MDedge Psychiatry

The public health crisis sparked by COVID-19 has engendered much debate in the realm where politics, journalism, law, and medicine meet.

Doctors have used the media to name other doctors as sources of harmful misinformation, in some cases going so far as to invoke medical practice board oversight as a potential intervention when doctors make public statements deemed too far out of bounds scientifically. Over the past year, some physicians have been harshly criticized for speaking about off-label prescribing, a widely accepted part of everyday medical practice.

The science and ethics of off-label prescribing have not changed; what has changed is the quality of dialogue around it. As psychiatrists, it does not fall within our scope of practice to offer definitive public opinions on the treatment of COVID-19, nor is that our purpose here. However, we can speak to a process that damages patients and doctors alike by undermining trust. All of this heat around bad medical information, in our opinion, amounts to using the methods of other fields to evaluate science and clinical practice. A remedy, then, to improve the quality of public medical intelligence would be to clarify the rules of scientific debate and to once again clearly state that off-label prescribing is part and parcel of the good practice of clinical medicine.

Medical disciplinary boards and the news media were neither designed nor are they equipped to adjudicate scientific debates. Science is never settled: Hypothesis and theory are always open to testing and revision as new evidence emerges. There is a place in medicine for formal disciplinary processes, as well-delineated by professional bodies such as the APA Ethics Committee. Another important part of protecting the public is to support an environment of scientific inquiry in which diversity of opinion is welcomed. As physicians, we translate science into excellent clinical care every day in our practices, and we advance science by sharing what we learn through friendly collegial communication and collaboration.

Dr. Emmons is part-time clinical associate professor in the department of psychiatry at the University of Vermont, Burlington, and is a past chair of the Ethics Committee for the Vermont District Branch of the American Psychiatric Association. He is in private practice in Moretown, Vt., and disclosed no relevant financial relationships. Dr. Kohanski is in private practice in Dayton, N.J., and is a diplomate of the American Board of Psychiatry & Neurology. She also is the host and author of Clinical Correlation, a series of the Psychcast. Dr. Kohanski disclosed no relevant financial relationships.

The public health crisis sparked by COVID-19 has engendered much debate in the realm where politics, journalism, law, and medicine meet.

Doctors have used the media to name other doctors as sources of harmful misinformation, in some cases going so far as to invoke medical practice board oversight as a potential intervention when doctors make public statements deemed too far out of bounds scientifically. Over the past year, some physicians have been harshly criticized for speaking about off-label prescribing, a widely accepted part of everyday medical practice.

The science and ethics of off-label prescribing have not changed; what has changed is the quality of dialogue around it. As psychiatrists, it does not fall within our scope of practice to offer definitive public opinions on the treatment of COVID-19, nor is that our purpose here. However, we can speak to a process that damages patients and doctors alike by undermining trust. All of this heat around bad medical information, in our opinion, amounts to using the methods of other fields to evaluate science and clinical practice. A remedy, then, to improve the quality of public medical intelligence would be to clarify the rules of scientific debate and to once again clearly state that off-label prescribing is part and parcel of the good practice of clinical medicine.

Medical disciplinary boards and the news media were neither designed nor are they equipped to adjudicate scientific debates. Science is never settled: Hypothesis and theory are always open to testing and revision as new evidence emerges. There is a place in medicine for formal disciplinary processes, as well-delineated by professional bodies such as the APA Ethics Committee. Another important part of protecting the public is to support an environment of scientific inquiry in which diversity of opinion is welcomed. As physicians, we translate science into excellent clinical care every day in our practices, and we advance science by sharing what we learn through friendly collegial communication and collaboration.

Dr. Emmons is part-time clinical associate professor in the department of psychiatry at the University of Vermont, Burlington, and is a past chair of the Ethics Committee for the Vermont District Branch of the American Psychiatric Association. He is in private practice in Moretown, Vt., and disclosed no relevant financial relationships. Dr. Kohanski is in private practice in Dayton, N.J., and is a diplomate of the American Board of Psychiatry & Neurology. She also is the host and author of Clinical Correlation, a series of the Psychcast. Dr. Kohanski disclosed no relevant financial relationships.

The public health crisis sparked by COVID-19 has engendered much debate in the realm where politics, journalism, law, and medicine meet.

Doctors have used the media to name other doctors as sources of harmful misinformation, in some cases going so far as to invoke medical practice board oversight as a potential intervention when doctors make public statements deemed too far out of bounds scientifically. Over the past year, some physicians have been harshly criticized for speaking about off-label prescribing, a widely accepted part of everyday medical practice.

The science and ethics of off-label prescribing have not changed; what has changed is the quality of dialogue around it. As psychiatrists, it does not fall within our scope of practice to offer definitive public opinions on the treatment of COVID-19, nor is that our purpose here. However, we can speak to a process that damages patients and doctors alike by undermining trust. All of this heat around bad medical information, in our opinion, amounts to using the methods of other fields to evaluate science and clinical practice. A remedy, then, to improve the quality of public medical intelligence would be to clarify the rules of scientific debate and to once again clearly state that off-label prescribing is part and parcel of the good practice of clinical medicine.

Medical disciplinary boards and the news media were neither designed nor are they equipped to adjudicate scientific debates. Science is never settled: Hypothesis and theory are always open to testing and revision as new evidence emerges. There is a place in medicine for formal disciplinary processes, as well-delineated by professional bodies such as the APA Ethics Committee. Another important part of protecting the public is to support an environment of scientific inquiry in which diversity of opinion is welcomed. As physicians, we translate science into excellent clinical care every day in our practices, and we advance science by sharing what we learn through friendly collegial communication and collaboration.

Dr. Emmons is part-time clinical associate professor in the department of psychiatry at the University of Vermont, Burlington, and is a past chair of the Ethics Committee for the Vermont District Branch of the American Psychiatric Association. He is in private practice in Moretown, Vt., and disclosed no relevant financial relationships. Dr. Kohanski is in private practice in Dayton, N.J., and is a diplomate of the American Board of Psychiatry & Neurology. She also is the host and author of Clinical Correlation, a series of the Psychcast. Dr. Kohanski disclosed no relevant financial relationships.

Hooray for back to school! But not for everyone. ... what to do with those who have trouble transitioning back?

As we have now passed a year since COVID-19–related shutdowns were implemented throughout the United States; and with returns to in-person schooling continuing to vary based on location, many of us either in our personal lives, or through conversations with patients and families, are experiencing a yearning for the “good old days” of fully in-person schooling. As the place where children and adolescents spend a good portion of their waking hours, school is integral to not just children’s academic development, but to emotional and social development as well. One interesting phenomenon I’ve seen working with many children and families is that the strong desire to go back to school is not universal. Some of my patients are perfectly happy to be doing “remote schooling”, as it reduces the stress that they were experiencing in this setting before the pandemic.¹ These families find themselves wondering – how will I get my child to return to school? As we (hopefully) turn the corner toward a return to normalcy, I believe many of us may find ourselves counseling families on whether a return to in-person schooling is in their child’s best interest. Even when a family decides it is best for their child to return, we might encounter scenarios in which children and adolescents outright refuse to go to school, or engage in avoidant behavior, which is broadly known as “school refusal.” Discussion of a treatment approach to this often challenging clinical scenario is warranted.

The first step in addressing the issue is defining it. School refusal is not a “diagnosis” in psychiatric lexicon, rather it describes a behavior which may be a symptom or manifestation of any number of underlying factors. One helpful definition proposed is (a) missing 25% of total school time for at least 2 weeks or (b) experiencing difficulty attending school such that there is significant interference in the child’s or family’s daily routine for at least 2 weeks, or (c) missing at least 10 days of school over a period of 15 weeks.² The common thread of this, and any other definition, is sustained absenteeism or avoidance with significant impact to education, family life, or both. It is estimated that the prevalence of this phenomenon is between 1% and 2% of school-aged children.

Next to consider is what might be prompting or underlying the behavior. A comprehensive evaluation approach should include consideration of environmental factors such as bullying and learning difficulties, as well as presence of an anxiety or depressive disorder. Awareness of whether the child/adolescent has a 504 plan or individualized education program (IEP) is vital, as these can be marshaled for additional support. Family factors, including parental illness (medical and/or psychiatric), should also be considered. As school avoidance behaviors often include somatic symptoms of anxiety such as palpitations, shortness of breath, and abdominal pain; a rule out of medical etiology is recommended, as well as a caution to consider both medical and behavioral factors simultaneously, as focus on either separately can lead to missing the other.

Separation anxiety and social anxiety disorders are two specific conditions that may manifest in school refusal and should be evaluated for specifically. Separation anxiety is characterized by developmentally inappropriate, excessive worry or distress associated with separation from a primary caregiver or major attachment figure. Social anxiety is characterized by excessive fear or worry about being negatively evaluated by others in social situations.³ One publicly available tool that can be helpful for screening for a variety of anxiety disorders in children and adolescents is the SCARED.⁴ The PHQ-9 Adolescent⁵ is one such screening instrument for depression, which can be a driving factor or co-occur in children with school refusal.

When it comes to treatment, the best evidence out there is for a cognitive-behavioral therapy (CBT)–based approach motivated toward a return to the school setting as soon as possible.^6,7 This will involve looking at how thoughts, behaviors, and feelings are interacting with each other in the clinical scenario and how these might be challenged or changed in a positive manner. Coping and problem-solving skills are often incorporated. This approach may also involve gradual exposure to the anxiety-producing situation in a hierarchical fashion starting with less anxiety-provoking scenarios and moving toward increasingly challenging ones. CBT for school refusal is likely most effective when including both school and family involvement to ensure consistency across settings. Making sure that there are not inadvertent reinforcing factors motivating staying home (for instance unrestricted access to electronic devices) is an important step to consider. If anxiety or depression is moderately to severely impairing – which is frequently the case when school refusal comes to clinical attention, consider use of medication as part of the treatment strategy. Selective serotonin reuptake inhibitors as a class are the most commonly used medications and deserve strong consideration.

To summarize, school refusal can occur for a variety of reasons. Early identification and comprehensive treatment taking into account child and family preference and using a multimodal approach to encourage and support a quick return to the school environment is considered best practice.
 

Dr. Hoffnung is a pediatric psychiatrist at the University of Vermont Children’s Hospital and an assistant professor of psychiatry at the Robert Larner, M.D. College of Medicine at the University of Vermont, both in Burlington. He has no relevant financial disclosures. Email him at [email protected].

References

1. See, for example: www.npr.org/2021/03/08/971457441/as-many-parents-fret-over-remote-learning-some-find-their-kids-are-thriving.

2. Kearney CA. Educ Psychol Rev. 2008;20:257-82.

3. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, Va.: American Psychiatric Association, 2013.

4. Available at: www.pediatricbipolar.pitt.edu/resources/instruments.

5. Available at: www.aacap.org/App_Themes/AACAP/docs/member_resources/toolbox_for_clinical_practice_and_outcomes/symptoms/GLAD-PC_PHQ-9.pdf.

6. Elliott JG and Place M. J Child Psychol Psychiatry. 2019;60(1):4-15.

7. Prabhuswamy M. J Paed Child Health. 2018;54(10):1117-20.

Hooray for back to school! But not for everyone. ... what to do with those who have trouble transitioning back?

As we have now passed a year since COVID-19–related shutdowns were implemented throughout the United States; and with returns to in-person schooling continuing to vary based on location, many of us either in our personal lives, or through conversations with patients and families, are experiencing a yearning for the “good old days” of fully in-person schooling. As the place where children and adolescents spend a good portion of their waking hours, school is integral to not just children’s academic development, but to emotional and social development as well. One interesting phenomenon I’ve seen working with many children and families is that the strong desire to go back to school is not universal. Some of my patients are perfectly happy to be doing “remote schooling”, as it reduces the stress that they were experiencing in this setting before the pandemic.¹ These families find themselves wondering – how will I get my child to return to school? As we (hopefully) turn the corner toward a return to normalcy, I believe many of us may find ourselves counseling families on whether a return to in-person schooling is in their child’s best interest. Even when a family decides it is best for their child to return, we might encounter scenarios in which children and adolescents outright refuse to go to school, or engage in avoidant behavior, which is broadly known as “school refusal.” Discussion of a treatment approach to this often challenging clinical scenario is warranted.

The first step in addressing the issue is defining it. School refusal is not a “diagnosis” in psychiatric lexicon, rather it describes a behavior which may be a symptom or manifestation of any number of underlying factors. One helpful definition proposed is (a) missing 25% of total school time for at least 2 weeks or (b) experiencing difficulty attending school such that there is significant interference in the child’s or family’s daily routine for at least 2 weeks, or (c) missing at least 10 days of school over a period of 15 weeks.² The common thread of this, and any other definition, is sustained absenteeism or avoidance with significant impact to education, family life, or both. It is estimated that the prevalence of this phenomenon is between 1% and 2% of school-aged children.

Next to consider is what might be prompting or underlying the behavior. A comprehensive evaluation approach should include consideration of environmental factors such as bullying and learning difficulties, as well as presence of an anxiety or depressive disorder. Awareness of whether the child/adolescent has a 504 plan or individualized education program (IEP) is vital, as these can be marshaled for additional support. Family factors, including parental illness (medical and/or psychiatric), should also be considered. As school avoidance behaviors often include somatic symptoms of anxiety such as palpitations, shortness of breath, and abdominal pain; a rule out of medical etiology is recommended, as well as a caution to consider both medical and behavioral factors simultaneously, as focus on either separately can lead to missing the other.

Separation anxiety and social anxiety disorders are two specific conditions that may manifest in school refusal and should be evaluated for specifically. Separation anxiety is characterized by developmentally inappropriate, excessive worry or distress associated with separation from a primary caregiver or major attachment figure. Social anxiety is characterized by excessive fear or worry about being negatively evaluated by others in social situations.³ One publicly available tool that can be helpful for screening for a variety of anxiety disorders in children and adolescents is the SCARED.⁴ The PHQ-9 Adolescent⁵ is one such screening instrument for depression, which can be a driving factor or co-occur in children with school refusal.

When it comes to treatment, the best evidence out there is for a cognitive-behavioral therapy (CBT)–based approach motivated toward a return to the school setting as soon as possible.^6,7 This will involve looking at how thoughts, behaviors, and feelings are interacting with each other in the clinical scenario and how these might be challenged or changed in a positive manner. Coping and problem-solving skills are often incorporated. This approach may also involve gradual exposure to the anxiety-producing situation in a hierarchical fashion starting with less anxiety-provoking scenarios and moving toward increasingly challenging ones. CBT for school refusal is likely most effective when including both school and family involvement to ensure consistency across settings. Making sure that there are not inadvertent reinforcing factors motivating staying home (for instance unrestricted access to electronic devices) is an important step to consider. If anxiety or depression is moderately to severely impairing – which is frequently the case when school refusal comes to clinical attention, consider use of medication as part of the treatment strategy. Selective serotonin reuptake inhibitors as a class are the most commonly used medications and deserve strong consideration.

To summarize, school refusal can occur for a variety of reasons. Early identification and comprehensive treatment taking into account child and family preference and using a multimodal approach to encourage and support a quick return to the school environment is considered best practice.
 

Dr. Hoffnung is a pediatric psychiatrist at the University of Vermont Children’s Hospital and an assistant professor of psychiatry at the Robert Larner, M.D. College of Medicine at the University of Vermont, both in Burlington. He has no relevant financial disclosures. Email him at [email protected].

References

1. See, for example: www.npr.org/2021/03/08/971457441/as-many-parents-fret-over-remote-learning-some-find-their-kids-are-thriving.

2. Kearney CA. Educ Psychol Rev. 2008;20:257-82.

3. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, Va.: American Psychiatric Association, 2013.

4. Available at: www.pediatricbipolar.pitt.edu/resources/instruments.

5. Available at: www.aacap.org/App_Themes/AACAP/docs/member_resources/toolbox_for_clinical_practice_and_outcomes/symptoms/GLAD-PC_PHQ-9.pdf.

6. Elliott JG and Place M. J Child Psychol Psychiatry. 2019;60(1):4-15.

7. Prabhuswamy M. J Paed Child Health. 2018;54(10):1117-20.

Hooray for back to school! But not for everyone. ... what to do with those who have trouble transitioning back?

As we have now passed a year since COVID-19–related shutdowns were implemented throughout the United States; and with returns to in-person schooling continuing to vary based on location, many of us either in our personal lives, or through conversations with patients and families, are experiencing a yearning for the “good old days” of fully in-person schooling. As the place where children and adolescents spend a good portion of their waking hours, school is integral to not just children’s academic development, but to emotional and social development as well. One interesting phenomenon I’ve seen working with many children and families is that the strong desire to go back to school is not universal. Some of my patients are perfectly happy to be doing “remote schooling”, as it reduces the stress that they were experiencing in this setting before the pandemic.¹ These families find themselves wondering – how will I get my child to return to school? As we (hopefully) turn the corner toward a return to normalcy, I believe many of us may find ourselves counseling families on whether a return to in-person schooling is in their child’s best interest. Even when a family decides it is best for their child to return, we might encounter scenarios in which children and adolescents outright refuse to go to school, or engage in avoidant behavior, which is broadly known as “school refusal.” Discussion of a treatment approach to this often challenging clinical scenario is warranted.

The first step in addressing the issue is defining it. School refusal is not a “diagnosis” in psychiatric lexicon, rather it describes a behavior which may be a symptom or manifestation of any number of underlying factors. One helpful definition proposed is (a) missing 25% of total school time for at least 2 weeks or (b) experiencing difficulty attending school such that there is significant interference in the child’s or family’s daily routine for at least 2 weeks, or (c) missing at least 10 days of school over a period of 15 weeks.² The common thread of this, and any other definition, is sustained absenteeism or avoidance with significant impact to education, family life, or both. It is estimated that the prevalence of this phenomenon is between 1% and 2% of school-aged children.

Next to consider is what might be prompting or underlying the behavior. A comprehensive evaluation approach should include consideration of environmental factors such as bullying and learning difficulties, as well as presence of an anxiety or depressive disorder. Awareness of whether the child/adolescent has a 504 plan or individualized education program (IEP) is vital, as these can be marshaled for additional support. Family factors, including parental illness (medical and/or psychiatric), should also be considered. As school avoidance behaviors often include somatic symptoms of anxiety such as palpitations, shortness of breath, and abdominal pain; a rule out of medical etiology is recommended, as well as a caution to consider both medical and behavioral factors simultaneously, as focus on either separately can lead to missing the other.

Separation anxiety and social anxiety disorders are two specific conditions that may manifest in school refusal and should be evaluated for specifically. Separation anxiety is characterized by developmentally inappropriate, excessive worry or distress associated with separation from a primary caregiver or major attachment figure. Social anxiety is characterized by excessive fear or worry about being negatively evaluated by others in social situations.³ One publicly available tool that can be helpful for screening for a variety of anxiety disorders in children and adolescents is the SCARED.⁴ The PHQ-9 Adolescent⁵ is one such screening instrument for depression, which can be a driving factor or co-occur in children with school refusal.

When it comes to treatment, the best evidence out there is for a cognitive-behavioral therapy (CBT)–based approach motivated toward a return to the school setting as soon as possible.^6,7 This will involve looking at how thoughts, behaviors, and feelings are interacting with each other in the clinical scenario and how these might be challenged or changed in a positive manner. Coping and problem-solving skills are often incorporated. This approach may also involve gradual exposure to the anxiety-producing situation in a hierarchical fashion starting with less anxiety-provoking scenarios and moving toward increasingly challenging ones. CBT for school refusal is likely most effective when including both school and family involvement to ensure consistency across settings. Making sure that there are not inadvertent reinforcing factors motivating staying home (for instance unrestricted access to electronic devices) is an important step to consider. If anxiety or depression is moderately to severely impairing – which is frequently the case when school refusal comes to clinical attention, consider use of medication as part of the treatment strategy. Selective serotonin reuptake inhibitors as a class are the most commonly used medications and deserve strong consideration.

To summarize, school refusal can occur for a variety of reasons. Early identification and comprehensive treatment taking into account child and family preference and using a multimodal approach to encourage and support a quick return to the school environment is considered best practice.
 

Dr. Hoffnung is a pediatric psychiatrist at the University of Vermont Children’s Hospital and an assistant professor of psychiatry at the Robert Larner, M.D. College of Medicine at the University of Vermont, both in Burlington. He has no relevant financial disclosures. Email him at [email protected].

References

1. See, for example: www.npr.org/2021/03/08/971457441/as-many-parents-fret-over-remote-learning-some-find-their-kids-are-thriving.

2. Kearney CA. Educ Psychol Rev. 2008;20:257-82.

3. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, Va.: American Psychiatric Association, 2013.

4. Available at: www.pediatricbipolar.pitt.edu/resources/instruments.

5. Available at: www.aacap.org/App_Themes/AACAP/docs/member_resources/toolbox_for_clinical_practice_and_outcomes/symptoms/GLAD-PC_PHQ-9.pdf.

6. Elliott JG and Place M. J Child Psychol Psychiatry. 2019;60(1):4-15.

7. Prabhuswamy M. J Paed Child Health. 2018;54(10):1117-20.

New analyses of both observational and genetic data have provided “convincing evidence” that type 2 diabetes is associated with an increased risk for Parkinson’s disease.

“The fact that we see the same effects in both types of analysis separately makes it more likely that these results are real – that type 2 diabetes really is a driver of Parkinson’s disease risk,” Alastair Noyce, PhD, senior author of the new studies, said in an interview.

The two analyses are reported in one paper published online March 8 in the journal Movement Disorders.

Dr. Noyce, clinical senior lecturer in the preventive neurology unit at the Wolfson Institute of Preventive Medicine, Queen Mary University of London, explained that his group is interested in risk factors for Parkinson’s disease, particularly those relevant at the population level and which might be modifiable.

“Several studies have looked at diabetes as a risk factor for Parkinson’s but very few have focused on type 2 diabetes, and, as this is such a growing health issue, we wanted to look at that in more detail,” he said.

The researchers performed two different analyses: a meta-analysis of observational studies investigating an association between type 2 diabetes and Parkinson’s; and a separate Mendelian randomization analysis of genetic data on the two conditions.

They found similar results in both studies, with the observational data suggesting type 2 diabetes was associated with a 21% increased risk for Parkinson’s disease and the genetic data suggesting an 8% increased risk. There were also hints that type 2 diabetes might also be associated with faster progression of Parkinson’s symptoms.

“I don’t think type 2 diabetes is a major cause of Parkinson’s, but it probably makes some contribution and may increase the risk of a more aggressive form of the condition,” Dr. Noyce said.

“I would say the increased risk of Parkinson’s disease attributable to type 2 diabetes may be similar to that of head injury or pesticide exposure, but it is important, as type 2 diabetes is very prevalent and is increasing,” he added.  “As we see the growth in type 2 diabetes, this could lead to a later increase in Parkinson’s, which is already one of the fastest-growing diseases worldwide.”

For the meta-analysis of observational data, the researchers included nine studies that investigated preceding type 2 diabetes specifically and its effect on the risk for Parkinson’s disease and progression.

The pooled effect estimates showed that type 2 diabetes was associated with an increased risk for Parkinson’s disease (odds ratio, 1.21; 95% confidence interval, 1.07-1.36), and there was some evidence that type 2 diabetes was associated with faster progression of motor symptoms (standardized mean difference [SMD], 0.55) and cognitive decline (SMD, −0.92).

The observational meta-analysis included seven cohort studies and two case-control studies, and these different types of studies showed different results in regard to the association between diabetes and Parkinson’s. While the cohort studies showed a detrimental effect of diabetes on Parkinson’s risk (OR, 1.29), the case-control studies suggested protective effect (OR, 0.51). 

Addressing this, Dr. Noyce noted that the case-control studies may be less reliable as they suffered more from survivor bias. “Diabetes may cause deaths in mid-life before people go on to develop Parkinson’s, and this would cause a protective effect to be seen, but we believe this to be a spurious result. Cohort studies are generally more reliable and are less susceptible to survivor bias,” he said.  

For the genetic analysis, the researchers combined results from two large publicly available genome-wide association studies – one for type 2 diabetes and one for Parkinson’s disease to assess whether individuals with a genetic tendency to type 2 diabetes had a higher risk of developing Parkinson’s.

Results showed an increased risk for Parkinson’s in those individuals with genetic variants associated with type 2 diabetes, with an odds ratio of 1.08 (P = .010). There was also some evidence of an effect on motor progression (OR, 1.10; P = .032) but not on cognitive progression.

On the possible mechanism behind this observation, Dr. Noyce noted type 2 diabetes and Parkinson’s have some similarities in biology, including abnormal protein aggregation.

In the study, the authors also suggest that circulating insulin may have a neuroprotective role, whereas systemic and local insulin resistance can influence pathways known to be important in Parkinson’s pathogenesis, including those that relate to mitochondrial dysfunction, neuroinflammation, synaptic plasticity, and mitochondrial dysfunction.

Dr. Noyce further pointed out that several drugs used for the treatment of type 2 diabetes have been repurposed as possible treatments for Parkinson’s disease and are now being tested for this new indication. “Our results support that approach and raise the idea that some of these drugs may even prevent Parkinson’s in people at risk,” he said.  

Most people who have type 2 diabetes won’t get Parkinson’s disease, he added. Other outcomes such as heart disease, kidney disease, and microvascular complications are far more likely, and the main aim of preventing and treating type 2 diabetes is to prevent these far more common outcomes. “But our data suggests that this could also have a possible benefit in reducing future Parkinson’s risk,” he said.  

Not on the horizon at present is the possibility of screening patients with type 2 diabetes for signs of early Parkinson’s, Dr. Noyce said.

“There isn’t a test for identifying presymptomatic neurodegenerative diseases such as Parkinson’s yet, but perhaps in the future there will be, and type 2 diabetes may be one risk factor to take into account when considering such screening,” he added.

This work was financially supported by grants from The Michael J. Fox Foundation; the Canadian Consortium on Neurodegeneration in Aging (CCNA); the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) initiative; and Parkinson Canada, and the Intramural Research Program of the NIH, National Institute on Aging.

Dr. Noyce reports grants from the Barts Charity, Parkinson’s UK, Aligning Science Across Parkinson’s and Michael J. Fox Foundation, and the Virginia Keiley Benefaction; and personal fees/honoraria from Britannia, BIAL, AbbVie, Global Kinetics Corporation, Profile, Biogen, Roche, and UCB outside of the submitted work.

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

New analyses of both observational and genetic data have provided “convincing evidence” that type 2 diabetes is associated with an increased risk for Parkinson’s disease.

“The fact that we see the same effects in both types of analysis separately makes it more likely that these results are real – that type 2 diabetes really is a driver of Parkinson’s disease risk,” Alastair Noyce, PhD, senior author of the new studies, said in an interview.

The two analyses are reported in one paper published online March 8 in the journal Movement Disorders.

Dr. Noyce, clinical senior lecturer in the preventive neurology unit at the Wolfson Institute of Preventive Medicine, Queen Mary University of London, explained that his group is interested in risk factors for Parkinson’s disease, particularly those relevant at the population level and which might be modifiable.

“Several studies have looked at diabetes as a risk factor for Parkinson’s but very few have focused on type 2 diabetes, and, as this is such a growing health issue, we wanted to look at that in more detail,” he said.

The researchers performed two different analyses: a meta-analysis of observational studies investigating an association between type 2 diabetes and Parkinson’s; and a separate Mendelian randomization analysis of genetic data on the two conditions.

They found similar results in both studies, with the observational data suggesting type 2 diabetes was associated with a 21% increased risk for Parkinson’s disease and the genetic data suggesting an 8% increased risk. There were also hints that type 2 diabetes might also be associated with faster progression of Parkinson’s symptoms.

“I don’t think type 2 diabetes is a major cause of Parkinson’s, but it probably makes some contribution and may increase the risk of a more aggressive form of the condition,” Dr. Noyce said.

“I would say the increased risk of Parkinson’s disease attributable to type 2 diabetes may be similar to that of head injury or pesticide exposure, but it is important, as type 2 diabetes is very prevalent and is increasing,” he added.  “As we see the growth in type 2 diabetes, this could lead to a later increase in Parkinson’s, which is already one of the fastest-growing diseases worldwide.”

For the meta-analysis of observational data, the researchers included nine studies that investigated preceding type 2 diabetes specifically and its effect on the risk for Parkinson’s disease and progression.

The pooled effect estimates showed that type 2 diabetes was associated with an increased risk for Parkinson’s disease (odds ratio, 1.21; 95% confidence interval, 1.07-1.36), and there was some evidence that type 2 diabetes was associated with faster progression of motor symptoms (standardized mean difference [SMD], 0.55) and cognitive decline (SMD, −0.92).

The observational meta-analysis included seven cohort studies and two case-control studies, and these different types of studies showed different results in regard to the association between diabetes and Parkinson’s. While the cohort studies showed a detrimental effect of diabetes on Parkinson’s risk (OR, 1.29), the case-control studies suggested protective effect (OR, 0.51). 

Addressing this, Dr. Noyce noted that the case-control studies may be less reliable as they suffered more from survivor bias. “Diabetes may cause deaths in mid-life before people go on to develop Parkinson’s, and this would cause a protective effect to be seen, but we believe this to be a spurious result. Cohort studies are generally more reliable and are less susceptible to survivor bias,” he said.  

For the genetic analysis, the researchers combined results from two large publicly available genome-wide association studies – one for type 2 diabetes and one for Parkinson’s disease to assess whether individuals with a genetic tendency to type 2 diabetes had a higher risk of developing Parkinson’s.

Results showed an increased risk for Parkinson’s in those individuals with genetic variants associated with type 2 diabetes, with an odds ratio of 1.08 (P = .010). There was also some evidence of an effect on motor progression (OR, 1.10; P = .032) but not on cognitive progression.

On the possible mechanism behind this observation, Dr. Noyce noted type 2 diabetes and Parkinson’s have some similarities in biology, including abnormal protein aggregation.

In the study, the authors also suggest that circulating insulin may have a neuroprotective role, whereas systemic and local insulin resistance can influence pathways known to be important in Parkinson’s pathogenesis, including those that relate to mitochondrial dysfunction, neuroinflammation, synaptic plasticity, and mitochondrial dysfunction.

Dr. Noyce further pointed out that several drugs used for the treatment of type 2 diabetes have been repurposed as possible treatments for Parkinson’s disease and are now being tested for this new indication. “Our results support that approach and raise the idea that some of these drugs may even prevent Parkinson’s in people at risk,” he said.  

Most people who have type 2 diabetes won’t get Parkinson’s disease, he added. Other outcomes such as heart disease, kidney disease, and microvascular complications are far more likely, and the main aim of preventing and treating type 2 diabetes is to prevent these far more common outcomes. “But our data suggests that this could also have a possible benefit in reducing future Parkinson’s risk,” he said.  

Not on the horizon at present is the possibility of screening patients with type 2 diabetes for signs of early Parkinson’s, Dr. Noyce said.

“There isn’t a test for identifying presymptomatic neurodegenerative diseases such as Parkinson’s yet, but perhaps in the future there will be, and type 2 diabetes may be one risk factor to take into account when considering such screening,” he added.

This work was financially supported by grants from The Michael J. Fox Foundation; the Canadian Consortium on Neurodegeneration in Aging (CCNA); the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) initiative; and Parkinson Canada, and the Intramural Research Program of the NIH, National Institute on Aging.

Dr. Noyce reports grants from the Barts Charity, Parkinson’s UK, Aligning Science Across Parkinson’s and Michael J. Fox Foundation, and the Virginia Keiley Benefaction; and personal fees/honoraria from Britannia, BIAL, AbbVie, Global Kinetics Corporation, Profile, Biogen, Roche, and UCB outside of the submitted work.

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

New analyses of both observational and genetic data have provided “convincing evidence” that type 2 diabetes is associated with an increased risk for Parkinson’s disease.

“The fact that we see the same effects in both types of analysis separately makes it more likely that these results are real – that type 2 diabetes really is a driver of Parkinson’s disease risk,” Alastair Noyce, PhD, senior author of the new studies, said in an interview.

The two analyses are reported in one paper published online March 8 in the journal Movement Disorders.

Dr. Noyce, clinical senior lecturer in the preventive neurology unit at the Wolfson Institute of Preventive Medicine, Queen Mary University of London, explained that his group is interested in risk factors for Parkinson’s disease, particularly those relevant at the population level and which might be modifiable.

“Several studies have looked at diabetes as a risk factor for Parkinson’s but very few have focused on type 2 diabetes, and, as this is such a growing health issue, we wanted to look at that in more detail,” he said.

The researchers performed two different analyses: a meta-analysis of observational studies investigating an association between type 2 diabetes and Parkinson’s; and a separate Mendelian randomization analysis of genetic data on the two conditions.

They found similar results in both studies, with the observational data suggesting type 2 diabetes was associated with a 21% increased risk for Parkinson’s disease and the genetic data suggesting an 8% increased risk. There were also hints that type 2 diabetes might also be associated with faster progression of Parkinson’s symptoms.

“I don’t think type 2 diabetes is a major cause of Parkinson’s, but it probably makes some contribution and may increase the risk of a more aggressive form of the condition,” Dr. Noyce said.

“I would say the increased risk of Parkinson’s disease attributable to type 2 diabetes may be similar to that of head injury or pesticide exposure, but it is important, as type 2 diabetes is very prevalent and is increasing,” he added.  “As we see the growth in type 2 diabetes, this could lead to a later increase in Parkinson’s, which is already one of the fastest-growing diseases worldwide.”

For the meta-analysis of observational data, the researchers included nine studies that investigated preceding type 2 diabetes specifically and its effect on the risk for Parkinson’s disease and progression.

The pooled effect estimates showed that type 2 diabetes was associated with an increased risk for Parkinson’s disease (odds ratio, 1.21; 95% confidence interval, 1.07-1.36), and there was some evidence that type 2 diabetes was associated with faster progression of motor symptoms (standardized mean difference [SMD], 0.55) and cognitive decline (SMD, −0.92).

The observational meta-analysis included seven cohort studies and two case-control studies, and these different types of studies showed different results in regard to the association between diabetes and Parkinson’s. While the cohort studies showed a detrimental effect of diabetes on Parkinson’s risk (OR, 1.29), the case-control studies suggested protective effect (OR, 0.51). 

Addressing this, Dr. Noyce noted that the case-control studies may be less reliable as they suffered more from survivor bias. “Diabetes may cause deaths in mid-life before people go on to develop Parkinson’s, and this would cause a protective effect to be seen, but we believe this to be a spurious result. Cohort studies are generally more reliable and are less susceptible to survivor bias,” he said.  

For the genetic analysis, the researchers combined results from two large publicly available genome-wide association studies – one for type 2 diabetes and one for Parkinson’s disease to assess whether individuals with a genetic tendency to type 2 diabetes had a higher risk of developing Parkinson’s.

Results showed an increased risk for Parkinson’s in those individuals with genetic variants associated with type 2 diabetes, with an odds ratio of 1.08 (P = .010). There was also some evidence of an effect on motor progression (OR, 1.10; P = .032) but not on cognitive progression.

On the possible mechanism behind this observation, Dr. Noyce noted type 2 diabetes and Parkinson’s have some similarities in biology, including abnormal protein aggregation.

In the study, the authors also suggest that circulating insulin may have a neuroprotective role, whereas systemic and local insulin resistance can influence pathways known to be important in Parkinson’s pathogenesis, including those that relate to mitochondrial dysfunction, neuroinflammation, synaptic plasticity, and mitochondrial dysfunction.

Dr. Noyce further pointed out that several drugs used for the treatment of type 2 diabetes have been repurposed as possible treatments for Parkinson’s disease and are now being tested for this new indication. “Our results support that approach and raise the idea that some of these drugs may even prevent Parkinson’s in people at risk,” he said.  

Most people who have type 2 diabetes won’t get Parkinson’s disease, he added. Other outcomes such as heart disease, kidney disease, and microvascular complications are far more likely, and the main aim of preventing and treating type 2 diabetes is to prevent these far more common outcomes. “But our data suggests that this could also have a possible benefit in reducing future Parkinson’s risk,” he said.  

Not on the horizon at present is the possibility of screening patients with type 2 diabetes for signs of early Parkinson’s, Dr. Noyce said.

“There isn’t a test for identifying presymptomatic neurodegenerative diseases such as Parkinson’s yet, but perhaps in the future there will be, and type 2 diabetes may be one risk factor to take into account when considering such screening,” he added.

This work was financially supported by grants from The Michael J. Fox Foundation; the Canadian Consortium on Neurodegeneration in Aging (CCNA); the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) initiative; and Parkinson Canada, and the Intramural Research Program of the NIH, National Institute on Aging.

Dr. Noyce reports grants from the Barts Charity, Parkinson’s UK, Aligning Science Across Parkinson’s and Michael J. Fox Foundation, and the Virginia Keiley Benefaction; and personal fees/honoraria from Britannia, BIAL, AbbVie, Global Kinetics Corporation, Profile, Biogen, Roche, and UCB outside of the submitted work.

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

Congratulations, you’ve been vaccinated!

It’s been a year like no other, and outpatient psychiatrists turned to Zoom and other telemental health platforms to provide treatment for our patients. Offices sit empty as the dust lands and the plants wilt. Perhaps a few patients are seen in person, masked and carefully distanced, after health screening and temperature checks, with surfaces sanitized between visits, all in accordance with health department regulations. But now the vaccine offers both safety and the promise of a return to a new normal, one that is certain to look different from the normal that was left behind.

Courtesy CDC

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Congratulations, you’ve been vaccinated!

It’s been a year like no other, and outpatient psychiatrists turned to Zoom and other telemental health platforms to provide treatment for our patients. Offices sit empty as the dust lands and the plants wilt. Perhaps a few patients are seen in person, masked and carefully distanced, after health screening and temperature checks, with surfaces sanitized between visits, all in accordance with health department regulations. But now the vaccine offers both safety and the promise of a return to a new normal, one that is certain to look different from the normal that was left behind.

Courtesy CDC

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Congratulations, you’ve been vaccinated!

It’s been a year like no other, and outpatient psychiatrists turned to Zoom and other telemental health platforms to provide treatment for our patients. Offices sit empty as the dust lands and the plants wilt. Perhaps a few patients are seen in person, masked and carefully distanced, after health screening and temperature checks, with surfaces sanitized between visits, all in accordance with health department regulations. But now the vaccine offers both safety and the promise of a return to a new normal, one that is certain to look different from the normal that was left behind.

Courtesy CDC

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Medicare payments for branded neurologic drugs jumped 50% over a 5-year period, while claims for these medications increased by just 8%, new research shows. Results of the retrospective study also showed that most of the increased costs for these agents were due to rising costs for neuroimmunology drugs, mainly for those used to treat multiple sclerosis (MS).

“The same brand name medication in 2017 cost approximately 50% more than in 2013,” said Adam de Havenon, MD, assistant professor of neurology, University of Utah, Salt Lake City.

“An analogy would be if you bought an iPhone 5 in 2013 for $500, and then in 2017, you were asked to pay $750 for the exact same iPhone 5,” Dr. de Havenon added.

The study findings were published online March 10 in the journal Neurology.
 

$26 billion in payments

Both neurologists and patients are concerned about the high cost of prescription drugs for neurologic diseases, and Medicare Part D data indicate that these drugs are the most expensive component of neurologic care, the researchers noted. In addition, out-of-pocket costs have increased significantly for patients with neurologic disease such as Parkinson’s disease, epilepsy, and MS.

To understand trends in payments for neurologic drugs, Dr. de Havenon and colleagues analyzed Medicare Part D claims filed from 2013 to 2017. The payments include costs paid by Medicare, the patient, government subsidies, and other third-party payers.

In addition to examining more current Medicare Part D data than previous studies, the current analysis examined all medications prescribed by neurologists that consistently remained branded or generic during the 5-year study period, said Dr. de Havenon. This approach resulted in a large number of claims and a large total cost.

To calculate the percentage change in annual payment claims, the researchers used 2013 prices as a reference point. They identified drugs named in 2013 claims and classified them as generic, brand-name only, or brand-name with generic equivalent. Researchers also divided the drugs by neurologic subspecialty.

The analysis included 520 drugs, all of which were available in each year of the study period. Of these drugs, 322 were generic, 61 were brand-name only, and 137 were brand-name with a generic equivalent. There were 90.7 million total claims.

Results showed total payments amounted to $26.65 billion. Yearly total payments increased from $4.05 billion in 2013 to $6.09 billion in 2017, representing a 50.4% increase, even after adjusting for inflation. Total claims increased by 7.6% – from 17.1 million in 2013 to 18.4 million in 2017.

From 2013 to 2017, claim payments increased by 0.6% for generic drugs, 42.4% for brand-name only drugs, and 45% for brand-name drugs with generic equivalents. The proportion of claims increased from 81.9% to 88% for generic drugs and from 4.9% to 6.2% for brand-name only drugs.

However, the proportion of claims for brand-name drugs with generic equivalents decreased from 13.3% to 5.8%.
 

Treatment barrier

Neuroimmunologic drugs, most of which were prescribed for MS, had exceptional cost, the researchers noted. These drugs accounted for more than 50% of payments but only 4.3% of claims. Claim payment for these drugs increased by 46.9% during the study period, from $3,337 to $4,902.

When neuroimmunologic drugs were removed from the analysis there was still significant increase in claim payments for brand-name only drugs (50.4%) and brand-name drugs with generic equivalents (45.6%).

Although neuroimmunologic medicines, including monoclonal antibodies, are more expensive to produce, this factor alone does not explain their exceptional cost, said Dr. de Havenon. “The high cost of brand-name drugs in this speciality is likely because the market bears it,” he added. “In other words, MS is a disabling disease and the medications work, so historically the Centers for Medicare & Medicaid Services have been willing to tolerate the high cost of these primarily brand-name medications.”

Several countries have controlled drug costs by negotiating with pharmaceutical companies and through legislation, Dr. de Havenon noted.

“My intent with this article was to raise awareness on the topic, which I struggle with frequently as a clinician. I know I want my patients to have a medication, but the cost prevents it,” he said.
 

‘Unfettered’ price-setting

Commenting on the findings, Robert J. Fox, MD, vice chair for research at the Neurological Institute of the Cleveland Clinic, said the study “brings into clear light” what neurologists, particularly those who treat MS, have long suspected but did not really know. These neurologists “are typically distanced from the payment aspects of the medications they prescribe,” said Dr. Fox, who was not involved with the research.

Although a particular strength of the study was its comprehensiveness, the researchers excluded infusion claims – which account for a large portion of total patient care costs for many disorders, he noted.

Drugs for MS historically have been expensive, ostensibly because of their high cost of development. In addition, the large and continued price increase that occurs long after these drugs have been approved remains unexplained, said Dr. Fox.

He noted that the study findings might not directly affect clinical practice because neurologists will continue prescribing medications they think are best for their patients. “Instead, I think this is a lesson to lawmakers about the massive error in the Medicare Modernization Act of 2003, where the federal government was prohibited from negotiating drug prices. If the seller is unfettered in setting a price, then no one should be surprised when the price rises,” Dr. Fox said.

Because many new drugs and new generic formulations for treating MS have become available during the past year, “repeating these types of economic studies for the period 2020-2025 will help us understand if generic competition – as well as new laws if they are passed – alter price,” he concluded.

The study was funded by the American Academy of Neurology, which publishes Neurology. Dr. de Havenon has received clinical research funding from AMAG Pharmaceuticals and Regeneron Pharmaceuticals. Dr. Fox receives consulting fees from many pharmaceutical companies involved in the development of therapies for MS.

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

Medicare payments for branded neurologic drugs jumped 50% over a 5-year period, while claims for these medications increased by just 8%, new research shows. Results of the retrospective study also showed that most of the increased costs for these agents were due to rising costs for neuroimmunology drugs, mainly for those used to treat multiple sclerosis (MS).

“The same brand name medication in 2017 cost approximately 50% more than in 2013,” said Adam de Havenon, MD, assistant professor of neurology, University of Utah, Salt Lake City.

“An analogy would be if you bought an iPhone 5 in 2013 for $500, and then in 2017, you were asked to pay $750 for the exact same iPhone 5,” Dr. de Havenon added.

The study findings were published online March 10 in the journal Neurology.
 

$26 billion in payments

Both neurologists and patients are concerned about the high cost of prescription drugs for neurologic diseases, and Medicare Part D data indicate that these drugs are the most expensive component of neurologic care, the researchers noted. In addition, out-of-pocket costs have increased significantly for patients with neurologic disease such as Parkinson’s disease, epilepsy, and MS.

To understand trends in payments for neurologic drugs, Dr. de Havenon and colleagues analyzed Medicare Part D claims filed from 2013 to 2017. The payments include costs paid by Medicare, the patient, government subsidies, and other third-party payers.

In addition to examining more current Medicare Part D data than previous studies, the current analysis examined all medications prescribed by neurologists that consistently remained branded or generic during the 5-year study period, said Dr. de Havenon. This approach resulted in a large number of claims and a large total cost.

To calculate the percentage change in annual payment claims, the researchers used 2013 prices as a reference point. They identified drugs named in 2013 claims and classified them as generic, brand-name only, or brand-name with generic equivalent. Researchers also divided the drugs by neurologic subspecialty.

The analysis included 520 drugs, all of which were available in each year of the study period. Of these drugs, 322 were generic, 61 were brand-name only, and 137 were brand-name with a generic equivalent. There were 90.7 million total claims.

Results showed total payments amounted to $26.65 billion. Yearly total payments increased from $4.05 billion in 2013 to $6.09 billion in 2017, representing a 50.4% increase, even after adjusting for inflation. Total claims increased by 7.6% – from 17.1 million in 2013 to 18.4 million in 2017.

From 2013 to 2017, claim payments increased by 0.6% for generic drugs, 42.4% for brand-name only drugs, and 45% for brand-name drugs with generic equivalents. The proportion of claims increased from 81.9% to 88% for generic drugs and from 4.9% to 6.2% for brand-name only drugs.

However, the proportion of claims for brand-name drugs with generic equivalents decreased from 13.3% to 5.8%.
 

Treatment barrier

Neuroimmunologic drugs, most of which were prescribed for MS, had exceptional cost, the researchers noted. These drugs accounted for more than 50% of payments but only 4.3% of claims. Claim payment for these drugs increased by 46.9% during the study period, from $3,337 to $4,902.

When neuroimmunologic drugs were removed from the analysis there was still significant increase in claim payments for brand-name only drugs (50.4%) and brand-name drugs with generic equivalents (45.6%).

Although neuroimmunologic medicines, including monoclonal antibodies, are more expensive to produce, this factor alone does not explain their exceptional cost, said Dr. de Havenon. “The high cost of brand-name drugs in this speciality is likely because the market bears it,” he added. “In other words, MS is a disabling disease and the medications work, so historically the Centers for Medicare & Medicaid Services have been willing to tolerate the high cost of these primarily brand-name medications.”

Several countries have controlled drug costs by negotiating with pharmaceutical companies and through legislation, Dr. de Havenon noted.

“My intent with this article was to raise awareness on the topic, which I struggle with frequently as a clinician. I know I want my patients to have a medication, but the cost prevents it,” he said.
 

‘Unfettered’ price-setting

Commenting on the findings, Robert J. Fox, MD, vice chair for research at the Neurological Institute of the Cleveland Clinic, said the study “brings into clear light” what neurologists, particularly those who treat MS, have long suspected but did not really know. These neurologists “are typically distanced from the payment aspects of the medications they prescribe,” said Dr. Fox, who was not involved with the research.

Although a particular strength of the study was its comprehensiveness, the researchers excluded infusion claims – which account for a large portion of total patient care costs for many disorders, he noted.

Drugs for MS historically have been expensive, ostensibly because of their high cost of development. In addition, the large and continued price increase that occurs long after these drugs have been approved remains unexplained, said Dr. Fox.

He noted that the study findings might not directly affect clinical practice because neurologists will continue prescribing medications they think are best for their patients. “Instead, I think this is a lesson to lawmakers about the massive error in the Medicare Modernization Act of 2003, where the federal government was prohibited from negotiating drug prices. If the seller is unfettered in setting a price, then no one should be surprised when the price rises,” Dr. Fox said.

Because many new drugs and new generic formulations for treating MS have become available during the past year, “repeating these types of economic studies for the period 2020-2025 will help us understand if generic competition – as well as new laws if they are passed – alter price,” he concluded.

The study was funded by the American Academy of Neurology, which publishes Neurology. Dr. de Havenon has received clinical research funding from AMAG Pharmaceuticals and Regeneron Pharmaceuticals. Dr. Fox receives consulting fees from many pharmaceutical companies involved in the development of therapies for MS.

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

Medicare payments for branded neurologic drugs jumped 50% over a 5-year period, while claims for these medications increased by just 8%, new research shows. Results of the retrospective study also showed that most of the increased costs for these agents were due to rising costs for neuroimmunology drugs, mainly for those used to treat multiple sclerosis (MS).

“The same brand name medication in 2017 cost approximately 50% more than in 2013,” said Adam de Havenon, MD, assistant professor of neurology, University of Utah, Salt Lake City.

“An analogy would be if you bought an iPhone 5 in 2013 for $500, and then in 2017, you were asked to pay $750 for the exact same iPhone 5,” Dr. de Havenon added.

The study findings were published online March 10 in the journal Neurology.
 

$26 billion in payments

Both neurologists and patients are concerned about the high cost of prescription drugs for neurologic diseases, and Medicare Part D data indicate that these drugs are the most expensive component of neurologic care, the researchers noted. In addition, out-of-pocket costs have increased significantly for patients with neurologic disease such as Parkinson’s disease, epilepsy, and MS.

To understand trends in payments for neurologic drugs, Dr. de Havenon and colleagues analyzed Medicare Part D claims filed from 2013 to 2017. The payments include costs paid by Medicare, the patient, government subsidies, and other third-party payers.

In addition to examining more current Medicare Part D data than previous studies, the current analysis examined all medications prescribed by neurologists that consistently remained branded or generic during the 5-year study period, said Dr. de Havenon. This approach resulted in a large number of claims and a large total cost.

To calculate the percentage change in annual payment claims, the researchers used 2013 prices as a reference point. They identified drugs named in 2013 claims and classified them as generic, brand-name only, or brand-name with generic equivalent. Researchers also divided the drugs by neurologic subspecialty.

The analysis included 520 drugs, all of which were available in each year of the study period. Of these drugs, 322 were generic, 61 were brand-name only, and 137 were brand-name with a generic equivalent. There were 90.7 million total claims.

Results showed total payments amounted to $26.65 billion. Yearly total payments increased from $4.05 billion in 2013 to $6.09 billion in 2017, representing a 50.4% increase, even after adjusting for inflation. Total claims increased by 7.6% – from 17.1 million in 2013 to 18.4 million in 2017.

From 2013 to 2017, claim payments increased by 0.6% for generic drugs, 42.4% for brand-name only drugs, and 45% for brand-name drugs with generic equivalents. The proportion of claims increased from 81.9% to 88% for generic drugs and from 4.9% to 6.2% for brand-name only drugs.

However, the proportion of claims for brand-name drugs with generic equivalents decreased from 13.3% to 5.8%.
 

Treatment barrier

Neuroimmunologic drugs, most of which were prescribed for MS, had exceptional cost, the researchers noted. These drugs accounted for more than 50% of payments but only 4.3% of claims. Claim payment for these drugs increased by 46.9% during the study period, from $3,337 to $4,902.

When neuroimmunologic drugs were removed from the analysis there was still significant increase in claim payments for brand-name only drugs (50.4%) and brand-name drugs with generic equivalents (45.6%).

Although neuroimmunologic medicines, including monoclonal antibodies, are more expensive to produce, this factor alone does not explain their exceptional cost, said Dr. de Havenon. “The high cost of brand-name drugs in this speciality is likely because the market bears it,” he added. “In other words, MS is a disabling disease and the medications work, so historically the Centers for Medicare & Medicaid Services have been willing to tolerate the high cost of these primarily brand-name medications.”

Several countries have controlled drug costs by negotiating with pharmaceutical companies and through legislation, Dr. de Havenon noted.

“My intent with this article was to raise awareness on the topic, which I struggle with frequently as a clinician. I know I want my patients to have a medication, but the cost prevents it,” he said.
 

‘Unfettered’ price-setting

Commenting on the findings, Robert J. Fox, MD, vice chair for research at the Neurological Institute of the Cleveland Clinic, said the study “brings into clear light” what neurologists, particularly those who treat MS, have long suspected but did not really know. These neurologists “are typically distanced from the payment aspects of the medications they prescribe,” said Dr. Fox, who was not involved with the research.

Although a particular strength of the study was its comprehensiveness, the researchers excluded infusion claims – which account for a large portion of total patient care costs for many disorders, he noted.

Drugs for MS historically have been expensive, ostensibly because of their high cost of development. In addition, the large and continued price increase that occurs long after these drugs have been approved remains unexplained, said Dr. Fox.

He noted that the study findings might not directly affect clinical practice because neurologists will continue prescribing medications they think are best for their patients. “Instead, I think this is a lesson to lawmakers about the massive error in the Medicare Modernization Act of 2003, where the federal government was prohibited from negotiating drug prices. If the seller is unfettered in setting a price, then no one should be surprised when the price rises,” Dr. Fox said.

Because many new drugs and new generic formulations for treating MS have become available during the past year, “repeating these types of economic studies for the period 2020-2025 will help us understand if generic competition – as well as new laws if they are passed – alter price,” he concluded.

The study was funded by the American Academy of Neurology, which publishes Neurology. Dr. de Havenon has received clinical research funding from AMAG Pharmaceuticals and Regeneron Pharmaceuticals. Dr. Fox receives consulting fees from many pharmaceutical companies involved in the development of therapies for MS.

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

Anthony Fauci, MD, says he’s concerned about how Americans will react once the coronavirus pandemic is brought under control, CBS News reports.

Courtesy American College of Chest Physicians

Noting that an American Psychological Association survey showed people reporting high stress levels because of the pandemic, CBS’s Norah O’Donnell asked if Dr. Fauci was concerned about a possible “mental health pandemic.”

“Very much so,” Dr. Fauci, director of the National Institute of Allergy and Infectious Diseases and a top White House coronavirus adviser, replied.

“That’s the reason why I want to get the virological aspect of this pandemic behind us as quickly as we possibly can because the long-term ravages of this are so multifaceted,” Dr. Fauci said.

Some of the problems could include prolonged physical symptoms and the economic effects of the pandemic, he said.

“And then the other things: Not only the mental health effects, but many people have put off routine types of medical examinations that they normally would have done,” Dr. Fauci said.

“I hope we don’t see an increase in some preventable situations that would not have happened if people had the normal access to medical care, which clearly was interrupted by the shutdown associated with COVID-19,” he added.

The American Psychological Association released the survey results March 11 in what many people consider the 1-year anniversary of the start of the coronavirus pandemic.

“The prolonged stress experienced by adults, especially the high levels of stress reported by Americans directly linked to the pandemic, is seriously affecting mental and physical health, including changes to weight, sleep and alcohol use,” the APA said in a news release.

Some of the key findings of the survey include:
 

• 61% of respondents reported experiencing undesired weight changes since the start of the pandemic.
• 67% said their sleep habits changed, with 35% saying they slept more and 31% less.
• 23% reported drinking more alcohol to cope with stress.
• 47% said they delayed or canceled health care services because of the pandemic.
• 48% said their stress levels had increased.

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

Anthony Fauci, MD, says he’s concerned about how Americans will react once the coronavirus pandemic is brought under control, CBS News reports.

Courtesy American College of Chest Physicians

Noting that an American Psychological Association survey showed people reporting high stress levels because of the pandemic, CBS’s Norah O’Donnell asked if Dr. Fauci was concerned about a possible “mental health pandemic.”

“Very much so,” Dr. Fauci, director of the National Institute of Allergy and Infectious Diseases and a top White House coronavirus adviser, replied.

“That’s the reason why I want to get the virological aspect of this pandemic behind us as quickly as we possibly can because the long-term ravages of this are so multifaceted,” Dr. Fauci said.

Some of the problems could include prolonged physical symptoms and the economic effects of the pandemic, he said.

“And then the other things: Not only the mental health effects, but many people have put off routine types of medical examinations that they normally would have done,” Dr. Fauci said.

“I hope we don’t see an increase in some preventable situations that would not have happened if people had the normal access to medical care, which clearly was interrupted by the shutdown associated with COVID-19,” he added.

The American Psychological Association released the survey results March 11 in what many people consider the 1-year anniversary of the start of the coronavirus pandemic.

“The prolonged stress experienced by adults, especially the high levels of stress reported by Americans directly linked to the pandemic, is seriously affecting mental and physical health, including changes to weight, sleep and alcohol use,” the APA said in a news release.

Some of the key findings of the survey include:
 

• 61% of respondents reported experiencing undesired weight changes since the start of the pandemic.
• 67% said their sleep habits changed, with 35% saying they slept more and 31% less.
• 23% reported drinking more alcohol to cope with stress.
• 47% said they delayed or canceled health care services because of the pandemic.
• 48% said their stress levels had increased.

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

Anthony Fauci, MD, says he’s concerned about how Americans will react once the coronavirus pandemic is brought under control, CBS News reports.

Courtesy American College of Chest Physicians

Noting that an American Psychological Association survey showed people reporting high stress levels because of the pandemic, CBS’s Norah O’Donnell asked if Dr. Fauci was concerned about a possible “mental health pandemic.”

“Very much so,” Dr. Fauci, director of the National Institute of Allergy and Infectious Diseases and a top White House coronavirus adviser, replied.

“That’s the reason why I want to get the virological aspect of this pandemic behind us as quickly as we possibly can because the long-term ravages of this are so multifaceted,” Dr. Fauci said.

Some of the problems could include prolonged physical symptoms and the economic effects of the pandemic, he said.

“And then the other things: Not only the mental health effects, but many people have put off routine types of medical examinations that they normally would have done,” Dr. Fauci said.

“I hope we don’t see an increase in some preventable situations that would not have happened if people had the normal access to medical care, which clearly was interrupted by the shutdown associated with COVID-19,” he added.

The American Psychological Association released the survey results March 11 in what many people consider the 1-year anniversary of the start of the coronavirus pandemic.

“The prolonged stress experienced by adults, especially the high levels of stress reported by Americans directly linked to the pandemic, is seriously affecting mental and physical health, including changes to weight, sleep and alcohol use,” the APA said in a news release.

Some of the key findings of the survey include:
 

• 61% of respondents reported experiencing undesired weight changes since the start of the pandemic.
• 67% said their sleep habits changed, with 35% saying they slept more and 31% less.
• 23% reported drinking more alcohol to cope with stress.
• 47% said they delayed or canceled health care services because of the pandemic.
• 48% said their stress levels had increased.

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

A significant proportion of community-dwelling older adults with dementia take three or more central nervous system medications despite guidelines that say to avoid this dangerous practice, new research suggests.

Investigators found that 14% of these individuals were receiving CNS-active polypharmacy, defined as combinations of multiple psychotropic and opioid medications taken for more than 30 days.

“For most patients, the risks of these medications, particularly in combination, are almost certainly greater than the potential benefits,” said Donovan Maust, MD, associate director of the geriatric psychiatry program, University of Michigan, Ann Arbor.

The study was published online March 9 in JAMA.
 

Serious risks

Memory impairment is the cardinal feature of dementia, but behavioral and psychological symptoms, which can include apathy, delusions, and agitation, are common during all stages of illness and cause significant caregiver distress, the researchers noted.

They noted that there is a dearth of high-quality evidence to support prescribing these medications in this patient population, yet “clinicians regularly prescribe psychotropic medications to community-dwelling persons with dementia in rates that far exceed use in the general older adult population.”

The Beers Criteria, from the American Geriatrics Society, advise against the practice of CNS polypharmacy because of the significant increase in risk for falls as well as impaired cognition, cardiac conduction abnormalities, respiratory suppression, and death when polypharmacy involves opioids.

They note that previous studies from Europe of polypharmacy for patients with dementia have not included antiepileptic medications or opioids, so the true extent of CNS-active polypharmacy may be “significantly” underestimated.

To determine the prevalence of polypharmacy with CNS-active medications among community-dwelling older adults with dementia, the researchers analyzed data on prescription fills for nearly 1.2 million community-dwelling Medicare patients with dementia.

The primary outcome was the prevalence of CNS-active polypharmacy in 2018. They defined CNS-active polypharmacy as exposure to three or more medications for more than 30 consecutive days from the following drug classes: antidepressants, antipsychotics, antiepileptics, benzodiazepines, nonbenzodiazepines, benzodiazepine receptor agonist hypnotics, and opioids.

They found that roughly one in seven (13.9%) patients met criteria for CNS-active polypharmacy. Of those receiving a CNS-active polypharmacy regimen, 57.8% had been doing so for longer than 180 days, and 6.8% had been doing so for a year. Nearly 30% of patients were exposed to five or more medications, and 5.2% were exposed to five or more medication classes.
 

Conservative approach warranted

Nearly all (92%) patients taking three or more CNS-active medications were taking an antidepressant, “consistent with their place as the psychotropic class most commonly prescribed both to older adults overall and those with dementia,” the investigators noted.

There is minimal high-quality evidence to support the efficacy of antidepressants for the treatment of depression for patients with dementia, they pointed out.

Nearly half (47%) of patients who were taking three or more CNS-active medications received at least one antipsychotic, most often quetiapine. Antipsychotics are not approved for people with dementia but are often prescribed off label for agitation, anxiety, and sleep problems, the researchers noted.

Nearly two thirds (62%) of patients with dementia who were taking three or more CNS drugs were taking an antiepileptic (most commonly, gabapentin); 41%, benzodiazepines; 32%, opioids; and 6%, Z-drugs.

The most common polypharmacy class combination included at least one antidepressant, one antiepileptic, and one antipsychotic. These accounted for 12.9% of polypharmacy days.

Despite limited high-quality evidence of efficacy, the prescribing of psychotropic medications and opioids is “pervasive” for adults with dementia in the United States, the investigators noted.

“Especially given that older adults with dementia might not be able to convey side effects they are experiencing, I think clinicians should be more conservative in how they are prescribing these medications and skeptical about the potential for benefit,” said Dr. Maust.

Regarding study limitations, the researchers noted that prescription medication claims may have led to an overestimation of the exposure to polypharmacy, insofar as the prescriptions may have been filled but not taken or were taken only on an as-needed basis.

In addition, the investigators were unable to determine the appropriateness of the particular combinations used or to examine the specific harms associated with CNS-active polypharmacy.
 

A major clinical challenge

Weighing in on the results, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study is important because polypharmacy is one of the “geriatric giants, and the question is, what do you do about it?”

Dr. Fillit said it is important to conduct a careful medication review for all older patients, “making sure that the use of each drug is appropriate. The most important thing is to define what is the appropriate utilization of these kinds of drugs. That goes for both overutilization or misuse of these drugs and underutilization, where people are undertreated for symptoms that can’t be managed by behavioral management, for example,” Dr. Fillit said.

Dr. Fillit also said the finding that about 14% of dementia patients were receiving three or more of these drugs “may not be an outrageous number, because these patients, especially as they get into moderate and severe stages of disease, can be incredibly difficult to manage.

“Very often, dementia patients have depression, and up to 90% will have agitation and even psychosis during the course of dementia. And many of these patients need these types of drugs,” said Dr. Fillit.

Echoing the authors, Dr. Fillit said a key limitation of the study is not knowing whether the prescribing was appropriate or not.

The study was supported by a grant from the National Institute on Aging. Dr. Maust and Dr. Fillit have disclosed no relevant financial relationships.

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

A significant proportion of community-dwelling older adults with dementia take three or more central nervous system medications despite guidelines that say to avoid this dangerous practice, new research suggests.

Investigators found that 14% of these individuals were receiving CNS-active polypharmacy, defined as combinations of multiple psychotropic and opioid medications taken for more than 30 days.

“For most patients, the risks of these medications, particularly in combination, are almost certainly greater than the potential benefits,” said Donovan Maust, MD, associate director of the geriatric psychiatry program, University of Michigan, Ann Arbor.

The study was published online March 9 in JAMA.
 

Serious risks

Memory impairment is the cardinal feature of dementia, but behavioral and psychological symptoms, which can include apathy, delusions, and agitation, are common during all stages of illness and cause significant caregiver distress, the researchers noted.

They noted that there is a dearth of high-quality evidence to support prescribing these medications in this patient population, yet “clinicians regularly prescribe psychotropic medications to community-dwelling persons with dementia in rates that far exceed use in the general older adult population.”

The Beers Criteria, from the American Geriatrics Society, advise against the practice of CNS polypharmacy because of the significant increase in risk for falls as well as impaired cognition, cardiac conduction abnormalities, respiratory suppression, and death when polypharmacy involves opioids.

They note that previous studies from Europe of polypharmacy for patients with dementia have not included antiepileptic medications or opioids, so the true extent of CNS-active polypharmacy may be “significantly” underestimated.

To determine the prevalence of polypharmacy with CNS-active medications among community-dwelling older adults with dementia, the researchers analyzed data on prescription fills for nearly 1.2 million community-dwelling Medicare patients with dementia.

The primary outcome was the prevalence of CNS-active polypharmacy in 2018. They defined CNS-active polypharmacy as exposure to three or more medications for more than 30 consecutive days from the following drug classes: antidepressants, antipsychotics, antiepileptics, benzodiazepines, nonbenzodiazepines, benzodiazepine receptor agonist hypnotics, and opioids.

They found that roughly one in seven (13.9%) patients met criteria for CNS-active polypharmacy. Of those receiving a CNS-active polypharmacy regimen, 57.8% had been doing so for longer than 180 days, and 6.8% had been doing so for a year. Nearly 30% of patients were exposed to five or more medications, and 5.2% were exposed to five or more medication classes.
 

Conservative approach warranted

Nearly all (92%) patients taking three or more CNS-active medications were taking an antidepressant, “consistent with their place as the psychotropic class most commonly prescribed both to older adults overall and those with dementia,” the investigators noted.

There is minimal high-quality evidence to support the efficacy of antidepressants for the treatment of depression for patients with dementia, they pointed out.

Nearly half (47%) of patients who were taking three or more CNS-active medications received at least one antipsychotic, most often quetiapine. Antipsychotics are not approved for people with dementia but are often prescribed off label for agitation, anxiety, and sleep problems, the researchers noted.

Nearly two thirds (62%) of patients with dementia who were taking three or more CNS drugs were taking an antiepileptic (most commonly, gabapentin); 41%, benzodiazepines; 32%, opioids; and 6%, Z-drugs.

The most common polypharmacy class combination included at least one antidepressant, one antiepileptic, and one antipsychotic. These accounted for 12.9% of polypharmacy days.

Despite limited high-quality evidence of efficacy, the prescribing of psychotropic medications and opioids is “pervasive” for adults with dementia in the United States, the investigators noted.

“Especially given that older adults with dementia might not be able to convey side effects they are experiencing, I think clinicians should be more conservative in how they are prescribing these medications and skeptical about the potential for benefit,” said Dr. Maust.

Regarding study limitations, the researchers noted that prescription medication claims may have led to an overestimation of the exposure to polypharmacy, insofar as the prescriptions may have been filled but not taken or were taken only on an as-needed basis.

In addition, the investigators were unable to determine the appropriateness of the particular combinations used or to examine the specific harms associated with CNS-active polypharmacy.
 

A major clinical challenge

Weighing in on the results, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study is important because polypharmacy is one of the “geriatric giants, and the question is, what do you do about it?”

Dr. Fillit said it is important to conduct a careful medication review for all older patients, “making sure that the use of each drug is appropriate. The most important thing is to define what is the appropriate utilization of these kinds of drugs. That goes for both overutilization or misuse of these drugs and underutilization, where people are undertreated for symptoms that can’t be managed by behavioral management, for example,” Dr. Fillit said.

Dr. Fillit also said the finding that about 14% of dementia patients were receiving three or more of these drugs “may not be an outrageous number, because these patients, especially as they get into moderate and severe stages of disease, can be incredibly difficult to manage.

“Very often, dementia patients have depression, and up to 90% will have agitation and even psychosis during the course of dementia. And many of these patients need these types of drugs,” said Dr. Fillit.

Echoing the authors, Dr. Fillit said a key limitation of the study is not knowing whether the prescribing was appropriate or not.

The study was supported by a grant from the National Institute on Aging. Dr. Maust and Dr. Fillit have disclosed no relevant financial relationships.

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

A significant proportion of community-dwelling older adults with dementia take three or more central nervous system medications despite guidelines that say to avoid this dangerous practice, new research suggests.

Investigators found that 14% of these individuals were receiving CNS-active polypharmacy, defined as combinations of multiple psychotropic and opioid medications taken for more than 30 days.

“For most patients, the risks of these medications, particularly in combination, are almost certainly greater than the potential benefits,” said Donovan Maust, MD, associate director of the geriatric psychiatry program, University of Michigan, Ann Arbor.

The study was published online March 9 in JAMA.
 

Serious risks

Memory impairment is the cardinal feature of dementia, but behavioral and psychological symptoms, which can include apathy, delusions, and agitation, are common during all stages of illness and cause significant caregiver distress, the researchers noted.

They noted that there is a dearth of high-quality evidence to support prescribing these medications in this patient population, yet “clinicians regularly prescribe psychotropic medications to community-dwelling persons with dementia in rates that far exceed use in the general older adult population.”

The Beers Criteria, from the American Geriatrics Society, advise against the practice of CNS polypharmacy because of the significant increase in risk for falls as well as impaired cognition, cardiac conduction abnormalities, respiratory suppression, and death when polypharmacy involves opioids.

They note that previous studies from Europe of polypharmacy for patients with dementia have not included antiepileptic medications or opioids, so the true extent of CNS-active polypharmacy may be “significantly” underestimated.

To determine the prevalence of polypharmacy with CNS-active medications among community-dwelling older adults with dementia, the researchers analyzed data on prescription fills for nearly 1.2 million community-dwelling Medicare patients with dementia.

The primary outcome was the prevalence of CNS-active polypharmacy in 2018. They defined CNS-active polypharmacy as exposure to three or more medications for more than 30 consecutive days from the following drug classes: antidepressants, antipsychotics, antiepileptics, benzodiazepines, nonbenzodiazepines, benzodiazepine receptor agonist hypnotics, and opioids.

They found that roughly one in seven (13.9%) patients met criteria for CNS-active polypharmacy. Of those receiving a CNS-active polypharmacy regimen, 57.8% had been doing so for longer than 180 days, and 6.8% had been doing so for a year. Nearly 30% of patients were exposed to five or more medications, and 5.2% were exposed to five or more medication classes.
 

Conservative approach warranted

Nearly all (92%) patients taking three or more CNS-active medications were taking an antidepressant, “consistent with their place as the psychotropic class most commonly prescribed both to older adults overall and those with dementia,” the investigators noted.

There is minimal high-quality evidence to support the efficacy of antidepressants for the treatment of depression for patients with dementia, they pointed out.

Nearly half (47%) of patients who were taking three or more CNS-active medications received at least one antipsychotic, most often quetiapine. Antipsychotics are not approved for people with dementia but are often prescribed off label for agitation, anxiety, and sleep problems, the researchers noted.

Nearly two thirds (62%) of patients with dementia who were taking three or more CNS drugs were taking an antiepileptic (most commonly, gabapentin); 41%, benzodiazepines; 32%, opioids; and 6%, Z-drugs.

The most common polypharmacy class combination included at least one antidepressant, one antiepileptic, and one antipsychotic. These accounted for 12.9% of polypharmacy days.

Despite limited high-quality evidence of efficacy, the prescribing of psychotropic medications and opioids is “pervasive” for adults with dementia in the United States, the investigators noted.

“Especially given that older adults with dementia might not be able to convey side effects they are experiencing, I think clinicians should be more conservative in how they are prescribing these medications and skeptical about the potential for benefit,” said Dr. Maust.

Regarding study limitations, the researchers noted that prescription medication claims may have led to an overestimation of the exposure to polypharmacy, insofar as the prescriptions may have been filled but not taken or were taken only on an as-needed basis.

In addition, the investigators were unable to determine the appropriateness of the particular combinations used or to examine the specific harms associated with CNS-active polypharmacy.
 

A major clinical challenge

Weighing in on the results, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study is important because polypharmacy is one of the “geriatric giants, and the question is, what do you do about it?”

Dr. Fillit said it is important to conduct a careful medication review for all older patients, “making sure that the use of each drug is appropriate. The most important thing is to define what is the appropriate utilization of these kinds of drugs. That goes for both overutilization or misuse of these drugs and underutilization, where people are undertreated for symptoms that can’t be managed by behavioral management, for example,” Dr. Fillit said.

Dr. Fillit also said the finding that about 14% of dementia patients were receiving three or more of these drugs “may not be an outrageous number, because these patients, especially as they get into moderate and severe stages of disease, can be incredibly difficult to manage.

“Very often, dementia patients have depression, and up to 90% will have agitation and even psychosis during the course of dementia. And many of these patients need these types of drugs,” said Dr. Fillit.

Echoing the authors, Dr. Fillit said a key limitation of the study is not knowing whether the prescribing was appropriate or not.

The study was supported by a grant from the National Institute on Aging. Dr. Maust and Dr. Fillit have disclosed no relevant financial relationships.

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

Results from a phase 2 placebo-controlled trial of the investigational antiamyloid drug donanemab show that the novel agent met the primary outcome of slowing cognitive decline in patients with early symptomatic Alzheimer’s disease (AD). 

Results from the TRAILBLAZER-ALZ trial were presented at the 2021 International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) and were simultaneously published online March 13 in the New England Journal of Medicine.

As previously reported by Medscape Medical News, topline results showed that donanemab slowed cognitive decline by 32% on the Integrated AD Rating Scale (iADRS) from baseline to 76 weeks relative to placebo.

The newly released detailed findings showed that “the use of donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed,” the investigators, with first author Mark A. Mintun, MD, an employee of Eli Lilly, reported.   

Results revealed improvement in scores on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) and the 13-item cognitive subscale of the AD Assessment Scale (ADAS-Cog13), but the differences between the two treatment groups were not significant. In addition, score changes on the AD Cooperative Study–Instrumental Activities of Daily Inventory (ADCS-iADL) and the Mini-Mental State Examination (MMSE) were not “substantial.”

However, the donanemab group did show an 85-centiloid greater reduction in amyloid plaque level at 76 weeks, as shown on PET, compared with the placebo group.
 

Proof of concept?

The humanized antibody donanemab, which was previously known as LY3002813, targets a modified form of deposited amyloid-beta (A-beta) peptide called N3pG.

The randomized, placebo-controlled, double-blind TRAILBLAZER-ALZ trial, which was described as a “phase 2 proof of concept trial” in the AD/PD program, was conducted at 56 sites in the United States and Canada and included 257 patients between the ages of 60 and 85 years (52% were women). PET confirmed tau and amyloid deposition in all participants.

The active treatment group (n = 131) was randomly assigned to receive donanemab 700 mg for three doses; after that, treatment was bumped up to 1,400 mg. Both the donanemab and placebo groups (n = 126) received treatment intravenously every 4 weeks for up to 72 weeks.

Participants also underwent F-florbetapir and F-flortaucipir PET scans at various timepoints and completed a slew of cognitive tests.

The study’s primary outcome measure was change between baseline and 76 weeks post treatment on composite score for cognition, as measured by the iADRS. The iADRS combines the ADAS-Cog13 and the ADCS-iADL.

This measure ranges from 0 to 144, with lower scores associated with greater cognitive impairment. Both treatment groups had an iADRS score of 106 at baseline.
 

More research needed

Results showed that the score change from baseline on the iADRS was –6.86 for the active treatment group vs –10.06 for the placebo group (group difference, 3.2; 95% confidence interval [CI], 0.12-6.27; P = .04). Although significant, “the trial was powered to show a 6-point difference,” which was not met, the investigators note.

Differences in score changes from baseline to 76 weeks for the treatment vs. placebo groups on the following secondary outcome measures were:

• CDR-SB: –0.36 (95% CI, –0.83 to –0.12).
• ADAS-Cog13: –1.86 (95% CI, –3.63 to –0.09).
• ADCS-iADL: 1.21 (95% CI, –0.77 to 3.2).
• MMSE: 0.64 (95% CI, –0.4 to 1.67).

The CDR-SB was designated as the first secondary outcome, and because it did not show a significant between-group difference, “the hierarchy failed and no definite conclusions can be drawn from data regarding the differences between groups in the change in the ADAS-Cog13,” the investigators wrote.

In addition, the differences in scores on the latter two secondary outcomes were not “substantial,” they reported.

However, at 76 weeks, the donanemab group showed a reduction of 84.13 centiloids in amyloid plaque level vs. an increase of 0.93 centiloids in the placebo group (between-group difference, 85.06 centiloids). At 24 weeks, the active-treatment group had a 67.83-centiloids greater reduction vs. the placebo group.

In addition, 40%, 59.8%, and 67.8% of the donanemab group achieved “amyloid-negative status” at 24, 52, and 76 weeks, respectively. Amyloid-negative status was defined as an amyloid plaque level of less than 24.1 centiloids.

Total incidence of death or serious adverse events did not differ significantly between the groups. However, the donanemab group had significantly more reports of ARIA-E compared with the placebo group (26.7% vs. 0.8%).

Overall, the researchers noted that more trials of longer duration with larger patient numbers are warranted “to further determine the efficacy and safety of donanemab” in AD.
 

Positive signal?

In a statement, Maria Carrillo, PhD, chief science officer for the Alzheimer’s Association, said the organization “is encouraged by this promising data.

“It is the first phase 2 Alzheimer’s trial to show positive results on a primary outcome measure related to memory and thinking,” Dr. Carrillo said. However, “more work needs to be done on this experimental drug therapy.”

Dr. Carrillo noted that because the trial was moderately sized and only 180 participants completed the study, “we look forward to the results of a second, larger phase 2 trial of this drug.”

Still, she added, there were several “novel and innovative aspects” in the way the study was conducted noting that it showcases the evolution of AD research.

“I’m hopeful for the future,” Dr. Carrillo said.

Also commenting on the results, Howard Fillit, MD, neuroscientist and founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study showed “the pharmacology works” and that the drug did what it was supposed to do in terms of removing A-beta plaque.

“It also gave us a signal in a relatively small phase 2 study that there might be a modest cognitive benefit,” said Dr. Fillit, who was not involved with the research.

He noted that although the rate of decline slowing was statistically significant it remains to be seen whether this is clinically meaningful, particularly in light of the fact that the secondary outcome results were mixed.  

“Basically, it was a positive study that probably needs to be followed by another, much larger study to get us to really see the benefit,” Dr. Fillit said.

Dr. Mintun is an employee of Eli Lilly, which funded the study. Dr. Carrillo and Dr. Fillit have reported no relevant financial relationships.

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

Results from a phase 2 placebo-controlled trial of the investigational antiamyloid drug donanemab show that the novel agent met the primary outcome of slowing cognitive decline in patients with early symptomatic Alzheimer’s disease (AD). 

Results from the TRAILBLAZER-ALZ trial were presented at the 2021 International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) and were simultaneously published online March 13 in the New England Journal of Medicine.

As previously reported by Medscape Medical News, topline results showed that donanemab slowed cognitive decline by 32% on the Integrated AD Rating Scale (iADRS) from baseline to 76 weeks relative to placebo.

The newly released detailed findings showed that “the use of donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed,” the investigators, with first author Mark A. Mintun, MD, an employee of Eli Lilly, reported.   

Results revealed improvement in scores on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) and the 13-item cognitive subscale of the AD Assessment Scale (ADAS-Cog13), but the differences between the two treatment groups were not significant. In addition, score changes on the AD Cooperative Study–Instrumental Activities of Daily Inventory (ADCS-iADL) and the Mini-Mental State Examination (MMSE) were not “substantial.”

However, the donanemab group did show an 85-centiloid greater reduction in amyloid plaque level at 76 weeks, as shown on PET, compared with the placebo group.
 

Proof of concept?

The humanized antibody donanemab, which was previously known as LY3002813, targets a modified form of deposited amyloid-beta (A-beta) peptide called N3pG.

The randomized, placebo-controlled, double-blind TRAILBLAZER-ALZ trial, which was described as a “phase 2 proof of concept trial” in the AD/PD program, was conducted at 56 sites in the United States and Canada and included 257 patients between the ages of 60 and 85 years (52% were women). PET confirmed tau and amyloid deposition in all participants.

The active treatment group (n = 131) was randomly assigned to receive donanemab 700 mg for three doses; after that, treatment was bumped up to 1,400 mg. Both the donanemab and placebo groups (n = 126) received treatment intravenously every 4 weeks for up to 72 weeks.

Participants also underwent F-florbetapir and F-flortaucipir PET scans at various timepoints and completed a slew of cognitive tests.

The study’s primary outcome measure was change between baseline and 76 weeks post treatment on composite score for cognition, as measured by the iADRS. The iADRS combines the ADAS-Cog13 and the ADCS-iADL.

This measure ranges from 0 to 144, with lower scores associated with greater cognitive impairment. Both treatment groups had an iADRS score of 106 at baseline.
 

More research needed

Results showed that the score change from baseline on the iADRS was –6.86 for the active treatment group vs –10.06 for the placebo group (group difference, 3.2; 95% confidence interval [CI], 0.12-6.27; P = .04). Although significant, “the trial was powered to show a 6-point difference,” which was not met, the investigators note.

Differences in score changes from baseline to 76 weeks for the treatment vs. placebo groups on the following secondary outcome measures were:

• CDR-SB: –0.36 (95% CI, –0.83 to –0.12).
• ADAS-Cog13: –1.86 (95% CI, –3.63 to –0.09).
• ADCS-iADL: 1.21 (95% CI, –0.77 to 3.2).
• MMSE: 0.64 (95% CI, –0.4 to 1.67).

The CDR-SB was designated as the first secondary outcome, and because it did not show a significant between-group difference, “the hierarchy failed and no definite conclusions can be drawn from data regarding the differences between groups in the change in the ADAS-Cog13,” the investigators wrote.

In addition, the differences in scores on the latter two secondary outcomes were not “substantial,” they reported.

However, at 76 weeks, the donanemab group showed a reduction of 84.13 centiloids in amyloid plaque level vs. an increase of 0.93 centiloids in the placebo group (between-group difference, 85.06 centiloids). At 24 weeks, the active-treatment group had a 67.83-centiloids greater reduction vs. the placebo group.

In addition, 40%, 59.8%, and 67.8% of the donanemab group achieved “amyloid-negative status” at 24, 52, and 76 weeks, respectively. Amyloid-negative status was defined as an amyloid plaque level of less than 24.1 centiloids.

Total incidence of death or serious adverse events did not differ significantly between the groups. However, the donanemab group had significantly more reports of ARIA-E compared with the placebo group (26.7% vs. 0.8%).

Overall, the researchers noted that more trials of longer duration with larger patient numbers are warranted “to further determine the efficacy and safety of donanemab” in AD.
 

Positive signal?

In a statement, Maria Carrillo, PhD, chief science officer for the Alzheimer’s Association, said the organization “is encouraged by this promising data.

“It is the first phase 2 Alzheimer’s trial to show positive results on a primary outcome measure related to memory and thinking,” Dr. Carrillo said. However, “more work needs to be done on this experimental drug therapy.”

Dr. Carrillo noted that because the trial was moderately sized and only 180 participants completed the study, “we look forward to the results of a second, larger phase 2 trial of this drug.”

Still, she added, there were several “novel and innovative aspects” in the way the study was conducted noting that it showcases the evolution of AD research.

“I’m hopeful for the future,” Dr. Carrillo said.

Also commenting on the results, Howard Fillit, MD, neuroscientist and founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study showed “the pharmacology works” and that the drug did what it was supposed to do in terms of removing A-beta plaque.

“It also gave us a signal in a relatively small phase 2 study that there might be a modest cognitive benefit,” said Dr. Fillit, who was not involved with the research.

He noted that although the rate of decline slowing was statistically significant it remains to be seen whether this is clinically meaningful, particularly in light of the fact that the secondary outcome results were mixed.  

“Basically, it was a positive study that probably needs to be followed by another, much larger study to get us to really see the benefit,” Dr. Fillit said.

Dr. Mintun is an employee of Eli Lilly, which funded the study. Dr. Carrillo and Dr. Fillit have reported no relevant financial relationships.

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

Results from a phase 2 placebo-controlled trial of the investigational antiamyloid drug donanemab show that the novel agent met the primary outcome of slowing cognitive decline in patients with early symptomatic Alzheimer’s disease (AD). 

Results from the TRAILBLAZER-ALZ trial were presented at the 2021 International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) and were simultaneously published online March 13 in the New England Journal of Medicine.

As previously reported by Medscape Medical News, topline results showed that donanemab slowed cognitive decline by 32% on the Integrated AD Rating Scale (iADRS) from baseline to 76 weeks relative to placebo.

The newly released detailed findings showed that “the use of donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed,” the investigators, with first author Mark A. Mintun, MD, an employee of Eli Lilly, reported.   

Results revealed improvement in scores on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) and the 13-item cognitive subscale of the AD Assessment Scale (ADAS-Cog13), but the differences between the two treatment groups were not significant. In addition, score changes on the AD Cooperative Study–Instrumental Activities of Daily Inventory (ADCS-iADL) and the Mini-Mental State Examination (MMSE) were not “substantial.”

However, the donanemab group did show an 85-centiloid greater reduction in amyloid plaque level at 76 weeks, as shown on PET, compared with the placebo group.
 

Proof of concept?

The humanized antibody donanemab, which was previously known as LY3002813, targets a modified form of deposited amyloid-beta (A-beta) peptide called N3pG.

The randomized, placebo-controlled, double-blind TRAILBLAZER-ALZ trial, which was described as a “phase 2 proof of concept trial” in the AD/PD program, was conducted at 56 sites in the United States and Canada and included 257 patients between the ages of 60 and 85 years (52% were women). PET confirmed tau and amyloid deposition in all participants.

The active treatment group (n = 131) was randomly assigned to receive donanemab 700 mg for three doses; after that, treatment was bumped up to 1,400 mg. Both the donanemab and placebo groups (n = 126) received treatment intravenously every 4 weeks for up to 72 weeks.

Participants also underwent F-florbetapir and F-flortaucipir PET scans at various timepoints and completed a slew of cognitive tests.

The study’s primary outcome measure was change between baseline and 76 weeks post treatment on composite score for cognition, as measured by the iADRS. The iADRS combines the ADAS-Cog13 and the ADCS-iADL.

This measure ranges from 0 to 144, with lower scores associated with greater cognitive impairment. Both treatment groups had an iADRS score of 106 at baseline.
 

More research needed

Results showed that the score change from baseline on the iADRS was –6.86 for the active treatment group vs –10.06 for the placebo group (group difference, 3.2; 95% confidence interval [CI], 0.12-6.27; P = .04). Although significant, “the trial was powered to show a 6-point difference,” which was not met, the investigators note.

Differences in score changes from baseline to 76 weeks for the treatment vs. placebo groups on the following secondary outcome measures were:

• CDR-SB: –0.36 (95% CI, –0.83 to –0.12).
• ADAS-Cog13: –1.86 (95% CI, –3.63 to –0.09).
• ADCS-iADL: 1.21 (95% CI, –0.77 to 3.2).
• MMSE: 0.64 (95% CI, –0.4 to 1.67).

The CDR-SB was designated as the first secondary outcome, and because it did not show a significant between-group difference, “the hierarchy failed and no definite conclusions can be drawn from data regarding the differences between groups in the change in the ADAS-Cog13,” the investigators wrote.

In addition, the differences in scores on the latter two secondary outcomes were not “substantial,” they reported.

However, at 76 weeks, the donanemab group showed a reduction of 84.13 centiloids in amyloid plaque level vs. an increase of 0.93 centiloids in the placebo group (between-group difference, 85.06 centiloids). At 24 weeks, the active-treatment group had a 67.83-centiloids greater reduction vs. the placebo group.

In addition, 40%, 59.8%, and 67.8% of the donanemab group achieved “amyloid-negative status” at 24, 52, and 76 weeks, respectively. Amyloid-negative status was defined as an amyloid plaque level of less than 24.1 centiloids.

Total incidence of death or serious adverse events did not differ significantly between the groups. However, the donanemab group had significantly more reports of ARIA-E compared with the placebo group (26.7% vs. 0.8%).

Overall, the researchers noted that more trials of longer duration with larger patient numbers are warranted “to further determine the efficacy and safety of donanemab” in AD.
 

Positive signal?

In a statement, Maria Carrillo, PhD, chief science officer for the Alzheimer’s Association, said the organization “is encouraged by this promising data.

“It is the first phase 2 Alzheimer’s trial to show positive results on a primary outcome measure related to memory and thinking,” Dr. Carrillo said. However, “more work needs to be done on this experimental drug therapy.”

Dr. Carrillo noted that because the trial was moderately sized and only 180 participants completed the study, “we look forward to the results of a second, larger phase 2 trial of this drug.”

Still, she added, there were several “novel and innovative aspects” in the way the study was conducted noting that it showcases the evolution of AD research.

“I’m hopeful for the future,” Dr. Carrillo said.

Also commenting on the results, Howard Fillit, MD, neuroscientist and founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study showed “the pharmacology works” and that the drug did what it was supposed to do in terms of removing A-beta plaque.

“It also gave us a signal in a relatively small phase 2 study that there might be a modest cognitive benefit,” said Dr. Fillit, who was not involved with the research.

He noted that although the rate of decline slowing was statistically significant it remains to be seen whether this is clinically meaningful, particularly in light of the fact that the secondary outcome results were mixed.  

“Basically, it was a positive study that probably needs to be followed by another, much larger study to get us to really see the benefit,” Dr. Fillit said.

Dr. Mintun is an employee of Eli Lilly, which funded the study. Dr. Carrillo and Dr. Fillit have reported no relevant financial relationships.

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

Older adults with chronic obstructive pulmonary disease who began using synthetic cannabinoids showed a 64% increase in all-cause mortality, compared with nonusers, findings from a large study have shown.

Synthetic cannabinoids drugs, such as nabilone and dronabinol, have been approved by the Food and Drug Administration for nausea and vomiting caused by chemotherapy. But their off-label use by adults with COPD to help manage chronic musculoskeletal pain, insomnia, and refractory dyspnea is on the rise, wrote Nicholas T. Vozoris, MD, of the University of Toronto and colleagues.

Cannabinoids may actually contribute to negative respiratory outcomes among individuals with COPD through several possible mechanisms including causing sedation, inducing anxiety, and provoking respiratory muscle weakness, they said.

“Possible adverse respiratory effects of cannabinoids may occur with greater likelihood among older adults (in whom COPD is more prevalent), as this group is known to less efficiently metabolise drugs,” they noted.

In a retrospective, population-based cohort study published in Thorax the researchers identified 185,876 adults aged 66 years and older with COPD using health administrative database information from 2006 to 2016. New cannabinoid users (those starting nabilone or dronabinol) were matched with control nonusers (defined as new users of noncannabinoid drugs). Individuals receiving palliative care, or having a diagnosis of cancer or HIV, were excluded because these are settings where synthetic cannabinoids may be prescribed for nausea or vomiting, and these patients are more likely to be in a poorer state of health.

Overall, new cannabinoid users had significantly higher all-cause mortality rates, compared with nonusers (hazard ratio, 1.64). The effects was greater in high-dose users.

Daniel R. Ouellette, MD, associate professor of medicine at Wayne State University and a senior staff physician at Henry Ford Hospital, both in Detroit, commented that this study has value for clinicians. “Many states are liberalizing cannabinoid use, and it is important to know the health effects of this type of drug on patients with chronic respiratory disease,” he noted. “The study is somewhat surprising. While one might have expected adverse consequences in patients with COPD who inhaled smoke from cannabinoids, it is somewhat unexpected that oral use would be associated with adverse consequences.” He added, “Pain in older adults is a complex problem. Cannabinoids are often recommended for pain in the general community, but pain per se is not a primary symptom for most patients with COPD from their respiratory problems. Physicians treating patients with COPD should diagnose the cause of the pain and provide appropriate treatment.”


 

Dose makes a difference

All-cause mortality increased by 231% and hospitalization for COPD or pneumonia increased by 178% among new users of higher-dose cannabinoids, compared with nonusers. Higher dose was defined in this study as more than 1.5mg/day of nabilone. No significant differences appeared in new users vs. nonusers in hospitalization for COPD or pneumonia at lower doses, and no significant differences appeared overall in outpatient respiratory exacerbations, emergency department visits for COPD or pneumonia, or COPD- or pneumonia-related mortality.
 

Potential limitations and implications

“The fact that COPD- or pneumonia-related mortality was not observed to occur with significantly greater rates among cannabinoid users with COPD may suggest that the increased all-cause mortality finding was not being driven by adverse respiratory-related drug effects, as we hypothesized, and instead was possibly a result of unresolved confounding,” the researchers noted.

The study findings were limited by several factors including the inability to prove causation in an observational study, and the potential for confounding based on unmeasured differences between cannabinoid users and nonusers, the researchers said. “Our findings may not be generalizable to all individuals with COPD, as our study included only those aged 66 years and older, and our COPD identification algorithm, while highly specific, had modest sensitivity,” they added. However, the results were strengthened by the large study population and suggest that cannabinoids are not contraindicated for older adults with COPD, the researchers said. “There can be legitimate reasons for using cannabinoids in this population, such as to help treat chemotherapy-related nausea and vomiting, and possibly for end-of-life care,” they emphasized.

The study findings serve to inform clinicians of the significantly increased mortality risk when older adults with COPD initiate cannabinoids, and “this information should be discussed with patients and incorporated in prescribing decision-making and management plans,” along with consideration of using lower doses when possible to minimize adverse events, they concluded.

The study was supported by The Lung Association – Ontario Grant Review/Grant-In-Aid. The researchers had no financial conflicts to disclose.

Older adults with chronic obstructive pulmonary disease who began using synthetic cannabinoids showed a 64% increase in all-cause mortality, compared with nonusers, findings from a large study have shown.

Synthetic cannabinoids drugs, such as nabilone and dronabinol, have been approved by the Food and Drug Administration for nausea and vomiting caused by chemotherapy. But their off-label use by adults with COPD to help manage chronic musculoskeletal pain, insomnia, and refractory dyspnea is on the rise, wrote Nicholas T. Vozoris, MD, of the University of Toronto and colleagues.

Cannabinoids may actually contribute to negative respiratory outcomes among individuals with COPD through several possible mechanisms including causing sedation, inducing anxiety, and provoking respiratory muscle weakness, they said.

“Possible adverse respiratory effects of cannabinoids may occur with greater likelihood among older adults (in whom COPD is more prevalent), as this group is known to less efficiently metabolise drugs,” they noted.

In a retrospective, population-based cohort study published in Thorax the researchers identified 185,876 adults aged 66 years and older with COPD using health administrative database information from 2006 to 2016. New cannabinoid users (those starting nabilone or dronabinol) were matched with control nonusers (defined as new users of noncannabinoid drugs). Individuals receiving palliative care, or having a diagnosis of cancer or HIV, were excluded because these are settings where synthetic cannabinoids may be prescribed for nausea or vomiting, and these patients are more likely to be in a poorer state of health.

Overall, new cannabinoid users had significantly higher all-cause mortality rates, compared with nonusers (hazard ratio, 1.64). The effects was greater in high-dose users.

Daniel R. Ouellette, MD, associate professor of medicine at Wayne State University and a senior staff physician at Henry Ford Hospital, both in Detroit, commented that this study has value for clinicians. “Many states are liberalizing cannabinoid use, and it is important to know the health effects of this type of drug on patients with chronic respiratory disease,” he noted. “The study is somewhat surprising. While one might have expected adverse consequences in patients with COPD who inhaled smoke from cannabinoids, it is somewhat unexpected that oral use would be associated with adverse consequences.” He added, “Pain in older adults is a complex problem. Cannabinoids are often recommended for pain in the general community, but pain per se is not a primary symptom for most patients with COPD from their respiratory problems. Physicians treating patients with COPD should diagnose the cause of the pain and provide appropriate treatment.”


 

Dose makes a difference

All-cause mortality increased by 231% and hospitalization for COPD or pneumonia increased by 178% among new users of higher-dose cannabinoids, compared with nonusers. Higher dose was defined in this study as more than 1.5mg/day of nabilone. No significant differences appeared in new users vs. nonusers in hospitalization for COPD or pneumonia at lower doses, and no significant differences appeared overall in outpatient respiratory exacerbations, emergency department visits for COPD or pneumonia, or COPD- or pneumonia-related mortality.
 

Potential limitations and implications

“The fact that COPD- or pneumonia-related mortality was not observed to occur with significantly greater rates among cannabinoid users with COPD may suggest that the increased all-cause mortality finding was not being driven by adverse respiratory-related drug effects, as we hypothesized, and instead was possibly a result of unresolved confounding,” the researchers noted.

The study findings were limited by several factors including the inability to prove causation in an observational study, and the potential for confounding based on unmeasured differences between cannabinoid users and nonusers, the researchers said. “Our findings may not be generalizable to all individuals with COPD, as our study included only those aged 66 years and older, and our COPD identification algorithm, while highly specific, had modest sensitivity,” they added. However, the results were strengthened by the large study population and suggest that cannabinoids are not contraindicated for older adults with COPD, the researchers said. “There can be legitimate reasons for using cannabinoids in this population, such as to help treat chemotherapy-related nausea and vomiting, and possibly for end-of-life care,” they emphasized.

The study findings serve to inform clinicians of the significantly increased mortality risk when older adults with COPD initiate cannabinoids, and “this information should be discussed with patients and incorporated in prescribing decision-making and management plans,” along with consideration of using lower doses when possible to minimize adverse events, they concluded.

The study was supported by The Lung Association – Ontario Grant Review/Grant-In-Aid. The researchers had no financial conflicts to disclose.

Older adults with chronic obstructive pulmonary disease who began using synthetic cannabinoids showed a 64% increase in all-cause mortality, compared with nonusers, findings from a large study have shown.

Synthetic cannabinoids drugs, such as nabilone and dronabinol, have been approved by the Food and Drug Administration for nausea and vomiting caused by chemotherapy. But their off-label use by adults with COPD to help manage chronic musculoskeletal pain, insomnia, and refractory dyspnea is on the rise, wrote Nicholas T. Vozoris, MD, of the University of Toronto and colleagues.

Cannabinoids may actually contribute to negative respiratory outcomes among individuals with COPD through several possible mechanisms including causing sedation, inducing anxiety, and provoking respiratory muscle weakness, they said.

“Possible adverse respiratory effects of cannabinoids may occur with greater likelihood among older adults (in whom COPD is more prevalent), as this group is known to less efficiently metabolise drugs,” they noted.

In a retrospective, population-based cohort study published in Thorax the researchers identified 185,876 adults aged 66 years and older with COPD using health administrative database information from 2006 to 2016. New cannabinoid users (those starting nabilone or dronabinol) were matched with control nonusers (defined as new users of noncannabinoid drugs). Individuals receiving palliative care, or having a diagnosis of cancer or HIV, were excluded because these are settings where synthetic cannabinoids may be prescribed for nausea or vomiting, and these patients are more likely to be in a poorer state of health.

Overall, new cannabinoid users had significantly higher all-cause mortality rates, compared with nonusers (hazard ratio, 1.64). The effects was greater in high-dose users.

Daniel R. Ouellette, MD, associate professor of medicine at Wayne State University and a senior staff physician at Henry Ford Hospital, both in Detroit, commented that this study has value for clinicians. “Many states are liberalizing cannabinoid use, and it is important to know the health effects of this type of drug on patients with chronic respiratory disease,” he noted. “The study is somewhat surprising. While one might have expected adverse consequences in patients with COPD who inhaled smoke from cannabinoids, it is somewhat unexpected that oral use would be associated with adverse consequences.” He added, “Pain in older adults is a complex problem. Cannabinoids are often recommended for pain in the general community, but pain per se is not a primary symptom for most patients with COPD from their respiratory problems. Physicians treating patients with COPD should diagnose the cause of the pain and provide appropriate treatment.”


 

Dose makes a difference

All-cause mortality increased by 231% and hospitalization for COPD or pneumonia increased by 178% among new users of higher-dose cannabinoids, compared with nonusers. Higher dose was defined in this study as more than 1.5mg/day of nabilone. No significant differences appeared in new users vs. nonusers in hospitalization for COPD or pneumonia at lower doses, and no significant differences appeared overall in outpatient respiratory exacerbations, emergency department visits for COPD or pneumonia, or COPD- or pneumonia-related mortality.
 

Potential limitations and implications

“The fact that COPD- or pneumonia-related mortality was not observed to occur with significantly greater rates among cannabinoid users with COPD may suggest that the increased all-cause mortality finding was not being driven by adverse respiratory-related drug effects, as we hypothesized, and instead was possibly a result of unresolved confounding,” the researchers noted.

The study findings were limited by several factors including the inability to prove causation in an observational study, and the potential for confounding based on unmeasured differences between cannabinoid users and nonusers, the researchers said. “Our findings may not be generalizable to all individuals with COPD, as our study included only those aged 66 years and older, and our COPD identification algorithm, while highly specific, had modest sensitivity,” they added. However, the results were strengthened by the large study population and suggest that cannabinoids are not contraindicated for older adults with COPD, the researchers said. “There can be legitimate reasons for using cannabinoids in this population, such as to help treat chemotherapy-related nausea and vomiting, and possibly for end-of-life care,” they emphasized.

The study findings serve to inform clinicians of the significantly increased mortality risk when older adults with COPD initiate cannabinoids, and “this information should be discussed with patients and incorporated in prescribing decision-making and management plans,” along with consideration of using lower doses when possible to minimize adverse events, they concluded.

The study was supported by The Lung Association – Ontario Grant Review/Grant-In-Aid. The researchers had no financial conflicts to disclose.

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

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

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

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

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

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