” he said.
Insomnia among older patients
Interest in helping older patients with insomnia dominated the chat session associated with the talk.
Insomnia increases with age and older patients have often been using prescription or over-the-counter sleep aids for decades.
Additionally, “insomnia is the second-most common reason why people get admitted to long-term care facilities, second only to urinary incontinence,” Dr. Lettieri said.
If physicians use medications with older patients, he said, extra caution is needed. Older people have more neurocognitive impairments than younger adults and may already be taking several other medications. Sleep medications may come with longer elimination half-lives. Polypharmacy may increase risk for falls and have other consequences.
“If you have to go to a medication, try something simple like melatonin,” he said, adding that it should be pharmaceutical grade and extended release.
Also, bright lights during the day, movement throughout the day, and dim lights closer to bedtime are especially important for the elderly, Dr. Lettieri said.
Andrew Corr, MD, a geriatric specialist in primary care with the Riverside (Calif.) Medical Clinic, said in an interview the main message he will take back to his physician group is more CBT and less medication.
He said that, although he has long known CBT is the top first-line treatment, it is difficult to find experts in his area who are trained to do CBT for insomnia, so he was glad to hear online programs and self-directed reading are typically effective.
He also said there’s a common misperception that there’s no harm in prescribing medications such as trazodone (Desyrel), an antidepressant commonly used off label as a sleep aid.
Dr. Lettieri’s talk highlighted his recommendation against using trazodone for sleep. “Despite several recommendations against its use for insomnia, it is still commonly prescribed. You just shouldn’t use it for insomnia,” Dr. Lettieri said.
“It has no measurable effect in a third of patients and at least unacceptable side effects in another third. Right off the bat, it’s not efficacious in two thirds of patients.”
Additionally, priapism, a prolonged erection, has been associated with trazodone, Dr. Lettieri said, “and I have literally never met a patient on trazodone who was counseled about this.”
Trazodone also has a black box warning from the Food and Drug Administration warning about increased risk for suicidal thoughts.
Dr. Lettieri and Dr. Corr disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Too often, medications are the treatment of choice, and when used long term they can perpetuate a problematic cycle, said Dr. Lettieri, professor in pulmonary, critical care, and sleep medicine at Johns Hopkins University, Baltimore.
However, medications alone won’t work without other behavior modifications and they come with potential side effects, he said in his talk. Prescription medications typically don’t treat the cause of the insomnia, just the symptoms.
“In the 15 years I’ve been practicing sleep medicine, I can honestly say I only have a handful of patients that I treat with long-term pharmacotherapy,” Dr. Lettieri said.
He said he typically uses pharmacotherapy only when conservative measures have failed or to help jump-start patients to behavior modifications.
Restricted sleep is a good place to start for chronic insomnia, he continued.
Physicians should ask patients the latest time they can wake up to make it to school, work, etc. If that time is 6 a.m., the goal is to move bedtime back to 10 p.m.–11 p.m. If the patient, however, is unable to sleep until 12:30 a.m., move bedtime there, he said.
Though the 5.5-hour window is not ideal, it’s better to get into bed when ready for sleep. From there, try to get the patient to move bedtime back 15 minutes each week as they train themselves to fall asleep earlier, he said.
“I promise you this works in the majority of patients and doesn’t require any medication. You can also accomplish this with one or two office visits, so it is not a huge drain on resources,” he said.
Sleep specialists in short supply
Cognitive-behavioral therapy (CBT) is “without question the best way to treat chronic insomnia and it’s recommended as first-line therapy by all published guidelines,” Dr. Lettieri said.
He defined chronic insomnia as happening most nights over at least 3 months. It affects twice as many women as men.
CBT offers a formalized way of changing sleep patterns with the help of an expert in sleep behavior disorders. It combines cognitive therapies with education about sleep and stimulus control and uses techniques such as mindfulness and relaxation.
However, most programs take 4-8 sessions with a sleep medicine provider and are usually not covered by insurance. In addition, the number of insomnia specialists is not nearly adequate to meet demand, he added.
Online and mobile-platform CBT programs are widely effective, Dr. Lettieri said. Many are free and all are convenient for patients to use. He said many of his patients use Sleepio, but many other online programs are effective.
“You can provide sufficient therapy for many of your patients and reserve CBT for patients who can’t be fixed with more conservative measures,” he said.
Insomnia among older patients
Interest in helping older patients with insomnia dominated the chat session associated with the talk.
Insomnia increases with age and older patients have often been using prescription or over-the-counter sleep aids for decades.
Additionally, “insomnia is the second-most common reason why people get admitted to long-term care facilities, second only to urinary incontinence,” Dr. Lettieri said.
If physicians use medications with older patients, he said, extra caution is needed. Older people have more neurocognitive impairments than younger adults and may already be taking several other medications. Sleep medications may come with longer elimination half-lives. Polypharmacy may increase risk for falls and have other consequences.
“If you have to go to a medication, try something simple like melatonin,” he said, adding that it should be pharmaceutical grade and extended release.
Also, bright lights during the day, movement throughout the day, and dim lights closer to bedtime are especially important for the elderly, Dr. Lettieri said.
Andrew Corr, MD, a geriatric specialist in primary care with the Riverside (Calif.) Medical Clinic, said in an interview the main message he will take back to his physician group is more CBT and less medication.
He said that, although he has long known CBT is the top first-line treatment, it is difficult to find experts in his area who are trained to do CBT for insomnia, so he was glad to hear online programs and self-directed reading are typically effective.
He also said there’s a common misperception that there’s no harm in prescribing medications such as trazodone (Desyrel), an antidepressant commonly used off label as a sleep aid.
Dr. Lettieri’s talk highlighted his recommendation against using trazodone for sleep. “Despite several recommendations against its use for insomnia, it is still commonly prescribed. You just shouldn’t use it for insomnia,” Dr. Lettieri said.
“It has no measurable effect in a third of patients and at least unacceptable side effects in another third. Right off the bat, it’s not efficacious in two thirds of patients.”
Additionally, priapism, a prolonged erection, has been associated with trazodone, Dr. Lettieri said, “and I have literally never met a patient on trazodone who was counseled about this.”
Trazodone also has a black box warning from the Food and Drug Administration warning about increased risk for suicidal thoughts.
Dr. Lettieri and Dr. Corr disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Too often, medications are the treatment of choice, and when used long term they can perpetuate a problematic cycle, said Dr. Lettieri, professor in pulmonary, critical care, and sleep medicine at Johns Hopkins University, Baltimore.
However, medications alone won’t work without other behavior modifications and they come with potential side effects, he said in his talk. Prescription medications typically don’t treat the cause of the insomnia, just the symptoms.
“In the 15 years I’ve been practicing sleep medicine, I can honestly say I only have a handful of patients that I treat with long-term pharmacotherapy,” Dr. Lettieri said.
He said he typically uses pharmacotherapy only when conservative measures have failed or to help jump-start patients to behavior modifications.
Restricted sleep is a good place to start for chronic insomnia, he continued.
Physicians should ask patients the latest time they can wake up to make it to school, work, etc. If that time is 6 a.m., the goal is to move bedtime back to 10 p.m.–11 p.m. If the patient, however, is unable to sleep until 12:30 a.m., move bedtime there, he said.
Though the 5.5-hour window is not ideal, it’s better to get into bed when ready for sleep. From there, try to get the patient to move bedtime back 15 minutes each week as they train themselves to fall asleep earlier, he said.
“I promise you this works in the majority of patients and doesn’t require any medication. You can also accomplish this with one or two office visits, so it is not a huge drain on resources,” he said.
Sleep specialists in short supply
Cognitive-behavioral therapy (CBT) is “without question the best way to treat chronic insomnia and it’s recommended as first-line therapy by all published guidelines,” Dr. Lettieri said.
He defined chronic insomnia as happening most nights over at least 3 months. It affects twice as many women as men.
CBT offers a formalized way of changing sleep patterns with the help of an expert in sleep behavior disorders. It combines cognitive therapies with education about sleep and stimulus control and uses techniques such as mindfulness and relaxation.
However, most programs take 4-8 sessions with a sleep medicine provider and are usually not covered by insurance. In addition, the number of insomnia specialists is not nearly adequate to meet demand, he added.
Online and mobile-platform CBT programs are widely effective, Dr. Lettieri said. Many are free and all are convenient for patients to use. He said many of his patients use Sleepio, but many other online programs are effective.
“You can provide sufficient therapy for many of your patients and reserve CBT for patients who can’t be fixed with more conservative measures,” he said.
Insomnia among older patients
Interest in helping older patients with insomnia dominated the chat session associated with the talk.
Insomnia increases with age and older patients have often been using prescription or over-the-counter sleep aids for decades.
Additionally, “insomnia is the second-most common reason why people get admitted to long-term care facilities, second only to urinary incontinence,” Dr. Lettieri said.
If physicians use medications with older patients, he said, extra caution is needed. Older people have more neurocognitive impairments than younger adults and may already be taking several other medications. Sleep medications may come with longer elimination half-lives. Polypharmacy may increase risk for falls and have other consequences.
“If you have to go to a medication, try something simple like melatonin,” he said, adding that it should be pharmaceutical grade and extended release.
Also, bright lights during the day, movement throughout the day, and dim lights closer to bedtime are especially important for the elderly, Dr. Lettieri said.
Andrew Corr, MD, a geriatric specialist in primary care with the Riverside (Calif.) Medical Clinic, said in an interview the main message he will take back to his physician group is more CBT and less medication.
He said that, although he has long known CBT is the top first-line treatment, it is difficult to find experts in his area who are trained to do CBT for insomnia, so he was glad to hear online programs and self-directed reading are typically effective.
He also said there’s a common misperception that there’s no harm in prescribing medications such as trazodone (Desyrel), an antidepressant commonly used off label as a sleep aid.
Dr. Lettieri’s talk highlighted his recommendation against using trazodone for sleep. “Despite several recommendations against its use for insomnia, it is still commonly prescribed. You just shouldn’t use it for insomnia,” Dr. Lettieri said.
“It has no measurable effect in a third of patients and at least unacceptable side effects in another third. Right off the bat, it’s not efficacious in two thirds of patients.”
Additionally, priapism, a prolonged erection, has been associated with trazodone, Dr. Lettieri said, “and I have literally never met a patient on trazodone who was counseled about this.”
Trazodone also has a black box warning from the Food and Drug Administration warning about increased risk for suicidal thoughts.
Dr. Lettieri and Dr. Corr disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM INTERNAL MEDICINE 2021