Neurology

Alerting neurologists via telemedicine that a patient with suspected acute stroke is en route to the hospital significantly enhances the speed at which thrombolysis is administered and increases the number of patients who receive timelier, potentially lifesaving treatment, new research showed.

“This preliminary evidence supports adopting teleneurology prenotification as a best practice within health systems that have telestroke capabilities,” said study investigator Mark McDonald, MD, a neurologist at TeleSpecialists, Fort Myers, Florida.

The findings were presented at the 2024 annual meeting of the American Academy of Neurology.
 

Best Practices

The impact of emergency medical services prenotification, which refers to paramedics alerting receiving hospital emergency departments (EDs) of a suspected stroke on the way for appropriate preparations to be made, is well-defined, said Dr. McDonald.

“What we’re proposing as a best practice is not only should the ED or ED provider be aware, but there needs to be a system in place for standardizing communication to the neurology team so they’re aware, too.”

Prenotification allows a neurologist to “get on the screen to begin coordinating with the ED team to adequately prepare for the possibility of thrombolytic treatment,” he added.

Currently, teleneurology prenotification, he said, is variable and its benefits unclear.

Dr. McDonald said “his organization, TeleSpecialists, maintains a large detailed medical records database for emergency-related, teleneurology, and other cases. For stroke, it recommends 15 best practices” for facilities including prenotification of teleneurology.

Other best practices include evaluating and administering thrombolysis in the CT imaging suite, a preassembled stroke kit that includes antihypertensives and thrombolytic agents, ensuring a weigh bed is available to determine the exact dose of thrombolysis treatment, and implementing “mock” stroke alerts, said Dr. McDonald.

From the database, researchers extracted acute telestroke consultations seen in the ED in 103 facilities in 15 states. Facilities that did not adhere to the 14 best practices other than teleneurologist prenotification were excluded from the analysis.

Of 9290 patients included in the study, 731 were treated with thrombolysis at prenotification facilities (median age, 69 years; median National Institutes of Health Stroke Score [NIHSS], 8) and 31 were treated at facilities without prenotification (median age, 63 years; median NIHSS score, 4). The thrombolytic treatment rate was 8.5% at prenotification facilities versus 4.8% at facilities without prenotification — a difference that was statistically significant.

Prenotification facilities had a significantly shorter median door-to-needle (DTN) time than those without such a process at 35 versus 43 minutes. In addition, there was a statistically significant difference in the percentage of patients with times less than 60 minutes at approximately 88% at prenotification facilities versus about 68% at the facilities without prenotification.
 

Case-Level Analysis

However, just because a facility adheres to teleneurology prenotification as a whole, doesn’t mean it occurs in every case. Researchers explored the impact of teleneurology prenotification at the case level rather than the facility level.

“That gave us a bit more insight into the real impact because it’s not just being at a facility with the best practice; it’s actually working case by case to see whether it happened or not and that’s where we get the most compelling findings,” said Dr. McDonald.

Of 761 treatment cases, there was prenotification to the neurology team in 401 cases. In 360 cases, prenotification did not occur.

The median DTN time was 29 minutes in the group with actual prenotification vs 41.5 minutes in the group without actual prenotification, a difference that was statistically significant, Dr. McDonald said.

As for treatment within 30 minutes of arrival, 50.4% of patients in the teleneurology prenotification group versus 18.9% in the no prenotification group — a statistically significant difference.

DTN time of less than 30 minutes is increasingly used as a target. “Being treated within this time frame improves outcomes and reduces length of hospital stay,” said Dr. McDonald.

The prenotification group also had a statistically significant higher percentage of treatment within 60 minutes of hospital arrival (93.5% vs 80%).

These new findings should help convince health and telestroke systems that teleneurology prenotification is worth implementing. “We want to achieve consensus on this as a best practice,” said Dr. McDonald.

Prenotification, he added, “coordinates the process and eliminates unnecessary and time-consuming steps.”

Dr. McDonald plans to prospectively study prenotification by collecting data on a facility before and after implementing a prenotification process.
 

Compelling Evidence

Commenting on the research, David L. Tirschwell, MD, Harborview Medical Center, Department of Neurology, Seattle, who cochaired the AAN session featuring the research, said the study provides compelling evidence that teleneurologist prenotification improves DTN time.

“Prenotifications are often standard of care in many healthcare settings and should likely be considered a best practice. When possible, extending such prenotification to a teleconsultant would make sense, and these preliminary data support that approach.”

However, more details are needed “to consider whether the intervention is possibly generalizable to other telestroke practices across the United States,” said Dr. Tirschwell.

Dr. McDonald reported receiving personal compensation for serving as a consultant for Syntrillo Inc. and has stock in Syntrillo Inc. Dr. Tirschwell reported no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Alerting neurologists via telemedicine that a patient with suspected acute stroke is en route to the hospital significantly enhances the speed at which thrombolysis is administered and increases the number of patients who receive timelier, potentially lifesaving treatment, new research showed.

“This preliminary evidence supports adopting teleneurology prenotification as a best practice within health systems that have telestroke capabilities,” said study investigator Mark McDonald, MD, a neurologist at TeleSpecialists, Fort Myers, Florida.

The findings were presented at the 2024 annual meeting of the American Academy of Neurology.
 

Best Practices

The impact of emergency medical services prenotification, which refers to paramedics alerting receiving hospital emergency departments (EDs) of a suspected stroke on the way for appropriate preparations to be made, is well-defined, said Dr. McDonald.

“What we’re proposing as a best practice is not only should the ED or ED provider be aware, but there needs to be a system in place for standardizing communication to the neurology team so they’re aware, too.”

Prenotification allows a neurologist to “get on the screen to begin coordinating with the ED team to adequately prepare for the possibility of thrombolytic treatment,” he added.

Currently, teleneurology prenotification, he said, is variable and its benefits unclear.

Dr. McDonald said “his organization, TeleSpecialists, maintains a large detailed medical records database for emergency-related, teleneurology, and other cases. For stroke, it recommends 15 best practices” for facilities including prenotification of teleneurology.

Other best practices include evaluating and administering thrombolysis in the CT imaging suite, a preassembled stroke kit that includes antihypertensives and thrombolytic agents, ensuring a weigh bed is available to determine the exact dose of thrombolysis treatment, and implementing “mock” stroke alerts, said Dr. McDonald.

From the database, researchers extracted acute telestroke consultations seen in the ED in 103 facilities in 15 states. Facilities that did not adhere to the 14 best practices other than teleneurologist prenotification were excluded from the analysis.

Of 9290 patients included in the study, 731 were treated with thrombolysis at prenotification facilities (median age, 69 years; median National Institutes of Health Stroke Score [NIHSS], 8) and 31 were treated at facilities without prenotification (median age, 63 years; median NIHSS score, 4). The thrombolytic treatment rate was 8.5% at prenotification facilities versus 4.8% at facilities without prenotification — a difference that was statistically significant.

Prenotification facilities had a significantly shorter median door-to-needle (DTN) time than those without such a process at 35 versus 43 minutes. In addition, there was a statistically significant difference in the percentage of patients with times less than 60 minutes at approximately 88% at prenotification facilities versus about 68% at the facilities without prenotification.
 

Case-Level Analysis

However, just because a facility adheres to teleneurology prenotification as a whole, doesn’t mean it occurs in every case. Researchers explored the impact of teleneurology prenotification at the case level rather than the facility level.

“That gave us a bit more insight into the real impact because it’s not just being at a facility with the best practice; it’s actually working case by case to see whether it happened or not and that’s where we get the most compelling findings,” said Dr. McDonald.

Of 761 treatment cases, there was prenotification to the neurology team in 401 cases. In 360 cases, prenotification did not occur.

The median DTN time was 29 minutes in the group with actual prenotification vs 41.5 minutes in the group without actual prenotification, a difference that was statistically significant, Dr. McDonald said.

As for treatment within 30 minutes of arrival, 50.4% of patients in the teleneurology prenotification group versus 18.9% in the no prenotification group — a statistically significant difference.

DTN time of less than 30 minutes is increasingly used as a target. “Being treated within this time frame improves outcomes and reduces length of hospital stay,” said Dr. McDonald.

The prenotification group also had a statistically significant higher percentage of treatment within 60 minutes of hospital arrival (93.5% vs 80%).

These new findings should help convince health and telestroke systems that teleneurology prenotification is worth implementing. “We want to achieve consensus on this as a best practice,” said Dr. McDonald.

Prenotification, he added, “coordinates the process and eliminates unnecessary and time-consuming steps.”

Dr. McDonald plans to prospectively study prenotification by collecting data on a facility before and after implementing a prenotification process.
 

Compelling Evidence

Commenting on the research, David L. Tirschwell, MD, Harborview Medical Center, Department of Neurology, Seattle, who cochaired the AAN session featuring the research, said the study provides compelling evidence that teleneurologist prenotification improves DTN time.

“Prenotifications are often standard of care in many healthcare settings and should likely be considered a best practice. When possible, extending such prenotification to a teleconsultant would make sense, and these preliminary data support that approach.”

However, more details are needed “to consider whether the intervention is possibly generalizable to other telestroke practices across the United States,” said Dr. Tirschwell.

Dr. McDonald reported receiving personal compensation for serving as a consultant for Syntrillo Inc. and has stock in Syntrillo Inc. Dr. Tirschwell reported no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Alerting neurologists via telemedicine that a patient with suspected acute stroke is en route to the hospital significantly enhances the speed at which thrombolysis is administered and increases the number of patients who receive timelier, potentially lifesaving treatment, new research showed.

“This preliminary evidence supports adopting teleneurology prenotification as a best practice within health systems that have telestroke capabilities,” said study investigator Mark McDonald, MD, a neurologist at TeleSpecialists, Fort Myers, Florida.

The findings were presented at the 2024 annual meeting of the American Academy of Neurology.
 

Best Practices

The impact of emergency medical services prenotification, which refers to paramedics alerting receiving hospital emergency departments (EDs) of a suspected stroke on the way for appropriate preparations to be made, is well-defined, said Dr. McDonald.

“What we’re proposing as a best practice is not only should the ED or ED provider be aware, but there needs to be a system in place for standardizing communication to the neurology team so they’re aware, too.”

Prenotification allows a neurologist to “get on the screen to begin coordinating with the ED team to adequately prepare for the possibility of thrombolytic treatment,” he added.

Currently, teleneurology prenotification, he said, is variable and its benefits unclear.

Dr. McDonald said “his organization, TeleSpecialists, maintains a large detailed medical records database for emergency-related, teleneurology, and other cases. For stroke, it recommends 15 best practices” for facilities including prenotification of teleneurology.

Other best practices include evaluating and administering thrombolysis in the CT imaging suite, a preassembled stroke kit that includes antihypertensives and thrombolytic agents, ensuring a weigh bed is available to determine the exact dose of thrombolysis treatment, and implementing “mock” stroke alerts, said Dr. McDonald.

From the database, researchers extracted acute telestroke consultations seen in the ED in 103 facilities in 15 states. Facilities that did not adhere to the 14 best practices other than teleneurologist prenotification were excluded from the analysis.

Of 9290 patients included in the study, 731 were treated with thrombolysis at prenotification facilities (median age, 69 years; median National Institutes of Health Stroke Score [NIHSS], 8) and 31 were treated at facilities without prenotification (median age, 63 years; median NIHSS score, 4). The thrombolytic treatment rate was 8.5% at prenotification facilities versus 4.8% at facilities without prenotification — a difference that was statistically significant.

Prenotification facilities had a significantly shorter median door-to-needle (DTN) time than those without such a process at 35 versus 43 minutes. In addition, there was a statistically significant difference in the percentage of patients with times less than 60 minutes at approximately 88% at prenotification facilities versus about 68% at the facilities without prenotification.
 

Case-Level Analysis

However, just because a facility adheres to teleneurology prenotification as a whole, doesn’t mean it occurs in every case. Researchers explored the impact of teleneurology prenotification at the case level rather than the facility level.

“That gave us a bit more insight into the real impact because it’s not just being at a facility with the best practice; it’s actually working case by case to see whether it happened or not and that’s where we get the most compelling findings,” said Dr. McDonald.

Of 761 treatment cases, there was prenotification to the neurology team in 401 cases. In 360 cases, prenotification did not occur.

The median DTN time was 29 minutes in the group with actual prenotification vs 41.5 minutes in the group without actual prenotification, a difference that was statistically significant, Dr. McDonald said.

As for treatment within 30 minutes of arrival, 50.4% of patients in the teleneurology prenotification group versus 18.9% in the no prenotification group — a statistically significant difference.

DTN time of less than 30 minutes is increasingly used as a target. “Being treated within this time frame improves outcomes and reduces length of hospital stay,” said Dr. McDonald.

The prenotification group also had a statistically significant higher percentage of treatment within 60 minutes of hospital arrival (93.5% vs 80%).

These new findings should help convince health and telestroke systems that teleneurology prenotification is worth implementing. “We want to achieve consensus on this as a best practice,” said Dr. McDonald.

Prenotification, he added, “coordinates the process and eliminates unnecessary and time-consuming steps.”

Dr. McDonald plans to prospectively study prenotification by collecting data on a facility before and after implementing a prenotification process.
 

Compelling Evidence

Commenting on the research, David L. Tirschwell, MD, Harborview Medical Center, Department of Neurology, Seattle, who cochaired the AAN session featuring the research, said the study provides compelling evidence that teleneurologist prenotification improves DTN time.

“Prenotifications are often standard of care in many healthcare settings and should likely be considered a best practice. When possible, extending such prenotification to a teleconsultant would make sense, and these preliminary data support that approach.”

However, more details are needed “to consider whether the intervention is possibly generalizable to other telestroke practices across the United States,” said Dr. Tirschwell.

Dr. McDonald reported receiving personal compensation for serving as a consultant for Syntrillo Inc. and has stock in Syntrillo Inc. Dr. Tirschwell reported no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

DENVER — Treatment with AXS-05, a combination of dextromethorphan and bupropion, demonstrated rapid, sustained, and clinically meaningful improvement in agitation related to Alzheimer’s disease and was generally well tolerated in the phase 3 ACCORD trial. 

More than half of participants in the open-label extension period of the randomized clinical trial responded to the medication, which was associated with a 3.6-fold lower risk for relapse compared with placebo. 

“The positive efficacy and favorable safety results with AXS-05 support its potential to fulfill a high unmet need for the treatment of Alzheimer’s disease agitation,” said Anton P. Porsteinsson, MD, director of the Alzheimer’s Disease Care, Research and Education Program, University of Rochester, New York. 

The findings were presented at the 2024 annual meeting of the American Academy of Neurology. 
 

Common and Disruptive

Agitation is reported in up to 70% of patients with Alzheimer’s disease and is characterized by emotional distress, aggressive behaviors, disruptive irritability, and disinhibition. Alzheimer’s disease-related agitation has been associated with increased caregiver burden, decreased functioning, accelerated cognitive decline, earlier nursing home placement, and increased mortality.

A previous phase 2/3 study of AXS-05 showed that the investigative agent led to rapid and significantly improvement in Alzheimer’s disease agitation, as measured by the Cohen-Mansfield Agitation Inventory (CMAI) total score, compared with placebo. 

ACCORD was a phase 3, randomized, double-blind, placebo-controlled withdrawal trial evaluating the efficacy and safety of AXS-05 in patients with Alzheimer’s disease agitation. 

In the open-label period, 178 adults with probable Alzheimer’s disease and clinically significant agitation received AXS-05 (titrated to 45 mg dextromethorphan/105 mg bupropion twice daily) for up to 9 weeks.

A total of 108 (61%) patients had a sustained response, with 30% or more improvement from baseline in the CMAI total score and improvement on the Patient Global Impression of Change that were both maintained for 4 or more consecutive weeks. These patients entered the double-blind phase and were randomly allocated to receive twice-daily AXS-05 or placebo for up to 26 weeks.

In the double-blind period, AXS-05 “substantially and statistically” increased the time to relapse of agitation symptoms compared with placebo (hazard ratio [HR], 0.275; P = .014).

“The risk of relapse was 3.6-fold lower with AXS-05 compared with placebo,” Dr. Porsteinsson reported. 

AXS-05 was also associated with a significantly lower relapse rate compared with placebo (7.5% vs 25.9%; P = .018).

Rates of discontinuation in the double-blind period owing to adverse events (AEs) were low (0% for AXS-05 and 1.9% for placebo). Three serious AEs were reported: one in the AXS-05 group (fecaloma), which was not related to study medication, and two in the placebo group (cardiac arrest, femur fracture).

Falls were reported in four participants in the AXS-05 group, none of which were related to study medication or associated with serious AEs, and in two participants in the placebo group, one of which was associated with femur fracture.

One death was reported in the placebo group. There was no evidence of cognitive decline with AXS-05, and treatment was not associated with sedation. 
 

Promising Agent 

Commenting on this research, Glen R. Finney, MD, director of the Geisinger Memory and Cognition Clinic in Wilkes-Barre, Pennsylvania, said the data “look promising as a safe way to help address acute agitation and reduce agitation reoccurrence.

“Agitation is a common, distressing, and sometimes safety issue for people fighting Alzheimer’s disease, and there’s very little evidence for efficacy and significant side effect issues for current medical management of agitation in Alzheimer’s disease,” said Dr. Finney, who was not part of the study.

He noted that first-line strategies for addressing agitation involve behavioral and environmental interventions. 

“See if there’s a reason for the agitation and address that. Look for triggers for agitation and avoid those. Find places, things, and interactions that help people with Alzheimer’s disease avoid agitation: familiar locations, music, simple engaging activities. Reassurance, redirection, and distraction can help de-escalate agitation. Provide a safe environment that reduces safety risks,” Dr. Finney explained. 

The next step, when medically appropriate, is trying acetylcholinesterase inhibitors such as donepezil, rivastigmine, and galantamine, and then adding memantine, a weak N-methyl-D-aspartate receptor antagonist. 

“These medications can help reduce the risk of agitation,” Dr. Finney said. 

“Beyond that, the evidence becomes weaker for any specific treatments, and that is where treatments with emerging evidence of efficacy and safety like dextromethorphan-bupropion become important,” Dr. Finney added. 

Last May, the US Food and Drug Administration (FDA) approved the antipsychotic brexpiprazole (Rexulti) for Alzheimer’s disease-related agitation, making it the first FDA-approved drug for this indication. 

The drug includes a boxed warning for medications in this class that older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk for death.

“There’s certainly a need to have multiple options for treating agitation in individuals with Alzheimer’s disease,” said Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association. 

Dr. Edelmayer, who was not part of the study, noted that in the ACCORD study, AXS-05 “significantly delayed the relapse or prevented the relapse with Alzheimer’s disease agitation compared with the placebo group and it was generally well tolerated, but it will be important to make sure that there’s more thorough review of the data overall to be sure that it’s both safe and effective.”

The study was funded by Axsome Therapeutics, the manufacturer of AXS-05. Dr. Porsteinsson has disclosed no relevant conflicts of interest. Dr. Finney and Dr. Edelmayer have no relevant disclosures.

A version of this article appeared on Medscape.com.

DENVER — Treatment with AXS-05, a combination of dextromethorphan and bupropion, demonstrated rapid, sustained, and clinically meaningful improvement in agitation related to Alzheimer’s disease and was generally well tolerated in the phase 3 ACCORD trial. 

More than half of participants in the open-label extension period of the randomized clinical trial responded to the medication, which was associated with a 3.6-fold lower risk for relapse compared with placebo. 

“The positive efficacy and favorable safety results with AXS-05 support its potential to fulfill a high unmet need for the treatment of Alzheimer’s disease agitation,” said Anton P. Porsteinsson, MD, director of the Alzheimer’s Disease Care, Research and Education Program, University of Rochester, New York. 

The findings were presented at the 2024 annual meeting of the American Academy of Neurology. 
 

Common and Disruptive

Agitation is reported in up to 70% of patients with Alzheimer’s disease and is characterized by emotional distress, aggressive behaviors, disruptive irritability, and disinhibition. Alzheimer’s disease-related agitation has been associated with increased caregiver burden, decreased functioning, accelerated cognitive decline, earlier nursing home placement, and increased mortality.

A previous phase 2/3 study of AXS-05 showed that the investigative agent led to rapid and significantly improvement in Alzheimer’s disease agitation, as measured by the Cohen-Mansfield Agitation Inventory (CMAI) total score, compared with placebo. 

ACCORD was a phase 3, randomized, double-blind, placebo-controlled withdrawal trial evaluating the efficacy and safety of AXS-05 in patients with Alzheimer’s disease agitation. 

In the open-label period, 178 adults with probable Alzheimer’s disease and clinically significant agitation received AXS-05 (titrated to 45 mg dextromethorphan/105 mg bupropion twice daily) for up to 9 weeks.

A total of 108 (61%) patients had a sustained response, with 30% or more improvement from baseline in the CMAI total score and improvement on the Patient Global Impression of Change that were both maintained for 4 or more consecutive weeks. These patients entered the double-blind phase and were randomly allocated to receive twice-daily AXS-05 or placebo for up to 26 weeks.

In the double-blind period, AXS-05 “substantially and statistically” increased the time to relapse of agitation symptoms compared with placebo (hazard ratio [HR], 0.275; P = .014).

“The risk of relapse was 3.6-fold lower with AXS-05 compared with placebo,” Dr. Porsteinsson reported. 

AXS-05 was also associated with a significantly lower relapse rate compared with placebo (7.5% vs 25.9%; P = .018).

Rates of discontinuation in the double-blind period owing to adverse events (AEs) were low (0% for AXS-05 and 1.9% for placebo). Three serious AEs were reported: one in the AXS-05 group (fecaloma), which was not related to study medication, and two in the placebo group (cardiac arrest, femur fracture).

Falls were reported in four participants in the AXS-05 group, none of which were related to study medication or associated with serious AEs, and in two participants in the placebo group, one of which was associated with femur fracture.

One death was reported in the placebo group. There was no evidence of cognitive decline with AXS-05, and treatment was not associated with sedation. 
 

Promising Agent 

Commenting on this research, Glen R. Finney, MD, director of the Geisinger Memory and Cognition Clinic in Wilkes-Barre, Pennsylvania, said the data “look promising as a safe way to help address acute agitation and reduce agitation reoccurrence.

“Agitation is a common, distressing, and sometimes safety issue for people fighting Alzheimer’s disease, and there’s very little evidence for efficacy and significant side effect issues for current medical management of agitation in Alzheimer’s disease,” said Dr. Finney, who was not part of the study.

He noted that first-line strategies for addressing agitation involve behavioral and environmental interventions. 

“See if there’s a reason for the agitation and address that. Look for triggers for agitation and avoid those. Find places, things, and interactions that help people with Alzheimer’s disease avoid agitation: familiar locations, music, simple engaging activities. Reassurance, redirection, and distraction can help de-escalate agitation. Provide a safe environment that reduces safety risks,” Dr. Finney explained. 

The next step, when medically appropriate, is trying acetylcholinesterase inhibitors such as donepezil, rivastigmine, and galantamine, and then adding memantine, a weak N-methyl-D-aspartate receptor antagonist. 

“These medications can help reduce the risk of agitation,” Dr. Finney said. 

“Beyond that, the evidence becomes weaker for any specific treatments, and that is where treatments with emerging evidence of efficacy and safety like dextromethorphan-bupropion become important,” Dr. Finney added. 

Last May, the US Food and Drug Administration (FDA) approved the antipsychotic brexpiprazole (Rexulti) for Alzheimer’s disease-related agitation, making it the first FDA-approved drug for this indication. 

The drug includes a boxed warning for medications in this class that older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk for death.

“There’s certainly a need to have multiple options for treating agitation in individuals with Alzheimer’s disease,” said Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association. 

Dr. Edelmayer, who was not part of the study, noted that in the ACCORD study, AXS-05 “significantly delayed the relapse or prevented the relapse with Alzheimer’s disease agitation compared with the placebo group and it was generally well tolerated, but it will be important to make sure that there’s more thorough review of the data overall to be sure that it’s both safe and effective.”

The study was funded by Axsome Therapeutics, the manufacturer of AXS-05. Dr. Porsteinsson has disclosed no relevant conflicts of interest. Dr. Finney and Dr. Edelmayer have no relevant disclosures.

A version of this article appeared on Medscape.com.

DENVER — Treatment with AXS-05, a combination of dextromethorphan and bupropion, demonstrated rapid, sustained, and clinically meaningful improvement in agitation related to Alzheimer’s disease and was generally well tolerated in the phase 3 ACCORD trial. 

More than half of participants in the open-label extension period of the randomized clinical trial responded to the medication, which was associated with a 3.6-fold lower risk for relapse compared with placebo. 

“The positive efficacy and favorable safety results with AXS-05 support its potential to fulfill a high unmet need for the treatment of Alzheimer’s disease agitation,” said Anton P. Porsteinsson, MD, director of the Alzheimer’s Disease Care, Research and Education Program, University of Rochester, New York. 

The findings were presented at the 2024 annual meeting of the American Academy of Neurology. 
 

Common and Disruptive

Agitation is reported in up to 70% of patients with Alzheimer’s disease and is characterized by emotional distress, aggressive behaviors, disruptive irritability, and disinhibition. Alzheimer’s disease-related agitation has been associated with increased caregiver burden, decreased functioning, accelerated cognitive decline, earlier nursing home placement, and increased mortality.

A previous phase 2/3 study of AXS-05 showed that the investigative agent led to rapid and significantly improvement in Alzheimer’s disease agitation, as measured by the Cohen-Mansfield Agitation Inventory (CMAI) total score, compared with placebo. 

ACCORD was a phase 3, randomized, double-blind, placebo-controlled withdrawal trial evaluating the efficacy and safety of AXS-05 in patients with Alzheimer’s disease agitation. 

In the open-label period, 178 adults with probable Alzheimer’s disease and clinically significant agitation received AXS-05 (titrated to 45 mg dextromethorphan/105 mg bupropion twice daily) for up to 9 weeks.

A total of 108 (61%) patients had a sustained response, with 30% or more improvement from baseline in the CMAI total score and improvement on the Patient Global Impression of Change that were both maintained for 4 or more consecutive weeks. These patients entered the double-blind phase and were randomly allocated to receive twice-daily AXS-05 or placebo for up to 26 weeks.

In the double-blind period, AXS-05 “substantially and statistically” increased the time to relapse of agitation symptoms compared with placebo (hazard ratio [HR], 0.275; P = .014).

“The risk of relapse was 3.6-fold lower with AXS-05 compared with placebo,” Dr. Porsteinsson reported. 

AXS-05 was also associated with a significantly lower relapse rate compared with placebo (7.5% vs 25.9%; P = .018).

Rates of discontinuation in the double-blind period owing to adverse events (AEs) were low (0% for AXS-05 and 1.9% for placebo). Three serious AEs were reported: one in the AXS-05 group (fecaloma), which was not related to study medication, and two in the placebo group (cardiac arrest, femur fracture).

Falls were reported in four participants in the AXS-05 group, none of which were related to study medication or associated with serious AEs, and in two participants in the placebo group, one of which was associated with femur fracture.

One death was reported in the placebo group. There was no evidence of cognitive decline with AXS-05, and treatment was not associated with sedation. 
 

Promising Agent 

Commenting on this research, Glen R. Finney, MD, director of the Geisinger Memory and Cognition Clinic in Wilkes-Barre, Pennsylvania, said the data “look promising as a safe way to help address acute agitation and reduce agitation reoccurrence.

“Agitation is a common, distressing, and sometimes safety issue for people fighting Alzheimer’s disease, and there’s very little evidence for efficacy and significant side effect issues for current medical management of agitation in Alzheimer’s disease,” said Dr. Finney, who was not part of the study.

He noted that first-line strategies for addressing agitation involve behavioral and environmental interventions. 

“See if there’s a reason for the agitation and address that. Look for triggers for agitation and avoid those. Find places, things, and interactions that help people with Alzheimer’s disease avoid agitation: familiar locations, music, simple engaging activities. Reassurance, redirection, and distraction can help de-escalate agitation. Provide a safe environment that reduces safety risks,” Dr. Finney explained. 

The next step, when medically appropriate, is trying acetylcholinesterase inhibitors such as donepezil, rivastigmine, and galantamine, and then adding memantine, a weak N-methyl-D-aspartate receptor antagonist. 

“These medications can help reduce the risk of agitation,” Dr. Finney said. 

“Beyond that, the evidence becomes weaker for any specific treatments, and that is where treatments with emerging evidence of efficacy and safety like dextromethorphan-bupropion become important,” Dr. Finney added. 

Last May, the US Food and Drug Administration (FDA) approved the antipsychotic brexpiprazole (Rexulti) for Alzheimer’s disease-related agitation, making it the first FDA-approved drug for this indication. 

The drug includes a boxed warning for medications in this class that older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk for death.

“There’s certainly a need to have multiple options for treating agitation in individuals with Alzheimer’s disease,” said Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association. 

Dr. Edelmayer, who was not part of the study, noted that in the ACCORD study, AXS-05 “significantly delayed the relapse or prevented the relapse with Alzheimer’s disease agitation compared with the placebo group and it was generally well tolerated, but it will be important to make sure that there’s more thorough review of the data overall to be sure that it’s both safe and effective.”

The study was funded by Axsome Therapeutics, the manufacturer of AXS-05. Dr. Porsteinsson has disclosed no relevant conflicts of interest. Dr. Finney and Dr. Edelmayer have no relevant disclosures.

A version of this article appeared on Medscape.com.

DENVER — Patients with pediatric-onset multiple sclerosis (POMS) are often prescribed low-efficacy disease-modifying therapies (DMTs), but a new retrospective analysis suggests that, like adults, this patient population may benefit from early treatment with high-efficacy DMTs.

“I think it’s very important to highlight that we are seeing that traditionally, kids are just started on lower-efficacy treatments and they keep relapsing. If we can show that when they get transitioned to high-efficacy treatments, the relapses are lessening, I’m hoping that can then push for better clinical trials with pediatric patients included,” said Frederick Bassal, DO, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology. He is a pediatric neurologist at University of California, Davis.

The first line for POMS is generally low-efficacy DMTs like interferon-beta and glatiramer acetate, but these medications may not effectively control disease progression, according to the study authors, and this could lead to pediatric patients being changed to more potent therapies. That can include moderate-efficacy drugs like S1P inhibitors and fumarates, or high-efficacy DMTS such as B cell depletors and alpha 4 integrin receptor antibodies.
 

Treatment Strategies

“Right now what we’re seeing is the conservative approach — starting low and working up with the younger and adolescent patients. I’m speculating, and I want to look more into it. Is [it maybe] because of insurance approval?” said study coauthor Amara Miller, a medical student at the University of Arizona College of Medicine in Phoenix.

The findings aren’t surprising, according to Barbara Giesser, MD, who was asked to comment on the study. “It is in line with what we think we know about people with adult MS — that if you start early on with a more effective therapy, you tend to have better outcomes,” said Dr. Giesser, director of the MS program at the Pacific Neuroscience Institute.

Another reason to consider higher-efficacy DMTs is that children with MS can have cognitive problems and delays. “There’s a suggestion that if you treat with highly-effective DMT that you might be able to abrogate some of that,” said Dr. Giesser.

Among the approximately two dozen FDA-approved disease-modifying therapies for MS, only fingolimod (Gilenya, Novartis) is approved for children and adolescents. “All of the others are used off label, but I think perhaps, if you have more studies that [show] that children do better if you treat with more effective therapies early on, perhaps we might see more on-label indications for use in a pediatric population,” said Dr. Giesser.

The finding that obesity was associated with a higher likelihood of having multiple therapies is also interesting, she said. “We’re beginning to see that obesity in adults as well seems to portend less favorable neurologic outcomes.”
 

Study Methodology

The researchers analyzed data from 135 POMS patients between 2012 and 2023.

The mean age of participants was 15 years, 60% were female, and 120 of 135 were White, while 76 were of Hispanic ethnicity. Overweight and obesity were common, with 36 and 43 participants in each category. The initial therapy was a low-efficacy DMT in 23.0% of participants, moderate-efficacy in 37.0%, and high-efficacy in 24.4%, while 1.5% received some other kind of medication and 14.1% received no medication. The annualized relapse rate was 0.932, and the mean EDSS score was 0.88.

Patients who underwent three or medication changes had lower EDSS scores than those who underwent zero to 2 (P = .00607).

Over the course of the study, the percentage of patients who received high-efficacy DMTs rose from 25.9% to 48.9%, largely due to changes in medication. Of those initially prescribed low-efficacy DMTs, 77.4% were eventually switched to high-efficacy DMTs.

Every patient who underwent three or more medication changes was initially prescribed a low-efficacy DMT.

Patients started on low-efficacy drugs had a mean of 1.42 medication changes, compared with 0.94 in the moderate-efficacy group and 0.51 in the high-efficacy group. The reasons for changing from the first medication included relapse (36), side effects (11), patient choice or compliance (8), and pregnancy (2).

Patients 10 years or younger were more likely to be initially prescribed a low-efficacy therapy (odds ratio [OR], 5.72; P = .0366), while older patients were more likely to be prescribed moderate- or high-efficacy therapies (OR, 14.44; P = .0012).

There were more total medication changes in the low-efficacy group than the high initial DMT group (P = .000305).

Asked what advice they would give to physicians treating POMS patients, Ms. Miller suggested a top-down approach. “We want to look at if maybe we can start with higher efficacy DMT’s and maybe titering it down. That may be an option,” said Ms. Miller.

Dr. Bassal highlighted the importance of shared decision-making. “We want to go over the options, that we recommend higher-efficacy [DMTs] for these reasons. But every individual is different. And there may be fears that are very reasonable that families have. I think in those cases, it’s also reasonable to make a shared decision. And if that means going with something like an oral, moderate- to lower-efficacy [therapy], that’s okay, because compliance is key, and if you start something where the family is afraid of side effects, or there are side effects, then you kind of lost that opportunity,” he said.

Dr. Bassal, Dr. Giesser, and Ms. Miller have no relevant financial disclosures.

DENVER — Patients with pediatric-onset multiple sclerosis (POMS) are often prescribed low-efficacy disease-modifying therapies (DMTs), but a new retrospective analysis suggests that, like adults, this patient population may benefit from early treatment with high-efficacy DMTs.

“I think it’s very important to highlight that we are seeing that traditionally, kids are just started on lower-efficacy treatments and they keep relapsing. If we can show that when they get transitioned to high-efficacy treatments, the relapses are lessening, I’m hoping that can then push for better clinical trials with pediatric patients included,” said Frederick Bassal, DO, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology. He is a pediatric neurologist at University of California, Davis.

The first line for POMS is generally low-efficacy DMTs like interferon-beta and glatiramer acetate, but these medications may not effectively control disease progression, according to the study authors, and this could lead to pediatric patients being changed to more potent therapies. That can include moderate-efficacy drugs like S1P inhibitors and fumarates, or high-efficacy DMTS such as B cell depletors and alpha 4 integrin receptor antibodies.
 

Treatment Strategies

“Right now what we’re seeing is the conservative approach — starting low and working up with the younger and adolescent patients. I’m speculating, and I want to look more into it. Is [it maybe] because of insurance approval?” said study coauthor Amara Miller, a medical student at the University of Arizona College of Medicine in Phoenix.

The findings aren’t surprising, according to Barbara Giesser, MD, who was asked to comment on the study. “It is in line with what we think we know about people with adult MS — that if you start early on with a more effective therapy, you tend to have better outcomes,” said Dr. Giesser, director of the MS program at the Pacific Neuroscience Institute.

Another reason to consider higher-efficacy DMTs is that children with MS can have cognitive problems and delays. “There’s a suggestion that if you treat with highly-effective DMT that you might be able to abrogate some of that,” said Dr. Giesser.

Among the approximately two dozen FDA-approved disease-modifying therapies for MS, only fingolimod (Gilenya, Novartis) is approved for children and adolescents. “All of the others are used off label, but I think perhaps, if you have more studies that [show] that children do better if you treat with more effective therapies early on, perhaps we might see more on-label indications for use in a pediatric population,” said Dr. Giesser.

The finding that obesity was associated with a higher likelihood of having multiple therapies is also interesting, she said. “We’re beginning to see that obesity in adults as well seems to portend less favorable neurologic outcomes.”
 

Study Methodology

The researchers analyzed data from 135 POMS patients between 2012 and 2023.

The mean age of participants was 15 years, 60% were female, and 120 of 135 were White, while 76 were of Hispanic ethnicity. Overweight and obesity were common, with 36 and 43 participants in each category. The initial therapy was a low-efficacy DMT in 23.0% of participants, moderate-efficacy in 37.0%, and high-efficacy in 24.4%, while 1.5% received some other kind of medication and 14.1% received no medication. The annualized relapse rate was 0.932, and the mean EDSS score was 0.88.

Patients who underwent three or medication changes had lower EDSS scores than those who underwent zero to 2 (P = .00607).

Over the course of the study, the percentage of patients who received high-efficacy DMTs rose from 25.9% to 48.9%, largely due to changes in medication. Of those initially prescribed low-efficacy DMTs, 77.4% were eventually switched to high-efficacy DMTs.

Every patient who underwent three or more medication changes was initially prescribed a low-efficacy DMT.

Patients started on low-efficacy drugs had a mean of 1.42 medication changes, compared with 0.94 in the moderate-efficacy group and 0.51 in the high-efficacy group. The reasons for changing from the first medication included relapse (36), side effects (11), patient choice or compliance (8), and pregnancy (2).

Patients 10 years or younger were more likely to be initially prescribed a low-efficacy therapy (odds ratio [OR], 5.72; P = .0366), while older patients were more likely to be prescribed moderate- or high-efficacy therapies (OR, 14.44; P = .0012).

There were more total medication changes in the low-efficacy group than the high initial DMT group (P = .000305).

Asked what advice they would give to physicians treating POMS patients, Ms. Miller suggested a top-down approach. “We want to look at if maybe we can start with higher efficacy DMT’s and maybe titering it down. That may be an option,” said Ms. Miller.

Dr. Bassal highlighted the importance of shared decision-making. “We want to go over the options, that we recommend higher-efficacy [DMTs] for these reasons. But every individual is different. And there may be fears that are very reasonable that families have. I think in those cases, it’s also reasonable to make a shared decision. And if that means going with something like an oral, moderate- to lower-efficacy [therapy], that’s okay, because compliance is key, and if you start something where the family is afraid of side effects, or there are side effects, then you kind of lost that opportunity,” he said.

Dr. Bassal, Dr. Giesser, and Ms. Miller have no relevant financial disclosures.

DENVER — Patients with pediatric-onset multiple sclerosis (POMS) are often prescribed low-efficacy disease-modifying therapies (DMTs), but a new retrospective analysis suggests that, like adults, this patient population may benefit from early treatment with high-efficacy DMTs.

“I think it’s very important to highlight that we are seeing that traditionally, kids are just started on lower-efficacy treatments and they keep relapsing. If we can show that when they get transitioned to high-efficacy treatments, the relapses are lessening, I’m hoping that can then push for better clinical trials with pediatric patients included,” said Frederick Bassal, DO, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology. He is a pediatric neurologist at University of California, Davis.

The first line for POMS is generally low-efficacy DMTs like interferon-beta and glatiramer acetate, but these medications may not effectively control disease progression, according to the study authors, and this could lead to pediatric patients being changed to more potent therapies. That can include moderate-efficacy drugs like S1P inhibitors and fumarates, or high-efficacy DMTS such as B cell depletors and alpha 4 integrin receptor antibodies.
 

Treatment Strategies

“Right now what we’re seeing is the conservative approach — starting low and working up with the younger and adolescent patients. I’m speculating, and I want to look more into it. Is [it maybe] because of insurance approval?” said study coauthor Amara Miller, a medical student at the University of Arizona College of Medicine in Phoenix.

The findings aren’t surprising, according to Barbara Giesser, MD, who was asked to comment on the study. “It is in line with what we think we know about people with adult MS — that if you start early on with a more effective therapy, you tend to have better outcomes,” said Dr. Giesser, director of the MS program at the Pacific Neuroscience Institute.

Another reason to consider higher-efficacy DMTs is that children with MS can have cognitive problems and delays. “There’s a suggestion that if you treat with highly-effective DMT that you might be able to abrogate some of that,” said Dr. Giesser.

Among the approximately two dozen FDA-approved disease-modifying therapies for MS, only fingolimod (Gilenya, Novartis) is approved for children and adolescents. “All of the others are used off label, but I think perhaps, if you have more studies that [show] that children do better if you treat with more effective therapies early on, perhaps we might see more on-label indications for use in a pediatric population,” said Dr. Giesser.

The finding that obesity was associated with a higher likelihood of having multiple therapies is also interesting, she said. “We’re beginning to see that obesity in adults as well seems to portend less favorable neurologic outcomes.”
 

Study Methodology

The researchers analyzed data from 135 POMS patients between 2012 and 2023.

The mean age of participants was 15 years, 60% were female, and 120 of 135 were White, while 76 were of Hispanic ethnicity. Overweight and obesity were common, with 36 and 43 participants in each category. The initial therapy was a low-efficacy DMT in 23.0% of participants, moderate-efficacy in 37.0%, and high-efficacy in 24.4%, while 1.5% received some other kind of medication and 14.1% received no medication. The annualized relapse rate was 0.932, and the mean EDSS score was 0.88.

Patients who underwent three or medication changes had lower EDSS scores than those who underwent zero to 2 (P = .00607).

Over the course of the study, the percentage of patients who received high-efficacy DMTs rose from 25.9% to 48.9%, largely due to changes in medication. Of those initially prescribed low-efficacy DMTs, 77.4% were eventually switched to high-efficacy DMTs.

Every patient who underwent three or more medication changes was initially prescribed a low-efficacy DMT.

Patients started on low-efficacy drugs had a mean of 1.42 medication changes, compared with 0.94 in the moderate-efficacy group and 0.51 in the high-efficacy group. The reasons for changing from the first medication included relapse (36), side effects (11), patient choice or compliance (8), and pregnancy (2).

Patients 10 years or younger were more likely to be initially prescribed a low-efficacy therapy (odds ratio [OR], 5.72; P = .0366), while older patients were more likely to be prescribed moderate- or high-efficacy therapies (OR, 14.44; P = .0012).

There were more total medication changes in the low-efficacy group than the high initial DMT group (P = .000305).

Asked what advice they would give to physicians treating POMS patients, Ms. Miller suggested a top-down approach. “We want to look at if maybe we can start with higher efficacy DMT’s and maybe titering it down. That may be an option,” said Ms. Miller.

Dr. Bassal highlighted the importance of shared decision-making. “We want to go over the options, that we recommend higher-efficacy [DMTs] for these reasons. But every individual is different. And there may be fears that are very reasonable that families have. I think in those cases, it’s also reasonable to make a shared decision. And if that means going with something like an oral, moderate- to lower-efficacy [therapy], that’s okay, because compliance is key, and if you start something where the family is afraid of side effects, or there are side effects, then you kind of lost that opportunity,” he said.

Dr. Bassal, Dr. Giesser, and Ms. Miller have no relevant financial disclosures.

The first peer-reviewed consensus statement on healthcare for children with neurodevelopmental disabilities (NDDs) is meant to start correcting the inequitable access to appropriate care that these children experience compared with their peers without NDDs. The statement was published in Pediatrics.

The disparities in healthcare culture, mindset, and practice often start in childhood for young people with conditions including autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder (ADHD), wrote co–first authors Carol Weitzman, MD, co-director of the Autism Spectrum Center at Boston Children’s Hospital, Boston, Massachusetts, and Cy Nadler, PhD, section chief of Autism Psychology at Children’s Mercy in Kansas City, Missouri, and colleagues.

Without better access to safe and appropriate care, people with NDDs experience more seclusion, accidents, restraints, and injury in healthcare encounters, the researchers wrote.
 

‘Accessible, Humane, Effective Care’

“At the heart of this consensus statement is an affirmation that all people are entitled to healthcare that is accessible, humane, and effective,” they wrote.

The consensus statement was developed as part of the Supporting Access for Everyone (SAFE) Initiative, launched by the Developmental Behavioral Pediatric Research Network and the Association of University Centers on Disability. The consensus panel comprised professionals, caregivers, and adults with NDDs. After a 2-day public forum, the consensus panel held a conference and developed a statement on SAFE care, an NDD Health Care Bill of Rights and Transition Considerations. They developed 10 statements across five domains: training; communication; access and planning; diversity, equity, inclusion, belonging, and anti-ableism; and policy and structural change.
 

Asking the Patient ‘What do You Need?’

One theme in the statement that may have the most impact is “the importance of asking the person in front of you what they need,” and building a care plan around that, said senior author Marilyn Augustyn, MD, Director of the Division of Developmental and Behavioral Pediatrics at Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts. “The medical community hasn’t done that very well for individuals with neurodevelopmental disabilities.”

Dr. Weitzman added: “Traditionally in healthcare settings, we’ve asked people to check their disabilities at the door.” Many people with neurodevelopmental disabilities often have “invisible disabilities,” she said, explaining that patients may have accommodation needs that aren’t immediately obvious, but could improve their access to care, so asking them what they need is critical.
 

Examples of ‘Ableism’

The consensus statement also calls attention to structural “ableism” or policies or practices that favor able-bodied people over those with disabilities and details the need for more training and changed policies.

The paper gives some examples of ableism, such as inappropriately excluding people with NDDs from research; staff assuming nonspeaking patients have no capacity for communication; or lack of awareness of sensory needs before using cold stethoscopes or flashing direct light into eyes.

Dr. Weitzman says this work is just the beginning of a complex process. It is intended to be the driver for developing curriculum to train all clinicians and others working with patients about neurodevelopmental disabilities. The hope is it will lead to more research to formalize best practices and make policies mandatory rather than optional.

The urgency in highlighting these issues is partly related to the prevalence of children and adolescents with neurodevelopmental disabilities, which the paper states is approximately 1 in 6.

But there are personal reasons as well for the team who developed the statement.

“We just believe that it is just a human right,” Dr. Weitzman said. “Having a neurodevelopmental disability does not make you any less entitled to good care. “

Dr. Augustyn added, “The children I’ve had the honor of caring for for the last 30 years deserve all this care and more. I think it’s time.”

This work was supported by the Developmental Behavioral Pediatric Research Network and the Association of University Centers on Disability. Dr. Weitzman is a past consultant for Helios/Meliora. The other authors report no relevant financial relationships.

The first peer-reviewed consensus statement on healthcare for children with neurodevelopmental disabilities (NDDs) is meant to start correcting the inequitable access to appropriate care that these children experience compared with their peers without NDDs. The statement was published in Pediatrics.

The disparities in healthcare culture, mindset, and practice often start in childhood for young people with conditions including autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder (ADHD), wrote co–first authors Carol Weitzman, MD, co-director of the Autism Spectrum Center at Boston Children’s Hospital, Boston, Massachusetts, and Cy Nadler, PhD, section chief of Autism Psychology at Children’s Mercy in Kansas City, Missouri, and colleagues.

Without better access to safe and appropriate care, people with NDDs experience more seclusion, accidents, restraints, and injury in healthcare encounters, the researchers wrote.
 

‘Accessible, Humane, Effective Care’

“At the heart of this consensus statement is an affirmation that all people are entitled to healthcare that is accessible, humane, and effective,” they wrote.

The consensus statement was developed as part of the Supporting Access for Everyone (SAFE) Initiative, launched by the Developmental Behavioral Pediatric Research Network and the Association of University Centers on Disability. The consensus panel comprised professionals, caregivers, and adults with NDDs. After a 2-day public forum, the consensus panel held a conference and developed a statement on SAFE care, an NDD Health Care Bill of Rights and Transition Considerations. They developed 10 statements across five domains: training; communication; access and planning; diversity, equity, inclusion, belonging, and anti-ableism; and policy and structural change.
 

Asking the Patient ‘What do You Need?’

One theme in the statement that may have the most impact is “the importance of asking the person in front of you what they need,” and building a care plan around that, said senior author Marilyn Augustyn, MD, Director of the Division of Developmental and Behavioral Pediatrics at Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts. “The medical community hasn’t done that very well for individuals with neurodevelopmental disabilities.”

Dr. Weitzman added: “Traditionally in healthcare settings, we’ve asked people to check their disabilities at the door.” Many people with neurodevelopmental disabilities often have “invisible disabilities,” she said, explaining that patients may have accommodation needs that aren’t immediately obvious, but could improve their access to care, so asking them what they need is critical.
 

Examples of ‘Ableism’

The consensus statement also calls attention to structural “ableism” or policies or practices that favor able-bodied people over those with disabilities and details the need for more training and changed policies.

The paper gives some examples of ableism, such as inappropriately excluding people with NDDs from research; staff assuming nonspeaking patients have no capacity for communication; or lack of awareness of sensory needs before using cold stethoscopes or flashing direct light into eyes.

Dr. Weitzman says this work is just the beginning of a complex process. It is intended to be the driver for developing curriculum to train all clinicians and others working with patients about neurodevelopmental disabilities. The hope is it will lead to more research to formalize best practices and make policies mandatory rather than optional.

The urgency in highlighting these issues is partly related to the prevalence of children and adolescents with neurodevelopmental disabilities, which the paper states is approximately 1 in 6.

But there are personal reasons as well for the team who developed the statement.

“We just believe that it is just a human right,” Dr. Weitzman said. “Having a neurodevelopmental disability does not make you any less entitled to good care. “

Dr. Augustyn added, “The children I’ve had the honor of caring for for the last 30 years deserve all this care and more. I think it’s time.”

This work was supported by the Developmental Behavioral Pediatric Research Network and the Association of University Centers on Disability. Dr. Weitzman is a past consultant for Helios/Meliora. The other authors report no relevant financial relationships.

The first peer-reviewed consensus statement on healthcare for children with neurodevelopmental disabilities (NDDs) is meant to start correcting the inequitable access to appropriate care that these children experience compared with their peers without NDDs. The statement was published in Pediatrics.

The disparities in healthcare culture, mindset, and practice often start in childhood for young people with conditions including autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder (ADHD), wrote co–first authors Carol Weitzman, MD, co-director of the Autism Spectrum Center at Boston Children’s Hospital, Boston, Massachusetts, and Cy Nadler, PhD, section chief of Autism Psychology at Children’s Mercy in Kansas City, Missouri, and colleagues.

Without better access to safe and appropriate care, people with NDDs experience more seclusion, accidents, restraints, and injury in healthcare encounters, the researchers wrote.
 

‘Accessible, Humane, Effective Care’

“At the heart of this consensus statement is an affirmation that all people are entitled to healthcare that is accessible, humane, and effective,” they wrote.

The consensus statement was developed as part of the Supporting Access for Everyone (SAFE) Initiative, launched by the Developmental Behavioral Pediatric Research Network and the Association of University Centers on Disability. The consensus panel comprised professionals, caregivers, and adults with NDDs. After a 2-day public forum, the consensus panel held a conference and developed a statement on SAFE care, an NDD Health Care Bill of Rights and Transition Considerations. They developed 10 statements across five domains: training; communication; access and planning; diversity, equity, inclusion, belonging, and anti-ableism; and policy and structural change.
 

Asking the Patient ‘What do You Need?’

One theme in the statement that may have the most impact is “the importance of asking the person in front of you what they need,” and building a care plan around that, said senior author Marilyn Augustyn, MD, Director of the Division of Developmental and Behavioral Pediatrics at Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts. “The medical community hasn’t done that very well for individuals with neurodevelopmental disabilities.”

Dr. Weitzman added: “Traditionally in healthcare settings, we’ve asked people to check their disabilities at the door.” Many people with neurodevelopmental disabilities often have “invisible disabilities,” she said, explaining that patients may have accommodation needs that aren’t immediately obvious, but could improve their access to care, so asking them what they need is critical.
 

Examples of ‘Ableism’

The consensus statement also calls attention to structural “ableism” or policies or practices that favor able-bodied people over those with disabilities and details the need for more training and changed policies.

The paper gives some examples of ableism, such as inappropriately excluding people with NDDs from research; staff assuming nonspeaking patients have no capacity for communication; or lack of awareness of sensory needs before using cold stethoscopes or flashing direct light into eyes.

Dr. Weitzman says this work is just the beginning of a complex process. It is intended to be the driver for developing curriculum to train all clinicians and others working with patients about neurodevelopmental disabilities. The hope is it will lead to more research to formalize best practices and make policies mandatory rather than optional.

The urgency in highlighting these issues is partly related to the prevalence of children and adolescents with neurodevelopmental disabilities, which the paper states is approximately 1 in 6.

But there are personal reasons as well for the team who developed the statement.

“We just believe that it is just a human right,” Dr. Weitzman said. “Having a neurodevelopmental disability does not make you any less entitled to good care. “

Dr. Augustyn added, “The children I’ve had the honor of caring for for the last 30 years deserve all this care and more. I think it’s time.”

This work was supported by the Developmental Behavioral Pediatric Research Network and the Association of University Centers on Disability. Dr. Weitzman is a past consultant for Helios/Meliora. The other authors report no relevant financial relationships.

DENVER — Lidocaine injections into the greater occipital nerve relieve severe, refractory migraine attacks in children, results of a randomized controlled trial show. 

Investigators found children receiving bilateral occipital nerve blocks with 2% lidocaine had significantly greater pain relief than that of peers receiving saline injections. 

Cases series have shown a benefit of peripheral nerve blocks (PNBs) — injections of local anesthetics over branches of the occipital or trigeminal nerve — for severe, refractory headache in children.  

Although 80% of pediatric headache specialists use PNBs, there is “inconsistent insurance coverage” for this treatment, which had not been tested in a randomized controlled trial in children before now, lead investigator Christina Szperka, MD, with the Pediatric Headache Program, Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, told delegates attending the 2024 annual meeting of the American Academy of Neurology. 
 

Significant Results

Investigators enrolled 58 children and adolescents with acute status migrainosus. The mean age was 16 years, and reported gender was female for 44 participants, male for 11 participants, and nonbinary or transgender in 3 participants. Participants had a migraine flare duration of 22 days and had not responded to other treatments. 

All participants had topical lidocaine cream applied for 30 minutes as a run-in step and could decline injections if they experienced sufficient benefit from cream alone. 

“We used a lidocaine cream lead-in for two reasons. One was to try to see if we could address the issue of high placebo response in pediatric trials in particular, and also to see if we could help with blinding to injection,” said Dr. Szperka. 

Topical lidocaine cream led to a small decrease in pain score overall (0.2 point on a 0-10 scale), and all participants proceeded to randomized blinded bilateral greater occipital nerve injection with 2% lidocaine or saline, she reported. 

On the primary endpoint — change in pain score at 30 minutes — lidocaine was significantly more effective than saline, achieving a 2.3-point decrease on average (on a 0-10 scale) vs a 1.1-point decrease with saline (P = .01).

A 2-point pain reduction was achieved in 69% of patients in the lidocaine group versus 34% in the saline group.

Three quarters (76%) of patients getting lidocaine reported at least partial relief in severity or location of pain compared with 48% of those getting saline (P = .03). Rates of pain freedom at 30 minutes were 17% and 7%, respectively, and at 24 hours were 14% and 0%, respectively.

The majority of adverse events were mild and fairly equal across groups and included anxiety, worsening headache, injection site pain, dizziness, and numbness (more so with lidocaine). There was one case of anaphylaxis after lidocaine injection.

Quite unexpectedly, said Dr. Szperka, patients rated the saline injection as more painful than the lidocaine injection. “This was not what I expected going in, and I think is relevant for future trials,” she said.
 

Encouraging Results 

Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, said that as a neurologist and pain physician, he sees firsthand the “devastating impact of status migrainosus on children.”

“These debilitating headaches can rob them of precious school days, hindering learning and social interaction,” said Dr. Lakhan. “The constant pain and fear of the next attack can also take a toll on their emotional well-being.”

The impact on families is significant as well, highlighting the need to find more effective treatments, Dr. Lakhan said. 

“Traditionally, we’ve relied on case studies to see the benefits of nerve blocks for migraine in younger patients. This is the first randomized controlled trial that shows lidocaine injections can be significantly more effective than a placebo for these unrelenting migraines,” he said.

“It’s important to note that this is a relatively small study, and not without safety concerns, including rare but potentially life-threatening anaphylaxis to lidocaine,” Dr. Lakhan added. “More research is needed, but these findings are encouraging. Lidocaine injections could become a valuable tool for managing treatment-resistant migraines in adolescents and young adults.”

The study was supported by a grant from the National Institute of Neurological Disorders and Stroke. Dr. Szperka is a consultant for AbbVie and Teva; serves on a Data Safety Monitoring Board for Eli Lilly and Upsher-Smith; and is a site principal investigator for AbbVie, Amgen, Biohaven/Pfizer, Teva, and Theranica. Dr. Lakhan had no disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — Lidocaine injections into the greater occipital nerve relieve severe, refractory migraine attacks in children, results of a randomized controlled trial show. 

Investigators found children receiving bilateral occipital nerve blocks with 2% lidocaine had significantly greater pain relief than that of peers receiving saline injections. 

Cases series have shown a benefit of peripheral nerve blocks (PNBs) — injections of local anesthetics over branches of the occipital or trigeminal nerve — for severe, refractory headache in children.  

Although 80% of pediatric headache specialists use PNBs, there is “inconsistent insurance coverage” for this treatment, which had not been tested in a randomized controlled trial in children before now, lead investigator Christina Szperka, MD, with the Pediatric Headache Program, Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, told delegates attending the 2024 annual meeting of the American Academy of Neurology. 
 

Significant Results

Investigators enrolled 58 children and adolescents with acute status migrainosus. The mean age was 16 years, and reported gender was female for 44 participants, male for 11 participants, and nonbinary or transgender in 3 participants. Participants had a migraine flare duration of 22 days and had not responded to other treatments. 

All participants had topical lidocaine cream applied for 30 minutes as a run-in step and could decline injections if they experienced sufficient benefit from cream alone. 

“We used a lidocaine cream lead-in for two reasons. One was to try to see if we could address the issue of high placebo response in pediatric trials in particular, and also to see if we could help with blinding to injection,” said Dr. Szperka. 

Topical lidocaine cream led to a small decrease in pain score overall (0.2 point on a 0-10 scale), and all participants proceeded to randomized blinded bilateral greater occipital nerve injection with 2% lidocaine or saline, she reported. 

On the primary endpoint — change in pain score at 30 minutes — lidocaine was significantly more effective than saline, achieving a 2.3-point decrease on average (on a 0-10 scale) vs a 1.1-point decrease with saline (P = .01).

A 2-point pain reduction was achieved in 69% of patients in the lidocaine group versus 34% in the saline group.

Three quarters (76%) of patients getting lidocaine reported at least partial relief in severity or location of pain compared with 48% of those getting saline (P = .03). Rates of pain freedom at 30 minutes were 17% and 7%, respectively, and at 24 hours were 14% and 0%, respectively.

The majority of adverse events were mild and fairly equal across groups and included anxiety, worsening headache, injection site pain, dizziness, and numbness (more so with lidocaine). There was one case of anaphylaxis after lidocaine injection.

Quite unexpectedly, said Dr. Szperka, patients rated the saline injection as more painful than the lidocaine injection. “This was not what I expected going in, and I think is relevant for future trials,” she said.
 

Encouraging Results 

Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, said that as a neurologist and pain physician, he sees firsthand the “devastating impact of status migrainosus on children.”

“These debilitating headaches can rob them of precious school days, hindering learning and social interaction,” said Dr. Lakhan. “The constant pain and fear of the next attack can also take a toll on their emotional well-being.”

The impact on families is significant as well, highlighting the need to find more effective treatments, Dr. Lakhan said. 

“Traditionally, we’ve relied on case studies to see the benefits of nerve blocks for migraine in younger patients. This is the first randomized controlled trial that shows lidocaine injections can be significantly more effective than a placebo for these unrelenting migraines,” he said.

“It’s important to note that this is a relatively small study, and not without safety concerns, including rare but potentially life-threatening anaphylaxis to lidocaine,” Dr. Lakhan added. “More research is needed, but these findings are encouraging. Lidocaine injections could become a valuable tool for managing treatment-resistant migraines in adolescents and young adults.”

The study was supported by a grant from the National Institute of Neurological Disorders and Stroke. Dr. Szperka is a consultant for AbbVie and Teva; serves on a Data Safety Monitoring Board for Eli Lilly and Upsher-Smith; and is a site principal investigator for AbbVie, Amgen, Biohaven/Pfizer, Teva, and Theranica. Dr. Lakhan had no disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — Lidocaine injections into the greater occipital nerve relieve severe, refractory migraine attacks in children, results of a randomized controlled trial show. 

Investigators found children receiving bilateral occipital nerve blocks with 2% lidocaine had significantly greater pain relief than that of peers receiving saline injections. 

Cases series have shown a benefit of peripheral nerve blocks (PNBs) — injections of local anesthetics over branches of the occipital or trigeminal nerve — for severe, refractory headache in children.  

Although 80% of pediatric headache specialists use PNBs, there is “inconsistent insurance coverage” for this treatment, which had not been tested in a randomized controlled trial in children before now, lead investigator Christina Szperka, MD, with the Pediatric Headache Program, Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, told delegates attending the 2024 annual meeting of the American Academy of Neurology. 
 

Significant Results

Investigators enrolled 58 children and adolescents with acute status migrainosus. The mean age was 16 years, and reported gender was female for 44 participants, male for 11 participants, and nonbinary or transgender in 3 participants. Participants had a migraine flare duration of 22 days and had not responded to other treatments. 

All participants had topical lidocaine cream applied for 30 minutes as a run-in step and could decline injections if they experienced sufficient benefit from cream alone. 

“We used a lidocaine cream lead-in for two reasons. One was to try to see if we could address the issue of high placebo response in pediatric trials in particular, and also to see if we could help with blinding to injection,” said Dr. Szperka. 

Topical lidocaine cream led to a small decrease in pain score overall (0.2 point on a 0-10 scale), and all participants proceeded to randomized blinded bilateral greater occipital nerve injection with 2% lidocaine or saline, she reported. 

On the primary endpoint — change in pain score at 30 minutes — lidocaine was significantly more effective than saline, achieving a 2.3-point decrease on average (on a 0-10 scale) vs a 1.1-point decrease with saline (P = .01).

A 2-point pain reduction was achieved in 69% of patients in the lidocaine group versus 34% in the saline group.

Three quarters (76%) of patients getting lidocaine reported at least partial relief in severity or location of pain compared with 48% of those getting saline (P = .03). Rates of pain freedom at 30 minutes were 17% and 7%, respectively, and at 24 hours were 14% and 0%, respectively.

The majority of adverse events were mild and fairly equal across groups and included anxiety, worsening headache, injection site pain, dizziness, and numbness (more so with lidocaine). There was one case of anaphylaxis after lidocaine injection.

Quite unexpectedly, said Dr. Szperka, patients rated the saline injection as more painful than the lidocaine injection. “This was not what I expected going in, and I think is relevant for future trials,” she said.
 

Encouraging Results 

Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, said that as a neurologist and pain physician, he sees firsthand the “devastating impact of status migrainosus on children.”

“These debilitating headaches can rob them of precious school days, hindering learning and social interaction,” said Dr. Lakhan. “The constant pain and fear of the next attack can also take a toll on their emotional well-being.”

The impact on families is significant as well, highlighting the need to find more effective treatments, Dr. Lakhan said. 

“Traditionally, we’ve relied on case studies to see the benefits of nerve blocks for migraine in younger patients. This is the first randomized controlled trial that shows lidocaine injections can be significantly more effective than a placebo for these unrelenting migraines,” he said.

“It’s important to note that this is a relatively small study, and not without safety concerns, including rare but potentially life-threatening anaphylaxis to lidocaine,” Dr. Lakhan added. “More research is needed, but these findings are encouraging. Lidocaine injections could become a valuable tool for managing treatment-resistant migraines in adolescents and young adults.”

The study was supported by a grant from the National Institute of Neurological Disorders and Stroke. Dr. Szperka is a consultant for AbbVie and Teva; serves on a Data Safety Monitoring Board for Eli Lilly and Upsher-Smith; and is a site principal investigator for AbbVie, Amgen, Biohaven/Pfizer, Teva, and Theranica. Dr. Lakhan had no disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — Intravenous (IV) ketamine is an effective and safe treatment option for children with severe refractory headache, new research suggests. In a retrospective chart review, IV ketamine led to in a 50% reduction in pain at discharge, with “nearly two-thirds” of patients having no recurrence within 30 days, noted lead investigator Scott Rosenthal, MD, from the University of Colorado Anschutz Medical Campus, Aurora.

Dr. Rosenthal reported the findings at the 2024 annual meeting of the American Academy of Neurology.
 

Statistically Significant Pain Relief

“IV ketamine has shown benefit in nonheadache chronic pain syndromes and refractory mood disorders. Patients with refractory status migraines are often left with ongoing pain and dysfunction after failing typical interventions,” Dr. Rosenthal said. 

“Ketamine has emerged as a potential treatment option in this population. However, there’s very little research on the efficacy and tolerability of it in general as well as the pediatric population,” he noted. 

Dr. Rosenthal and colleagues took a look back at patients admitted to Children’s Hospital Colorado between 2019 and 2022 for treatment of severe refractory headache who were treated with continuous IV ketamine. 

They analyzed 68 encounters of 41 unique patients aged 5-21 years (median age 16 years; 85% girls). Chronic migraine without aura made up 79% of cases. 

On presentation, most patients had an exacerbation or ongoing worsening of pain for about 10 days, and all but two were taking a preventive medication. Nearly 70% had a comorbid psychiatric diagnosis such as anxiety or depression, and 60% had a comorbid chronic pain diagnosis separate from their headache diagnosis. 

The primary outcome was percent pain reduction at discharge and headache recurrence within 72 hours, with headache recurrence defined as receipt of neurology care via phone, clinic, or hospital encounter. 

Patients received IV ketamine at a median dose of 0.25 mg/kg/hr for a median of 3 days.

Overall, the treatment was “safe and well tolerated,” Dr. Rosenthal said. 

There were no serious adverse events and no cardiac side effects; 7% (five out of 68) stopped treatment due to side effects. The most common side effects were dizziness (23%), nausea (16%), blurred vision (12%), hallucinations (19%), cognitive fog (7%), vomiting (6%) and dysphoria (4%), worsening headache (4%), and paresthesia and cramping (1.5%).
 

‘Exciting Starting Point’

At baseline, pain scores were 8 (on a scale of 0-10) and progressively fell (improved) during treatment. Pain scores were 6 on day 1 and were 5 on day 2, with a slight rebound to 5 at discharge, although the pain reduction at discharge (vs baseline) remained statistically significant (P < .001). 

“The median percent pain reduction after 3 days of ketamine was about 40%,” Dr. Rosenthal said. 

He noted that on the first day of treatment, 16% of patients responded to treatment (with a > 50% reduction in their initial pain); this doubled to 33% on day 2 and increased to 44% at discharge. 

In terms of recurrence, 38% had a recurrence within 1 month, “meaning two thirds did not,” Dr. Rosenthal noted. Median time to recurrence was 7 days. There were no recurrences within 72 hours. 

The researchers also tried to tease out which patients might respond best to ketamine.

“Surprisingly,” there wasn’t a strong effect of most demographic variables such as age, sex, gender identity, chronic pain, psychiatric comorbidities, duration of headache, or prior interventions, Dr. Rosenthal noted. 

“Interestingly,” he said, patients who were on two or more preventive medications had a 50% reduction in their pain at discharge compared with a 33% reduction in patients taking one or no preventive medication. It’s possible that more preventative medications may “prime” a patient’s response to ketamine, Dr. Rosenthal said. 

She added that future randomized studies are needed to further assess IV ketamine for refractory headache in children, but these results are “an exciting starting point.” 
 

‘Still an Unknown’

Seniha Nur Ozudogru, MD, assistant professor of clinical neurology at Penn Medicine in Philadelphia, echoed the need for further study.

The role of IV ketamine in refractory pediatric headache is “still an unknown,” said Dr. Ozudogru, who was not involved in the study. 

She noted that currently, there is “no standard protocol for ketamine infusion, even for adults. Every institution has their own protocols, which makes it difficult.” 

Dr. Ozudogru also wonders how “doable” in-hospital IV infusions over 3 days may be for children. 

“Especially for chronic migraine patients, it can be really tricky to manage expectations in that even if they don’t respond and the headache doesn’t go away, they still may have to be discharged. That requires a specific approach and discussion with the patients,” Dr. Ozudogru said. 

Intranasal ketamine is another potential option, she said, with a recent study suggesting that intranasal ketamine is an effective treatment for children hospitalized with refractory migraine. 

“However, there is some concern about the potential of addiction and the side effects of hallucinations and what the main protocol will be, so this not a standard treatment and has to be studied further,” she said. 

The study had no specific funding. Dr. Rosenthal and Dr. Ozudogru have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — Intravenous (IV) ketamine is an effective and safe treatment option for children with severe refractory headache, new research suggests. In a retrospective chart review, IV ketamine led to in a 50% reduction in pain at discharge, with “nearly two-thirds” of patients having no recurrence within 30 days, noted lead investigator Scott Rosenthal, MD, from the University of Colorado Anschutz Medical Campus, Aurora.

Dr. Rosenthal reported the findings at the 2024 annual meeting of the American Academy of Neurology.
 

Statistically Significant Pain Relief

“IV ketamine has shown benefit in nonheadache chronic pain syndromes and refractory mood disorders. Patients with refractory status migraines are often left with ongoing pain and dysfunction after failing typical interventions,” Dr. Rosenthal said. 

“Ketamine has emerged as a potential treatment option in this population. However, there’s very little research on the efficacy and tolerability of it in general as well as the pediatric population,” he noted. 

Dr. Rosenthal and colleagues took a look back at patients admitted to Children’s Hospital Colorado between 2019 and 2022 for treatment of severe refractory headache who were treated with continuous IV ketamine. 

They analyzed 68 encounters of 41 unique patients aged 5-21 years (median age 16 years; 85% girls). Chronic migraine without aura made up 79% of cases. 

On presentation, most patients had an exacerbation or ongoing worsening of pain for about 10 days, and all but two were taking a preventive medication. Nearly 70% had a comorbid psychiatric diagnosis such as anxiety or depression, and 60% had a comorbid chronic pain diagnosis separate from their headache diagnosis. 

The primary outcome was percent pain reduction at discharge and headache recurrence within 72 hours, with headache recurrence defined as receipt of neurology care via phone, clinic, or hospital encounter. 

Patients received IV ketamine at a median dose of 0.25 mg/kg/hr for a median of 3 days.

Overall, the treatment was “safe and well tolerated,” Dr. Rosenthal said. 

There were no serious adverse events and no cardiac side effects; 7% (five out of 68) stopped treatment due to side effects. The most common side effects were dizziness (23%), nausea (16%), blurred vision (12%), hallucinations (19%), cognitive fog (7%), vomiting (6%) and dysphoria (4%), worsening headache (4%), and paresthesia and cramping (1.5%).
 

‘Exciting Starting Point’

At baseline, pain scores were 8 (on a scale of 0-10) and progressively fell (improved) during treatment. Pain scores were 6 on day 1 and were 5 on day 2, with a slight rebound to 5 at discharge, although the pain reduction at discharge (vs baseline) remained statistically significant (P < .001). 

“The median percent pain reduction after 3 days of ketamine was about 40%,” Dr. Rosenthal said. 

He noted that on the first day of treatment, 16% of patients responded to treatment (with a > 50% reduction in their initial pain); this doubled to 33% on day 2 and increased to 44% at discharge. 

In terms of recurrence, 38% had a recurrence within 1 month, “meaning two thirds did not,” Dr. Rosenthal noted. Median time to recurrence was 7 days. There were no recurrences within 72 hours. 

The researchers also tried to tease out which patients might respond best to ketamine.

“Surprisingly,” there wasn’t a strong effect of most demographic variables such as age, sex, gender identity, chronic pain, psychiatric comorbidities, duration of headache, or prior interventions, Dr. Rosenthal noted. 

“Interestingly,” he said, patients who were on two or more preventive medications had a 50% reduction in their pain at discharge compared with a 33% reduction in patients taking one or no preventive medication. It’s possible that more preventative medications may “prime” a patient’s response to ketamine, Dr. Rosenthal said. 

She added that future randomized studies are needed to further assess IV ketamine for refractory headache in children, but these results are “an exciting starting point.” 
 

‘Still an Unknown’

Seniha Nur Ozudogru, MD, assistant professor of clinical neurology at Penn Medicine in Philadelphia, echoed the need for further study.

The role of IV ketamine in refractory pediatric headache is “still an unknown,” said Dr. Ozudogru, who was not involved in the study. 

She noted that currently, there is “no standard protocol for ketamine infusion, even for adults. Every institution has their own protocols, which makes it difficult.” 

Dr. Ozudogru also wonders how “doable” in-hospital IV infusions over 3 days may be for children. 

“Especially for chronic migraine patients, it can be really tricky to manage expectations in that even if they don’t respond and the headache doesn’t go away, they still may have to be discharged. That requires a specific approach and discussion with the patients,” Dr. Ozudogru said. 

Intranasal ketamine is another potential option, she said, with a recent study suggesting that intranasal ketamine is an effective treatment for children hospitalized with refractory migraine. 

“However, there is some concern about the potential of addiction and the side effects of hallucinations and what the main protocol will be, so this not a standard treatment and has to be studied further,” she said. 

The study had no specific funding. Dr. Rosenthal and Dr. Ozudogru have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — Intravenous (IV) ketamine is an effective and safe treatment option for children with severe refractory headache, new research suggests. In a retrospective chart review, IV ketamine led to in a 50% reduction in pain at discharge, with “nearly two-thirds” of patients having no recurrence within 30 days, noted lead investigator Scott Rosenthal, MD, from the University of Colorado Anschutz Medical Campus, Aurora.

Dr. Rosenthal reported the findings at the 2024 annual meeting of the American Academy of Neurology.
 

Statistically Significant Pain Relief

“IV ketamine has shown benefit in nonheadache chronic pain syndromes and refractory mood disorders. Patients with refractory status migraines are often left with ongoing pain and dysfunction after failing typical interventions,” Dr. Rosenthal said. 

“Ketamine has emerged as a potential treatment option in this population. However, there’s very little research on the efficacy and tolerability of it in general as well as the pediatric population,” he noted. 

Dr. Rosenthal and colleagues took a look back at patients admitted to Children’s Hospital Colorado between 2019 and 2022 for treatment of severe refractory headache who were treated with continuous IV ketamine. 

They analyzed 68 encounters of 41 unique patients aged 5-21 years (median age 16 years; 85% girls). Chronic migraine without aura made up 79% of cases. 

On presentation, most patients had an exacerbation or ongoing worsening of pain for about 10 days, and all but two were taking a preventive medication. Nearly 70% had a comorbid psychiatric diagnosis such as anxiety or depression, and 60% had a comorbid chronic pain diagnosis separate from their headache diagnosis. 

The primary outcome was percent pain reduction at discharge and headache recurrence within 72 hours, with headache recurrence defined as receipt of neurology care via phone, clinic, or hospital encounter. 

Patients received IV ketamine at a median dose of 0.25 mg/kg/hr for a median of 3 days.

Overall, the treatment was “safe and well tolerated,” Dr. Rosenthal said. 

There were no serious adverse events and no cardiac side effects; 7% (five out of 68) stopped treatment due to side effects. The most common side effects were dizziness (23%), nausea (16%), blurred vision (12%), hallucinations (19%), cognitive fog (7%), vomiting (6%) and dysphoria (4%), worsening headache (4%), and paresthesia and cramping (1.5%).
 

‘Exciting Starting Point’

At baseline, pain scores were 8 (on a scale of 0-10) and progressively fell (improved) during treatment. Pain scores were 6 on day 1 and were 5 on day 2, with a slight rebound to 5 at discharge, although the pain reduction at discharge (vs baseline) remained statistically significant (P < .001). 

“The median percent pain reduction after 3 days of ketamine was about 40%,” Dr. Rosenthal said. 

He noted that on the first day of treatment, 16% of patients responded to treatment (with a > 50% reduction in their initial pain); this doubled to 33% on day 2 and increased to 44% at discharge. 

In terms of recurrence, 38% had a recurrence within 1 month, “meaning two thirds did not,” Dr. Rosenthal noted. Median time to recurrence was 7 days. There were no recurrences within 72 hours. 

The researchers also tried to tease out which patients might respond best to ketamine.

“Surprisingly,” there wasn’t a strong effect of most demographic variables such as age, sex, gender identity, chronic pain, psychiatric comorbidities, duration of headache, or prior interventions, Dr. Rosenthal noted. 

“Interestingly,” he said, patients who were on two or more preventive medications had a 50% reduction in their pain at discharge compared with a 33% reduction in patients taking one or no preventive medication. It’s possible that more preventative medications may “prime” a patient’s response to ketamine, Dr. Rosenthal said. 

She added that future randomized studies are needed to further assess IV ketamine for refractory headache in children, but these results are “an exciting starting point.” 
 

‘Still an Unknown’

Seniha Nur Ozudogru, MD, assistant professor of clinical neurology at Penn Medicine in Philadelphia, echoed the need for further study.

The role of IV ketamine in refractory pediatric headache is “still an unknown,” said Dr. Ozudogru, who was not involved in the study. 

She noted that currently, there is “no standard protocol for ketamine infusion, even for adults. Every institution has their own protocols, which makes it difficult.” 

Dr. Ozudogru also wonders how “doable” in-hospital IV infusions over 3 days may be for children. 

“Especially for chronic migraine patients, it can be really tricky to manage expectations in that even if they don’t respond and the headache doesn’t go away, they still may have to be discharged. That requires a specific approach and discussion with the patients,” Dr. Ozudogru said. 

Intranasal ketamine is another potential option, she said, with a recent study suggesting that intranasal ketamine is an effective treatment for children hospitalized with refractory migraine. 

“However, there is some concern about the potential of addiction and the side effects of hallucinations and what the main protocol will be, so this not a standard treatment and has to be studied further,” she said. 

The study had no specific funding. Dr. Rosenthal and Dr. Ozudogru have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

DENVER – Headaches, including tension-type, migraine, and posttraumatic, are robustly associated with both attempted and completed suicide, results of a large study suggest. 

The risk for suicide attempt was four times higher in people with trigeminal and autonomic cephalalgias (TAC), and the risk for completed suicide was double among those with posttraumatic headache compared with individuals with no headache.

The retrospective analysis included data on more than 100,000 headache patients from a Danish registry. 

“The results suggest there’s a unique risk among headache patients for attempted and completed suicide,” lead investigator Holly Elser, MD, MPH, PhD, resident, Department of Neurology, University of Pennsylvania, Philadelphia, said at the 2024 annual meeting of the American Academy of Neurology, where the findings were presented. “This really underscores the potential importance of complementary psychiatric evaluation and treatment for individuals diagnosed with headache.”
 

Underestimated Problem

Headache disorders affect about half of working-age adults and are among the leading causes of productivity loss, absence from work, and disability. 

Prior research suggests headache disorders often co-occur with psychiatric illness including depression, anxiety, posttraumatic stress disorder, and even attempted suicide.

However, previous studies that showed an increased risk for attempted suicide in patients with headache relied heavily on survey data and mostly focused on patients with migraine. There was little information on other headache types and on the risk for completed suicide.

Researchers used Danish registries to identify 64,057 patients with migraine, 40,160 with tension-type headache (TTH), 5743 with TAC, and 4253 with posttraumatic headache, all diagnosed from 1995 to 2019.

Some 5.8% of those with migraine, 6.3% with TAC, 7.2% with TTH, and 7.2% with posttraumatic headache, had a mood disorder (depression and anxiety combined) at baseline.

Those without a headache diagnosis were matched 5:1 to those with a headache diagnosis by sex and birth year.

Across all headache disorders, baseline prevalence of mood disorder was higher among those with headache versus population-matched controls. Dr. Elser emphasized that these are people diagnosed with a mood disorder in the inpatient, emergency department, or outpatient specialist clinic setting, “which means we are almost certainly underestimating the true burden of mood symptoms in our cohort,” she said.

Researchers identified attempted suicides using diagnostic codes. For completed suicide, they determined whether those who attempted suicide died within 30 days of the attempt.

For each headache type, investigators examined both the absolute and relative risk for attempted and completed suicides and estimated the risk at intervals of 5, 10, and 20 years after initial headache diagnosis.
 

Robust Link

The “power of this study is that we asked a simple, but important question, and answered it with simple, but appropriate, methodologic techniques,” Dr. Elser said.

The estimated risk differences (RDs) for attempted suicide were strongest for TAC and posttraumatic headache and for longer follow-ups. The RDs for completed suicide were largely the same but of a smaller magnitude and were “relatively less precise,” reflecting the “rarity of this outcome,” said Dr. Elser.

After adjusting for sex, age, education, income, comorbidities, and baseline medical and psychiatric diagnoses, researchers found the strongest association or attempted suicide was among those with TAC (adjusted hazard ratio [aHR], 4.25; 95% CI, 2.85-6.33).

“A hazard ratio of 4 is enormous” for this type of comparison, Dr. Elser noted.

For completed suicide, the strongest association was with posttraumatic headache (aHR, 2.19; 95% CI, 0.78-6.16).

The study revealed a robust association with attempted and completed suicide across all headache types, including TTH, noted Dr. Elser. The link between tension headaches and suicide “was the most striking finding to me because I think of that as sort of a benign and common headache disorder,” she said.

The was an observational study, so “it’s not clear whether headache is playing an etiological role in the relationship with suicide,” she said. “It’s possible there are common shared risk factors or confounders that explain the relationship in full or in part that aren’t accounted for in this study.”
 

Ask About Mood

The results underscore the need for psychiatric evaluations in patients with a headache disorder. “For me, this is just going to make me that much more likely to ask my patients about their mood when I see them in clinic,” Dr. Elser said.

After asking patients with headache about their mood and stress at home and at work, physicians should have a “low threshold to refer to a behavioral health provider,” she added.

Future research should aim to better understand the link between headache and suicide risk, with a focus on the mechanisms behind low- and high-risk subgroups, said Dr. Elser.

A limitation of the study was that headache diagnoses were based on inpatient, emergency department, and outpatient specialist visits but not on visits to primary care practitioners. The study didn’t include information on headache severity or frequency and included only people who sought treatment for their headaches.

Though it’s unlikely the results “are perfectly generalizable” with respect to other geographical or cultural contexts, “I don’t think this relationship is unique to Denmark based on the literature to date,” Dr. Elser said.

Commenting on the study, session co-chair Todd J. Schwedt, MD, professor of neurology, Mayo Clinic Arizona, Phoenix, and president-elect of the American Headache Society, noted that the study offers important findings “that demonstrate the enormous negative impact that headaches can exert.”

It’s “a strong reminder” that clinicians should assess the mental health of their patients with headaches and offer treatment when appropriate, he said.

The study received support from Aarhus University. No relevant conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

DENVER – Headaches, including tension-type, migraine, and posttraumatic, are robustly associated with both attempted and completed suicide, results of a large study suggest. 

The risk for suicide attempt was four times higher in people with trigeminal and autonomic cephalalgias (TAC), and the risk for completed suicide was double among those with posttraumatic headache compared with individuals with no headache.

The retrospective analysis included data on more than 100,000 headache patients from a Danish registry. 

“The results suggest there’s a unique risk among headache patients for attempted and completed suicide,” lead investigator Holly Elser, MD, MPH, PhD, resident, Department of Neurology, University of Pennsylvania, Philadelphia, said at the 2024 annual meeting of the American Academy of Neurology, where the findings were presented. “This really underscores the potential importance of complementary psychiatric evaluation and treatment for individuals diagnosed with headache.”
 

Underestimated Problem

Headache disorders affect about half of working-age adults and are among the leading causes of productivity loss, absence from work, and disability. 

Prior research suggests headache disorders often co-occur with psychiatric illness including depression, anxiety, posttraumatic stress disorder, and even attempted suicide.

However, previous studies that showed an increased risk for attempted suicide in patients with headache relied heavily on survey data and mostly focused on patients with migraine. There was little information on other headache types and on the risk for completed suicide.

Researchers used Danish registries to identify 64,057 patients with migraine, 40,160 with tension-type headache (TTH), 5743 with TAC, and 4253 with posttraumatic headache, all diagnosed from 1995 to 2019.

Some 5.8% of those with migraine, 6.3% with TAC, 7.2% with TTH, and 7.2% with posttraumatic headache, had a mood disorder (depression and anxiety combined) at baseline.

Those without a headache diagnosis were matched 5:1 to those with a headache diagnosis by sex and birth year.

Across all headache disorders, baseline prevalence of mood disorder was higher among those with headache versus population-matched controls. Dr. Elser emphasized that these are people diagnosed with a mood disorder in the inpatient, emergency department, or outpatient specialist clinic setting, “which means we are almost certainly underestimating the true burden of mood symptoms in our cohort,” she said.

Researchers identified attempted suicides using diagnostic codes. For completed suicide, they determined whether those who attempted suicide died within 30 days of the attempt.

For each headache type, investigators examined both the absolute and relative risk for attempted and completed suicides and estimated the risk at intervals of 5, 10, and 20 years after initial headache diagnosis.
 

Robust Link

The “power of this study is that we asked a simple, but important question, and answered it with simple, but appropriate, methodologic techniques,” Dr. Elser said.

The estimated risk differences (RDs) for attempted suicide were strongest for TAC and posttraumatic headache and for longer follow-ups. The RDs for completed suicide were largely the same but of a smaller magnitude and were “relatively less precise,” reflecting the “rarity of this outcome,” said Dr. Elser.

After adjusting for sex, age, education, income, comorbidities, and baseline medical and psychiatric diagnoses, researchers found the strongest association or attempted suicide was among those with TAC (adjusted hazard ratio [aHR], 4.25; 95% CI, 2.85-6.33).

“A hazard ratio of 4 is enormous” for this type of comparison, Dr. Elser noted.

For completed suicide, the strongest association was with posttraumatic headache (aHR, 2.19; 95% CI, 0.78-6.16).

The study revealed a robust association with attempted and completed suicide across all headache types, including TTH, noted Dr. Elser. The link between tension headaches and suicide “was the most striking finding to me because I think of that as sort of a benign and common headache disorder,” she said.

The was an observational study, so “it’s not clear whether headache is playing an etiological role in the relationship with suicide,” she said. “It’s possible there are common shared risk factors or confounders that explain the relationship in full or in part that aren’t accounted for in this study.”
 

Ask About Mood

The results underscore the need for psychiatric evaluations in patients with a headache disorder. “For me, this is just going to make me that much more likely to ask my patients about their mood when I see them in clinic,” Dr. Elser said.

After asking patients with headache about their mood and stress at home and at work, physicians should have a “low threshold to refer to a behavioral health provider,” she added.

Future research should aim to better understand the link between headache and suicide risk, with a focus on the mechanisms behind low- and high-risk subgroups, said Dr. Elser.

A limitation of the study was that headache diagnoses were based on inpatient, emergency department, and outpatient specialist visits but not on visits to primary care practitioners. The study didn’t include information on headache severity or frequency and included only people who sought treatment for their headaches.

Though it’s unlikely the results “are perfectly generalizable” with respect to other geographical or cultural contexts, “I don’t think this relationship is unique to Denmark based on the literature to date,” Dr. Elser said.

Commenting on the study, session co-chair Todd J. Schwedt, MD, professor of neurology, Mayo Clinic Arizona, Phoenix, and president-elect of the American Headache Society, noted that the study offers important findings “that demonstrate the enormous negative impact that headaches can exert.”

It’s “a strong reminder” that clinicians should assess the mental health of their patients with headaches and offer treatment when appropriate, he said.

The study received support from Aarhus University. No relevant conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

DENVER – Headaches, including tension-type, migraine, and posttraumatic, are robustly associated with both attempted and completed suicide, results of a large study suggest. 

The risk for suicide attempt was four times higher in people with trigeminal and autonomic cephalalgias (TAC), and the risk for completed suicide was double among those with posttraumatic headache compared with individuals with no headache.

The retrospective analysis included data on more than 100,000 headache patients from a Danish registry. 

“The results suggest there’s a unique risk among headache patients for attempted and completed suicide,” lead investigator Holly Elser, MD, MPH, PhD, resident, Department of Neurology, University of Pennsylvania, Philadelphia, said at the 2024 annual meeting of the American Academy of Neurology, where the findings were presented. “This really underscores the potential importance of complementary psychiatric evaluation and treatment for individuals diagnosed with headache.”
 

Underestimated Problem

Headache disorders affect about half of working-age adults and are among the leading causes of productivity loss, absence from work, and disability. 

Prior research suggests headache disorders often co-occur with psychiatric illness including depression, anxiety, posttraumatic stress disorder, and even attempted suicide.

However, previous studies that showed an increased risk for attempted suicide in patients with headache relied heavily on survey data and mostly focused on patients with migraine. There was little information on other headache types and on the risk for completed suicide.

Researchers used Danish registries to identify 64,057 patients with migraine, 40,160 with tension-type headache (TTH), 5743 with TAC, and 4253 with posttraumatic headache, all diagnosed from 1995 to 2019.

Some 5.8% of those with migraine, 6.3% with TAC, 7.2% with TTH, and 7.2% with posttraumatic headache, had a mood disorder (depression and anxiety combined) at baseline.

Those without a headache diagnosis were matched 5:1 to those with a headache diagnosis by sex and birth year.

Across all headache disorders, baseline prevalence of mood disorder was higher among those with headache versus population-matched controls. Dr. Elser emphasized that these are people diagnosed with a mood disorder in the inpatient, emergency department, or outpatient specialist clinic setting, “which means we are almost certainly underestimating the true burden of mood symptoms in our cohort,” she said.

Researchers identified attempted suicides using diagnostic codes. For completed suicide, they determined whether those who attempted suicide died within 30 days of the attempt.

For each headache type, investigators examined both the absolute and relative risk for attempted and completed suicides and estimated the risk at intervals of 5, 10, and 20 years after initial headache diagnosis.
 

Robust Link

The “power of this study is that we asked a simple, but important question, and answered it with simple, but appropriate, methodologic techniques,” Dr. Elser said.

The estimated risk differences (RDs) for attempted suicide were strongest for TAC and posttraumatic headache and for longer follow-ups. The RDs for completed suicide were largely the same but of a smaller magnitude and were “relatively less precise,” reflecting the “rarity of this outcome,” said Dr. Elser.

After adjusting for sex, age, education, income, comorbidities, and baseline medical and psychiatric diagnoses, researchers found the strongest association or attempted suicide was among those with TAC (adjusted hazard ratio [aHR], 4.25; 95% CI, 2.85-6.33).

“A hazard ratio of 4 is enormous” for this type of comparison, Dr. Elser noted.

For completed suicide, the strongest association was with posttraumatic headache (aHR, 2.19; 95% CI, 0.78-6.16).

The study revealed a robust association with attempted and completed suicide across all headache types, including TTH, noted Dr. Elser. The link between tension headaches and suicide “was the most striking finding to me because I think of that as sort of a benign and common headache disorder,” she said.

The was an observational study, so “it’s not clear whether headache is playing an etiological role in the relationship with suicide,” she said. “It’s possible there are common shared risk factors or confounders that explain the relationship in full or in part that aren’t accounted for in this study.”
 

Ask About Mood

The results underscore the need for psychiatric evaluations in patients with a headache disorder. “For me, this is just going to make me that much more likely to ask my patients about their mood when I see them in clinic,” Dr. Elser said.

After asking patients with headache about their mood and stress at home and at work, physicians should have a “low threshold to refer to a behavioral health provider,” she added.

Future research should aim to better understand the link between headache and suicide risk, with a focus on the mechanisms behind low- and high-risk subgroups, said Dr. Elser.

A limitation of the study was that headache diagnoses were based on inpatient, emergency department, and outpatient specialist visits but not on visits to primary care practitioners. The study didn’t include information on headache severity or frequency and included only people who sought treatment for their headaches.

Though it’s unlikely the results “are perfectly generalizable” with respect to other geographical or cultural contexts, “I don’t think this relationship is unique to Denmark based on the literature to date,” Dr. Elser said.

Commenting on the study, session co-chair Todd J. Schwedt, MD, professor of neurology, Mayo Clinic Arizona, Phoenix, and president-elect of the American Headache Society, noted that the study offers important findings “that demonstrate the enormous negative impact that headaches can exert.”

It’s “a strong reminder” that clinicians should assess the mental health of their patients with headaches and offer treatment when appropriate, he said.

The study received support from Aarhus University. No relevant conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

DENVER — Upon entry into the open-label extension (OLE) of the pivotal trial that led to approval of lecanemab for Alzheimer’s disease, placebo patients failed to show any appreciable catch up to the benefit achieved in the experimental arm, according to a first report of 6-month OLE data.

Due to the steady disease progression observed after the switch of placebo to active therapy, the message of these data is that “early initiation of lecanemab is important,” according to Michael Irizarry, MD, the senior vice president of clinical research at Eisai Ltd, which markets lecanemab.

The 6-month OLE data along with data from a tau PET substudy were presented by Dr. Irizarry at the 2024 annual meeting of the American Academy of Neurology.

From the start of the OLE through the 6-month follow-up, the downward trajectory of cognitive function, as measured with the Clinical Dementia Rating – Sum of Boxes (CDR-SB), has been parallel for the lecanemab-start and switch arms. As a result, the degree of separation between active and placebo groups over the course of the OLE has remained unchanged from the end of the randomized trial.

This does not rule out any benefit in the switch arm, according to Dr. Irizarry. Although there was no discernible change in the trajectory of decline among placebo patients after they were switched to lecanemab, Dr. Irizarry postulated that this might overlook the greater likely decline over time with no treatment.

“There was no placebo group in the OLE to compare with those on active treatment,” he pointed out. He then juxtaposed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Over the same 6-month timeframe, these data show a hypothetical separation of the curves if no treatment had been received.

The 6-month OLE data provide a preliminary look at outcomes in a planned 4-year follow-up. At the end of the randomized CLARITY trial, the mean decline from the baseline CDR-SB score of 3.2, was 1.21 in the lecanemab group, translating into a 38% decline, and 1.66 in the placebo group, translating into about a 50% decline. Over the 6 months of OLE, there has been a further mean CDR-SB reduction of approximately 0.6 in both arms, suggesting a further 18% decline from baseline.
 

Additional Data

In the pivotal CLARITY trial, which was published a few months prior to regulatory approval early last year, 1785 patients were randomized to 10 mg/kg lecanemab or placebo infused every 2 weeks. At the end of 18 months, the superiority of lecanemab for the primary endpoint of adverse change in CDR-SB was highly significant (P < .001) as were the differences in key secondary endpoints, such as Alzheimer’s Disease Composite Score (P < .001).

Of those who participated in CLARITY, 1385 patients entered the OLE. Placebo patients were switched to lecanemab which is being maintained in all patients on the trial schedule of 10 mg/kg administered by intravenous infusion every 2 weeks.

In addition to the overall OLE 6-month data, which has not raised any new safety signals, Dr. Irizarry provided a new look at the PET TAU substudy with a focus on patients who entered the study with a low relative tau burden. Of the three classifications, which also included medium and high tau, as measured with positron-emission tomography (PET), the low tau group represented 41.2% of the 342 tau PET substudy participants. With only 2.9% entering the study with a high tau burden, almost all the others fell in the medium stratification.

Due to the potential for a lower therapeutic response, “patients with low Tau are often excluded from trials,” Dr. Irizarry said. But the sizable proportion of low tau patients has permitted an assessment of relative response with lecanemab, which turned out to be substantial.

“Consistent rates of clinical stability or improvements were observed regardless of baseline tau levels with the highest rates of improvements observed for the low tau group after 24 months of follow-up,” Dr. Irizarry reported.

In previously reported results from the tau PET substudy, lecanemab was shown to slow tau spread at least numerically in every section of the brain evaluated, including the frontal, cingulate, parietal, and whole cortical gray matter areas. The reductions reached significance for the medial temporal (P = .0024), meta temporal (P = .012), and temporal (P = .16) portions.

When most recently evaluated in the OLE, the CDR-SB score declined 38% less among those treated with lecanemab than those treated with placebo in the subgroup enrolled in the tau PET substudy.

Relative to those with intermediate or high tau, patients in the low tau had an even greater reduction in cognitive decline than those with higher tau burdens. Although Dr. Irizarry cautioned that greater baseline CDR-SB scores exaggerated the treatment effect in the low tau group, the message is that “a lecanemab treatment effect is seen even when baseline tau levels are low.”

Now, with the recent market withdrawal of aducanumab, another anti-amyloid monoclonal antibody that was previously approved for Alzheimer’s disease, lecanemab is the only therapy currently available for the goal of changing disease progression, not just modifying symptoms.
 

Looking Long Term

Both sets of data provide important messages for clinicians, according to Marcelo Matiello, MD, a physician investigator at Mass General Hospital and associate professor of neurology at Harvard Medical School, Boston.

“Clinicians are really looking for more data because this remains a relatively new drug,” he said. Both sets of findings presented by Dr. Irizarry “look good but the follow-up is still short, so I think everyone is still looking closely at long-term safety and efficacy.”

The need for continuous indefinite therapy is one concern that Dr. Matiello expressed. As moderator of the session in which these data were presented, Dr. Matiello specifically asked Dr. Irizarry if there are plans to explore whether periods without treatment might be a means to reduce the cost and burden of frequent infusions while preserving cognitive gains.

In response, Dr. Irizarry said that earlier studies showed rapid progression when lecanemab was stopped. On this basis, he thinks therapy must be maintained, but he did say that there are plans to look at less frequent dosing, such as once per month. He also said that a subcutaneous formulation in development might also reduce the burden of prolonged treatment.

Dr. Irizarry is an employee of Eisai Ltd., which manufacturers lecanemab. Dr. Matiello reports no potential conflicts of interest.

DENVER — Upon entry into the open-label extension (OLE) of the pivotal trial that led to approval of lecanemab for Alzheimer’s disease, placebo patients failed to show any appreciable catch up to the benefit achieved in the experimental arm, according to a first report of 6-month OLE data.

Due to the steady disease progression observed after the switch of placebo to active therapy, the message of these data is that “early initiation of lecanemab is important,” according to Michael Irizarry, MD, the senior vice president of clinical research at Eisai Ltd, which markets lecanemab.

The 6-month OLE data along with data from a tau PET substudy were presented by Dr. Irizarry at the 2024 annual meeting of the American Academy of Neurology.

From the start of the OLE through the 6-month follow-up, the downward trajectory of cognitive function, as measured with the Clinical Dementia Rating – Sum of Boxes (CDR-SB), has been parallel for the lecanemab-start and switch arms. As a result, the degree of separation between active and placebo groups over the course of the OLE has remained unchanged from the end of the randomized trial.

This does not rule out any benefit in the switch arm, according to Dr. Irizarry. Although there was no discernible change in the trajectory of decline among placebo patients after they were switched to lecanemab, Dr. Irizarry postulated that this might overlook the greater likely decline over time with no treatment.

“There was no placebo group in the OLE to compare with those on active treatment,” he pointed out. He then juxtaposed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Over the same 6-month timeframe, these data show a hypothetical separation of the curves if no treatment had been received.

The 6-month OLE data provide a preliminary look at outcomes in a planned 4-year follow-up. At the end of the randomized CLARITY trial, the mean decline from the baseline CDR-SB score of 3.2, was 1.21 in the lecanemab group, translating into a 38% decline, and 1.66 in the placebo group, translating into about a 50% decline. Over the 6 months of OLE, there has been a further mean CDR-SB reduction of approximately 0.6 in both arms, suggesting a further 18% decline from baseline.
 

Additional Data

In the pivotal CLARITY trial, which was published a few months prior to regulatory approval early last year, 1785 patients were randomized to 10 mg/kg lecanemab or placebo infused every 2 weeks. At the end of 18 months, the superiority of lecanemab for the primary endpoint of adverse change in CDR-SB was highly significant (P < .001) as were the differences in key secondary endpoints, such as Alzheimer’s Disease Composite Score (P < .001).

Of those who participated in CLARITY, 1385 patients entered the OLE. Placebo patients were switched to lecanemab which is being maintained in all patients on the trial schedule of 10 mg/kg administered by intravenous infusion every 2 weeks.

In addition to the overall OLE 6-month data, which has not raised any new safety signals, Dr. Irizarry provided a new look at the PET TAU substudy with a focus on patients who entered the study with a low relative tau burden. Of the three classifications, which also included medium and high tau, as measured with positron-emission tomography (PET), the low tau group represented 41.2% of the 342 tau PET substudy participants. With only 2.9% entering the study with a high tau burden, almost all the others fell in the medium stratification.

Due to the potential for a lower therapeutic response, “patients with low Tau are often excluded from trials,” Dr. Irizarry said. But the sizable proportion of low tau patients has permitted an assessment of relative response with lecanemab, which turned out to be substantial.

“Consistent rates of clinical stability or improvements were observed regardless of baseline tau levels with the highest rates of improvements observed for the low tau group after 24 months of follow-up,” Dr. Irizarry reported.

In previously reported results from the tau PET substudy, lecanemab was shown to slow tau spread at least numerically in every section of the brain evaluated, including the frontal, cingulate, parietal, and whole cortical gray matter areas. The reductions reached significance for the medial temporal (P = .0024), meta temporal (P = .012), and temporal (P = .16) portions.

When most recently evaluated in the OLE, the CDR-SB score declined 38% less among those treated with lecanemab than those treated with placebo in the subgroup enrolled in the tau PET substudy.

Relative to those with intermediate or high tau, patients in the low tau had an even greater reduction in cognitive decline than those with higher tau burdens. Although Dr. Irizarry cautioned that greater baseline CDR-SB scores exaggerated the treatment effect in the low tau group, the message is that “a lecanemab treatment effect is seen even when baseline tau levels are low.”

Now, with the recent market withdrawal of aducanumab, another anti-amyloid monoclonal antibody that was previously approved for Alzheimer’s disease, lecanemab is the only therapy currently available for the goal of changing disease progression, not just modifying symptoms.
 

Looking Long Term

Both sets of data provide important messages for clinicians, according to Marcelo Matiello, MD, a physician investigator at Mass General Hospital and associate professor of neurology at Harvard Medical School, Boston.

“Clinicians are really looking for more data because this remains a relatively new drug,” he said. Both sets of findings presented by Dr. Irizarry “look good but the follow-up is still short, so I think everyone is still looking closely at long-term safety and efficacy.”

The need for continuous indefinite therapy is one concern that Dr. Matiello expressed. As moderator of the session in which these data were presented, Dr. Matiello specifically asked Dr. Irizarry if there are plans to explore whether periods without treatment might be a means to reduce the cost and burden of frequent infusions while preserving cognitive gains.

In response, Dr. Irizarry said that earlier studies showed rapid progression when lecanemab was stopped. On this basis, he thinks therapy must be maintained, but he did say that there are plans to look at less frequent dosing, such as once per month. He also said that a subcutaneous formulation in development might also reduce the burden of prolonged treatment.

Dr. Irizarry is an employee of Eisai Ltd., which manufacturers lecanemab. Dr. Matiello reports no potential conflicts of interest.

DENVER — Upon entry into the open-label extension (OLE) of the pivotal trial that led to approval of lecanemab for Alzheimer’s disease, placebo patients failed to show any appreciable catch up to the benefit achieved in the experimental arm, according to a first report of 6-month OLE data.

Due to the steady disease progression observed after the switch of placebo to active therapy, the message of these data is that “early initiation of lecanemab is important,” according to Michael Irizarry, MD, the senior vice president of clinical research at Eisai Ltd, which markets lecanemab.

The 6-month OLE data along with data from a tau PET substudy were presented by Dr. Irizarry at the 2024 annual meeting of the American Academy of Neurology.

From the start of the OLE through the 6-month follow-up, the downward trajectory of cognitive function, as measured with the Clinical Dementia Rating – Sum of Boxes (CDR-SB), has been parallel for the lecanemab-start and switch arms. As a result, the degree of separation between active and placebo groups over the course of the OLE has remained unchanged from the end of the randomized trial.

This does not rule out any benefit in the switch arm, according to Dr. Irizarry. Although there was no discernible change in the trajectory of decline among placebo patients after they were switched to lecanemab, Dr. Irizarry postulated that this might overlook the greater likely decline over time with no treatment.

“There was no placebo group in the OLE to compare with those on active treatment,” he pointed out. He then juxtaposed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Over the same 6-month timeframe, these data show a hypothetical separation of the curves if no treatment had been received.

The 6-month OLE data provide a preliminary look at outcomes in a planned 4-year follow-up. At the end of the randomized CLARITY trial, the mean decline from the baseline CDR-SB score of 3.2, was 1.21 in the lecanemab group, translating into a 38% decline, and 1.66 in the placebo group, translating into about a 50% decline. Over the 6 months of OLE, there has been a further mean CDR-SB reduction of approximately 0.6 in both arms, suggesting a further 18% decline from baseline.
 

Additional Data

In the pivotal CLARITY trial, which was published a few months prior to regulatory approval early last year, 1785 patients were randomized to 10 mg/kg lecanemab or placebo infused every 2 weeks. At the end of 18 months, the superiority of lecanemab for the primary endpoint of adverse change in CDR-SB was highly significant (P < .001) as were the differences in key secondary endpoints, such as Alzheimer’s Disease Composite Score (P < .001).

Of those who participated in CLARITY, 1385 patients entered the OLE. Placebo patients were switched to lecanemab which is being maintained in all patients on the trial schedule of 10 mg/kg administered by intravenous infusion every 2 weeks.

In addition to the overall OLE 6-month data, which has not raised any new safety signals, Dr. Irizarry provided a new look at the PET TAU substudy with a focus on patients who entered the study with a low relative tau burden. Of the three classifications, which also included medium and high tau, as measured with positron-emission tomography (PET), the low tau group represented 41.2% of the 342 tau PET substudy participants. With only 2.9% entering the study with a high tau burden, almost all the others fell in the medium stratification.

Due to the potential for a lower therapeutic response, “patients with low Tau are often excluded from trials,” Dr. Irizarry said. But the sizable proportion of low tau patients has permitted an assessment of relative response with lecanemab, which turned out to be substantial.

“Consistent rates of clinical stability or improvements were observed regardless of baseline tau levels with the highest rates of improvements observed for the low tau group after 24 months of follow-up,” Dr. Irizarry reported.

In previously reported results from the tau PET substudy, lecanemab was shown to slow tau spread at least numerically in every section of the brain evaluated, including the frontal, cingulate, parietal, and whole cortical gray matter areas. The reductions reached significance for the medial temporal (P = .0024), meta temporal (P = .012), and temporal (P = .16) portions.

When most recently evaluated in the OLE, the CDR-SB score declined 38% less among those treated with lecanemab than those treated with placebo in the subgroup enrolled in the tau PET substudy.

Relative to those with intermediate or high tau, patients in the low tau had an even greater reduction in cognitive decline than those with higher tau burdens. Although Dr. Irizarry cautioned that greater baseline CDR-SB scores exaggerated the treatment effect in the low tau group, the message is that “a lecanemab treatment effect is seen even when baseline tau levels are low.”

Now, with the recent market withdrawal of aducanumab, another anti-amyloid monoclonal antibody that was previously approved for Alzheimer’s disease, lecanemab is the only therapy currently available for the goal of changing disease progression, not just modifying symptoms.
 

Looking Long Term

Both sets of data provide important messages for clinicians, according to Marcelo Matiello, MD, a physician investigator at Mass General Hospital and associate professor of neurology at Harvard Medical School, Boston.

“Clinicians are really looking for more data because this remains a relatively new drug,” he said. Both sets of findings presented by Dr. Irizarry “look good but the follow-up is still short, so I think everyone is still looking closely at long-term safety and efficacy.”

The need for continuous indefinite therapy is one concern that Dr. Matiello expressed. As moderator of the session in which these data were presented, Dr. Matiello specifically asked Dr. Irizarry if there are plans to explore whether periods without treatment might be a means to reduce the cost and burden of frequent infusions while preserving cognitive gains.

In response, Dr. Irizarry said that earlier studies showed rapid progression when lecanemab was stopped. On this basis, he thinks therapy must be maintained, but he did say that there are plans to look at less frequent dosing, such as once per month. He also said that a subcutaneous formulation in development might also reduce the burden of prolonged treatment.

Dr. Irizarry is an employee of Eisai Ltd., which manufacturers lecanemab. Dr. Matiello reports no potential conflicts of interest.

Recent cases of botulism-like illness following neurotoxin injections in nonmedical settings have prompted the American Society for Dermatologic Surgery Association (ASDSA) to call on states to increase oversight of medical care in all settings, including medical spas.

In a press release issued on April 12, the ASDSA referenced investigations in Illinois and Tennessee in which suspected counterfeit neurotoxins were associated with individuals’ symptoms resembling botulism, including several that required hospitalization. These cases “emphasize the patient safety risks associated with receiving medical procedures in unlicensed, unapproved settings without proper oversight of medical care,” the release adds.

The cases also “highlight the need for increased public protection measures, like the recommendations in the ASDSA’s “Medical Spa Safety Act” to ensure patients’ safety,” according to the press release, which notes the increasing demand for facial fillers and neuromodulators in the United States.

Enforcement is needed to ensure that all patients receive US Food and Drug Administration (FDA)-approved products “and not counterfeit products or unsafe treatments,” ASDSA president Seth L. Matarasso, MD, who practices dermatology in San Francisco, said in the press release. “Lack of regulation and enforcement has enabled many to offer medical procedures for cosmetic purposes outside of their training and expertise,” he said.

Key Takeaways

All clinicians need to understand that aesthetic procedures are medical procedures and require a level of due diligence in patient evaluation and care before, during, and after the procedure, Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, said in an interview.

Dr. Sodha

“FDA-approved medications should only be offered, and these should be obtained through well-defined sources to ensure their safety and purity,” she said.

However, some challenges to the enforcement of safety in medical spa settings persist, Dr. Sodha told this news organization. “To my knowledge, state and federal policies providing clear and up-to-date safety and legal guidelines for aesthetic procedures performed at medical spas by registered nurses, nurse practitioners, physician assistants, and physicians are limited, and in our current medical care structure, national oversight is challenging,” she said.

A pretreatment checklist assessment, she suggested, could be helpful “to ensure patient safety and help to standardize clinical practice in nonmedical settings.”

Other challenges include a lack of clear guidelines for aesthetic providers regarding initial assessment examinations, postprocedure follow-up, and evaluation for any future medical treatment, as well as “continued ambiguity on the exact meaning of physician oversight for those sites that delegate aesthetic services and appropriate and clear guidelines on what procedures require a licensed provider to perform versus oversee the treatment,” she said.
 

Additional Guidance, Actions Needed

As for additional guidance or actions, “we may be migrating towards a system that designates and assigns clearer licenses and authorizations to perform these services and care for patients,” said Dr. Sodha. A licensing process would entail academic understanding of anatomy, pharmacology, and tissue interactions, as well as practical hands-on training that emphasizes the importance of the preprocedure consultation and postprocedure follow-up and care, she said. “Experience in caring for the unintended outcomes is vital to delivering the best care we can,” she added.

D. Sodha had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

Recent cases of botulism-like illness following neurotoxin injections in nonmedical settings have prompted the American Society for Dermatologic Surgery Association (ASDSA) to call on states to increase oversight of medical care in all settings, including medical spas.

In a press release issued on April 12, the ASDSA referenced investigations in Illinois and Tennessee in which suspected counterfeit neurotoxins were associated with individuals’ symptoms resembling botulism, including several that required hospitalization. These cases “emphasize the patient safety risks associated with receiving medical procedures in unlicensed, unapproved settings without proper oversight of medical care,” the release adds.

The cases also “highlight the need for increased public protection measures, like the recommendations in the ASDSA’s “Medical Spa Safety Act” to ensure patients’ safety,” according to the press release, which notes the increasing demand for facial fillers and neuromodulators in the United States.

Enforcement is needed to ensure that all patients receive US Food and Drug Administration (FDA)-approved products “and not counterfeit products or unsafe treatments,” ASDSA president Seth L. Matarasso, MD, who practices dermatology in San Francisco, said in the press release. “Lack of regulation and enforcement has enabled many to offer medical procedures for cosmetic purposes outside of their training and expertise,” he said.

Key Takeaways

All clinicians need to understand that aesthetic procedures are medical procedures and require a level of due diligence in patient evaluation and care before, during, and after the procedure, Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, said in an interview.

Dr. Sodha

“FDA-approved medications should only be offered, and these should be obtained through well-defined sources to ensure their safety and purity,” she said.

However, some challenges to the enforcement of safety in medical spa settings persist, Dr. Sodha told this news organization. “To my knowledge, state and federal policies providing clear and up-to-date safety and legal guidelines for aesthetic procedures performed at medical spas by registered nurses, nurse practitioners, physician assistants, and physicians are limited, and in our current medical care structure, national oversight is challenging,” she said.

A pretreatment checklist assessment, she suggested, could be helpful “to ensure patient safety and help to standardize clinical practice in nonmedical settings.”

Other challenges include a lack of clear guidelines for aesthetic providers regarding initial assessment examinations, postprocedure follow-up, and evaluation for any future medical treatment, as well as “continued ambiguity on the exact meaning of physician oversight for those sites that delegate aesthetic services and appropriate and clear guidelines on what procedures require a licensed provider to perform versus oversee the treatment,” she said.
 

Additional Guidance, Actions Needed

As for additional guidance or actions, “we may be migrating towards a system that designates and assigns clearer licenses and authorizations to perform these services and care for patients,” said Dr. Sodha. A licensing process would entail academic understanding of anatomy, pharmacology, and tissue interactions, as well as practical hands-on training that emphasizes the importance of the preprocedure consultation and postprocedure follow-up and care, she said. “Experience in caring for the unintended outcomes is vital to delivering the best care we can,” she added.

D. Sodha had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

Recent cases of botulism-like illness following neurotoxin injections in nonmedical settings have prompted the American Society for Dermatologic Surgery Association (ASDSA) to call on states to increase oversight of medical care in all settings, including medical spas.

In a press release issued on April 12, the ASDSA referenced investigations in Illinois and Tennessee in which suspected counterfeit neurotoxins were associated with individuals’ symptoms resembling botulism, including several that required hospitalization. These cases “emphasize the patient safety risks associated with receiving medical procedures in unlicensed, unapproved settings without proper oversight of medical care,” the release adds.

The cases also “highlight the need for increased public protection measures, like the recommendations in the ASDSA’s “Medical Spa Safety Act” to ensure patients’ safety,” according to the press release, which notes the increasing demand for facial fillers and neuromodulators in the United States.

Enforcement is needed to ensure that all patients receive US Food and Drug Administration (FDA)-approved products “and not counterfeit products or unsafe treatments,” ASDSA president Seth L. Matarasso, MD, who practices dermatology in San Francisco, said in the press release. “Lack of regulation and enforcement has enabled many to offer medical procedures for cosmetic purposes outside of their training and expertise,” he said.

Key Takeaways

All clinicians need to understand that aesthetic procedures are medical procedures and require a level of due diligence in patient evaluation and care before, during, and after the procedure, Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, said in an interview.

Dr. Sodha

“FDA-approved medications should only be offered, and these should be obtained through well-defined sources to ensure their safety and purity,” she said.

However, some challenges to the enforcement of safety in medical spa settings persist, Dr. Sodha told this news organization. “To my knowledge, state and federal policies providing clear and up-to-date safety and legal guidelines for aesthetic procedures performed at medical spas by registered nurses, nurse practitioners, physician assistants, and physicians are limited, and in our current medical care structure, national oversight is challenging,” she said.

A pretreatment checklist assessment, she suggested, could be helpful “to ensure patient safety and help to standardize clinical practice in nonmedical settings.”

Other challenges include a lack of clear guidelines for aesthetic providers regarding initial assessment examinations, postprocedure follow-up, and evaluation for any future medical treatment, as well as “continued ambiguity on the exact meaning of physician oversight for those sites that delegate aesthetic services and appropriate and clear guidelines on what procedures require a licensed provider to perform versus oversee the treatment,” she said.
 

Additional Guidance, Actions Needed

As for additional guidance or actions, “we may be migrating towards a system that designates and assigns clearer licenses and authorizations to perform these services and care for patients,” said Dr. Sodha. A licensing process would entail academic understanding of anatomy, pharmacology, and tissue interactions, as well as practical hands-on training that emphasizes the importance of the preprocedure consultation and postprocedure follow-up and care, she said. “Experience in caring for the unintended outcomes is vital to delivering the best care we can,” she added.

D. Sodha had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

At least 19 people from nine states have reported serious reactions after receiving botulinum toxin injections from unlicensed or untrained individuals or in non-healthcare settings, such as homes and spas, according to an announcement of an investigation into these reports from the Centers for Disease Control and Prevention posted online April 15.

Reactions have included blurry vision, double vision, drooping eyelids, difficult swallowing or breathing, and other symptoms of botulism.

Of the 19 individuals — all of whom identified as female and had a mean age of 39 years — 9 (60%) were hospitalized and 4 (21%) were treated with botulism antitoxin because of concerns that the botulinum toxin could have spread beyond the injection site. Also, five were tested for botulism and their results were negative.

The CDC, several state and local health departments, and the US Food and Drug Administration (FDA) are investigating these reports, according to the announcement.

States reporting these cases include Colorado, Florida, Illinois, Kentucky, Nebraska, New Jersey, New York, Tennessee, and Washington. According to the CDC summary, some of the individuals “received injections with counterfeit products or products with unverified sources. Investigation into the sources of these products is ongoing.” All but one report involved receiving botulinum toxin injections for cosmetic purposes.

Recent cases of botulism-like illnesses possibly related to counterfeit botulinum toxin reported in Illinois and Tennessee, prompted the American Society for Dermatologic Surgery Association (ASDSA) to call on states to increase oversight of medical care in all settings, including medical spas, the ASDSA announced on April 12.

The CDC summary advises clinicians to consider the possibility of adverse effects from botulinum toxin injection, including for cosmetic reasons, when patients present with signs and symptoms consistent with botulism near the injection site. Symptoms of botulism include blurry or double vision, drooping eyelids, difficulty swallowing, difficulty breathing, and muscle weakness.

For people who are considering botulinum toxin for cosmetic or medical reasons, recommendations from the CDC include asking the provider and setting, such as a clinic or spa, if they are licensed and trained to provide these injections, and to ask if the product is approved by the FDA and from a reliable source, and, “if in doubt, don’t get the injection.”

This ‘Should Never Happen’

“The report of people getting botulism from botulinum toxin injections is frightening, and should never happen,” Lawrence J. Green, MD, clinical professor of dermatology, George Washington University, Washington, told this news organization.

Dr. Green

These reports show “how important it is to receive botulinum toxin injections only in a medical office, and from or under the direction of a qualified, trained, and licensed individual, like a board certified dermatologist,” added Dr. Green, who practices in Rockville, Maryland. “Other types of practitioners may not adhere to the same standards of professionalism, especially not always putting patient safety first.”

Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.
 

For cases of suspected systemic botulism, the CDC recommends calling the local or state health department for consultation and antitoxin release (as well as information on reporting adverse events). Alternatively, the 24/7 phone number for the CDC clinical botulism service is 770-488-7100.

At least 19 people from nine states have reported serious reactions after receiving botulinum toxin injections from unlicensed or untrained individuals or in non-healthcare settings, such as homes and spas, according to an announcement of an investigation into these reports from the Centers for Disease Control and Prevention posted online April 15.

Reactions have included blurry vision, double vision, drooping eyelids, difficult swallowing or breathing, and other symptoms of botulism.

Of the 19 individuals — all of whom identified as female and had a mean age of 39 years — 9 (60%) were hospitalized and 4 (21%) were treated with botulism antitoxin because of concerns that the botulinum toxin could have spread beyond the injection site. Also, five were tested for botulism and their results were negative.

The CDC, several state and local health departments, and the US Food and Drug Administration (FDA) are investigating these reports, according to the announcement.

States reporting these cases include Colorado, Florida, Illinois, Kentucky, Nebraska, New Jersey, New York, Tennessee, and Washington. According to the CDC summary, some of the individuals “received injections with counterfeit products or products with unverified sources. Investigation into the sources of these products is ongoing.” All but one report involved receiving botulinum toxin injections for cosmetic purposes.

Recent cases of botulism-like illnesses possibly related to counterfeit botulinum toxin reported in Illinois and Tennessee, prompted the American Society for Dermatologic Surgery Association (ASDSA) to call on states to increase oversight of medical care in all settings, including medical spas, the ASDSA announced on April 12.

The CDC summary advises clinicians to consider the possibility of adverse effects from botulinum toxin injection, including for cosmetic reasons, when patients present with signs and symptoms consistent with botulism near the injection site. Symptoms of botulism include blurry or double vision, drooping eyelids, difficulty swallowing, difficulty breathing, and muscle weakness.

For people who are considering botulinum toxin for cosmetic or medical reasons, recommendations from the CDC include asking the provider and setting, such as a clinic or spa, if they are licensed and trained to provide these injections, and to ask if the product is approved by the FDA and from a reliable source, and, “if in doubt, don’t get the injection.”

This ‘Should Never Happen’

“The report of people getting botulism from botulinum toxin injections is frightening, and should never happen,” Lawrence J. Green, MD, clinical professor of dermatology, George Washington University, Washington, told this news organization.

Dr. Green

These reports show “how important it is to receive botulinum toxin injections only in a medical office, and from or under the direction of a qualified, trained, and licensed individual, like a board certified dermatologist,” added Dr. Green, who practices in Rockville, Maryland. “Other types of practitioners may not adhere to the same standards of professionalism, especially not always putting patient safety first.”

Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.
 

For cases of suspected systemic botulism, the CDC recommends calling the local or state health department for consultation and antitoxin release (as well as information on reporting adverse events). Alternatively, the 24/7 phone number for the CDC clinical botulism service is 770-488-7100.

At least 19 people from nine states have reported serious reactions after receiving botulinum toxin injections from unlicensed or untrained individuals or in non-healthcare settings, such as homes and spas, according to an announcement of an investigation into these reports from the Centers for Disease Control and Prevention posted online April 15.

Reactions have included blurry vision, double vision, drooping eyelids, difficult swallowing or breathing, and other symptoms of botulism.

Of the 19 individuals — all of whom identified as female and had a mean age of 39 years — 9 (60%) were hospitalized and 4 (21%) were treated with botulism antitoxin because of concerns that the botulinum toxin could have spread beyond the injection site. Also, five were tested for botulism and their results were negative.

The CDC, several state and local health departments, and the US Food and Drug Administration (FDA) are investigating these reports, according to the announcement.

States reporting these cases include Colorado, Florida, Illinois, Kentucky, Nebraska, New Jersey, New York, Tennessee, and Washington. According to the CDC summary, some of the individuals “received injections with counterfeit products or products with unverified sources. Investigation into the sources of these products is ongoing.” All but one report involved receiving botulinum toxin injections for cosmetic purposes.

Recent cases of botulism-like illnesses possibly related to counterfeit botulinum toxin reported in Illinois and Tennessee, prompted the American Society for Dermatologic Surgery Association (ASDSA) to call on states to increase oversight of medical care in all settings, including medical spas, the ASDSA announced on April 12.

The CDC summary advises clinicians to consider the possibility of adverse effects from botulinum toxin injection, including for cosmetic reasons, when patients present with signs and symptoms consistent with botulism near the injection site. Symptoms of botulism include blurry or double vision, drooping eyelids, difficulty swallowing, difficulty breathing, and muscle weakness.

For people who are considering botulinum toxin for cosmetic or medical reasons, recommendations from the CDC include asking the provider and setting, such as a clinic or spa, if they are licensed and trained to provide these injections, and to ask if the product is approved by the FDA and from a reliable source, and, “if in doubt, don’t get the injection.”

This ‘Should Never Happen’

“The report of people getting botulism from botulinum toxin injections is frightening, and should never happen,” Lawrence J. Green, MD, clinical professor of dermatology, George Washington University, Washington, told this news organization.

Dr. Green

These reports show “how important it is to receive botulinum toxin injections only in a medical office, and from or under the direction of a qualified, trained, and licensed individual, like a board certified dermatologist,” added Dr. Green, who practices in Rockville, Maryland. “Other types of practitioners may not adhere to the same standards of professionalism, especially not always putting patient safety first.”

Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.
 

For cases of suspected systemic botulism, the CDC recommends calling the local or state health department for consultation and antitoxin release (as well as information on reporting adverse events). Alternatively, the 24/7 phone number for the CDC clinical botulism service is 770-488-7100.