Clinical Psychiatry News

The Food and Drug Administration has approved a higher-dose naloxone hydrochloride nasal spray (Kloxxado) for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression.

Olivier Le Moal/Getty Images

Kloxxado delivers 8 mg of naloxone into the nasal cavity, which is twice as much as the 4 mg of naloxone contained in Narcan nasal spray.

When administered quickly, naloxone can counter opioid overdose effects, usually within minutes. A higher dose of naloxone provides an additional option for the treatment of opioid overdoses, the FDA said in a news release.

“This approval meets another critical need in combating opioid overdose,” Patrizia Cavazzoni, MD, director, FDA Center for Drug Evaluation and Research, said in the release.

“Addressing the opioid crisis is a top priority for the FDA, and we will continue our efforts to increase access to naloxone and place this important medicine in the hands of those who need it most,” said Dr. Cavazzoni.

In a company news release announcing the approval, manufacturer Hikma Pharmaceuticals noted that a recent survey of community organizations in which the 4-mg naloxone nasal spray had been distributed showed that for 34% of attempted reversals, two or more doses of naloxone were used.

A separate study found that the percentage of overdose-related emergency medical service calls in the United States that led to the administration of multiple doses of naloxone increased to 21% during the period of 2013-2016, which represents a 43% increase over 4 years.

“The approval of Kloxxado is an important step in providing patients, friends, and family members – as well as the public health community – with an important new option for treating opioid overdose,” Brian Hoffmann, president of Hikma Generics, said in the release.

The company expects Kloxxado to available in the second half of 2021.

The FDA approved Kloxxado through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.

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

The Food and Drug Administration has approved a higher-dose naloxone hydrochloride nasal spray (Kloxxado) for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression.

Olivier Le Moal/Getty Images

Kloxxado delivers 8 mg of naloxone into the nasal cavity, which is twice as much as the 4 mg of naloxone contained in Narcan nasal spray.

When administered quickly, naloxone can counter opioid overdose effects, usually within minutes. A higher dose of naloxone provides an additional option for the treatment of opioid overdoses, the FDA said in a news release.

“This approval meets another critical need in combating opioid overdose,” Patrizia Cavazzoni, MD, director, FDA Center for Drug Evaluation and Research, said in the release.

“Addressing the opioid crisis is a top priority for the FDA, and we will continue our efforts to increase access to naloxone and place this important medicine in the hands of those who need it most,” said Dr. Cavazzoni.

In a company news release announcing the approval, manufacturer Hikma Pharmaceuticals noted that a recent survey of community organizations in which the 4-mg naloxone nasal spray had been distributed showed that for 34% of attempted reversals, two or more doses of naloxone were used.

A separate study found that the percentage of overdose-related emergency medical service calls in the United States that led to the administration of multiple doses of naloxone increased to 21% during the period of 2013-2016, which represents a 43% increase over 4 years.

“The approval of Kloxxado is an important step in providing patients, friends, and family members – as well as the public health community – with an important new option for treating opioid overdose,” Brian Hoffmann, president of Hikma Generics, said in the release.

The company expects Kloxxado to available in the second half of 2021.

The FDA approved Kloxxado through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.

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

The Food and Drug Administration has approved a higher-dose naloxone hydrochloride nasal spray (Kloxxado) for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression.

Olivier Le Moal/Getty Images

Kloxxado delivers 8 mg of naloxone into the nasal cavity, which is twice as much as the 4 mg of naloxone contained in Narcan nasal spray.

When administered quickly, naloxone can counter opioid overdose effects, usually within minutes. A higher dose of naloxone provides an additional option for the treatment of opioid overdoses, the FDA said in a news release.

“This approval meets another critical need in combating opioid overdose,” Patrizia Cavazzoni, MD, director, FDA Center for Drug Evaluation and Research, said in the release.

“Addressing the opioid crisis is a top priority for the FDA, and we will continue our efforts to increase access to naloxone and place this important medicine in the hands of those who need it most,” said Dr. Cavazzoni.

In a company news release announcing the approval, manufacturer Hikma Pharmaceuticals noted that a recent survey of community organizations in which the 4-mg naloxone nasal spray had been distributed showed that for 34% of attempted reversals, two or more doses of naloxone were used.

A separate study found that the percentage of overdose-related emergency medical service calls in the United States that led to the administration of multiple doses of naloxone increased to 21% during the period of 2013-2016, which represents a 43% increase over 4 years.

“The approval of Kloxxado is an important step in providing patients, friends, and family members – as well as the public health community – with an important new option for treating opioid overdose,” Brian Hoffmann, president of Hikma Generics, said in the release.

The company expects Kloxxado to available in the second half of 2021.

The FDA approved Kloxxado through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.

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

Although the healing properties of cannabis have been touted for millennia, research into its potential neuropsychiatric applications truly began to take off in the 1990s following the discovery of the cannabinoid system in the brain. This led to speculation that cannabis could play a therapeutic role in regulating dopamine, serotonin, and other neurotransmitters and offer a new means of treating various ailments.

LPETTET/Getty Images

At the same time, efforts to liberalize marijuana laws have successfully played out in several nations, including the United States, where, as of April 29, 36 states provide some access to cannabis. These dual tracks – medical and political – have made cannabis an increasingly accepted part of the cultural fabric.

Yet with this development has come a new quandary for clinicians. Medical cannabis has been made widely available to patients and has largely outpaced the clinical evidence, leaving it unclear how and for which indications it should be used.
 

The many forms of medical cannabis

Cannabis is a genus of plants that includes marijuana (Cannabis sativa) and hemp. These plants contain over 100 compounds, including terpenes, flavonoids, and – most importantly for medicinal applications – cannabinoids.

The most abundant cannabinoid in marijuana is the psychotropic delta-9-tetrahydrocannabinol (THC), which imparts the “high” sensation. The next most abundant cannabinoid is cannabidiol (CBD), which is the nonpsychotropic. THC and CBD are the most extensively studied cannabinoids, together and in isolation. Evidence suggests that other cannabinoids and terpenoids may also hold medical promise and that cannabis’ various compounds can work synergistically to produce a so-called entourage effect.

Patients walking into a typical medical cannabis dispensary will be faced with several plant-derived and synthetic options, which can differ considerably in terms of the ratios and amounts of THC and CBD they contain, as well in how they are consumed (i.e., via smoke, vapor, ingestion, topical administration, or oromucosal spray), all of which can alter their effects. Further complicating matters is the varying level of oversight each state and country has in how and whether they test for and accurately label products’ potency, cannabinoid content, and possible impurities.

Medically authorized, prescription cannabis products go through an official regulatory review process, and indications/contraindications have been established for them. To date, the Food and Drug Administration has approved one cannabis-derived drug product – Epidiolex (purified CBD) – for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients aged 2 years and older. The FDA has also approved three synthetic cannabis-related drug products – Marinol, Syndros (or dronabinol, created from synthetic THC), and Cesamet (or nabilone, a synthetic cannabinoid similar to THC) – all of which are indicated for treatment-related nausea and anorexia associated with weight loss in AIDS patients.

Surveys of medical cannabis consumers indicate that most people cannot distinguish between THC and CBD, so the first role that physicians find themselves in when recommending this treatment may be in helping patients navigate the volume of options.
 

Promising treatment for pain

Chronic pain is the leading reason patients seek out medical cannabis. It is also the indication that most researchers agree has the strongest evidence to support its use.

“In my mind, the most promising immediate use for medical cannabis is with THC for pain,” Diana M. Martinez, MD, a professor of psychiatry at Columbia University, New York, who specializes in addiction research, said in a recent MDedge podcast. “THC could be added to the armamentarium of pain medications that we use today.”

In a 2015 systematic literature review, researchers assessed 28 randomized, controlled trials (RCTs) of the use of cannabinoids for chronic pain. They reported that a variety of formulations resulted in at least a 30% reduction in the odds of pain, compared with placebo. A meta-analysis of five RCTs involving patients with neuropathic pain found a 30% reduction in pain over placebo with inhaled, vaporized cannabis. Varying results have been reported in additional studies for this indication. The National Academies of Sciences, Engineering, and Medicine concluded that there was a substantial body of evidence that cannabis is an effective treatment for chronic pain in adults.

The ongoing opioid epidemic has lent these results additional relevance. Data indicate that patients with chronic pain who undergo treatment with medical cannabis can reduce their intake of opioids by more than 60%.

Seeing this firsthand has caused Mark Steven Wallace, MD, a pain management specialist and chair of the division of pain medicine at the University of California San Diego Health, to reconsider offering cannabis to his patients.

“I think it’s probably more efficacious, just from my personal experience, and it’s a much lower risk of abuse and dependence than the opioids,” he said.

Dr. Wallace advised that clinicians who treat pain consider the ratios of cannabinoids.

“This is anecdotal, but we do find that with the combination of the two, CBD reduces the psychoactive effects of the THC. The ratios we use during the daytime range around 20 mg of CBD to 1 mg of THC,” he said.

In a recent secondary analysis of an RCT involving patients with painful diabetic peripheral neuropathy, Dr. Wallace and colleagues showed that THC’s effects appear to reverse themselves at a certain level.

“As the THC level goes up, the pain reduces until you reach about 16 ng/mL; then it starts going in the opposite direction, and pain will start to increase,” he said. “Even recreational cannabis users have reported that they avoid high doses because it’s very aversive. Using cannabis is all about, start low and go slow.”
 

A mixed bag for neurologic indications

There are relatively limited data on the use of medical cannabis for other neurologic conditions, and results have varied. For uses other than pain management, the evidence that does exist is strongest regarding epilepsy, said Daniel Freedman, DO, assistant professor of neurology at the University of Texas at Austin. He noted “multiple high-quality RCTs showing that pharmaceutical-grade CBD can reduce seizures associated with two particular epilepsy syndromes: Dravet Syndrome and Lennox Gastaut.”

These findings led to the FDA’s 2018 approval of Epidiolex for these syndromes. In earlier years, interest in CBD for pediatric seizures was largely driven by anecdotal parental reports of its benefits. NASEM’s 2017 overview on medical cannabis found evidence from subsequent RCTs in this indication to be insufficient. Clinicians who prescribe CBD for this indication must be vigilant because it can interact with several commonly used antiepileptic drugs.

Cannabinoid treatments have also shown success in alleviating muscle spasticity resulting from multiple sclerosis, most prominently in the form of nabiximols (Sativex), a standardized oralmucosal spray containing approximately equal quantities of THC and CBD. Nabiximols is approved in Europe but not in the United States. Moderate evidence supports the efficacy of these and other treatments over placebo in reducing muscle spasticity. Patient ratings of its effects tend to be higher than clinician assessment.

Parkinson’s disease has not yet been approved as an indication for treatment with cannabis or cannabinoids, yet a growing body of preclinical data suggests these could influence the dopaminergic system, said Carsten Buhmann, MD, from the department of neurology at the University Medical Center Hamburg-Eppendorf (Germany).

“In general, cannabinoids modulate basal-ganglia function on two levels which are especially relevant in Parkinson’s disease, i.e., the glutamatergic/dopaminergic synaptic neurotransmission and the corticostriatal plasticity,” he said. “Furthermore, activation of the endocannabinoid system might induce neuroprotective effects related to direct receptor-independent mechanisms, activation of anti-inflammatory cascades in glial cells via the cannabinoid receptor type 2, and antiglutamatergic antiexcitotoxic properties.”

Dr. Buhmann said that currently, clinical evidence is scarce, consisting of only four double-blind, placebo-controlled RCTs involving 49 patients. Various cannabinoids and methods of administering treatment were employed. Improvement was only observed in one of these RCTs, which found that the cannabinoid receptor agonist nabilone significantly reduced levodopa-induced dyskinesia for patients with Parkinson’s disease. Subjective data support a beneficial effect. In a nationwide survey of 1,348 respondents conducted by Dr. Buhmann and colleagues, the majority of medical cannabis users reported that it improved their symptoms (54% with oral CBD and 68% with inhaled THC-containing cannabis).

NASEM concluded that there was insufficient evidence to support the efficacy of medical cannabis for other neurologic conditions, including Tourette syndrome, amyotrophic lateral sclerosis, Huntington disease, dystonia, or dementia. A 2020 position statement from the American Academy of Neurology cited the lack of sufficient peer-reviewed research as the reason it could not currently support the use of cannabis for neurologic disorders.

Yet, according to Dr. Freedman, who served as a coauthor of the AAN position statement, this hasn’t stymied research interest in the topic. He’s seen a substantial uptick in studies of CBD over the past 2 years. “The body of evidence grows, but I still see many claims being made without evidence. And no one seems to care about all the negative trials.”
 

Cannabis as a treatment for, and cause of, psychiatric disorders

Mental health problems – such as anxiety, depression, and PTSD – are among the most common reasons patients seek out medical cannabis. There is an understandable interest in using cannabis and cannabinoids to treat psychiatric disorders. Preclinical studies suggest that the endocannabinoid system plays a prominent role in modulating feelings of anxiety, mood, and fear. As with opioids and chronic pain management, there is hope that medical cannabis may provide a means of reducing prescription anxiolytics and their associated risks.

The authors of the first systematic review (BMC Psychiatry. 2020 Jan 16;20[1]:24) of the use of medical cannabis for major psychiatric disorders noted that the current evidence was “encouraging, albeit embryonic.”

Meta-analyses have indicated a small but positive association between cannabis use and anxiety, although this may reflect the fact that patients with anxiety sought out this treatment. Given the risks for substance use disorders among patients with anxiety, CBD may present a more viable option. Positive results have been shown as treatment for generalized social anxiety disorder.

Limited but encouraging results have also been reported regarding the alleviation of PTSD symptoms with both cannabis and CBD, although the body of high-quality evidence hasn’t notably progressed since 2017, when NASEM declared that the evidence was insufficient. Supportive evidence is similarly lacking regarding the treatment of depression. Longitudinal studies suggest that cannabis use, particularly heavy use, may increase the risk of developing this disorder. Because THC is psychoactive, it is advised that it be avoided by patients at risk for psychotic disorders. However, CBD has yielded limited benefits for patients with treatment-resistant schizophrenia and for young people at risk for psychosis.

The use of medical cannabis for psychiatric conditions requires a complex balancing act, inasmuch as these treatments may exacerbate the very problems they are intended to alleviate.

Marta Di Forti, MD, PhD, professor of psychiatric research at Kings College London, has been at the forefront of determining the mental health risks of continued cannabis use. In 2019, Dr. Di Forti developed the first and only Cannabis Clinic for Patients With Psychosis in London where she and her colleagues have continued to elucidate this connection.

Dr. Di Forti and colleagues have linked daily cannabis use to an increase in the risk of experiencing psychotic disorder, compared with never using it. That risk was further increased among users of high-potency cannabis (≥10% THC). The latter finding has troubling implications, because concentrations of THC have steadily risen since 1970. By contrast, CBD concentrations have remained generally stable. High-potency cannabis products are common in both recreational and medicinal settings.

“For somebody prescribing medicinal cannabis that has a ≥10% concentration of THC, I’d be particularly wary of the risk of psychosis,” said Dr. Di Forti. “If you’re expecting people to use a high content of THC daily to medicate pain or a chronic condition, you even more so need to be aware that this is a potential side effect.”

Dr. Di Forti noted that her findings come from a cohort of recreational users, most of whom were aged 18-35 years.

“There have actually not been studies developed from collecting data in this area from groups specifically using cannabis for medicinal rather than recreational purposes,” she said.

She added that she personally has no concerns about the use of medical cannabis but wants clinicians to be aware of the risk for psychosis, to structure their patient conversations to identify risk factors or family histories of psychosis, and to become knowledgeable in detecting the often subtle signs of its initial onset.

When cannabis-associated psychosis occurs, Dr. Di Forti said it is primarily treated with conventional means, such as antipsychotics and therapeutic interventions and by refraining from using cannabis. Achieving the latter goal can be a challenge for patients who are daily users of high-potency cannabis. Currently, there are no treatment options such as those offered to patients withdrawing from the use of alcohol or opioids. Dr. Di Forti and colleagues are currently researching a solution to that problem through the use of another medical cannabis, the oromucosal spray Sativex, which has been approved in the European Union.
 

The regulatory obstacles to clarifying cannabis’ role in medicine

That currently there is limited or no evidence to support the use of medical cannabis for the treatment of neuropsychiatric conditions points to the inherent difficulties in conducting high-level research in this area.

“There’s a tremendous shortage of reliable data, largely due to regulatory barriers,” said Dr. Martinez.

Since 1970, cannabis has been listed as a Schedule I drug that is illegal to prescribe (the Agriculture Improvement Act of 2018 removed hemp from such restrictions). The FDA has issued guidance for researchers who wish to investigate treatments using Cannabis sativa or its derivatives in which the THC content is greater than 0.3%. Such research requires regular interactions with several federal agencies, including the Drug Enforcement Administration.

“It’s impossible to do multicenter RCTs with large numbers of patients, because you can’t transport cannabis across state lines,” said Dr. Wallace.

Regulatory restrictions regarding medical cannabis vary considerably throughout the world (the European Monitoring Center for Drugs and Drug Addiction provides a useful breakdown of this on their website). The lack of consistency in regulatory oversight acts as an impediment for conducting large-scale international multicenter studies on the topic.

Dr. Buhmann noted that, in Germany, cannabis has been broadly approved for treatment-resistant conditions with severe symptoms that impair quality of life. In addition, it is easy to be reimbursed for the use of cannabis as a medical treatment. These factors serve as disincentives for the funding of high-quality studies.

“It’s likely that no pharmaceutical company will do an expensive RCT to get an approval for Parkinson’s disease because it is already possible to prescribe medical cannabis of any type of THC-containing cannabinoid, dose, or route of application,” Dr. Buhmann said.

In the face of such restrictions and barriers, researchers are turning to ambitious real-world data projects to better understand medical cannabis’ efficacy and safety. A notable example is ProjectTwenty21, which is supported by the Royal College of Psychiatrists. The project is collecting outcomes of the use of medical cannabis among 20,000 U.K. patients whose conventional treatments of chronic pain, anxiety disorder, epilepsy, multiple sclerosis, PTSD, substance use disorder, and Tourette syndrome failed.

Dr. Freedman noted that the continued lack of high-quality data creates a void that commercial interests fill with unfounded claims.

“The danger is that patients might abandon a medication or intervention backed by robust science in favor of something without any science or evidence behind it,” he said. “There is no reason not to expect the same level of data for claims about cannabis products as we would expect from pharmaceutical products.”

Getting to that point, however, will require that the authorities governing clinical trials begin to view cannabis as the research community does, as a possible treatment with potential value, rather than as an illicit drug that needs to be tamped down.

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

Although the healing properties of cannabis have been touted for millennia, research into its potential neuropsychiatric applications truly began to take off in the 1990s following the discovery of the cannabinoid system in the brain. This led to speculation that cannabis could play a therapeutic role in regulating dopamine, serotonin, and other neurotransmitters and offer a new means of treating various ailments.

LPETTET/Getty Images

At the same time, efforts to liberalize marijuana laws have successfully played out in several nations, including the United States, where, as of April 29, 36 states provide some access to cannabis. These dual tracks – medical and political – have made cannabis an increasingly accepted part of the cultural fabric.

Yet with this development has come a new quandary for clinicians. Medical cannabis has been made widely available to patients and has largely outpaced the clinical evidence, leaving it unclear how and for which indications it should be used.
 

The many forms of medical cannabis

Cannabis is a genus of plants that includes marijuana (Cannabis sativa) and hemp. These plants contain over 100 compounds, including terpenes, flavonoids, and – most importantly for medicinal applications – cannabinoids.

The most abundant cannabinoid in marijuana is the psychotropic delta-9-tetrahydrocannabinol (THC), which imparts the “high” sensation. The next most abundant cannabinoid is cannabidiol (CBD), which is the nonpsychotropic. THC and CBD are the most extensively studied cannabinoids, together and in isolation. Evidence suggests that other cannabinoids and terpenoids may also hold medical promise and that cannabis’ various compounds can work synergistically to produce a so-called entourage effect.

Patients walking into a typical medical cannabis dispensary will be faced with several plant-derived and synthetic options, which can differ considerably in terms of the ratios and amounts of THC and CBD they contain, as well in how they are consumed (i.e., via smoke, vapor, ingestion, topical administration, or oromucosal spray), all of which can alter their effects. Further complicating matters is the varying level of oversight each state and country has in how and whether they test for and accurately label products’ potency, cannabinoid content, and possible impurities.

Medically authorized, prescription cannabis products go through an official regulatory review process, and indications/contraindications have been established for them. To date, the Food and Drug Administration has approved one cannabis-derived drug product – Epidiolex (purified CBD) – for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients aged 2 years and older. The FDA has also approved three synthetic cannabis-related drug products – Marinol, Syndros (or dronabinol, created from synthetic THC), and Cesamet (or nabilone, a synthetic cannabinoid similar to THC) – all of which are indicated for treatment-related nausea and anorexia associated with weight loss in AIDS patients.

Surveys of medical cannabis consumers indicate that most people cannot distinguish between THC and CBD, so the first role that physicians find themselves in when recommending this treatment may be in helping patients navigate the volume of options.
 

Promising treatment for pain

Chronic pain is the leading reason patients seek out medical cannabis. It is also the indication that most researchers agree has the strongest evidence to support its use.

“In my mind, the most promising immediate use for medical cannabis is with THC for pain,” Diana M. Martinez, MD, a professor of psychiatry at Columbia University, New York, who specializes in addiction research, said in a recent MDedge podcast. “THC could be added to the armamentarium of pain medications that we use today.”

In a 2015 systematic literature review, researchers assessed 28 randomized, controlled trials (RCTs) of the use of cannabinoids for chronic pain. They reported that a variety of formulations resulted in at least a 30% reduction in the odds of pain, compared with placebo. A meta-analysis of five RCTs involving patients with neuropathic pain found a 30% reduction in pain over placebo with inhaled, vaporized cannabis. Varying results have been reported in additional studies for this indication. The National Academies of Sciences, Engineering, and Medicine concluded that there was a substantial body of evidence that cannabis is an effective treatment for chronic pain in adults.

The ongoing opioid epidemic has lent these results additional relevance. Data indicate that patients with chronic pain who undergo treatment with medical cannabis can reduce their intake of opioids by more than 60%.

Seeing this firsthand has caused Mark Steven Wallace, MD, a pain management specialist and chair of the division of pain medicine at the University of California San Diego Health, to reconsider offering cannabis to his patients.

“I think it’s probably more efficacious, just from my personal experience, and it’s a much lower risk of abuse and dependence than the opioids,” he said.

Dr. Wallace advised that clinicians who treat pain consider the ratios of cannabinoids.

“This is anecdotal, but we do find that with the combination of the two, CBD reduces the psychoactive effects of the THC. The ratios we use during the daytime range around 20 mg of CBD to 1 mg of THC,” he said.

In a recent secondary analysis of an RCT involving patients with painful diabetic peripheral neuropathy, Dr. Wallace and colleagues showed that THC’s effects appear to reverse themselves at a certain level.

“As the THC level goes up, the pain reduces until you reach about 16 ng/mL; then it starts going in the opposite direction, and pain will start to increase,” he said. “Even recreational cannabis users have reported that they avoid high doses because it’s very aversive. Using cannabis is all about, start low and go slow.”
 

A mixed bag for neurologic indications

There are relatively limited data on the use of medical cannabis for other neurologic conditions, and results have varied. For uses other than pain management, the evidence that does exist is strongest regarding epilepsy, said Daniel Freedman, DO, assistant professor of neurology at the University of Texas at Austin. He noted “multiple high-quality RCTs showing that pharmaceutical-grade CBD can reduce seizures associated with two particular epilepsy syndromes: Dravet Syndrome and Lennox Gastaut.”

These findings led to the FDA’s 2018 approval of Epidiolex for these syndromes. In earlier years, interest in CBD for pediatric seizures was largely driven by anecdotal parental reports of its benefits. NASEM’s 2017 overview on medical cannabis found evidence from subsequent RCTs in this indication to be insufficient. Clinicians who prescribe CBD for this indication must be vigilant because it can interact with several commonly used antiepileptic drugs.

Cannabinoid treatments have also shown success in alleviating muscle spasticity resulting from multiple sclerosis, most prominently in the form of nabiximols (Sativex), a standardized oralmucosal spray containing approximately equal quantities of THC and CBD. Nabiximols is approved in Europe but not in the United States. Moderate evidence supports the efficacy of these and other treatments over placebo in reducing muscle spasticity. Patient ratings of its effects tend to be higher than clinician assessment.

Parkinson’s disease has not yet been approved as an indication for treatment with cannabis or cannabinoids, yet a growing body of preclinical data suggests these could influence the dopaminergic system, said Carsten Buhmann, MD, from the department of neurology at the University Medical Center Hamburg-Eppendorf (Germany).

“In general, cannabinoids modulate basal-ganglia function on two levels which are especially relevant in Parkinson’s disease, i.e., the glutamatergic/dopaminergic synaptic neurotransmission and the corticostriatal plasticity,” he said. “Furthermore, activation of the endocannabinoid system might induce neuroprotective effects related to direct receptor-independent mechanisms, activation of anti-inflammatory cascades in glial cells via the cannabinoid receptor type 2, and antiglutamatergic antiexcitotoxic properties.”

Dr. Buhmann said that currently, clinical evidence is scarce, consisting of only four double-blind, placebo-controlled RCTs involving 49 patients. Various cannabinoids and methods of administering treatment were employed. Improvement was only observed in one of these RCTs, which found that the cannabinoid receptor agonist nabilone significantly reduced levodopa-induced dyskinesia for patients with Parkinson’s disease. Subjective data support a beneficial effect. In a nationwide survey of 1,348 respondents conducted by Dr. Buhmann and colleagues, the majority of medical cannabis users reported that it improved their symptoms (54% with oral CBD and 68% with inhaled THC-containing cannabis).

NASEM concluded that there was insufficient evidence to support the efficacy of medical cannabis for other neurologic conditions, including Tourette syndrome, amyotrophic lateral sclerosis, Huntington disease, dystonia, or dementia. A 2020 position statement from the American Academy of Neurology cited the lack of sufficient peer-reviewed research as the reason it could not currently support the use of cannabis for neurologic disorders.

Yet, according to Dr. Freedman, who served as a coauthor of the AAN position statement, this hasn’t stymied research interest in the topic. He’s seen a substantial uptick in studies of CBD over the past 2 years. “The body of evidence grows, but I still see many claims being made without evidence. And no one seems to care about all the negative trials.”
 

Cannabis as a treatment for, and cause of, psychiatric disorders

Mental health problems – such as anxiety, depression, and PTSD – are among the most common reasons patients seek out medical cannabis. There is an understandable interest in using cannabis and cannabinoids to treat psychiatric disorders. Preclinical studies suggest that the endocannabinoid system plays a prominent role in modulating feelings of anxiety, mood, and fear. As with opioids and chronic pain management, there is hope that medical cannabis may provide a means of reducing prescription anxiolytics and their associated risks.

The authors of the first systematic review (BMC Psychiatry. 2020 Jan 16;20[1]:24) of the use of medical cannabis for major psychiatric disorders noted that the current evidence was “encouraging, albeit embryonic.”

Meta-analyses have indicated a small but positive association between cannabis use and anxiety, although this may reflect the fact that patients with anxiety sought out this treatment. Given the risks for substance use disorders among patients with anxiety, CBD may present a more viable option. Positive results have been shown as treatment for generalized social anxiety disorder.

Limited but encouraging results have also been reported regarding the alleviation of PTSD symptoms with both cannabis and CBD, although the body of high-quality evidence hasn’t notably progressed since 2017, when NASEM declared that the evidence was insufficient. Supportive evidence is similarly lacking regarding the treatment of depression. Longitudinal studies suggest that cannabis use, particularly heavy use, may increase the risk of developing this disorder. Because THC is psychoactive, it is advised that it be avoided by patients at risk for psychotic disorders. However, CBD has yielded limited benefits for patients with treatment-resistant schizophrenia and for young people at risk for psychosis.

The use of medical cannabis for psychiatric conditions requires a complex balancing act, inasmuch as these treatments may exacerbate the very problems they are intended to alleviate.

Marta Di Forti, MD, PhD, professor of psychiatric research at Kings College London, has been at the forefront of determining the mental health risks of continued cannabis use. In 2019, Dr. Di Forti developed the first and only Cannabis Clinic for Patients With Psychosis in London where she and her colleagues have continued to elucidate this connection.

Dr. Di Forti and colleagues have linked daily cannabis use to an increase in the risk of experiencing psychotic disorder, compared with never using it. That risk was further increased among users of high-potency cannabis (≥10% THC). The latter finding has troubling implications, because concentrations of THC have steadily risen since 1970. By contrast, CBD concentrations have remained generally stable. High-potency cannabis products are common in both recreational and medicinal settings.

“For somebody prescribing medicinal cannabis that has a ≥10% concentration of THC, I’d be particularly wary of the risk of psychosis,” said Dr. Di Forti. “If you’re expecting people to use a high content of THC daily to medicate pain or a chronic condition, you even more so need to be aware that this is a potential side effect.”

Dr. Di Forti noted that her findings come from a cohort of recreational users, most of whom were aged 18-35 years.

“There have actually not been studies developed from collecting data in this area from groups specifically using cannabis for medicinal rather than recreational purposes,” she said.

She added that she personally has no concerns about the use of medical cannabis but wants clinicians to be aware of the risk for psychosis, to structure their patient conversations to identify risk factors or family histories of psychosis, and to become knowledgeable in detecting the often subtle signs of its initial onset.

When cannabis-associated psychosis occurs, Dr. Di Forti said it is primarily treated with conventional means, such as antipsychotics and therapeutic interventions and by refraining from using cannabis. Achieving the latter goal can be a challenge for patients who are daily users of high-potency cannabis. Currently, there are no treatment options such as those offered to patients withdrawing from the use of alcohol or opioids. Dr. Di Forti and colleagues are currently researching a solution to that problem through the use of another medical cannabis, the oromucosal spray Sativex, which has been approved in the European Union.
 

The regulatory obstacles to clarifying cannabis’ role in medicine

That currently there is limited or no evidence to support the use of medical cannabis for the treatment of neuropsychiatric conditions points to the inherent difficulties in conducting high-level research in this area.

“There’s a tremendous shortage of reliable data, largely due to regulatory barriers,” said Dr. Martinez.

Since 1970, cannabis has been listed as a Schedule I drug that is illegal to prescribe (the Agriculture Improvement Act of 2018 removed hemp from such restrictions). The FDA has issued guidance for researchers who wish to investigate treatments using Cannabis sativa or its derivatives in which the THC content is greater than 0.3%. Such research requires regular interactions with several federal agencies, including the Drug Enforcement Administration.

“It’s impossible to do multicenter RCTs with large numbers of patients, because you can’t transport cannabis across state lines,” said Dr. Wallace.

Regulatory restrictions regarding medical cannabis vary considerably throughout the world (the European Monitoring Center for Drugs and Drug Addiction provides a useful breakdown of this on their website). The lack of consistency in regulatory oversight acts as an impediment for conducting large-scale international multicenter studies on the topic.

Dr. Buhmann noted that, in Germany, cannabis has been broadly approved for treatment-resistant conditions with severe symptoms that impair quality of life. In addition, it is easy to be reimbursed for the use of cannabis as a medical treatment. These factors serve as disincentives for the funding of high-quality studies.

“It’s likely that no pharmaceutical company will do an expensive RCT to get an approval for Parkinson’s disease because it is already possible to prescribe medical cannabis of any type of THC-containing cannabinoid, dose, or route of application,” Dr. Buhmann said.

In the face of such restrictions and barriers, researchers are turning to ambitious real-world data projects to better understand medical cannabis’ efficacy and safety. A notable example is ProjectTwenty21, which is supported by the Royal College of Psychiatrists. The project is collecting outcomes of the use of medical cannabis among 20,000 U.K. patients whose conventional treatments of chronic pain, anxiety disorder, epilepsy, multiple sclerosis, PTSD, substance use disorder, and Tourette syndrome failed.

Dr. Freedman noted that the continued lack of high-quality data creates a void that commercial interests fill with unfounded claims.

“The danger is that patients might abandon a medication or intervention backed by robust science in favor of something without any science or evidence behind it,” he said. “There is no reason not to expect the same level of data for claims about cannabis products as we would expect from pharmaceutical products.”

Getting to that point, however, will require that the authorities governing clinical trials begin to view cannabis as the research community does, as a possible treatment with potential value, rather than as an illicit drug that needs to be tamped down.

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

Although the healing properties of cannabis have been touted for millennia, research into its potential neuropsychiatric applications truly began to take off in the 1990s following the discovery of the cannabinoid system in the brain. This led to speculation that cannabis could play a therapeutic role in regulating dopamine, serotonin, and other neurotransmitters and offer a new means of treating various ailments.

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At the same time, efforts to liberalize marijuana laws have successfully played out in several nations, including the United States, where, as of April 29, 36 states provide some access to cannabis. These dual tracks – medical and political – have made cannabis an increasingly accepted part of the cultural fabric.

Yet with this development has come a new quandary for clinicians. Medical cannabis has been made widely available to patients and has largely outpaced the clinical evidence, leaving it unclear how and for which indications it should be used.
 

The many forms of medical cannabis

Cannabis is a genus of plants that includes marijuana (Cannabis sativa) and hemp. These plants contain over 100 compounds, including terpenes, flavonoids, and – most importantly for medicinal applications – cannabinoids.

The most abundant cannabinoid in marijuana is the psychotropic delta-9-tetrahydrocannabinol (THC), which imparts the “high” sensation. The next most abundant cannabinoid is cannabidiol (CBD), which is the nonpsychotropic. THC and CBD are the most extensively studied cannabinoids, together and in isolation. Evidence suggests that other cannabinoids and terpenoids may also hold medical promise and that cannabis’ various compounds can work synergistically to produce a so-called entourage effect.

Patients walking into a typical medical cannabis dispensary will be faced with several plant-derived and synthetic options, which can differ considerably in terms of the ratios and amounts of THC and CBD they contain, as well in how they are consumed (i.e., via smoke, vapor, ingestion, topical administration, or oromucosal spray), all of which can alter their effects. Further complicating matters is the varying level of oversight each state and country has in how and whether they test for and accurately label products’ potency, cannabinoid content, and possible impurities.

Medically authorized, prescription cannabis products go through an official regulatory review process, and indications/contraindications have been established for them. To date, the Food and Drug Administration has approved one cannabis-derived drug product – Epidiolex (purified CBD) – for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients aged 2 years and older. The FDA has also approved three synthetic cannabis-related drug products – Marinol, Syndros (or dronabinol, created from synthetic THC), and Cesamet (or nabilone, a synthetic cannabinoid similar to THC) – all of which are indicated for treatment-related nausea and anorexia associated with weight loss in AIDS patients.

Surveys of medical cannabis consumers indicate that most people cannot distinguish between THC and CBD, so the first role that physicians find themselves in when recommending this treatment may be in helping patients navigate the volume of options.
 

Promising treatment for pain

Chronic pain is the leading reason patients seek out medical cannabis. It is also the indication that most researchers agree has the strongest evidence to support its use.

“In my mind, the most promising immediate use for medical cannabis is with THC for pain,” Diana M. Martinez, MD, a professor of psychiatry at Columbia University, New York, who specializes in addiction research, said in a recent MDedge podcast. “THC could be added to the armamentarium of pain medications that we use today.”

In a 2015 systematic literature review, researchers assessed 28 randomized, controlled trials (RCTs) of the use of cannabinoids for chronic pain. They reported that a variety of formulations resulted in at least a 30% reduction in the odds of pain, compared with placebo. A meta-analysis of five RCTs involving patients with neuropathic pain found a 30% reduction in pain over placebo with inhaled, vaporized cannabis. Varying results have been reported in additional studies for this indication. The National Academies of Sciences, Engineering, and Medicine concluded that there was a substantial body of evidence that cannabis is an effective treatment for chronic pain in adults.

The ongoing opioid epidemic has lent these results additional relevance. Data indicate that patients with chronic pain who undergo treatment with medical cannabis can reduce their intake of opioids by more than 60%.

Seeing this firsthand has caused Mark Steven Wallace, MD, a pain management specialist and chair of the division of pain medicine at the University of California San Diego Health, to reconsider offering cannabis to his patients.

“I think it’s probably more efficacious, just from my personal experience, and it’s a much lower risk of abuse and dependence than the opioids,” he said.

Dr. Wallace advised that clinicians who treat pain consider the ratios of cannabinoids.

“This is anecdotal, but we do find that with the combination of the two, CBD reduces the psychoactive effects of the THC. The ratios we use during the daytime range around 20 mg of CBD to 1 mg of THC,” he said.

In a recent secondary analysis of an RCT involving patients with painful diabetic peripheral neuropathy, Dr. Wallace and colleagues showed that THC’s effects appear to reverse themselves at a certain level.

“As the THC level goes up, the pain reduces until you reach about 16 ng/mL; then it starts going in the opposite direction, and pain will start to increase,” he said. “Even recreational cannabis users have reported that they avoid high doses because it’s very aversive. Using cannabis is all about, start low and go slow.”
 

A mixed bag for neurologic indications

There are relatively limited data on the use of medical cannabis for other neurologic conditions, and results have varied. For uses other than pain management, the evidence that does exist is strongest regarding epilepsy, said Daniel Freedman, DO, assistant professor of neurology at the University of Texas at Austin. He noted “multiple high-quality RCTs showing that pharmaceutical-grade CBD can reduce seizures associated with two particular epilepsy syndromes: Dravet Syndrome and Lennox Gastaut.”

These findings led to the FDA’s 2018 approval of Epidiolex for these syndromes. In earlier years, interest in CBD for pediatric seizures was largely driven by anecdotal parental reports of its benefits. NASEM’s 2017 overview on medical cannabis found evidence from subsequent RCTs in this indication to be insufficient. Clinicians who prescribe CBD for this indication must be vigilant because it can interact with several commonly used antiepileptic drugs.

Cannabinoid treatments have also shown success in alleviating muscle spasticity resulting from multiple sclerosis, most prominently in the form of nabiximols (Sativex), a standardized oralmucosal spray containing approximately equal quantities of THC and CBD. Nabiximols is approved in Europe but not in the United States. Moderate evidence supports the efficacy of these and other treatments over placebo in reducing muscle spasticity. Patient ratings of its effects tend to be higher than clinician assessment.

Parkinson’s disease has not yet been approved as an indication for treatment with cannabis or cannabinoids, yet a growing body of preclinical data suggests these could influence the dopaminergic system, said Carsten Buhmann, MD, from the department of neurology at the University Medical Center Hamburg-Eppendorf (Germany).

“In general, cannabinoids modulate basal-ganglia function on two levels which are especially relevant in Parkinson’s disease, i.e., the glutamatergic/dopaminergic synaptic neurotransmission and the corticostriatal plasticity,” he said. “Furthermore, activation of the endocannabinoid system might induce neuroprotective effects related to direct receptor-independent mechanisms, activation of anti-inflammatory cascades in glial cells via the cannabinoid receptor type 2, and antiglutamatergic antiexcitotoxic properties.”

Dr. Buhmann said that currently, clinical evidence is scarce, consisting of only four double-blind, placebo-controlled RCTs involving 49 patients. Various cannabinoids and methods of administering treatment were employed. Improvement was only observed in one of these RCTs, which found that the cannabinoid receptor agonist nabilone significantly reduced levodopa-induced dyskinesia for patients with Parkinson’s disease. Subjective data support a beneficial effect. In a nationwide survey of 1,348 respondents conducted by Dr. Buhmann and colleagues, the majority of medical cannabis users reported that it improved their symptoms (54% with oral CBD and 68% with inhaled THC-containing cannabis).

NASEM concluded that there was insufficient evidence to support the efficacy of medical cannabis for other neurologic conditions, including Tourette syndrome, amyotrophic lateral sclerosis, Huntington disease, dystonia, or dementia. A 2020 position statement from the American Academy of Neurology cited the lack of sufficient peer-reviewed research as the reason it could not currently support the use of cannabis for neurologic disorders.

Yet, according to Dr. Freedman, who served as a coauthor of the AAN position statement, this hasn’t stymied research interest in the topic. He’s seen a substantial uptick in studies of CBD over the past 2 years. “The body of evidence grows, but I still see many claims being made without evidence. And no one seems to care about all the negative trials.”
 

Cannabis as a treatment for, and cause of, psychiatric disorders

Mental health problems – such as anxiety, depression, and PTSD – are among the most common reasons patients seek out medical cannabis. There is an understandable interest in using cannabis and cannabinoids to treat psychiatric disorders. Preclinical studies suggest that the endocannabinoid system plays a prominent role in modulating feelings of anxiety, mood, and fear. As with opioids and chronic pain management, there is hope that medical cannabis may provide a means of reducing prescription anxiolytics and their associated risks.

The authors of the first systematic review (BMC Psychiatry. 2020 Jan 16;20[1]:24) of the use of medical cannabis for major psychiatric disorders noted that the current evidence was “encouraging, albeit embryonic.”

Meta-analyses have indicated a small but positive association between cannabis use and anxiety, although this may reflect the fact that patients with anxiety sought out this treatment. Given the risks for substance use disorders among patients with anxiety, CBD may present a more viable option. Positive results have been shown as treatment for generalized social anxiety disorder.

Limited but encouraging results have also been reported regarding the alleviation of PTSD symptoms with both cannabis and CBD, although the body of high-quality evidence hasn’t notably progressed since 2017, when NASEM declared that the evidence was insufficient. Supportive evidence is similarly lacking regarding the treatment of depression. Longitudinal studies suggest that cannabis use, particularly heavy use, may increase the risk of developing this disorder. Because THC is psychoactive, it is advised that it be avoided by patients at risk for psychotic disorders. However, CBD has yielded limited benefits for patients with treatment-resistant schizophrenia and for young people at risk for psychosis.

The use of medical cannabis for psychiatric conditions requires a complex balancing act, inasmuch as these treatments may exacerbate the very problems they are intended to alleviate.

Marta Di Forti, MD, PhD, professor of psychiatric research at Kings College London, has been at the forefront of determining the mental health risks of continued cannabis use. In 2019, Dr. Di Forti developed the first and only Cannabis Clinic for Patients With Psychosis in London where she and her colleagues have continued to elucidate this connection.

Dr. Di Forti and colleagues have linked daily cannabis use to an increase in the risk of experiencing psychotic disorder, compared with never using it. That risk was further increased among users of high-potency cannabis (≥10% THC). The latter finding has troubling implications, because concentrations of THC have steadily risen since 1970. By contrast, CBD concentrations have remained generally stable. High-potency cannabis products are common in both recreational and medicinal settings.

“For somebody prescribing medicinal cannabis that has a ≥10% concentration of THC, I’d be particularly wary of the risk of psychosis,” said Dr. Di Forti. “If you’re expecting people to use a high content of THC daily to medicate pain or a chronic condition, you even more so need to be aware that this is a potential side effect.”

Dr. Di Forti noted that her findings come from a cohort of recreational users, most of whom were aged 18-35 years.

“There have actually not been studies developed from collecting data in this area from groups specifically using cannabis for medicinal rather than recreational purposes,” she said.

She added that she personally has no concerns about the use of medical cannabis but wants clinicians to be aware of the risk for psychosis, to structure their patient conversations to identify risk factors or family histories of psychosis, and to become knowledgeable in detecting the often subtle signs of its initial onset.

When cannabis-associated psychosis occurs, Dr. Di Forti said it is primarily treated with conventional means, such as antipsychotics and therapeutic interventions and by refraining from using cannabis. Achieving the latter goal can be a challenge for patients who are daily users of high-potency cannabis. Currently, there are no treatment options such as those offered to patients withdrawing from the use of alcohol or opioids. Dr. Di Forti and colleagues are currently researching a solution to that problem through the use of another medical cannabis, the oromucosal spray Sativex, which has been approved in the European Union.
 

The regulatory obstacles to clarifying cannabis’ role in medicine

That currently there is limited or no evidence to support the use of medical cannabis for the treatment of neuropsychiatric conditions points to the inherent difficulties in conducting high-level research in this area.

“There’s a tremendous shortage of reliable data, largely due to regulatory barriers,” said Dr. Martinez.

Since 1970, cannabis has been listed as a Schedule I drug that is illegal to prescribe (the Agriculture Improvement Act of 2018 removed hemp from such restrictions). The FDA has issued guidance for researchers who wish to investigate treatments using Cannabis sativa or its derivatives in which the THC content is greater than 0.3%. Such research requires regular interactions with several federal agencies, including the Drug Enforcement Administration.

“It’s impossible to do multicenter RCTs with large numbers of patients, because you can’t transport cannabis across state lines,” said Dr. Wallace.

Regulatory restrictions regarding medical cannabis vary considerably throughout the world (the European Monitoring Center for Drugs and Drug Addiction provides a useful breakdown of this on their website). The lack of consistency in regulatory oversight acts as an impediment for conducting large-scale international multicenter studies on the topic.

Dr. Buhmann noted that, in Germany, cannabis has been broadly approved for treatment-resistant conditions with severe symptoms that impair quality of life. In addition, it is easy to be reimbursed for the use of cannabis as a medical treatment. These factors serve as disincentives for the funding of high-quality studies.

“It’s likely that no pharmaceutical company will do an expensive RCT to get an approval for Parkinson’s disease because it is already possible to prescribe medical cannabis of any type of THC-containing cannabinoid, dose, or route of application,” Dr. Buhmann said.

In the face of such restrictions and barriers, researchers are turning to ambitious real-world data projects to better understand medical cannabis’ efficacy and safety. A notable example is ProjectTwenty21, which is supported by the Royal College of Psychiatrists. The project is collecting outcomes of the use of medical cannabis among 20,000 U.K. patients whose conventional treatments of chronic pain, anxiety disorder, epilepsy, multiple sclerosis, PTSD, substance use disorder, and Tourette syndrome failed.

Dr. Freedman noted that the continued lack of high-quality data creates a void that commercial interests fill with unfounded claims.

“The danger is that patients might abandon a medication or intervention backed by robust science in favor of something without any science or evidence behind it,” he said. “There is no reason not to expect the same level of data for claims about cannabis products as we would expect from pharmaceutical products.”

Getting to that point, however, will require that the authorities governing clinical trials begin to view cannabis as the research community does, as a possible treatment with potential value, rather than as an illicit drug that needs to be tamped down.

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

Cognitive remediation (CR), a therapy that encompasses nonpharmacologic approaches to improving cognitive function for patients with severe mental illness, may lead to significant improvement for patients with schizophrenia, new research suggests.
 

verbaska_studio/Getty Images

A systematic review of 130 worldwide studies that included almost 9,000 participants showed that CR significantly improved global cognition and global functioning. In addition, investigators identified key patient characteristics that flagged ideal candidates for the therapy.

“Because pharmacological treatment exerts limited effects on cognitive deficits, and clinical remission does not necessarily result in functional recovery, widespread implementation of CR could be a game-changer for achieving the patient’s personal recovery goals,” the researchers wrote.

“We hope that this systematic review could help clinicians understand how to make CR even more effective and even more personalized,” lead author Antonio Vita, MD, PhD, department of clinical and experimental sciences, University of Brescia, Italy, said in an interview.

Dr. Vita noted that he would also encourage clinicians to consider “proposing it for clinical practice.”

The findings were presented at the virtual congress of the Schizophrenia International Research Society (SIRS 2021) and were published simultaneously in JAMA Psychiatry.
 

Resistance continues

Cognition “should be a focus of treatment because most of the disability and functional consequences of the disease are related to ... neurocognitive impairment and impairment of social cognition,” Dr. Vita said.

He noted that treatments that focus on cognition are crucial for the recovery of patients with schizophrenia.

However, despite a “solid body of evidence” supporting the efficacy of CR and guideline recommendations that CR be included in psychiatric services, reluctance remains, the investigators noted.

The study’s goal was to determine optimal candidates for CR and to assess outcomes of the therapy and its four core elements:

• The presence of an active and trained therapist.
• Repeated practice of cognitive exercises.
• Structured development of cognitive strategies.
• Techniques to improve the transfer of cognitive gains to the real world, such as integrated psychosocial rehabilitation.

The investigators conducted a systematic literature search of the PubMed, Scopus, and PsychInfo databases to find relevant studies of CR published between January 2011 and February 2020. They also “hand-searched” meta-analyses, reviews, and reference lists.

Ultimately, the analysis included 130 randomized clinical trials comparing CR with a control condition in 8,851 patients with schizophrenia spectrum disorders.

Of these studies, 57 were conducted in Europe, 38 in the United States, 22 in Asia, 4 in Canada, 4 in Middle Eastern countries, 3 in Australia, and 2 in Brazil.

The mean age of the participants was 36.7 years, and 68% were men. The average age at the time of schizophrenia onset was 23.3 years, and the mean duration of illness was 13.8 years.

The average duration of CR treatment was 15.2 weeks. The four elements were well represented; each was offered to at least 71% of patients.

The comparator therapy was treatment as usual (TAU), in 34.3% of cases, or active TAU with multidisciplinary rehabilitation, in 15.2% of cases. The remaining interventions were either nonspecific (30.8%) or were devised specifically for the study (19.9%).

Results showed that CR had a significant, albeit moderate, effect on global cognition (Cohen’s d effect size, 0.29; P < .001) and global functioning (effect size, 0.22; P < .01).

Having an active and trained therapist had a significant impact on cognition and functioning (P = .04 for both), as did the structured development of cognitive strategies (P = .002 for cognition; P = .004 for functioning).

The integration of psychosocial rehabilitation also had a significant effect on functioning (P = .003).

Interventions that included all of the core elements had a “highly significant” association with global cognition (P = .02) and global functioning (P < .001), the investigators reported. Longer treatments were significantly associated with greater functional improvement (P = .006).

The investigators found that improvements were greater among patients who had fewer years of education (P = .03 for cognition; P = .02 for functioning), lower premorbid IQ scores (P = .04 for functioning), and more severe symptoms at baseline (P = .005 for cognition).

The researchers noted that CR should become more widely available because it has the “potential to be an element of standard care rather than an optional intervention targeting selected individuals.”
 

An overlooked treatment option

Commenting on the findings for this news organization, Alice Medalia, PhD, director of the Lieber Recovery Clinic at Columbia University Irving Medical Center, New York, noted that this study is the second large-scale analysis of the use of CR for patients with schizophrenia to come out this year. The other was published in Schizophrenia Bulletin.

“So this is a banner year for large reviews,” she said. “It’s great to have two studies like this [that] tell a very consistent story.”

Dr. Medalia, who was not involved with the research, said individuals “don’t really talk about cognition very much.”

CR, she added, is “one of an array of services that one should be providing, and the bigger picture is that every single person should have their cognitive health needs addressed.

“If someone is having problems, and it’s getting in the way of them being the kind of person they want to be and doing want they want to do, we need to intervene. How we intervene should always be in the least disruptive and intense way,” she said.

These measures could include examining sleep hygiene, adjusting medications, or introducing exercise.

“But there really does come a time for some people where cognitive remediation is going to be helpful, so it should be more available,” Dr. Medalia said.

Although increased availability is partially dependent on having enough trained therapists, the main reason CR is not more widely available is because “people just don’t think about cognition and they don’t know how to talk about it,” she noted. In addition, she said, even when it is available, clinicians don’t refer patients.

“That tells you something. The solution here is not to put a cognitive remediation program everywhere but ... to get people comfortable talking about cognition and identifying when an intervention is needed,” said Dr. Medalia.

One study author received grants from the National Institute for Health Research during the conduct of the study and is the creator of CIRCuiTs, a cognitive remediation software program. The other investigators and Dr. Medalia have reported no relevant financial relationships.

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

Cognitive remediation (CR), a therapy that encompasses nonpharmacologic approaches to improving cognitive function for patients with severe mental illness, may lead to significant improvement for patients with schizophrenia, new research suggests.
 

verbaska_studio/Getty Images

A systematic review of 130 worldwide studies that included almost 9,000 participants showed that CR significantly improved global cognition and global functioning. In addition, investigators identified key patient characteristics that flagged ideal candidates for the therapy.

“Because pharmacological treatment exerts limited effects on cognitive deficits, and clinical remission does not necessarily result in functional recovery, widespread implementation of CR could be a game-changer for achieving the patient’s personal recovery goals,” the researchers wrote.

“We hope that this systematic review could help clinicians understand how to make CR even more effective and even more personalized,” lead author Antonio Vita, MD, PhD, department of clinical and experimental sciences, University of Brescia, Italy, said in an interview.

Dr. Vita noted that he would also encourage clinicians to consider “proposing it for clinical practice.”

The findings were presented at the virtual congress of the Schizophrenia International Research Society (SIRS 2021) and were published simultaneously in JAMA Psychiatry.
 

Resistance continues

Cognition “should be a focus of treatment because most of the disability and functional consequences of the disease are related to ... neurocognitive impairment and impairment of social cognition,” Dr. Vita said.

He noted that treatments that focus on cognition are crucial for the recovery of patients with schizophrenia.

However, despite a “solid body of evidence” supporting the efficacy of CR and guideline recommendations that CR be included in psychiatric services, reluctance remains, the investigators noted.

The study’s goal was to determine optimal candidates for CR and to assess outcomes of the therapy and its four core elements:

• The presence of an active and trained therapist.
• Repeated practice of cognitive exercises.
• Structured development of cognitive strategies.
• Techniques to improve the transfer of cognitive gains to the real world, such as integrated psychosocial rehabilitation.

The investigators conducted a systematic literature search of the PubMed, Scopus, and PsychInfo databases to find relevant studies of CR published between January 2011 and February 2020. They also “hand-searched” meta-analyses, reviews, and reference lists.

Ultimately, the analysis included 130 randomized clinical trials comparing CR with a control condition in 8,851 patients with schizophrenia spectrum disorders.

Of these studies, 57 were conducted in Europe, 38 in the United States, 22 in Asia, 4 in Canada, 4 in Middle Eastern countries, 3 in Australia, and 2 in Brazil.

The mean age of the participants was 36.7 years, and 68% were men. The average age at the time of schizophrenia onset was 23.3 years, and the mean duration of illness was 13.8 years.

The average duration of CR treatment was 15.2 weeks. The four elements were well represented; each was offered to at least 71% of patients.

The comparator therapy was treatment as usual (TAU), in 34.3% of cases, or active TAU with multidisciplinary rehabilitation, in 15.2% of cases. The remaining interventions were either nonspecific (30.8%) or were devised specifically for the study (19.9%).

Results showed that CR had a significant, albeit moderate, effect on global cognition (Cohen’s d effect size, 0.29; P < .001) and global functioning (effect size, 0.22; P < .01).

Having an active and trained therapist had a significant impact on cognition and functioning (P = .04 for both), as did the structured development of cognitive strategies (P = .002 for cognition; P = .004 for functioning).

The integration of psychosocial rehabilitation also had a significant effect on functioning (P = .003).

Interventions that included all of the core elements had a “highly significant” association with global cognition (P = .02) and global functioning (P < .001), the investigators reported. Longer treatments were significantly associated with greater functional improvement (P = .006).

The investigators found that improvements were greater among patients who had fewer years of education (P = .03 for cognition; P = .02 for functioning), lower premorbid IQ scores (P = .04 for functioning), and more severe symptoms at baseline (P = .005 for cognition).

The researchers noted that CR should become more widely available because it has the “potential to be an element of standard care rather than an optional intervention targeting selected individuals.”
 

An overlooked treatment option

Commenting on the findings for this news organization, Alice Medalia, PhD, director of the Lieber Recovery Clinic at Columbia University Irving Medical Center, New York, noted that this study is the second large-scale analysis of the use of CR for patients with schizophrenia to come out this year. The other was published in Schizophrenia Bulletin.

“So this is a banner year for large reviews,” she said. “It’s great to have two studies like this [that] tell a very consistent story.”

Dr. Medalia, who was not involved with the research, said individuals “don’t really talk about cognition very much.”

CR, she added, is “one of an array of services that one should be providing, and the bigger picture is that every single person should have their cognitive health needs addressed.

“If someone is having problems, and it’s getting in the way of them being the kind of person they want to be and doing want they want to do, we need to intervene. How we intervene should always be in the least disruptive and intense way,” she said.

These measures could include examining sleep hygiene, adjusting medications, or introducing exercise.

“But there really does come a time for some people where cognitive remediation is going to be helpful, so it should be more available,” Dr. Medalia said.

Although increased availability is partially dependent on having enough trained therapists, the main reason CR is not more widely available is because “people just don’t think about cognition and they don’t know how to talk about it,” she noted. In addition, she said, even when it is available, clinicians don’t refer patients.

“That tells you something. The solution here is not to put a cognitive remediation program everywhere but ... to get people comfortable talking about cognition and identifying when an intervention is needed,” said Dr. Medalia.

One study author received grants from the National Institute for Health Research during the conduct of the study and is the creator of CIRCuiTs, a cognitive remediation software program. The other investigators and Dr. Medalia have reported no relevant financial relationships.

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

Cognitive remediation (CR), a therapy that encompasses nonpharmacologic approaches to improving cognitive function for patients with severe mental illness, may lead to significant improvement for patients with schizophrenia, new research suggests.
 

verbaska_studio/Getty Images

A systematic review of 130 worldwide studies that included almost 9,000 participants showed that CR significantly improved global cognition and global functioning. In addition, investigators identified key patient characteristics that flagged ideal candidates for the therapy.

“Because pharmacological treatment exerts limited effects on cognitive deficits, and clinical remission does not necessarily result in functional recovery, widespread implementation of CR could be a game-changer for achieving the patient’s personal recovery goals,” the researchers wrote.

“We hope that this systematic review could help clinicians understand how to make CR even more effective and even more personalized,” lead author Antonio Vita, MD, PhD, department of clinical and experimental sciences, University of Brescia, Italy, said in an interview.

Dr. Vita noted that he would also encourage clinicians to consider “proposing it for clinical practice.”

The findings were presented at the virtual congress of the Schizophrenia International Research Society (SIRS 2021) and were published simultaneously in JAMA Psychiatry.
 

Resistance continues

Cognition “should be a focus of treatment because most of the disability and functional consequences of the disease are related to ... neurocognitive impairment and impairment of social cognition,” Dr. Vita said.

He noted that treatments that focus on cognition are crucial for the recovery of patients with schizophrenia.

However, despite a “solid body of evidence” supporting the efficacy of CR and guideline recommendations that CR be included in psychiatric services, reluctance remains, the investigators noted.

The study’s goal was to determine optimal candidates for CR and to assess outcomes of the therapy and its four core elements:

• The presence of an active and trained therapist.
• Repeated practice of cognitive exercises.
• Structured development of cognitive strategies.
• Techniques to improve the transfer of cognitive gains to the real world, such as integrated psychosocial rehabilitation.

The investigators conducted a systematic literature search of the PubMed, Scopus, and PsychInfo databases to find relevant studies of CR published between January 2011 and February 2020. They also “hand-searched” meta-analyses, reviews, and reference lists.

Ultimately, the analysis included 130 randomized clinical trials comparing CR with a control condition in 8,851 patients with schizophrenia spectrum disorders.

Of these studies, 57 were conducted in Europe, 38 in the United States, 22 in Asia, 4 in Canada, 4 in Middle Eastern countries, 3 in Australia, and 2 in Brazil.

The mean age of the participants was 36.7 years, and 68% were men. The average age at the time of schizophrenia onset was 23.3 years, and the mean duration of illness was 13.8 years.

The average duration of CR treatment was 15.2 weeks. The four elements were well represented; each was offered to at least 71% of patients.

The comparator therapy was treatment as usual (TAU), in 34.3% of cases, or active TAU with multidisciplinary rehabilitation, in 15.2% of cases. The remaining interventions were either nonspecific (30.8%) or were devised specifically for the study (19.9%).

Results showed that CR had a significant, albeit moderate, effect on global cognition (Cohen’s d effect size, 0.29; P < .001) and global functioning (effect size, 0.22; P < .01).

Having an active and trained therapist had a significant impact on cognition and functioning (P = .04 for both), as did the structured development of cognitive strategies (P = .002 for cognition; P = .004 for functioning).

The integration of psychosocial rehabilitation also had a significant effect on functioning (P = .003).

Interventions that included all of the core elements had a “highly significant” association with global cognition (P = .02) and global functioning (P < .001), the investigators reported. Longer treatments were significantly associated with greater functional improvement (P = .006).

The investigators found that improvements were greater among patients who had fewer years of education (P = .03 for cognition; P = .02 for functioning), lower premorbid IQ scores (P = .04 for functioning), and more severe symptoms at baseline (P = .005 for cognition).

The researchers noted that CR should become more widely available because it has the “potential to be an element of standard care rather than an optional intervention targeting selected individuals.”
 

An overlooked treatment option

Commenting on the findings for this news organization, Alice Medalia, PhD, director of the Lieber Recovery Clinic at Columbia University Irving Medical Center, New York, noted that this study is the second large-scale analysis of the use of CR for patients with schizophrenia to come out this year. The other was published in Schizophrenia Bulletin.

“So this is a banner year for large reviews,” she said. “It’s great to have two studies like this [that] tell a very consistent story.”

Dr. Medalia, who was not involved with the research, said individuals “don’t really talk about cognition very much.”

CR, she added, is “one of an array of services that one should be providing, and the bigger picture is that every single person should have their cognitive health needs addressed.

“If someone is having problems, and it’s getting in the way of them being the kind of person they want to be and doing want they want to do, we need to intervene. How we intervene should always be in the least disruptive and intense way,” she said.

These measures could include examining sleep hygiene, adjusting medications, or introducing exercise.

“But there really does come a time for some people where cognitive remediation is going to be helpful, so it should be more available,” Dr. Medalia said.

Although increased availability is partially dependent on having enough trained therapists, the main reason CR is not more widely available is because “people just don’t think about cognition and they don’t know how to talk about it,” she noted. In addition, she said, even when it is available, clinicians don’t refer patients.

“That tells you something. The solution here is not to put a cognitive remediation program everywhere but ... to get people comfortable talking about cognition and identifying when an intervention is needed,” said Dr. Medalia.

One study author received grants from the National Institute for Health Research during the conduct of the study and is the creator of CIRCuiTs, a cognitive remediation software program. The other investigators and Dr. Medalia have reported no relevant financial relationships.

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

COVID-19 and its resulting lockdowns are linked to posttraumatic stress disorder symptoms and other adverse outcomes among patients with eating disorders (EDs), two new studies show.

Courtesy Bill Branson/National Cancer Institute

Results of the first study show that patients with EDs had more stress, anxiety, depression, and PTSD-related symptoms during the lockdowns than their mentally healthy peers.

In the second study, treatment-related symptom improvement among patients with bulimia nervosa (BN) slowed following lockdown. In addition, patients with BN or anorexia nervosa (AN) experienced significant worsening of disorder-specific behaviors, including binge eating and overexercising.

Because of the strict lockdown measures introduced by the Italian government to contain the COVID-19 pandemic, “everyday life of all citizens was disrupted,” Veronica Nisticò, MS, Università Degli Studi Di Milano, who led the first study, told delegates attending the virtual European Psychiatric Association 2021 Congress.

In addition to difficulties in accessing health care, “it became difficult to go to the supermarket, to the gym, and to have the social support we were all used to,” all of which had a well-documented impact on mental health, added Ms. Nisticò, who is also affiliated with Aldo Ravelli Research Center for Neurotechnology and Experimental Brain Therapeutics.
 

Loss of control

Previous research suggests that individuals with EDs experience high levels of anxiety and an increase in binge eating, exercise, and purging behaviors, said Ms. Nisticò.

To investigate further, the researchers conducted a longitudinal study of the changes in prevalence of adverse outcomes. In the study, two assessments were conducted.

In the first assessment, conducted in April 2020, the researchers assessed 59 outpatients with EDs and 43 unaffected hospital staff and their acquaintances. The second group served as the control group.

Participants completed an online survey that included several standardized depression and anxiety scales, as well as an ad hoc survey adapted from the Eating Disorder Examination Questionnaire. This assessed changes in restrictive dieting, control over food, body image, and psychological well-being in comparison with prepandemic levels.

The results, which were also recently published online in Eating and Weight Disorders – Studies on Anorexia, Bulimia and Obesity, showed that patients with EDs experienced significantly more stress, anxiety, depression, and PTSD-related symptoms in comparison with control persons (P < .05 for all).

In addition, the investigators found that those with EDs were more fearful of losing control over their eating behavior, spent more time thinking about food and their body, and became more uncomfortable seeing their body than before the lockdown in comparison with those without EDs (P < .05).
 

Clinical implications

A second assessment, which occurred in June 2020, after lockdown restrictions were lifted, included 40 patients with EDs who had taken part in the first assessment. This time, participants were asked to compare their current eating behavior with their eating behavior during the lockdown.

Although the lifting of lockdown restrictions was associated with significant improvement in PTSD-related symptoms, the impact on stress, anxiety, and depression persisted.

These findings, said Ms. Nisticó, support the hypothesis that specific conditions that occurred during the lockdown had a direct effect on specific ED symptoms.

These findings, she added, should be considered when developing interventions for EDs in the context of individual psychotherapy and when designing large, preventive interventions.

In the second study, Eleonora Rossi, MD, psychiatric unit, department of health sciences, University of Florence (Italy), and colleagues examined the longitudinal impact of the pandemic on individuals with EDs.

They examined 74 patients with AN or BN who had undergone baseline assessments and had completed a number of questionnaires in the first months of 2019 in conjunction with being enrolled in another study.

Participants were treated with enhanced cognitive-behavioral therapy and were reevaluated between November 2019 and January 2020. They were then compared with 97 healthy individuals.
 

Bulimia patients more vulnerable

After the outbreak of the pandemic, most treatment was administered online, so patients were able to continue therapy, Dr. Rossi said during her presentation.

All participants were assessed again in April 2020, 6 weeks after the start of Italy’s lockdown.

The results, which were published in the International Journal of Eating Disorders, show that the patients with EDs “underwent a significant improvement in terms of general and eating disorder specific psychopathology” during the first treatment period, Dr. Rossi reported. In addition, among those with AN, body mass index increased significantly (P < .05 for all).

Patients with AN continued to improve during the lockdown when therapy was administered online. However, improvements that had occurred among those with BN slowed, Dr. Rossi noted.

In addition, both groups of patients with EDs experienced a worsening of their pathological eating behaviors during the lockdown, in particular, objective binge eating and compensatory physical exercise (P < .05).

“Indeed, the positive trajectory of improvement observed before lockdown was clearly interrupted during the pandemic period,” Dr. Rossi said. This could “represent a possible hint of an imminent exacerbation of the disease.”

The results also suggest that the occurrence of arguments within the household and fear regarding the safety of loved ones predicted an increase in symptoms during the lockdown, she added.

In addition, patients with BN reported more severe COVID-related PTSD symptoms than did those with AN and the control group. This increase in severity of symptoms was more prevalent among patients who had a history of childhood trauma and among those with insecure attachment, suggesting that such patients may be more vulnerable.
 

Evidence of recovery

Commenting on the studies, David Spiegel, MD, associate chair of psychiatry, Stanford (Calif.) University, noted that EDs commonly occur after physical or sexual trauma earlier in life.

“It’s a standard thing with trauma-related disorders that any other, even relatively minor, traumatic experience can exacerbate PTSD symptoms,” said Dr. Spiegel, who was not involved in the studies. In addition, the trauma of the COVID pandemic “was not minor.

“The relative isolation and the lack of outside contact may focus many people with eating disorders even more on their struggles with how they are taking care of their bodies,” said Dr. Spiegel.

“It struck me that the anorexia nervosa group were more impervious than the bulimia nervosa group, but I think that’s the case with the disorder. In some ways it’s more severe, obviously a more life-threatening disorder,” he added.

The “hopeful thing is that there seemed to be some evidence of recovery and improvement, particularly with the posttraumatic stress exacerbation, as time went on,” Dr. Spiegel said, “and that’s a good thing.”

The study authors and Dr. Spiegel reported no relevant financial relationships.

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

COVID-19 and its resulting lockdowns are linked to posttraumatic stress disorder symptoms and other adverse outcomes among patients with eating disorders (EDs), two new studies show.

Courtesy Bill Branson/National Cancer Institute

Results of the first study show that patients with EDs had more stress, anxiety, depression, and PTSD-related symptoms during the lockdowns than their mentally healthy peers.

In the second study, treatment-related symptom improvement among patients with bulimia nervosa (BN) slowed following lockdown. In addition, patients with BN or anorexia nervosa (AN) experienced significant worsening of disorder-specific behaviors, including binge eating and overexercising.

Because of the strict lockdown measures introduced by the Italian government to contain the COVID-19 pandemic, “everyday life of all citizens was disrupted,” Veronica Nisticò, MS, Università Degli Studi Di Milano, who led the first study, told delegates attending the virtual European Psychiatric Association 2021 Congress.

In addition to difficulties in accessing health care, “it became difficult to go to the supermarket, to the gym, and to have the social support we were all used to,” all of which had a well-documented impact on mental health, added Ms. Nisticò, who is also affiliated with Aldo Ravelli Research Center for Neurotechnology and Experimental Brain Therapeutics.
 

Loss of control

Previous research suggests that individuals with EDs experience high levels of anxiety and an increase in binge eating, exercise, and purging behaviors, said Ms. Nisticò.

To investigate further, the researchers conducted a longitudinal study of the changes in prevalence of adverse outcomes. In the study, two assessments were conducted.

In the first assessment, conducted in April 2020, the researchers assessed 59 outpatients with EDs and 43 unaffected hospital staff and their acquaintances. The second group served as the control group.

Participants completed an online survey that included several standardized depression and anxiety scales, as well as an ad hoc survey adapted from the Eating Disorder Examination Questionnaire. This assessed changes in restrictive dieting, control over food, body image, and psychological well-being in comparison with prepandemic levels.

The results, which were also recently published online in Eating and Weight Disorders – Studies on Anorexia, Bulimia and Obesity, showed that patients with EDs experienced significantly more stress, anxiety, depression, and PTSD-related symptoms in comparison with control persons (P < .05 for all).

In addition, the investigators found that those with EDs were more fearful of losing control over their eating behavior, spent more time thinking about food and their body, and became more uncomfortable seeing their body than before the lockdown in comparison with those without EDs (P < .05).
 

Clinical implications

A second assessment, which occurred in June 2020, after lockdown restrictions were lifted, included 40 patients with EDs who had taken part in the first assessment. This time, participants were asked to compare their current eating behavior with their eating behavior during the lockdown.

Although the lifting of lockdown restrictions was associated with significant improvement in PTSD-related symptoms, the impact on stress, anxiety, and depression persisted.

These findings, said Ms. Nisticó, support the hypothesis that specific conditions that occurred during the lockdown had a direct effect on specific ED symptoms.

These findings, she added, should be considered when developing interventions for EDs in the context of individual psychotherapy and when designing large, preventive interventions.

In the second study, Eleonora Rossi, MD, psychiatric unit, department of health sciences, University of Florence (Italy), and colleagues examined the longitudinal impact of the pandemic on individuals with EDs.

They examined 74 patients with AN or BN who had undergone baseline assessments and had completed a number of questionnaires in the first months of 2019 in conjunction with being enrolled in another study.

Participants were treated with enhanced cognitive-behavioral therapy and were reevaluated between November 2019 and January 2020. They were then compared with 97 healthy individuals.
 

Bulimia patients more vulnerable

After the outbreak of the pandemic, most treatment was administered online, so patients were able to continue therapy, Dr. Rossi said during her presentation.

All participants were assessed again in April 2020, 6 weeks after the start of Italy’s lockdown.

The results, which were published in the International Journal of Eating Disorders, show that the patients with EDs “underwent a significant improvement in terms of general and eating disorder specific psychopathology” during the first treatment period, Dr. Rossi reported. In addition, among those with AN, body mass index increased significantly (P < .05 for all).

Patients with AN continued to improve during the lockdown when therapy was administered online. However, improvements that had occurred among those with BN slowed, Dr. Rossi noted.

In addition, both groups of patients with EDs experienced a worsening of their pathological eating behaviors during the lockdown, in particular, objective binge eating and compensatory physical exercise (P < .05).

“Indeed, the positive trajectory of improvement observed before lockdown was clearly interrupted during the pandemic period,” Dr. Rossi said. This could “represent a possible hint of an imminent exacerbation of the disease.”

The results also suggest that the occurrence of arguments within the household and fear regarding the safety of loved ones predicted an increase in symptoms during the lockdown, she added.

In addition, patients with BN reported more severe COVID-related PTSD symptoms than did those with AN and the control group. This increase in severity of symptoms was more prevalent among patients who had a history of childhood trauma and among those with insecure attachment, suggesting that such patients may be more vulnerable.
 

Evidence of recovery

Commenting on the studies, David Spiegel, MD, associate chair of psychiatry, Stanford (Calif.) University, noted that EDs commonly occur after physical or sexual trauma earlier in life.

“It’s a standard thing with trauma-related disorders that any other, even relatively minor, traumatic experience can exacerbate PTSD symptoms,” said Dr. Spiegel, who was not involved in the studies. In addition, the trauma of the COVID pandemic “was not minor.

“The relative isolation and the lack of outside contact may focus many people with eating disorders even more on their struggles with how they are taking care of their bodies,” said Dr. Spiegel.

“It struck me that the anorexia nervosa group were more impervious than the bulimia nervosa group, but I think that’s the case with the disorder. In some ways it’s more severe, obviously a more life-threatening disorder,” he added.

The “hopeful thing is that there seemed to be some evidence of recovery and improvement, particularly with the posttraumatic stress exacerbation, as time went on,” Dr. Spiegel said, “and that’s a good thing.”

The study authors and Dr. Spiegel reported no relevant financial relationships.

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

COVID-19 and its resulting lockdowns are linked to posttraumatic stress disorder symptoms and other adverse outcomes among patients with eating disorders (EDs), two new studies show.

Courtesy Bill Branson/National Cancer Institute

Results of the first study show that patients with EDs had more stress, anxiety, depression, and PTSD-related symptoms during the lockdowns than their mentally healthy peers.

In the second study, treatment-related symptom improvement among patients with bulimia nervosa (BN) slowed following lockdown. In addition, patients with BN or anorexia nervosa (AN) experienced significant worsening of disorder-specific behaviors, including binge eating and overexercising.

Because of the strict lockdown measures introduced by the Italian government to contain the COVID-19 pandemic, “everyday life of all citizens was disrupted,” Veronica Nisticò, MS, Università Degli Studi Di Milano, who led the first study, told delegates attending the virtual European Psychiatric Association 2021 Congress.

In addition to difficulties in accessing health care, “it became difficult to go to the supermarket, to the gym, and to have the social support we were all used to,” all of which had a well-documented impact on mental health, added Ms. Nisticò, who is also affiliated with Aldo Ravelli Research Center for Neurotechnology and Experimental Brain Therapeutics.
 

Loss of control

Previous research suggests that individuals with EDs experience high levels of anxiety and an increase in binge eating, exercise, and purging behaviors, said Ms. Nisticò.

To investigate further, the researchers conducted a longitudinal study of the changes in prevalence of adverse outcomes. In the study, two assessments were conducted.

In the first assessment, conducted in April 2020, the researchers assessed 59 outpatients with EDs and 43 unaffected hospital staff and their acquaintances. The second group served as the control group.

Participants completed an online survey that included several standardized depression and anxiety scales, as well as an ad hoc survey adapted from the Eating Disorder Examination Questionnaire. This assessed changes in restrictive dieting, control over food, body image, and psychological well-being in comparison with prepandemic levels.

The results, which were also recently published online in Eating and Weight Disorders – Studies on Anorexia, Bulimia and Obesity, showed that patients with EDs experienced significantly more stress, anxiety, depression, and PTSD-related symptoms in comparison with control persons (P < .05 for all).

In addition, the investigators found that those with EDs were more fearful of losing control over their eating behavior, spent more time thinking about food and their body, and became more uncomfortable seeing their body than before the lockdown in comparison with those without EDs (P < .05).
 

Clinical implications

A second assessment, which occurred in June 2020, after lockdown restrictions were lifted, included 40 patients with EDs who had taken part in the first assessment. This time, participants were asked to compare their current eating behavior with their eating behavior during the lockdown.

Although the lifting of lockdown restrictions was associated with significant improvement in PTSD-related symptoms, the impact on stress, anxiety, and depression persisted.

These findings, said Ms. Nisticó, support the hypothesis that specific conditions that occurred during the lockdown had a direct effect on specific ED symptoms.

These findings, she added, should be considered when developing interventions for EDs in the context of individual psychotherapy and when designing large, preventive interventions.

In the second study, Eleonora Rossi, MD, psychiatric unit, department of health sciences, University of Florence (Italy), and colleagues examined the longitudinal impact of the pandemic on individuals with EDs.

They examined 74 patients with AN or BN who had undergone baseline assessments and had completed a number of questionnaires in the first months of 2019 in conjunction with being enrolled in another study.

Participants were treated with enhanced cognitive-behavioral therapy and were reevaluated between November 2019 and January 2020. They were then compared with 97 healthy individuals.
 

Bulimia patients more vulnerable

After the outbreak of the pandemic, most treatment was administered online, so patients were able to continue therapy, Dr. Rossi said during her presentation.

All participants were assessed again in April 2020, 6 weeks after the start of Italy’s lockdown.

The results, which were published in the International Journal of Eating Disorders, show that the patients with EDs “underwent a significant improvement in terms of general and eating disorder specific psychopathology” during the first treatment period, Dr. Rossi reported. In addition, among those with AN, body mass index increased significantly (P < .05 for all).

Patients with AN continued to improve during the lockdown when therapy was administered online. However, improvements that had occurred among those with BN slowed, Dr. Rossi noted.

In addition, both groups of patients with EDs experienced a worsening of their pathological eating behaviors during the lockdown, in particular, objective binge eating and compensatory physical exercise (P < .05).

“Indeed, the positive trajectory of improvement observed before lockdown was clearly interrupted during the pandemic period,” Dr. Rossi said. This could “represent a possible hint of an imminent exacerbation of the disease.”

The results also suggest that the occurrence of arguments within the household and fear regarding the safety of loved ones predicted an increase in symptoms during the lockdown, she added.

In addition, patients with BN reported more severe COVID-related PTSD symptoms than did those with AN and the control group. This increase in severity of symptoms was more prevalent among patients who had a history of childhood trauma and among those with insecure attachment, suggesting that such patients may be more vulnerable.
 

Evidence of recovery

Commenting on the studies, David Spiegel, MD, associate chair of psychiatry, Stanford (Calif.) University, noted that EDs commonly occur after physical or sexual trauma earlier in life.

“It’s a standard thing with trauma-related disorders that any other, even relatively minor, traumatic experience can exacerbate PTSD symptoms,” said Dr. Spiegel, who was not involved in the studies. In addition, the trauma of the COVID pandemic “was not minor.

“The relative isolation and the lack of outside contact may focus many people with eating disorders even more on their struggles with how they are taking care of their bodies,” said Dr. Spiegel.

“It struck me that the anorexia nervosa group were more impervious than the bulimia nervosa group, but I think that’s the case with the disorder. In some ways it’s more severe, obviously a more life-threatening disorder,” he added.

The “hopeful thing is that there seemed to be some evidence of recovery and improvement, particularly with the posttraumatic stress exacerbation, as time went on,” Dr. Spiegel said, “and that’s a good thing.”

The study authors and Dr. Spiegel reported no relevant financial relationships.

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

Hispanic adolescents were more likely to use e-cigarettes to vape marijuana than were their Black and White counterparts in 2020, according to a recent study conducted by the Centers for Disease Control and Prevention and published in JAMA Pediatrics.

Researchers found that 25.6% of Hispanic students reported vaping marijuana, compared to 19.4% of Black students and 18.2% of White students. The study, which is an analysis of 2017, 2018, and 2020 results from the National Youth Tobacco Survey, also revealed that increases in this recreational practice occurred among all racial and ethnic groups within those 3 years, with Hispanic students having the largest percent increase, 11.6%, followed by Black students at 8.8% and White students at 7.4%.

“The initial motivation [to do this study] was to gain a better understanding of the prevalence of use of marijuana in e-cigarettes among youth, particularly given the context of the 2019 outbreak of e-cigarette, or vaping, product use–associated lung injury (EVALI),” study author Christina Vaughan Watson, DrPH, health scientist at the CDC’s National Center for Chronic Disease Prevention and Health Promotion, said in an interview.

The findings could help clinicians and physicians understand demographic variations among marijuana vapers and help inform targeted interventions for specific populations.

“Understanding demographic variations among those who are using marijuana in e-cigarettes can help inform evidenced-based interventions that may resonate with specific populations,” Dr. Watson explained.

Margaret Thew, DNP, medical director of adolescent medicine at Children’s Wisconsin in Milwaukee, who was not involved in the study, said in an interview that the findings were “eye opening” and revealed a pattern she hasn’t seen before in her adolescent clinic.

“I would have thought African-American or non-Hispanic Blacks would’ve been a higher group of use, because when we screen kids that’s what we tend to get from the population we see here,” Ms. Thew said.

Ms. Thew said the findings also had made her reconsider her clinic’s approach to screening adolescents for marijuana use as well as address possible language barriers.

“We are probably missing access to some of the kids that we may need to seek out,” she explained. “I also thought it sends a good message that we need to direct some of our education probably a little differently, especially if it’s a Hispanic population and English may not be the primary language.”

Dr. Watson said more research is needed to assess why differences in marijuana use in e-cigarettes exist among youth.

Marijuana use in e-cigarettes has become increasingly popular among U.S. teens, with one in five students in grades 10 and 12 reporting vaping marijuana within the past year in a 2019 study conducted by the National Institute on Drug Abuse.

Dr. Watson and colleagues also found statistically significant increases in vaping marijuana, with 19.5% of students reporting smoking marijuana via e-cigarettes in 2020, compared to 11.1% of them vaping the drug in 2017. They believe the rise in marijuana vaping among youth may be attributed to states increasingly legalizing adult marijuana sales, which could impact ease of access and social acceptance.

Ms. Thew believes the rise in marijuana vaping among youth can be attributed to the legalization of marijuana, which may send “a message to adolescents that it must be safe for them to use,” as well as the increasing popularity of e-cigarettes.

In fact, as of April 2021, marijuana is legal for adults in 16 states and the District of Columbia. Meanwhile, medical marijuana is legal in 36 states, according to the National Conference of State Legislatures.

“I mean, there’s just definitely been a lot more use of [e-cigarettes]. Vaping and things like that definitely took off between 2019 and 2020,” Ms. Thew explained. “And I think marijuana use in itself is going up tremendously, I think more kids who would have used alcohol in the past use weed.”

Although public attitudes toward marijuana have relaxed, previous studies have linked it to memory dysfunction, as well as long-term cognitive effects that can interfere with perception of time and motor function. However, studies also have shown that cannabis use can combat age-related cognitive decline and help with pain reduction.

However, when it comes to adolescents, Dr. Watson and colleagues said e-cigarette use among youth and young adults is unsafe, regardless of the substances used in these products, including marijuana. Furthermore, they said marijuana use can lead to higher risks of more problematic use later in life, adding that evidence-based strategies to reduce marijuana use in e-cigarettes are important for protecting young people.

The study author and experts disclosed no relevant financial relationships.

Hispanic adolescents were more likely to use e-cigarettes to vape marijuana than were their Black and White counterparts in 2020, according to a recent study conducted by the Centers for Disease Control and Prevention and published in JAMA Pediatrics.

Researchers found that 25.6% of Hispanic students reported vaping marijuana, compared to 19.4% of Black students and 18.2% of White students. The study, which is an analysis of 2017, 2018, and 2020 results from the National Youth Tobacco Survey, also revealed that increases in this recreational practice occurred among all racial and ethnic groups within those 3 years, with Hispanic students having the largest percent increase, 11.6%, followed by Black students at 8.8% and White students at 7.4%.

“The initial motivation [to do this study] was to gain a better understanding of the prevalence of use of marijuana in e-cigarettes among youth, particularly given the context of the 2019 outbreak of e-cigarette, or vaping, product use–associated lung injury (EVALI),” study author Christina Vaughan Watson, DrPH, health scientist at the CDC’s National Center for Chronic Disease Prevention and Health Promotion, said in an interview.

The findings could help clinicians and physicians understand demographic variations among marijuana vapers and help inform targeted interventions for specific populations.

“Understanding demographic variations among those who are using marijuana in e-cigarettes can help inform evidenced-based interventions that may resonate with specific populations,” Dr. Watson explained.

Margaret Thew, DNP, medical director of adolescent medicine at Children’s Wisconsin in Milwaukee, who was not involved in the study, said in an interview that the findings were “eye opening” and revealed a pattern she hasn’t seen before in her adolescent clinic.

“I would have thought African-American or non-Hispanic Blacks would’ve been a higher group of use, because when we screen kids that’s what we tend to get from the population we see here,” Ms. Thew said.

Ms. Thew said the findings also had made her reconsider her clinic’s approach to screening adolescents for marijuana use as well as address possible language barriers.

“We are probably missing access to some of the kids that we may need to seek out,” she explained. “I also thought it sends a good message that we need to direct some of our education probably a little differently, especially if it’s a Hispanic population and English may not be the primary language.”

Dr. Watson said more research is needed to assess why differences in marijuana use in e-cigarettes exist among youth.

Marijuana use in e-cigarettes has become increasingly popular among U.S. teens, with one in five students in grades 10 and 12 reporting vaping marijuana within the past year in a 2019 study conducted by the National Institute on Drug Abuse.

Dr. Watson and colleagues also found statistically significant increases in vaping marijuana, with 19.5% of students reporting smoking marijuana via e-cigarettes in 2020, compared to 11.1% of them vaping the drug in 2017. They believe the rise in marijuana vaping among youth may be attributed to states increasingly legalizing adult marijuana sales, which could impact ease of access and social acceptance.

Ms. Thew believes the rise in marijuana vaping among youth can be attributed to the legalization of marijuana, which may send “a message to adolescents that it must be safe for them to use,” as well as the increasing popularity of e-cigarettes.

In fact, as of April 2021, marijuana is legal for adults in 16 states and the District of Columbia. Meanwhile, medical marijuana is legal in 36 states, according to the National Conference of State Legislatures.

“I mean, there’s just definitely been a lot more use of [e-cigarettes]. Vaping and things like that definitely took off between 2019 and 2020,” Ms. Thew explained. “And I think marijuana use in itself is going up tremendously, I think more kids who would have used alcohol in the past use weed.”

Although public attitudes toward marijuana have relaxed, previous studies have linked it to memory dysfunction, as well as long-term cognitive effects that can interfere with perception of time and motor function. However, studies also have shown that cannabis use can combat age-related cognitive decline and help with pain reduction.

However, when it comes to adolescents, Dr. Watson and colleagues said e-cigarette use among youth and young adults is unsafe, regardless of the substances used in these products, including marijuana. Furthermore, they said marijuana use can lead to higher risks of more problematic use later in life, adding that evidence-based strategies to reduce marijuana use in e-cigarettes are important for protecting young people.

The study author and experts disclosed no relevant financial relationships.

Hispanic adolescents were more likely to use e-cigarettes to vape marijuana than were their Black and White counterparts in 2020, according to a recent study conducted by the Centers for Disease Control and Prevention and published in JAMA Pediatrics.

Researchers found that 25.6% of Hispanic students reported vaping marijuana, compared to 19.4% of Black students and 18.2% of White students. The study, which is an analysis of 2017, 2018, and 2020 results from the National Youth Tobacco Survey, also revealed that increases in this recreational practice occurred among all racial and ethnic groups within those 3 years, with Hispanic students having the largest percent increase, 11.6%, followed by Black students at 8.8% and White students at 7.4%.

“The initial motivation [to do this study] was to gain a better understanding of the prevalence of use of marijuana in e-cigarettes among youth, particularly given the context of the 2019 outbreak of e-cigarette, or vaping, product use–associated lung injury (EVALI),” study author Christina Vaughan Watson, DrPH, health scientist at the CDC’s National Center for Chronic Disease Prevention and Health Promotion, said in an interview.

The findings could help clinicians and physicians understand demographic variations among marijuana vapers and help inform targeted interventions for specific populations.

“Understanding demographic variations among those who are using marijuana in e-cigarettes can help inform evidenced-based interventions that may resonate with specific populations,” Dr. Watson explained.

Margaret Thew, DNP, medical director of adolescent medicine at Children’s Wisconsin in Milwaukee, who was not involved in the study, said in an interview that the findings were “eye opening” and revealed a pattern she hasn’t seen before in her adolescent clinic.

“I would have thought African-American or non-Hispanic Blacks would’ve been a higher group of use, because when we screen kids that’s what we tend to get from the population we see here,” Ms. Thew said.

Ms. Thew said the findings also had made her reconsider her clinic’s approach to screening adolescents for marijuana use as well as address possible language barriers.

“We are probably missing access to some of the kids that we may need to seek out,” she explained. “I also thought it sends a good message that we need to direct some of our education probably a little differently, especially if it’s a Hispanic population and English may not be the primary language.”

Dr. Watson said more research is needed to assess why differences in marijuana use in e-cigarettes exist among youth.

Marijuana use in e-cigarettes has become increasingly popular among U.S. teens, with one in five students in grades 10 and 12 reporting vaping marijuana within the past year in a 2019 study conducted by the National Institute on Drug Abuse.

Dr. Watson and colleagues also found statistically significant increases in vaping marijuana, with 19.5% of students reporting smoking marijuana via e-cigarettes in 2020, compared to 11.1% of them vaping the drug in 2017. They believe the rise in marijuana vaping among youth may be attributed to states increasingly legalizing adult marijuana sales, which could impact ease of access and social acceptance.

Ms. Thew believes the rise in marijuana vaping among youth can be attributed to the legalization of marijuana, which may send “a message to adolescents that it must be safe for them to use,” as well as the increasing popularity of e-cigarettes.

In fact, as of April 2021, marijuana is legal for adults in 16 states and the District of Columbia. Meanwhile, medical marijuana is legal in 36 states, according to the National Conference of State Legislatures.

“I mean, there’s just definitely been a lot more use of [e-cigarettes]. Vaping and things like that definitely took off between 2019 and 2020,” Ms. Thew explained. “And I think marijuana use in itself is going up tremendously, I think more kids who would have used alcohol in the past use weed.”

Although public attitudes toward marijuana have relaxed, previous studies have linked it to memory dysfunction, as well as long-term cognitive effects that can interfere with perception of time and motor function. However, studies also have shown that cannabis use can combat age-related cognitive decline and help with pain reduction.

However, when it comes to adolescents, Dr. Watson and colleagues said e-cigarette use among youth and young adults is unsafe, regardless of the substances used in these products, including marijuana. Furthermore, they said marijuana use can lead to higher risks of more problematic use later in life, adding that evidence-based strategies to reduce marijuana use in e-cigarettes are important for protecting young people.

The study author and experts disclosed no relevant financial relationships.

Plasma levels of neurofilament light (NfL) are a better predictor of cognitive decline and changes in neuroimaging in comparison with total tau (T-tau), new research suggests. In certain contexts, T-tau improves cross-sectional analyses of these outcomes, but adding T-tau measurements to NfL measurements does not improve the predictive power of NfL, results of a longitudinal analysis show.

“The major distinction, for cognition at least, was that NfL cross-sectionally was associated with most cognitive outcomes, and longitudinally, higher NfL at baseline was associated with cognitive decline in every domain,” said study investigator Jordan Marks, an MD/PhD student at the Mayo Medical School, Rochester, Minn.

The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
 

New tool for dementia diagnosis?

In recent years, researchers have studied NfL and T-tau as potential blood-based biomarkers of neurodegeneration. In cross-sectional and longitudinal studies, NfL and T-tau have been associated with worse cognition and with neuroimaging measures of cortical thickness, cortical atrophy, white-matter hyperintensity, and white-matter integrity. However, no previous research has directly compared the prognostic ability of these two biomarkers.

The study included 995 participants without dementia in the Mayo Clinic Study on Aging. All participants underwent measurement of NfL and T-tau and assessment of cognitive status, as well as neuroimaging. The investigators measured NfL and T-tau on the Simoa HD-1 platform. They reexamined patients approximately every 15 months. The median follow-up time was 6.2 years.

To examine associations between baseline plasma NfL or T-tau and cognitive or neuroimaging outcomes, the researchers conducted data analyses using linear mixed effects models and adjusted the data for age, sex, and education. They replicated these analyses using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). For these analyses, they selected 387 participants without dementia who had been followed for a median of 3.0 years.

In all analyses, baseline plasma NfL was more strongly associated with cognitive and neuroimaging outcomes than T-tau. “Baseline plasma NfL was associated with cognitive decline in all domains measured, while T-tau was not associated with cognitive decline,” said Mr. Marks.

Plasma NfL was more strongly associated with decreases in cortical thickness over time than T-tau was. NfL was also more strongly associated with declining hippocampal volume and white-matter changes.

However, in cross-sectional analysis, the combination of elevated NfL levels and elevated T-tau levels at baseline was more strongly associated with decreased global cognition and memory, compared with elevated NfL levels alone. The combination also was more strongly associated with neuroimaging measures, such as temporal cortex thickness and increased number of infarcts. However, in longitudinal analyses, T-tau did not add to the predictive value of NfL.

The analyses using ADNI data yielded similar results. Overall, the results suggest that NfL is a better prognostic marker of neurodegeneration in general, said Mr. Marks.

These findings, he said, may have implications for screening and diagnosis. “I’m definitely hopeful that NfL will be useful in a clinical setting to screen for those at risk of dementia and will be helpful, along with other modalities, like cognitive testing, for dementia diagnosis,” said Mr. Marks.

Future research should examine how changes in these biomarkers are associated with cognitive and neuroimaging outcomes over time.

“We used plasma levels at one point in time in this study, but we need a better sense of how to interpret, for example, what a rise in plasma NfL over a certain time period means for someone’s risk of developing neurodegenerative disease,” Mr. Marks added.
 

An ‘exciting’ prospect

Commenting on the study, Glen R. Finney, MD, director of the Memory and Cognition Program for Geisinger Health in Wilkes-Barre, Pa., said the findings add to neurologists’ ability to screen for brain diseases. “Evidence of neurodegeneration is part of the modern diagnosis of several disorders. While brain imaging can also provide that and may be needed for other reasons, this could provide an easy, potentially inexpensive way to screen for damage to the brain, giving us an added tool,” said Dr. Finney.

The prospect of using blood plasma markers to explore disease of the brain is exciting, Dr. Finney added. “I would like to see ongoing refinement of this approach and would like to see if there’s other markers in blood that could be used to find what specifically may be causing the damage,” he said.

The study was funded by the National Institutes of Health, the National Institute on Aging, and the GHR Foundation. Mr. Marks and Dr. Finney have disclosed no relevant financial relationships.

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

Plasma levels of neurofilament light (NfL) are a better predictor of cognitive decline and changes in neuroimaging in comparison with total tau (T-tau), new research suggests. In certain contexts, T-tau improves cross-sectional analyses of these outcomes, but adding T-tau measurements to NfL measurements does not improve the predictive power of NfL, results of a longitudinal analysis show.

“The major distinction, for cognition at least, was that NfL cross-sectionally was associated with most cognitive outcomes, and longitudinally, higher NfL at baseline was associated with cognitive decline in every domain,” said study investigator Jordan Marks, an MD/PhD student at the Mayo Medical School, Rochester, Minn.

The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
 

New tool for dementia diagnosis?

In recent years, researchers have studied NfL and T-tau as potential blood-based biomarkers of neurodegeneration. In cross-sectional and longitudinal studies, NfL and T-tau have been associated with worse cognition and with neuroimaging measures of cortical thickness, cortical atrophy, white-matter hyperintensity, and white-matter integrity. However, no previous research has directly compared the prognostic ability of these two biomarkers.

The study included 995 participants without dementia in the Mayo Clinic Study on Aging. All participants underwent measurement of NfL and T-tau and assessment of cognitive status, as well as neuroimaging. The investigators measured NfL and T-tau on the Simoa HD-1 platform. They reexamined patients approximately every 15 months. The median follow-up time was 6.2 years.

To examine associations between baseline plasma NfL or T-tau and cognitive or neuroimaging outcomes, the researchers conducted data analyses using linear mixed effects models and adjusted the data for age, sex, and education. They replicated these analyses using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). For these analyses, they selected 387 participants without dementia who had been followed for a median of 3.0 years.

In all analyses, baseline plasma NfL was more strongly associated with cognitive and neuroimaging outcomes than T-tau. “Baseline plasma NfL was associated with cognitive decline in all domains measured, while T-tau was not associated with cognitive decline,” said Mr. Marks.

Plasma NfL was more strongly associated with decreases in cortical thickness over time than T-tau was. NfL was also more strongly associated with declining hippocampal volume and white-matter changes.

However, in cross-sectional analysis, the combination of elevated NfL levels and elevated T-tau levels at baseline was more strongly associated with decreased global cognition and memory, compared with elevated NfL levels alone. The combination also was more strongly associated with neuroimaging measures, such as temporal cortex thickness and increased number of infarcts. However, in longitudinal analyses, T-tau did not add to the predictive value of NfL.

The analyses using ADNI data yielded similar results. Overall, the results suggest that NfL is a better prognostic marker of neurodegeneration in general, said Mr. Marks.

These findings, he said, may have implications for screening and diagnosis. “I’m definitely hopeful that NfL will be useful in a clinical setting to screen for those at risk of dementia and will be helpful, along with other modalities, like cognitive testing, for dementia diagnosis,” said Mr. Marks.

Future research should examine how changes in these biomarkers are associated with cognitive and neuroimaging outcomes over time.

“We used plasma levels at one point in time in this study, but we need a better sense of how to interpret, for example, what a rise in plasma NfL over a certain time period means for someone’s risk of developing neurodegenerative disease,” Mr. Marks added.
 

An ‘exciting’ prospect

Commenting on the study, Glen R. Finney, MD, director of the Memory and Cognition Program for Geisinger Health in Wilkes-Barre, Pa., said the findings add to neurologists’ ability to screen for brain diseases. “Evidence of neurodegeneration is part of the modern diagnosis of several disorders. While brain imaging can also provide that and may be needed for other reasons, this could provide an easy, potentially inexpensive way to screen for damage to the brain, giving us an added tool,” said Dr. Finney.

The prospect of using blood plasma markers to explore disease of the brain is exciting, Dr. Finney added. “I would like to see ongoing refinement of this approach and would like to see if there’s other markers in blood that could be used to find what specifically may be causing the damage,” he said.

The study was funded by the National Institutes of Health, the National Institute on Aging, and the GHR Foundation. Mr. Marks and Dr. Finney have disclosed no relevant financial relationships.

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

Plasma levels of neurofilament light (NfL) are a better predictor of cognitive decline and changes in neuroimaging in comparison with total tau (T-tau), new research suggests. In certain contexts, T-tau improves cross-sectional analyses of these outcomes, but adding T-tau measurements to NfL measurements does not improve the predictive power of NfL, results of a longitudinal analysis show.

“The major distinction, for cognition at least, was that NfL cross-sectionally was associated with most cognitive outcomes, and longitudinally, higher NfL at baseline was associated with cognitive decline in every domain,” said study investigator Jordan Marks, an MD/PhD student at the Mayo Medical School, Rochester, Minn.

The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
 

New tool for dementia diagnosis?

In recent years, researchers have studied NfL and T-tau as potential blood-based biomarkers of neurodegeneration. In cross-sectional and longitudinal studies, NfL and T-tau have been associated with worse cognition and with neuroimaging measures of cortical thickness, cortical atrophy, white-matter hyperintensity, and white-matter integrity. However, no previous research has directly compared the prognostic ability of these two biomarkers.

The study included 995 participants without dementia in the Mayo Clinic Study on Aging. All participants underwent measurement of NfL and T-tau and assessment of cognitive status, as well as neuroimaging. The investigators measured NfL and T-tau on the Simoa HD-1 platform. They reexamined patients approximately every 15 months. The median follow-up time was 6.2 years.

To examine associations between baseline plasma NfL or T-tau and cognitive or neuroimaging outcomes, the researchers conducted data analyses using linear mixed effects models and adjusted the data for age, sex, and education. They replicated these analyses using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). For these analyses, they selected 387 participants without dementia who had been followed for a median of 3.0 years.

In all analyses, baseline plasma NfL was more strongly associated with cognitive and neuroimaging outcomes than T-tau. “Baseline plasma NfL was associated with cognitive decline in all domains measured, while T-tau was not associated with cognitive decline,” said Mr. Marks.

Plasma NfL was more strongly associated with decreases in cortical thickness over time than T-tau was. NfL was also more strongly associated with declining hippocampal volume and white-matter changes.

However, in cross-sectional analysis, the combination of elevated NfL levels and elevated T-tau levels at baseline was more strongly associated with decreased global cognition and memory, compared with elevated NfL levels alone. The combination also was more strongly associated with neuroimaging measures, such as temporal cortex thickness and increased number of infarcts. However, in longitudinal analyses, T-tau did not add to the predictive value of NfL.

The analyses using ADNI data yielded similar results. Overall, the results suggest that NfL is a better prognostic marker of neurodegeneration in general, said Mr. Marks.

These findings, he said, may have implications for screening and diagnosis. “I’m definitely hopeful that NfL will be useful in a clinical setting to screen for those at risk of dementia and will be helpful, along with other modalities, like cognitive testing, for dementia diagnosis,” said Mr. Marks.

Future research should examine how changes in these biomarkers are associated with cognitive and neuroimaging outcomes over time.

“We used plasma levels at one point in time in this study, but we need a better sense of how to interpret, for example, what a rise in plasma NfL over a certain time period means for someone’s risk of developing neurodegenerative disease,” Mr. Marks added.
 

An ‘exciting’ prospect

Commenting on the study, Glen R. Finney, MD, director of the Memory and Cognition Program for Geisinger Health in Wilkes-Barre, Pa., said the findings add to neurologists’ ability to screen for brain diseases. “Evidence of neurodegeneration is part of the modern diagnosis of several disorders. While brain imaging can also provide that and may be needed for other reasons, this could provide an easy, potentially inexpensive way to screen for damage to the brain, giving us an added tool,” said Dr. Finney.

The prospect of using blood plasma markers to explore disease of the brain is exciting, Dr. Finney added. “I would like to see ongoing refinement of this approach and would like to see if there’s other markers in blood that could be used to find what specifically may be causing the damage,” he said.

The study was funded by the National Institutes of Health, the National Institute on Aging, and the GHR Foundation. Mr. Marks and Dr. Finney have disclosed no relevant financial relationships.

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

COVID-19 survivors are at risk from a possible second pandemic, this time of opioid addiction, given the high rate of painkillers being prescribed to these patients, health experts say.

sdominick/Getty Images

A new study in Nature found alarmingly high rates of opioid use among COVID survivors with lingering symptoms at Veterans Affairs facilities. About 10% of COVID survivors develop “long COVID,” struggling with often disabling health problems even 6 months or longer after a diagnosis.

For every 1,000 long-COVID patients, known as “long-haulers,” who were treated at a VA facility, doctors wrote nine more prescriptions for opioids than they otherwise would have, along with 22 additional prescriptions for benzodiazepines, which include Xanax and other addictive pills used to treat anxiety.

Although previous studies have found many COVID survivors experience persistent health problems, the new article is the first to show they’re using more addictive medications, said Ziyad Al-Aly, MD, the paper’s lead author.

He’s concerned that even an apparently small increase in the inappropriate use of addictive pain pills will lead to a resurgence of the prescription opioid crisis, given the large number of COVID survivors. More than 3 million of the 31 million Americans infected with COVID develop long-term symptoms, which can include fatigue, shortness of breath, depression, anxiety, and memory problems known as “brain fog.”

The new study also found many patients have significant muscle and bone pain.

The frequent use of opioids was surprising, given concerns about their potential for addiction, said Dr. Al-Aly, chief of research and education service at the VA St. Louis Health Care System.

“Physicians now are supposed to shy away from prescribing opioids,” said Dr. Al-Aly, who studied more than 73,000 patients in the VA system. When Dr. Al-Aly saw the number of opioids prescriptions, he said, he thought to himself: “Is this really happening all over again?”

Doctors need to act now, before “it’s too late to do something,” Dr. Al-Aly said. “We must act now and ensure that people are getting the care they need. We do not want this to balloon into a suicide crisis or another opioid epidemic.”

As more doctors became aware of their addictive potential, new opioid prescriptions fell, by more than half since 2012. But U.S. doctors still prescribe far more of the drugs – which include OxyContin, Vicodin, and codeine – than physicians in other countries, said Andrew Kolodny, MD, medical director of opioid policy research at Brandeis University, Waltham, Mass.

Some patients who became addicted to prescription painkillers switched to heroin, either because it was cheaper or because they could no longer obtain opioids from their doctors. Overdose deaths surged in recent years as drug dealers began spiking heroin with a powerful synthetic opioid called fentanyl.

More than 88,000 Americans died from overdoses during the 12 months ending in August 2020, according to the Centers for Disease Control and Prevention. Health experts now advise doctors to avoid prescribing opioids for long periods.

The new study “suggests to me that many clinicians still don’t get it,” Dr. Kolodny said. “Many clinicians are under the false impression that opioids are appropriate for chronic pain patients.”

Hospitalized COVID patients often receive a lot of medication to control pain and anxiety, especially in ICUs, said Greg Martin, MD, president of the Society of Critical Care Medicine. Patients placed on ventilators, for example, are often sedated to make them more comfortable.

Martin said he’s concerned by the study’s findings, which suggest patients are unnecessarily continuing medications after leaving the hospital.

“I worry that COVID-19 patients, especially those who are severely and critically ill, receive a lot of medications during the hospitalization, and because they have persistent symptoms, the medications are continued after hospital discharge,” Dr. Martin said.

While some COVID patients are experiencing muscle and bone pain for the first time, others say the illness has intensified their preexisting pain.

Rachael Sunshine Burnett has suffered from chronic pain in her back and feet for 20 years, ever since an accident at a warehouse where she once worked. But Ms. Burnett, who first was diagnosed with COVID in April 2020, said the pain soon became 10 times worse and spread to the area between her shoulders and spine. Although she was already taking long-acting OxyContin twice a day, her doctor prescribed an additional opioid called oxycodone, which relieves pain immediately. She was reinfected with COVID in December.

“It’s been a horrible, horrible year,” said Ms. Burnett, 43, of Coxsackie, N.Y.

Doctors should recognize that pain can be a part of long COVID, Dr. Martin said. “We need to find the proper nonnarcotic treatment for it, just like we do with other forms of chronic pain,” he said.

The CDC recommends a number of alternatives to opioids – from physical therapy to biofeedback, over-the-counter anti-inflammatories, antidepressants, and antiseizure drugs that also relieve nerve pain.

The country also needs an overall strategy to cope with the wave of post-COVID complications, Dr. Al-Aly said.

“It’s better to be prepared than to be caught off guard years from now, when doctors realize: ‘Oh, we have a resurgence in opioids,’ ” Dr. Al-Aly said.

Dr. Al-Aly noted that his study may not capture the full complexity of post-COVID patient needs. Although women make up the majority of long-COVID patients in most studies, most patients in the VA system are men.

The study of VA patients makes it “abundantly clear that we are not prepared to meet the needs of 3 million Americans with long COVID,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute in San Diego. “We desperately need an intervention that will effectively treat these individuals.”

Dr. Al-Aly said COVID survivors may need care for years.

“That’s going to be a huge, significant burden on the health care system,” Dr. Al-Aly said. “Long COVID will reverberate in the health system for years or even decades to come.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

COVID-19 survivors are at risk from a possible second pandemic, this time of opioid addiction, given the high rate of painkillers being prescribed to these patients, health experts say.

sdominick/Getty Images

A new study in Nature found alarmingly high rates of opioid use among COVID survivors with lingering symptoms at Veterans Affairs facilities. About 10% of COVID survivors develop “long COVID,” struggling with often disabling health problems even 6 months or longer after a diagnosis.

For every 1,000 long-COVID patients, known as “long-haulers,” who were treated at a VA facility, doctors wrote nine more prescriptions for opioids than they otherwise would have, along with 22 additional prescriptions for benzodiazepines, which include Xanax and other addictive pills used to treat anxiety.

Although previous studies have found many COVID survivors experience persistent health problems, the new article is the first to show they’re using more addictive medications, said Ziyad Al-Aly, MD, the paper’s lead author.

He’s concerned that even an apparently small increase in the inappropriate use of addictive pain pills will lead to a resurgence of the prescription opioid crisis, given the large number of COVID survivors. More than 3 million of the 31 million Americans infected with COVID develop long-term symptoms, which can include fatigue, shortness of breath, depression, anxiety, and memory problems known as “brain fog.”

The new study also found many patients have significant muscle and bone pain.

The frequent use of opioids was surprising, given concerns about their potential for addiction, said Dr. Al-Aly, chief of research and education service at the VA St. Louis Health Care System.

“Physicians now are supposed to shy away from prescribing opioids,” said Dr. Al-Aly, who studied more than 73,000 patients in the VA system. When Dr. Al-Aly saw the number of opioids prescriptions, he said, he thought to himself: “Is this really happening all over again?”

Doctors need to act now, before “it’s too late to do something,” Dr. Al-Aly said. “We must act now and ensure that people are getting the care they need. We do not want this to balloon into a suicide crisis or another opioid epidemic.”

As more doctors became aware of their addictive potential, new opioid prescriptions fell, by more than half since 2012. But U.S. doctors still prescribe far more of the drugs – which include OxyContin, Vicodin, and codeine – than physicians in other countries, said Andrew Kolodny, MD, medical director of opioid policy research at Brandeis University, Waltham, Mass.

Some patients who became addicted to prescription painkillers switched to heroin, either because it was cheaper or because they could no longer obtain opioids from their doctors. Overdose deaths surged in recent years as drug dealers began spiking heroin with a powerful synthetic opioid called fentanyl.

More than 88,000 Americans died from overdoses during the 12 months ending in August 2020, according to the Centers for Disease Control and Prevention. Health experts now advise doctors to avoid prescribing opioids for long periods.

The new study “suggests to me that many clinicians still don’t get it,” Dr. Kolodny said. “Many clinicians are under the false impression that opioids are appropriate for chronic pain patients.”

Hospitalized COVID patients often receive a lot of medication to control pain and anxiety, especially in ICUs, said Greg Martin, MD, president of the Society of Critical Care Medicine. Patients placed on ventilators, for example, are often sedated to make them more comfortable.

Martin said he’s concerned by the study’s findings, which suggest patients are unnecessarily continuing medications after leaving the hospital.

“I worry that COVID-19 patients, especially those who are severely and critically ill, receive a lot of medications during the hospitalization, and because they have persistent symptoms, the medications are continued after hospital discharge,” Dr. Martin said.

While some COVID patients are experiencing muscle and bone pain for the first time, others say the illness has intensified their preexisting pain.

Rachael Sunshine Burnett has suffered from chronic pain in her back and feet for 20 years, ever since an accident at a warehouse where she once worked. But Ms. Burnett, who first was diagnosed with COVID in April 2020, said the pain soon became 10 times worse and spread to the area between her shoulders and spine. Although she was already taking long-acting OxyContin twice a day, her doctor prescribed an additional opioid called oxycodone, which relieves pain immediately. She was reinfected with COVID in December.

“It’s been a horrible, horrible year,” said Ms. Burnett, 43, of Coxsackie, N.Y.

Doctors should recognize that pain can be a part of long COVID, Dr. Martin said. “We need to find the proper nonnarcotic treatment for it, just like we do with other forms of chronic pain,” he said.

The CDC recommends a number of alternatives to opioids – from physical therapy to biofeedback, over-the-counter anti-inflammatories, antidepressants, and antiseizure drugs that also relieve nerve pain.

The country also needs an overall strategy to cope with the wave of post-COVID complications, Dr. Al-Aly said.

“It’s better to be prepared than to be caught off guard years from now, when doctors realize: ‘Oh, we have a resurgence in opioids,’ ” Dr. Al-Aly said.

Dr. Al-Aly noted that his study may not capture the full complexity of post-COVID patient needs. Although women make up the majority of long-COVID patients in most studies, most patients in the VA system are men.

The study of VA patients makes it “abundantly clear that we are not prepared to meet the needs of 3 million Americans with long COVID,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute in San Diego. “We desperately need an intervention that will effectively treat these individuals.”

Dr. Al-Aly said COVID survivors may need care for years.

“That’s going to be a huge, significant burden on the health care system,” Dr. Al-Aly said. “Long COVID will reverberate in the health system for years or even decades to come.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

COVID-19 survivors are at risk from a possible second pandemic, this time of opioid addiction, given the high rate of painkillers being prescribed to these patients, health experts say.

sdominick/Getty Images

A new study in Nature found alarmingly high rates of opioid use among COVID survivors with lingering symptoms at Veterans Affairs facilities. About 10% of COVID survivors develop “long COVID,” struggling with often disabling health problems even 6 months or longer after a diagnosis.

For every 1,000 long-COVID patients, known as “long-haulers,” who were treated at a VA facility, doctors wrote nine more prescriptions for opioids than they otherwise would have, along with 22 additional prescriptions for benzodiazepines, which include Xanax and other addictive pills used to treat anxiety.

Although previous studies have found many COVID survivors experience persistent health problems, the new article is the first to show they’re using more addictive medications, said Ziyad Al-Aly, MD, the paper’s lead author.

He’s concerned that even an apparently small increase in the inappropriate use of addictive pain pills will lead to a resurgence of the prescription opioid crisis, given the large number of COVID survivors. More than 3 million of the 31 million Americans infected with COVID develop long-term symptoms, which can include fatigue, shortness of breath, depression, anxiety, and memory problems known as “brain fog.”

The new study also found many patients have significant muscle and bone pain.

The frequent use of opioids was surprising, given concerns about their potential for addiction, said Dr. Al-Aly, chief of research and education service at the VA St. Louis Health Care System.

“Physicians now are supposed to shy away from prescribing opioids,” said Dr. Al-Aly, who studied more than 73,000 patients in the VA system. When Dr. Al-Aly saw the number of opioids prescriptions, he said, he thought to himself: “Is this really happening all over again?”

Doctors need to act now, before “it’s too late to do something,” Dr. Al-Aly said. “We must act now and ensure that people are getting the care they need. We do not want this to balloon into a suicide crisis or another opioid epidemic.”

As more doctors became aware of their addictive potential, new opioid prescriptions fell, by more than half since 2012. But U.S. doctors still prescribe far more of the drugs – which include OxyContin, Vicodin, and codeine – than physicians in other countries, said Andrew Kolodny, MD, medical director of opioid policy research at Brandeis University, Waltham, Mass.

Some patients who became addicted to prescription painkillers switched to heroin, either because it was cheaper or because they could no longer obtain opioids from their doctors. Overdose deaths surged in recent years as drug dealers began spiking heroin with a powerful synthetic opioid called fentanyl.

More than 88,000 Americans died from overdoses during the 12 months ending in August 2020, according to the Centers for Disease Control and Prevention. Health experts now advise doctors to avoid prescribing opioids for long periods.

The new study “suggests to me that many clinicians still don’t get it,” Dr. Kolodny said. “Many clinicians are under the false impression that opioids are appropriate for chronic pain patients.”

Hospitalized COVID patients often receive a lot of medication to control pain and anxiety, especially in ICUs, said Greg Martin, MD, president of the Society of Critical Care Medicine. Patients placed on ventilators, for example, are often sedated to make them more comfortable.

Martin said he’s concerned by the study’s findings, which suggest patients are unnecessarily continuing medications after leaving the hospital.

“I worry that COVID-19 patients, especially those who are severely and critically ill, receive a lot of medications during the hospitalization, and because they have persistent symptoms, the medications are continued after hospital discharge,” Dr. Martin said.

While some COVID patients are experiencing muscle and bone pain for the first time, others say the illness has intensified their preexisting pain.

Rachael Sunshine Burnett has suffered from chronic pain in her back and feet for 20 years, ever since an accident at a warehouse where she once worked. But Ms. Burnett, who first was diagnosed with COVID in April 2020, said the pain soon became 10 times worse and spread to the area between her shoulders and spine. Although she was already taking long-acting OxyContin twice a day, her doctor prescribed an additional opioid called oxycodone, which relieves pain immediately. She was reinfected with COVID in December.

“It’s been a horrible, horrible year,” said Ms. Burnett, 43, of Coxsackie, N.Y.

Doctors should recognize that pain can be a part of long COVID, Dr. Martin said. “We need to find the proper nonnarcotic treatment for it, just like we do with other forms of chronic pain,” he said.

The CDC recommends a number of alternatives to opioids – from physical therapy to biofeedback, over-the-counter anti-inflammatories, antidepressants, and antiseizure drugs that also relieve nerve pain.

The country also needs an overall strategy to cope with the wave of post-COVID complications, Dr. Al-Aly said.

“It’s better to be prepared than to be caught off guard years from now, when doctors realize: ‘Oh, we have a resurgence in opioids,’ ” Dr. Al-Aly said.

Dr. Al-Aly noted that his study may not capture the full complexity of post-COVID patient needs. Although women make up the majority of long-COVID patients in most studies, most patients in the VA system are men.

The study of VA patients makes it “abundantly clear that we are not prepared to meet the needs of 3 million Americans with long COVID,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute in San Diego. “We desperately need an intervention that will effectively treat these individuals.”

Dr. Al-Aly said COVID survivors may need care for years.

“That’s going to be a huge, significant burden on the health care system,” Dr. Al-Aly said. “Long COVID will reverberate in the health system for years or even decades to come.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

The Centers for Disease Control and Prevention is finalizing new guidelines to help clinicians diagnose and manage long COVID, or postacute sequelae of SARS-CoV-2 infection.

In a day-long congressional hearing on April 28, John Brooks, MD, a medical epidemiologist at the CDC’s division of HIV/AIDS prevention, testified that the guidelines were going through the clearance process at the agency, but would be forthcoming.

“They should be coming out very shortly,” Dr. Brooks said.

The guidelines, which were developed in collaboration with newly established long-COVID clinics and patient advocacy groups, will “illustrate how to diagnose and begin to pull together what we know about management,” of the complex condition, he said.

For many doctors and patients who are struggling to understand symptoms that persist for months after the initial viral infection, the guidelines can’t come soon enough.

National Institutes of Health Director Francis Collins, MD, PhD, who also testified at the hearing, estimated that as many as 3 million people could be left with chronic health problems after even mild COVID infections.

“I can’t overstate how serious this issue is for the health of our nation,” he said.

Dr. Collins said his estimate was based on studies showing that roughly 10% of people who get COVID could be affected by this and whose “long-term course is uncertain,” he said. So far, more than 32 million Americans are known to have been infected with the new coronavirus.

“We need to make sure we put our arms around them and bring answers and care to them,” said Rep. Anna Eshoo (D-Calif.), chairwoman of the Subcommittee on Health.

Jennifer Possick, MD, who directs the post-COVID recovery program at Yale New Haven (Conn.) Hospital, testified that the tidal wave of patients she and her colleagues were seeing was overwhelming.

“We are a well-resourced program at an academic medical center, but we are swamped by the need in our community. This year, we have seen more patients with post COVID-19 conditions in our clinic alone than we have new cases of asthma and COPD combined,” she said. “The magnitude of the challenge is daunting.”

Dr. Possick estimated that there are “over 60” clinics in the United States that have started to treat long-COVID patients, but said they are grassroots efforts and all very different from each other.

“Whoever had the resources, had the time, [and] was able to take the initiative and forge to the relationships because most of them are multidisciplinary, did so,” she said.
 

Patients testify

Several representatives shared moving personal stories of loved ones or staffers who remained ill months after a COVID diagnosis.

Rep. Ann Kuster, from New Hampshire, talked about her 34-year-old niece, a member of the U.S. Ski Team, who had COVID just over a year ago and “continues to struggle with everything, even the simplest activities of daily living” she said. “She has to choose between taking a shower or making dinner. I’m so proud of her for hanging in there.”

Long-COVID patients invited to testify by the subcommittee described months of disability that left them with soaring medical bills and no ability to work to pay them.

“I am now a poor, Black, disabled woman, living with long COVID,” said Chimere Smith, who said she had been a school teacher in Baltimore. “Saying it aloud makes it no more easy to accept.”

She said COVID had affected her ability to think clearly and caused debilitating fatigue, which prevented her from working. She said she lost her vision for almost 5 months because doctors misdiagnosed a cataract caused by long COVID as dry eye.

“If I did not have a loving family, I [would] be speaking to you today [from] my car, the only property I now own.”

Ms. Smith said that long-COVID clinics, which are mostly housed within academic medical centers, were not going to be accessible for all long-haulers, who are disproportionately women of color. She has started a clinic, based out of her church, to help other patients from her community.

“No one wants to hear that long COVID has decimated my life or the lives of other black women in less than a year,” Ms. Smith said. “We’ve just been waiting and hoping for compassionate doctors and politicians who would acknowledge us.”

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

The Centers for Disease Control and Prevention is finalizing new guidelines to help clinicians diagnose and manage long COVID, or postacute sequelae of SARS-CoV-2 infection.

In a day-long congressional hearing on April 28, John Brooks, MD, a medical epidemiologist at the CDC’s division of HIV/AIDS prevention, testified that the guidelines were going through the clearance process at the agency, but would be forthcoming.

“They should be coming out very shortly,” Dr. Brooks said.

The guidelines, which were developed in collaboration with newly established long-COVID clinics and patient advocacy groups, will “illustrate how to diagnose and begin to pull together what we know about management,” of the complex condition, he said.

For many doctors and patients who are struggling to understand symptoms that persist for months after the initial viral infection, the guidelines can’t come soon enough.

National Institutes of Health Director Francis Collins, MD, PhD, who also testified at the hearing, estimated that as many as 3 million people could be left with chronic health problems after even mild COVID infections.

“I can’t overstate how serious this issue is for the health of our nation,” he said.

Dr. Collins said his estimate was based on studies showing that roughly 10% of people who get COVID could be affected by this and whose “long-term course is uncertain,” he said. So far, more than 32 million Americans are known to have been infected with the new coronavirus.

“We need to make sure we put our arms around them and bring answers and care to them,” said Rep. Anna Eshoo (D-Calif.), chairwoman of the Subcommittee on Health.

Jennifer Possick, MD, who directs the post-COVID recovery program at Yale New Haven (Conn.) Hospital, testified that the tidal wave of patients she and her colleagues were seeing was overwhelming.

“We are a well-resourced program at an academic medical center, but we are swamped by the need in our community. This year, we have seen more patients with post COVID-19 conditions in our clinic alone than we have new cases of asthma and COPD combined,” she said. “The magnitude of the challenge is daunting.”

Dr. Possick estimated that there are “over 60” clinics in the United States that have started to treat long-COVID patients, but said they are grassroots efforts and all very different from each other.

“Whoever had the resources, had the time, [and] was able to take the initiative and forge to the relationships because most of them are multidisciplinary, did so,” she said.
 

Patients testify

Several representatives shared moving personal stories of loved ones or staffers who remained ill months after a COVID diagnosis.

Rep. Ann Kuster, from New Hampshire, talked about her 34-year-old niece, a member of the U.S. Ski Team, who had COVID just over a year ago and “continues to struggle with everything, even the simplest activities of daily living” she said. “She has to choose between taking a shower or making dinner. I’m so proud of her for hanging in there.”

Long-COVID patients invited to testify by the subcommittee described months of disability that left them with soaring medical bills and no ability to work to pay them.

“I am now a poor, Black, disabled woman, living with long COVID,” said Chimere Smith, who said she had been a school teacher in Baltimore. “Saying it aloud makes it no more easy to accept.”

She said COVID had affected her ability to think clearly and caused debilitating fatigue, which prevented her from working. She said she lost her vision for almost 5 months because doctors misdiagnosed a cataract caused by long COVID as dry eye.

“If I did not have a loving family, I [would] be speaking to you today [from] my car, the only property I now own.”

Ms. Smith said that long-COVID clinics, which are mostly housed within academic medical centers, were not going to be accessible for all long-haulers, who are disproportionately women of color. She has started a clinic, based out of her church, to help other patients from her community.

“No one wants to hear that long COVID has decimated my life or the lives of other black women in less than a year,” Ms. Smith said. “We’ve just been waiting and hoping for compassionate doctors and politicians who would acknowledge us.”

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

The Centers for Disease Control and Prevention is finalizing new guidelines to help clinicians diagnose and manage long COVID, or postacute sequelae of SARS-CoV-2 infection.

In a day-long congressional hearing on April 28, John Brooks, MD, a medical epidemiologist at the CDC’s division of HIV/AIDS prevention, testified that the guidelines were going through the clearance process at the agency, but would be forthcoming.

“They should be coming out very shortly,” Dr. Brooks said.

The guidelines, which were developed in collaboration with newly established long-COVID clinics and patient advocacy groups, will “illustrate how to diagnose and begin to pull together what we know about management,” of the complex condition, he said.

For many doctors and patients who are struggling to understand symptoms that persist for months after the initial viral infection, the guidelines can’t come soon enough.

National Institutes of Health Director Francis Collins, MD, PhD, who also testified at the hearing, estimated that as many as 3 million people could be left with chronic health problems after even mild COVID infections.

“I can’t overstate how serious this issue is for the health of our nation,” he said.

Dr. Collins said his estimate was based on studies showing that roughly 10% of people who get COVID could be affected by this and whose “long-term course is uncertain,” he said. So far, more than 32 million Americans are known to have been infected with the new coronavirus.

“We need to make sure we put our arms around them and bring answers and care to them,” said Rep. Anna Eshoo (D-Calif.), chairwoman of the Subcommittee on Health.

Jennifer Possick, MD, who directs the post-COVID recovery program at Yale New Haven (Conn.) Hospital, testified that the tidal wave of patients she and her colleagues were seeing was overwhelming.

“We are a well-resourced program at an academic medical center, but we are swamped by the need in our community. This year, we have seen more patients with post COVID-19 conditions in our clinic alone than we have new cases of asthma and COPD combined,” she said. “The magnitude of the challenge is daunting.”

Dr. Possick estimated that there are “over 60” clinics in the United States that have started to treat long-COVID patients, but said they are grassroots efforts and all very different from each other.

“Whoever had the resources, had the time, [and] was able to take the initiative and forge to the relationships because most of them are multidisciplinary, did so,” she said.
 

Patients testify

Several representatives shared moving personal stories of loved ones or staffers who remained ill months after a COVID diagnosis.

Rep. Ann Kuster, from New Hampshire, talked about her 34-year-old niece, a member of the U.S. Ski Team, who had COVID just over a year ago and “continues to struggle with everything, even the simplest activities of daily living” she said. “She has to choose between taking a shower or making dinner. I’m so proud of her for hanging in there.”

Long-COVID patients invited to testify by the subcommittee described months of disability that left them with soaring medical bills and no ability to work to pay them.

“I am now a poor, Black, disabled woman, living with long COVID,” said Chimere Smith, who said she had been a school teacher in Baltimore. “Saying it aloud makes it no more easy to accept.”

She said COVID had affected her ability to think clearly and caused debilitating fatigue, which prevented her from working. She said she lost her vision for almost 5 months because doctors misdiagnosed a cataract caused by long COVID as dry eye.

“If I did not have a loving family, I [would] be speaking to you today [from] my car, the only property I now own.”

Ms. Smith said that long-COVID clinics, which are mostly housed within academic medical centers, were not going to be accessible for all long-haulers, who are disproportionately women of color. She has started a clinic, based out of her church, to help other patients from her community.

“No one wants to hear that long COVID has decimated my life or the lives of other black women in less than a year,” Ms. Smith said. “We’ve just been waiting and hoping for compassionate doctors and politicians who would acknowledge us.”

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

The novel antipsychotic agent SEP-363856 (Sunovion Pharmaceuticals) has a significant and ongoing effect on negative symptoms in patients with schizophrenia, new research shows.

Results of a phase 2, placebo-controlled trial show SEP-363856 significantly decreased total scores on the Brief Negative Symptom Scale (BNSS), and lowered subscale scores for such symptoms as alogia and asociality, compared with placebo.

The active-treatment group also showed significantly lower scores on the negative subscale of the Positive and Negative Syndrome Scale (PANSS). During an open-label extension of the study, both BNSS total scores and PANSS negative symptom scores continued to decrease.

Overall, the results “provide further confirmation of the effectiveness of SEP-363856 in treating schizophrenia,” study investigator Kenneth Koblan, PhD, of Sunovion said in an interview.

He added that the compound also showed “a favorable safety and tolerability profile that is differentiated from first and second generation antipsychotics, and which is consistent with the absence of D2-receptor binding.”

The findings were presented at the 2021 annual congress of the Schizophrenia International Research Society.
 

FDA breakthrough designation

SEP-363856 has a completely different mechanism of action from currently available antipsychotics.

In May 2019, it was granted breakthrough therapy designation by the Food and Drug Administration as a novel treatment for patients with schizophrenia.

Phase 2 data published in the New England Journal of Medicine in 2020 showed it achieved significant and clinically meaningful improvements in PANSS total scores after 4 weeks in patients hospitalized with an acute exacerbation of schizophrenia. It also showed durable effects out to 26 weeks.

In the current analysis, the investigators focused on negative symptoms, both in the initial acute treatment phase and an open-label extension.

They analyzed data from the previous phase 2 trial using a validated Uncorrelated PANSS Score Matrix (UPSM) transformation of the PANSS to isolate the effects of the drug on apathy/avolition and deficit of expression. They also used the BNSS.

Patients aged 18-40 years with an acute exacerbation of schizophrenia were randomly assigned to receive either 50 mg or 75 mg of SEP-363856 per day (n = 120) or matching placebo (n = 125) for 4 weeks. Completers were eligible for enrollment in a 26-week phase 2 extension study of 25 mg, 50 mg, or 75 mg of SEP-363856 per day.

The mean age of the participants was 30 years, and 64% were men. The treatment groups were balanced in terms of demographics.

Significant improvement

The BNSS total score decreased significantly with SEP-363856 over placebo during the 4-week acute treatment period, at a mean reduction of 7.1 versus 2.7, or an effect size of 0.48 (P < .001).

Scores on the PANSS negative subscale also decreased significantly with the active drugs, with an effect size of 0.37 versus placebo (P < .05), as did scores on the UPSM apathy/avolition and deficit of expression subscales (effect size, 0.32; P < .05 for both).

In addition, there were significant reductions with SEP-363856 over placebo for the BNSS alogia, asociality, anhedonia, avolition, and blunted-affect subscales (P < .05 for all comparisons) but not for the distress subscale.

During the open-label extension, mean BNSS total scores continued to decrease for the SEP-363856 group, at an average reduction versus extension enrollment across the whole cohort of 11.3.

PANSS negative symptom scores also decreased by an average of 5.2 points, while UPSM apathy/volition scores decreased by 0.4 points on average. UPSM deficit expression scores decreased by 0.5 points.

When the researchers restricted the analysis to those who received SEP-363856 during the acute treatment phase and then continued using the drug during the open-label extension, they found BNSS total scores decreased by an additional 8 points.

Similarly, PANSS negative symptom scores decreased during the open-label extension by an average of 4 points. For UPSM apathy/avolition and deficit of expression, the additional decrease was 0.3 points on average.

In addition, an analysis of the drug’s safety and tolerability showed that, compared with the commonly prescribed antipsychotic lurasidone, it had a significantly lower risk of adverse effects. In addition, the drug was not associated with extrapyramidal symptoms and had no adverse cardiometabolic effects, Dr. Koblan reported.
 

Still in development

Commenting on the findings, René S. Kahn, MD, PhD, chair of the department of psychiatry, Icahn School of Medicine at Mount Sinai, New York, noted that, although the results showed that the drug had a “nice effect” on negative symptoms, it’s still in development.

Courtesy Mount Sinai Health System

Dr. Kahn, who was not involved in the research, said “we’ve all seen” drugs that were extremely promising in phase 2 trials that have then failed in phase 3 trials. “The proof of the pudding is phase 3, and we have to wait and see,” he added.

“Obviously I hope it’s going to work out, because we are in desperate need of new drugs, especially with a new mechanism of action and not ‘me too’ drugs. And this definitely not a ‘me too’ drug,” Dr. Kahn said. However, “we’ll have to wait.”

He noted that psychosis is often the primary focus of schizophrenia management. However, he added, cognitive and negative symptoms are also “very relevant” to the disorder.

“In fact, both of them may be more important in determining the long-term outcome of schizophrenia than psychosis, [and] most of the antipsychotics that we currently have are not very effective against negative symptoms,” he said.

“So it would really be a breakthrough if we have a drug that is really effective not only against positive psychotic symptoms, but also against negative and possibly cognitive, symptoms,” Dr. Kahn added.

Commenting on the drug’s safety, Dr. Kahn said there is a need for head-to-head studies of active drugs before any firm conclusions can be drawn.

However, he noted the exploratory analysis suggests it has a different side effect profile, compared with other medications on the market.

The study was supported by Sunovion Pharmaceuticals. Dr. Koblan and his coinvestigators are employees of Sunovion.

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

The novel antipsychotic agent SEP-363856 (Sunovion Pharmaceuticals) has a significant and ongoing effect on negative symptoms in patients with schizophrenia, new research shows.

Results of a phase 2, placebo-controlled trial show SEP-363856 significantly decreased total scores on the Brief Negative Symptom Scale (BNSS), and lowered subscale scores for such symptoms as alogia and asociality, compared with placebo.

The active-treatment group also showed significantly lower scores on the negative subscale of the Positive and Negative Syndrome Scale (PANSS). During an open-label extension of the study, both BNSS total scores and PANSS negative symptom scores continued to decrease.

Overall, the results “provide further confirmation of the effectiveness of SEP-363856 in treating schizophrenia,” study investigator Kenneth Koblan, PhD, of Sunovion said in an interview.

He added that the compound also showed “a favorable safety and tolerability profile that is differentiated from first and second generation antipsychotics, and which is consistent with the absence of D2-receptor binding.”

The findings were presented at the 2021 annual congress of the Schizophrenia International Research Society.
 

FDA breakthrough designation

SEP-363856 has a completely different mechanism of action from currently available antipsychotics.

In May 2019, it was granted breakthrough therapy designation by the Food and Drug Administration as a novel treatment for patients with schizophrenia.

Phase 2 data published in the New England Journal of Medicine in 2020 showed it achieved significant and clinically meaningful improvements in PANSS total scores after 4 weeks in patients hospitalized with an acute exacerbation of schizophrenia. It also showed durable effects out to 26 weeks.

In the current analysis, the investigators focused on negative symptoms, both in the initial acute treatment phase and an open-label extension.

They analyzed data from the previous phase 2 trial using a validated Uncorrelated PANSS Score Matrix (UPSM) transformation of the PANSS to isolate the effects of the drug on apathy/avolition and deficit of expression. They also used the BNSS.

Patients aged 18-40 years with an acute exacerbation of schizophrenia were randomly assigned to receive either 50 mg or 75 mg of SEP-363856 per day (n = 120) or matching placebo (n = 125) for 4 weeks. Completers were eligible for enrollment in a 26-week phase 2 extension study of 25 mg, 50 mg, or 75 mg of SEP-363856 per day.

The mean age of the participants was 30 years, and 64% were men. The treatment groups were balanced in terms of demographics.

Significant improvement

The BNSS total score decreased significantly with SEP-363856 over placebo during the 4-week acute treatment period, at a mean reduction of 7.1 versus 2.7, or an effect size of 0.48 (P < .001).

Scores on the PANSS negative subscale also decreased significantly with the active drugs, with an effect size of 0.37 versus placebo (P < .05), as did scores on the UPSM apathy/avolition and deficit of expression subscales (effect size, 0.32; P < .05 for both).

In addition, there were significant reductions with SEP-363856 over placebo for the BNSS alogia, asociality, anhedonia, avolition, and blunted-affect subscales (P < .05 for all comparisons) but not for the distress subscale.

During the open-label extension, mean BNSS total scores continued to decrease for the SEP-363856 group, at an average reduction versus extension enrollment across the whole cohort of 11.3.

PANSS negative symptom scores also decreased by an average of 5.2 points, while UPSM apathy/volition scores decreased by 0.4 points on average. UPSM deficit expression scores decreased by 0.5 points.

When the researchers restricted the analysis to those who received SEP-363856 during the acute treatment phase and then continued using the drug during the open-label extension, they found BNSS total scores decreased by an additional 8 points.

Similarly, PANSS negative symptom scores decreased during the open-label extension by an average of 4 points. For UPSM apathy/avolition and deficit of expression, the additional decrease was 0.3 points on average.

In addition, an analysis of the drug’s safety and tolerability showed that, compared with the commonly prescribed antipsychotic lurasidone, it had a significantly lower risk of adverse effects. In addition, the drug was not associated with extrapyramidal symptoms and had no adverse cardiometabolic effects, Dr. Koblan reported.
 

Still in development

Commenting on the findings, René S. Kahn, MD, PhD, chair of the department of psychiatry, Icahn School of Medicine at Mount Sinai, New York, noted that, although the results showed that the drug had a “nice effect” on negative symptoms, it’s still in development.

Courtesy Mount Sinai Health System

Dr. Kahn, who was not involved in the research, said “we’ve all seen” drugs that were extremely promising in phase 2 trials that have then failed in phase 3 trials. “The proof of the pudding is phase 3, and we have to wait and see,” he added.

“Obviously I hope it’s going to work out, because we are in desperate need of new drugs, especially with a new mechanism of action and not ‘me too’ drugs. And this definitely not a ‘me too’ drug,” Dr. Kahn said. However, “we’ll have to wait.”

He noted that psychosis is often the primary focus of schizophrenia management. However, he added, cognitive and negative symptoms are also “very relevant” to the disorder.

“In fact, both of them may be more important in determining the long-term outcome of schizophrenia than psychosis, [and] most of the antipsychotics that we currently have are not very effective against negative symptoms,” he said.

“So it would really be a breakthrough if we have a drug that is really effective not only against positive psychotic symptoms, but also against negative and possibly cognitive, symptoms,” Dr. Kahn added.

Commenting on the drug’s safety, Dr. Kahn said there is a need for head-to-head studies of active drugs before any firm conclusions can be drawn.

However, he noted the exploratory analysis suggests it has a different side effect profile, compared with other medications on the market.

The study was supported by Sunovion Pharmaceuticals. Dr. Koblan and his coinvestigators are employees of Sunovion.

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

The novel antipsychotic agent SEP-363856 (Sunovion Pharmaceuticals) has a significant and ongoing effect on negative symptoms in patients with schizophrenia, new research shows.

Results of a phase 2, placebo-controlled trial show SEP-363856 significantly decreased total scores on the Brief Negative Symptom Scale (BNSS), and lowered subscale scores for such symptoms as alogia and asociality, compared with placebo.

The active-treatment group also showed significantly lower scores on the negative subscale of the Positive and Negative Syndrome Scale (PANSS). During an open-label extension of the study, both BNSS total scores and PANSS negative symptom scores continued to decrease.

Overall, the results “provide further confirmation of the effectiveness of SEP-363856 in treating schizophrenia,” study investigator Kenneth Koblan, PhD, of Sunovion said in an interview.

He added that the compound also showed “a favorable safety and tolerability profile that is differentiated from first and second generation antipsychotics, and which is consistent with the absence of D2-receptor binding.”

The findings were presented at the 2021 annual congress of the Schizophrenia International Research Society.
 

FDA breakthrough designation

SEP-363856 has a completely different mechanism of action from currently available antipsychotics.

In May 2019, it was granted breakthrough therapy designation by the Food and Drug Administration as a novel treatment for patients with schizophrenia.

Phase 2 data published in the New England Journal of Medicine in 2020 showed it achieved significant and clinically meaningful improvements in PANSS total scores after 4 weeks in patients hospitalized with an acute exacerbation of schizophrenia. It also showed durable effects out to 26 weeks.

In the current analysis, the investigators focused on negative symptoms, both in the initial acute treatment phase and an open-label extension.

They analyzed data from the previous phase 2 trial using a validated Uncorrelated PANSS Score Matrix (UPSM) transformation of the PANSS to isolate the effects of the drug on apathy/avolition and deficit of expression. They also used the BNSS.

Patients aged 18-40 years with an acute exacerbation of schizophrenia were randomly assigned to receive either 50 mg or 75 mg of SEP-363856 per day (n = 120) or matching placebo (n = 125) for 4 weeks. Completers were eligible for enrollment in a 26-week phase 2 extension study of 25 mg, 50 mg, or 75 mg of SEP-363856 per day.

The mean age of the participants was 30 years, and 64% were men. The treatment groups were balanced in terms of demographics.

Significant improvement

The BNSS total score decreased significantly with SEP-363856 over placebo during the 4-week acute treatment period, at a mean reduction of 7.1 versus 2.7, or an effect size of 0.48 (P < .001).

Scores on the PANSS negative subscale also decreased significantly with the active drugs, with an effect size of 0.37 versus placebo (P < .05), as did scores on the UPSM apathy/avolition and deficit of expression subscales (effect size, 0.32; P < .05 for both).

In addition, there were significant reductions with SEP-363856 over placebo for the BNSS alogia, asociality, anhedonia, avolition, and blunted-affect subscales (P < .05 for all comparisons) but not for the distress subscale.

During the open-label extension, mean BNSS total scores continued to decrease for the SEP-363856 group, at an average reduction versus extension enrollment across the whole cohort of 11.3.

PANSS negative symptom scores also decreased by an average of 5.2 points, while UPSM apathy/volition scores decreased by 0.4 points on average. UPSM deficit expression scores decreased by 0.5 points.

When the researchers restricted the analysis to those who received SEP-363856 during the acute treatment phase and then continued using the drug during the open-label extension, they found BNSS total scores decreased by an additional 8 points.

Similarly, PANSS negative symptom scores decreased during the open-label extension by an average of 4 points. For UPSM apathy/avolition and deficit of expression, the additional decrease was 0.3 points on average.

In addition, an analysis of the drug’s safety and tolerability showed that, compared with the commonly prescribed antipsychotic lurasidone, it had a significantly lower risk of adverse effects. In addition, the drug was not associated with extrapyramidal symptoms and had no adverse cardiometabolic effects, Dr. Koblan reported.
 

Still in development

Commenting on the findings, René S. Kahn, MD, PhD, chair of the department of psychiatry, Icahn School of Medicine at Mount Sinai, New York, noted that, although the results showed that the drug had a “nice effect” on negative symptoms, it’s still in development.

Courtesy Mount Sinai Health System

Dr. Kahn, who was not involved in the research, said “we’ve all seen” drugs that were extremely promising in phase 2 trials that have then failed in phase 3 trials. “The proof of the pudding is phase 3, and we have to wait and see,” he added.

“Obviously I hope it’s going to work out, because we are in desperate need of new drugs, especially with a new mechanism of action and not ‘me too’ drugs. And this definitely not a ‘me too’ drug,” Dr. Kahn said. However, “we’ll have to wait.”

He noted that psychosis is often the primary focus of schizophrenia management. However, he added, cognitive and negative symptoms are also “very relevant” to the disorder.

“In fact, both of them may be more important in determining the long-term outcome of schizophrenia than psychosis, [and] most of the antipsychotics that we currently have are not very effective against negative symptoms,” he said.

“So it would really be a breakthrough if we have a drug that is really effective not only against positive psychotic symptoms, but also against negative and possibly cognitive, symptoms,” Dr. Kahn added.

Commenting on the drug’s safety, Dr. Kahn said there is a need for head-to-head studies of active drugs before any firm conclusions can be drawn.

However, he noted the exploratory analysis suggests it has a different side effect profile, compared with other medications on the market.

The study was supported by Sunovion Pharmaceuticals. Dr. Koblan and his coinvestigators are employees of Sunovion.

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

Accelerated brain aging among HIV-infected adults might be caused in part by altered deep sleep patterns, new research suggests.

Using a measure known as the brain age index (BAI) – a machine-learning model that measures deviations in brain activity during sleep relative to healthy individuals – investigators identified 34 sleep electroencephalogram features that were significantly altered by HIV infection. The most notable of these was the decline in slow-wave activity during non-REM sleep, which has been previously associated with MRI markers of brain aging in healthy adults.

“One of the functions of slow-wave sleep appears to be its association with the glymphatic system, which clears [metabolic] waste products and supports memory consolidation,” study coauthor Brandon Westover, MD, PhD, associate professor of neurology at Massachusetts General Hospital/Harvard Medical School, Boston, said in an interview. “It’s also believed to be associated with an accelerated risk for dementia and other cognitive issues.”

Previous work conducted at Johns Hopkins and other institutions confirm Dr. Westerson’s hypothesis. Charlene Gamaldo, MD, medical director of Johns Hopkins Sleep Disorders Center in Baltimore, pointed to other study findings in patients with neurodegenerative disease that have shown a link between predominant habitual sleep positions and dementia, potentially driven by inefficient glymphatic transport. Dr. Gamaldo was not involved in the current study.
 

Threefold acceleration vs. healthy volunteers

“We’ve been grappling with whether people with HIV on ART experience accelerated aging or accentuated aging,” coauthor Shibani Mukerji, MD, PhD, associate director of the neuroinfectious diseases unit at Massachusetts General, said in an interview. “We have yet to have biomarkers to address this question, and most of the tools are limited to invasive or expensive diagnostics. “In general, sleep and its influence on health have been understudied in the HIV population.”

To address this question, the researchers retrospectively examined a Massachusetts General Hospital database of diagnostic sleep study participants from 2008 to 2018, identifying 3,155 healthy, HIV-negative control subjects and 43 HIV-positive participants. Thirty-four (79%) of the HIV-positive participants were men, 30 (70%) were White, and 38 (93%) were virally suppressed at the time of their sleep study. Four patients were taking efavirenz, 13 were taking an integrase strand transfer inhibitor, and all were adherent to antiretroviral therapy (ART) at the time of their sleep study.

None of the HIV-positive participants had a history of secondary brain infection or brain tumor, although one patient had recovered fully from a previous HIV-associated encephalitis.

The study findings, which were published online March 30, 2021, in Sleep, first showed that HIV-positive participants had an average BAI of 3.19 years (standard error of the mean,1.43 years), compared with the control participants, who had an average BAI of –0.16 (SEM, 0.18 years).

These findings held after adjustment for potential confounders (age, sex, race, tobacco use disorder, and alcohol use disorder), yielding a total effect of HIV on BAI of 3.35 years (P < .01).

“Despite being well controlled on ART, HIV-positive individuals who had participated in the sleep studies still had elevated brain age,” said Dr. Westover. “We didn’t have enough information to determine the pathways by which HIV increases the BAI, but chronic inflammation appears to be an important factor.”

The findings also demonstrated that comorbidities accounted for roughly a quarter of the effect of HIV on BAI. However, the lack of statistical significance (in part because of the limited sample size) precluded the ability to determine if treating or preventing them might influence the degree to which HIV affects BAI and, in turn, cognitive decline.
 

HIV, sleep EEG, and brain aging

To estimate the effect of HIV on specific EEG features, the investigators again evaluated the total effect, this time replacing BAI with individual sleep EEG as the primary outcome. Among the 34 EEG features significantly altered by HIV, none were observed in the wake state and three were altered in REM (each associated with reduced delta band power). The rest were distributed in non-REM sleep, most notably in the deepest phase, corresponding to relative reductions in delta wave power.

The study findings build on the investigators’ previous research, which demonstrated an association between greater mean BAI and dementia, psychotic disorders, and anxiety/mood disorders in HIV-negative subjects, all of which correlated to attenuated slow-wave sleep.

More research is needed to determine if BAI, as it relates to sleep EEG, can effectively track the risk for cognitive decline among HIV-positive people, and if certain confounders might attenuate or accelerate this risk.

“While our team has not specifically looked at BAI, the findings in this study seem perfectly in line with what we have found with our own research,” Dr. Gamaldo said in an interview. “Not only have we observed a robust association between minimal cognitive deficits and patients’ sleep complaints (despite being virally controlled), but also, the potential value of measuring the architectural sleep features by ambulatory EEG to identify HIV patients’ vulnerability to cognitive decline.”

“BAI is a physiologic, easily repeatable measurement that can be used to track if an intervention is having a good effect,” Dr. Westover said.

Dr. Mukerji concurred, adding that “having a tool that can be used in resource-challenged settings and also be incorporated into longitudinal studies in a patient population with substantial age-related comorbidities, like HIV, would be really helpful.”

Dr. Westover and Dr. Mukerji disclosed no relevant financial relationships. Dr. Gamaldo is a consultant for Jazz Pharmaceuticals, and has received author royalties from UpToDate and honoraria from Medscape CME for content contribution.

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

Accelerated brain aging among HIV-infected adults might be caused in part by altered deep sleep patterns, new research suggests.

Using a measure known as the brain age index (BAI) – a machine-learning model that measures deviations in brain activity during sleep relative to healthy individuals – investigators identified 34 sleep electroencephalogram features that were significantly altered by HIV infection. The most notable of these was the decline in slow-wave activity during non-REM sleep, which has been previously associated with MRI markers of brain aging in healthy adults.

“One of the functions of slow-wave sleep appears to be its association with the glymphatic system, which clears [metabolic] waste products and supports memory consolidation,” study coauthor Brandon Westover, MD, PhD, associate professor of neurology at Massachusetts General Hospital/Harvard Medical School, Boston, said in an interview. “It’s also believed to be associated with an accelerated risk for dementia and other cognitive issues.”

Previous work conducted at Johns Hopkins and other institutions confirm Dr. Westerson’s hypothesis. Charlene Gamaldo, MD, medical director of Johns Hopkins Sleep Disorders Center in Baltimore, pointed to other study findings in patients with neurodegenerative disease that have shown a link between predominant habitual sleep positions and dementia, potentially driven by inefficient glymphatic transport. Dr. Gamaldo was not involved in the current study.
 

Threefold acceleration vs. healthy volunteers

“We’ve been grappling with whether people with HIV on ART experience accelerated aging or accentuated aging,” coauthor Shibani Mukerji, MD, PhD, associate director of the neuroinfectious diseases unit at Massachusetts General, said in an interview. “We have yet to have biomarkers to address this question, and most of the tools are limited to invasive or expensive diagnostics. “In general, sleep and its influence on health have been understudied in the HIV population.”

To address this question, the researchers retrospectively examined a Massachusetts General Hospital database of diagnostic sleep study participants from 2008 to 2018, identifying 3,155 healthy, HIV-negative control subjects and 43 HIV-positive participants. Thirty-four (79%) of the HIV-positive participants were men, 30 (70%) were White, and 38 (93%) were virally suppressed at the time of their sleep study. Four patients were taking efavirenz, 13 were taking an integrase strand transfer inhibitor, and all were adherent to antiretroviral therapy (ART) at the time of their sleep study.

None of the HIV-positive participants had a history of secondary brain infection or brain tumor, although one patient had recovered fully from a previous HIV-associated encephalitis.

The study findings, which were published online March 30, 2021, in Sleep, first showed that HIV-positive participants had an average BAI of 3.19 years (standard error of the mean,1.43 years), compared with the control participants, who had an average BAI of –0.16 (SEM, 0.18 years).

These findings held after adjustment for potential confounders (age, sex, race, tobacco use disorder, and alcohol use disorder), yielding a total effect of HIV on BAI of 3.35 years (P < .01).

“Despite being well controlled on ART, HIV-positive individuals who had participated in the sleep studies still had elevated brain age,” said Dr. Westover. “We didn’t have enough information to determine the pathways by which HIV increases the BAI, but chronic inflammation appears to be an important factor.”

The findings also demonstrated that comorbidities accounted for roughly a quarter of the effect of HIV on BAI. However, the lack of statistical significance (in part because of the limited sample size) precluded the ability to determine if treating or preventing them might influence the degree to which HIV affects BAI and, in turn, cognitive decline.
 

HIV, sleep EEG, and brain aging

To estimate the effect of HIV on specific EEG features, the investigators again evaluated the total effect, this time replacing BAI with individual sleep EEG as the primary outcome. Among the 34 EEG features significantly altered by HIV, none were observed in the wake state and three were altered in REM (each associated with reduced delta band power). The rest were distributed in non-REM sleep, most notably in the deepest phase, corresponding to relative reductions in delta wave power.

The study findings build on the investigators’ previous research, which demonstrated an association between greater mean BAI and dementia, psychotic disorders, and anxiety/mood disorders in HIV-negative subjects, all of which correlated to attenuated slow-wave sleep.

More research is needed to determine if BAI, as it relates to sleep EEG, can effectively track the risk for cognitive decline among HIV-positive people, and if certain confounders might attenuate or accelerate this risk.

“While our team has not specifically looked at BAI, the findings in this study seem perfectly in line with what we have found with our own research,” Dr. Gamaldo said in an interview. “Not only have we observed a robust association between minimal cognitive deficits and patients’ sleep complaints (despite being virally controlled), but also, the potential value of measuring the architectural sleep features by ambulatory EEG to identify HIV patients’ vulnerability to cognitive decline.”

“BAI is a physiologic, easily repeatable measurement that can be used to track if an intervention is having a good effect,” Dr. Westover said.

Dr. Mukerji concurred, adding that “having a tool that can be used in resource-challenged settings and also be incorporated into longitudinal studies in a patient population with substantial age-related comorbidities, like HIV, would be really helpful.”

Dr. Westover and Dr. Mukerji disclosed no relevant financial relationships. Dr. Gamaldo is a consultant for Jazz Pharmaceuticals, and has received author royalties from UpToDate and honoraria from Medscape CME for content contribution.

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

Accelerated brain aging among HIV-infected adults might be caused in part by altered deep sleep patterns, new research suggests.

Using a measure known as the brain age index (BAI) – a machine-learning model that measures deviations in brain activity during sleep relative to healthy individuals – investigators identified 34 sleep electroencephalogram features that were significantly altered by HIV infection. The most notable of these was the decline in slow-wave activity during non-REM sleep, which has been previously associated with MRI markers of brain aging in healthy adults.

“One of the functions of slow-wave sleep appears to be its association with the glymphatic system, which clears [metabolic] waste products and supports memory consolidation,” study coauthor Brandon Westover, MD, PhD, associate professor of neurology at Massachusetts General Hospital/Harvard Medical School, Boston, said in an interview. “It’s also believed to be associated with an accelerated risk for dementia and other cognitive issues.”

Previous work conducted at Johns Hopkins and other institutions confirm Dr. Westerson’s hypothesis. Charlene Gamaldo, MD, medical director of Johns Hopkins Sleep Disorders Center in Baltimore, pointed to other study findings in patients with neurodegenerative disease that have shown a link between predominant habitual sleep positions and dementia, potentially driven by inefficient glymphatic transport. Dr. Gamaldo was not involved in the current study.
 

Threefold acceleration vs. healthy volunteers

“We’ve been grappling with whether people with HIV on ART experience accelerated aging or accentuated aging,” coauthor Shibani Mukerji, MD, PhD, associate director of the neuroinfectious diseases unit at Massachusetts General, said in an interview. “We have yet to have biomarkers to address this question, and most of the tools are limited to invasive or expensive diagnostics. “In general, sleep and its influence on health have been understudied in the HIV population.”

To address this question, the researchers retrospectively examined a Massachusetts General Hospital database of diagnostic sleep study participants from 2008 to 2018, identifying 3,155 healthy, HIV-negative control subjects and 43 HIV-positive participants. Thirty-four (79%) of the HIV-positive participants were men, 30 (70%) were White, and 38 (93%) were virally suppressed at the time of their sleep study. Four patients were taking efavirenz, 13 were taking an integrase strand transfer inhibitor, and all were adherent to antiretroviral therapy (ART) at the time of their sleep study.

None of the HIV-positive participants had a history of secondary brain infection or brain tumor, although one patient had recovered fully from a previous HIV-associated encephalitis.

The study findings, which were published online March 30, 2021, in Sleep, first showed that HIV-positive participants had an average BAI of 3.19 years (standard error of the mean,1.43 years), compared with the control participants, who had an average BAI of –0.16 (SEM, 0.18 years).

These findings held after adjustment for potential confounders (age, sex, race, tobacco use disorder, and alcohol use disorder), yielding a total effect of HIV on BAI of 3.35 years (P < .01).

“Despite being well controlled on ART, HIV-positive individuals who had participated in the sleep studies still had elevated brain age,” said Dr. Westover. “We didn’t have enough information to determine the pathways by which HIV increases the BAI, but chronic inflammation appears to be an important factor.”

The findings also demonstrated that comorbidities accounted for roughly a quarter of the effect of HIV on BAI. However, the lack of statistical significance (in part because of the limited sample size) precluded the ability to determine if treating or preventing them might influence the degree to which HIV affects BAI and, in turn, cognitive decline.
 

HIV, sleep EEG, and brain aging

To estimate the effect of HIV on specific EEG features, the investigators again evaluated the total effect, this time replacing BAI with individual sleep EEG as the primary outcome. Among the 34 EEG features significantly altered by HIV, none were observed in the wake state and three were altered in REM (each associated with reduced delta band power). The rest were distributed in non-REM sleep, most notably in the deepest phase, corresponding to relative reductions in delta wave power.

The study findings build on the investigators’ previous research, which demonstrated an association between greater mean BAI and dementia, psychotic disorders, and anxiety/mood disorders in HIV-negative subjects, all of which correlated to attenuated slow-wave sleep.

More research is needed to determine if BAI, as it relates to sleep EEG, can effectively track the risk for cognitive decline among HIV-positive people, and if certain confounders might attenuate or accelerate this risk.

“While our team has not specifically looked at BAI, the findings in this study seem perfectly in line with what we have found with our own research,” Dr. Gamaldo said in an interview. “Not only have we observed a robust association between minimal cognitive deficits and patients’ sleep complaints (despite being virally controlled), but also, the potential value of measuring the architectural sleep features by ambulatory EEG to identify HIV patients’ vulnerability to cognitive decline.”

“BAI is a physiologic, easily repeatable measurement that can be used to track if an intervention is having a good effect,” Dr. Westover said.

Dr. Mukerji concurred, adding that “having a tool that can be used in resource-challenged settings and also be incorporated into longitudinal studies in a patient population with substantial age-related comorbidities, like HIV, would be really helpful.”

Dr. Westover and Dr. Mukerji disclosed no relevant financial relationships. Dr. Gamaldo is a consultant for Jazz Pharmaceuticals, and has received author royalties from UpToDate and honoraria from Medscape CME for content contribution.

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