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Acupuncture deep needling technique points to greater tension headache relief
(TTH), new research suggests. Result of a randomized trial showed that though the majority of participants reported some relief from TTH after 8 weeks of acupuncture treatment, those who received needling at a depth of 12.5-20.0 mm reported the greatest reduction in headache frequency and severity.
At this depth, acupuncture promotes deqi sensation, a feeling of numbness, soreness, heaviness, or irritating pain in the needling site that is considered key to successful acupuncture treatment in traditional Chinese acupuncture theory.
“Our study showed that deqi sensation could enhance the effect of acupuncture in the treatment of chronic TTH, and the effect of acupuncture lasted at least 6 months when the treatment was stopped,” said co-investigator Ying Li, MD, PhD, The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, China.
The findings were published online in Neurology.
Deqi sensation key
TTH is the most common type of headache, with a lifetime prevalence of up to 78% in some studies. The pain is often described as throbbing or a vice-like tightness on both sides of the head. TTH is considered chronic when it occurs at least 15 days a month.
Previous studies have suggested that acupuncture can offer relief from headache pain, but specific information on TTH, especially chronic TTH, has been lacking.
To address the issue, researchers designed a parallel-design, patient-and-assessor blinded randomized controlled trial with 218 individuals with a history of chronic TTH. All were untreated with prophylactic treatment in the previous 3 months.
The treatment group (n = 110) received 20 sessions of true acupuncture (TA) over 8 weeks. This included three sessions per week in the first 4 weeks and two sessions per week in the last 4 weeks. The depth of needling at each point ranged from 12.5 to 20 mm, which is needed to achieve deqi sensation.
The control group (n = 108) received superficial acupuncture (SA) on the same schedule as the TA group and at traditional acupuncture points. However, this was done at a maximum depth of 2 mm, which is not deep enough for deqi sensation.
At week 16, 68.2% of the participants receiving TA reported a greater than 50% reduction in monthly headache days, compared with 48.1% of those receiving SA (odds ratio, 2.65; P < .001).
Mean monthly headache days decreased from 20.38 days at baseline to 7.48 days at week 32 in the TA group versus 22.6 days at baseline to 11.94 days in the SA group.
Headache intensity and severity decreased in both groups, although those who achieved deqi sensation reported the most improvement.
Only four patients reported adverse effects, all of which were mild and none requiring treatment.
Patients in both groups reported some pain relief, suggesting that those who are not comfortable with deqi sensation may still benefit from superficial acupuncture, although to a lesser extent, Dr. Li said.
“We assume that the point-specific effect and placebo effect were combined to give the patients relief of headaches,” Dr. Li added. “Further, the effect of deqi sensation added more treatment effect. This might be explained by gate-control theory or other unknown mechanisms.”
Deeper understanding?
Commenting on the research, Jennifer Bickel, MD, a senior member of neurology at Moffit Cancer Center and professor of oncologic sciences at University of South Florida, Tampa, said that the study provides a deeper understanding of acupuncture’s efficacy for chronic TTH, which could aid clinicians who are unfamiliar with the therapy or when and how to refer treatment.
“This study provides a more descriptive outline for what type of acupuncture treatment and duration can be effective for patients so doctors can prep patients on what to expect and so doctors can better assess if patients received appropriate acupuncture for their headaches,” said Dr. Bickel, who was not involved with the research.
However, she noted that the acupuncture sites and techniques did not vary during the trial. Although that makes sense for a controlled study, it may not reflect real-world clinical practice, she added.
“The downside is that the study didn’t fully reflect that most acupuncturists in clinical practice would alter treatments during the 20 sessions based on the patient’s response and accompanying symptoms or comorbidities,” Dr. Bickel said.
The study also lacked information on medication overuse headache or patients’ prior history of TTH treatments.
“This could be helpful to understand which patients in clinical practice are most likely to benefit from treatment,” Dr. Bickel said.
Study authors received funding from the Department of Science and Technology of Sichuan Province and the National Natural Science Foundation of China. Dr. Li, Dr. Bickel, and Dr. Vickers report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(TTH), new research suggests. Result of a randomized trial showed that though the majority of participants reported some relief from TTH after 8 weeks of acupuncture treatment, those who received needling at a depth of 12.5-20.0 mm reported the greatest reduction in headache frequency and severity.
At this depth, acupuncture promotes deqi sensation, a feeling of numbness, soreness, heaviness, or irritating pain in the needling site that is considered key to successful acupuncture treatment in traditional Chinese acupuncture theory.
“Our study showed that deqi sensation could enhance the effect of acupuncture in the treatment of chronic TTH, and the effect of acupuncture lasted at least 6 months when the treatment was stopped,” said co-investigator Ying Li, MD, PhD, The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, China.
The findings were published online in Neurology.
Deqi sensation key
TTH is the most common type of headache, with a lifetime prevalence of up to 78% in some studies. The pain is often described as throbbing or a vice-like tightness on both sides of the head. TTH is considered chronic when it occurs at least 15 days a month.
Previous studies have suggested that acupuncture can offer relief from headache pain, but specific information on TTH, especially chronic TTH, has been lacking.
To address the issue, researchers designed a parallel-design, patient-and-assessor blinded randomized controlled trial with 218 individuals with a history of chronic TTH. All were untreated with prophylactic treatment in the previous 3 months.
The treatment group (n = 110) received 20 sessions of true acupuncture (TA) over 8 weeks. This included three sessions per week in the first 4 weeks and two sessions per week in the last 4 weeks. The depth of needling at each point ranged from 12.5 to 20 mm, which is needed to achieve deqi sensation.
The control group (n = 108) received superficial acupuncture (SA) on the same schedule as the TA group and at traditional acupuncture points. However, this was done at a maximum depth of 2 mm, which is not deep enough for deqi sensation.
At week 16, 68.2% of the participants receiving TA reported a greater than 50% reduction in monthly headache days, compared with 48.1% of those receiving SA (odds ratio, 2.65; P < .001).
Mean monthly headache days decreased from 20.38 days at baseline to 7.48 days at week 32 in the TA group versus 22.6 days at baseline to 11.94 days in the SA group.
Headache intensity and severity decreased in both groups, although those who achieved deqi sensation reported the most improvement.
Only four patients reported adverse effects, all of which were mild and none requiring treatment.
Patients in both groups reported some pain relief, suggesting that those who are not comfortable with deqi sensation may still benefit from superficial acupuncture, although to a lesser extent, Dr. Li said.
“We assume that the point-specific effect and placebo effect were combined to give the patients relief of headaches,” Dr. Li added. “Further, the effect of deqi sensation added more treatment effect. This might be explained by gate-control theory or other unknown mechanisms.”
Deeper understanding?
Commenting on the research, Jennifer Bickel, MD, a senior member of neurology at Moffit Cancer Center and professor of oncologic sciences at University of South Florida, Tampa, said that the study provides a deeper understanding of acupuncture’s efficacy for chronic TTH, which could aid clinicians who are unfamiliar with the therapy or when and how to refer treatment.
“This study provides a more descriptive outline for what type of acupuncture treatment and duration can be effective for patients so doctors can prep patients on what to expect and so doctors can better assess if patients received appropriate acupuncture for their headaches,” said Dr. Bickel, who was not involved with the research.
However, she noted that the acupuncture sites and techniques did not vary during the trial. Although that makes sense for a controlled study, it may not reflect real-world clinical practice, she added.
“The downside is that the study didn’t fully reflect that most acupuncturists in clinical practice would alter treatments during the 20 sessions based on the patient’s response and accompanying symptoms or comorbidities,” Dr. Bickel said.
The study also lacked information on medication overuse headache or patients’ prior history of TTH treatments.
“This could be helpful to understand which patients in clinical practice are most likely to benefit from treatment,” Dr. Bickel said.
Study authors received funding from the Department of Science and Technology of Sichuan Province and the National Natural Science Foundation of China. Dr. Li, Dr. Bickel, and Dr. Vickers report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(TTH), new research suggests. Result of a randomized trial showed that though the majority of participants reported some relief from TTH after 8 weeks of acupuncture treatment, those who received needling at a depth of 12.5-20.0 mm reported the greatest reduction in headache frequency and severity.
At this depth, acupuncture promotes deqi sensation, a feeling of numbness, soreness, heaviness, or irritating pain in the needling site that is considered key to successful acupuncture treatment in traditional Chinese acupuncture theory.
“Our study showed that deqi sensation could enhance the effect of acupuncture in the treatment of chronic TTH, and the effect of acupuncture lasted at least 6 months when the treatment was stopped,” said co-investigator Ying Li, MD, PhD, The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, China.
The findings were published online in Neurology.
Deqi sensation key
TTH is the most common type of headache, with a lifetime prevalence of up to 78% in some studies. The pain is often described as throbbing or a vice-like tightness on both sides of the head. TTH is considered chronic when it occurs at least 15 days a month.
Previous studies have suggested that acupuncture can offer relief from headache pain, but specific information on TTH, especially chronic TTH, has been lacking.
To address the issue, researchers designed a parallel-design, patient-and-assessor blinded randomized controlled trial with 218 individuals with a history of chronic TTH. All were untreated with prophylactic treatment in the previous 3 months.
The treatment group (n = 110) received 20 sessions of true acupuncture (TA) over 8 weeks. This included three sessions per week in the first 4 weeks and two sessions per week in the last 4 weeks. The depth of needling at each point ranged from 12.5 to 20 mm, which is needed to achieve deqi sensation.
The control group (n = 108) received superficial acupuncture (SA) on the same schedule as the TA group and at traditional acupuncture points. However, this was done at a maximum depth of 2 mm, which is not deep enough for deqi sensation.
At week 16, 68.2% of the participants receiving TA reported a greater than 50% reduction in monthly headache days, compared with 48.1% of those receiving SA (odds ratio, 2.65; P < .001).
Mean monthly headache days decreased from 20.38 days at baseline to 7.48 days at week 32 in the TA group versus 22.6 days at baseline to 11.94 days in the SA group.
Headache intensity and severity decreased in both groups, although those who achieved deqi sensation reported the most improvement.
Only four patients reported adverse effects, all of which were mild and none requiring treatment.
Patients in both groups reported some pain relief, suggesting that those who are not comfortable with deqi sensation may still benefit from superficial acupuncture, although to a lesser extent, Dr. Li said.
“We assume that the point-specific effect and placebo effect were combined to give the patients relief of headaches,” Dr. Li added. “Further, the effect of deqi sensation added more treatment effect. This might be explained by gate-control theory or other unknown mechanisms.”
Deeper understanding?
Commenting on the research, Jennifer Bickel, MD, a senior member of neurology at Moffit Cancer Center and professor of oncologic sciences at University of South Florida, Tampa, said that the study provides a deeper understanding of acupuncture’s efficacy for chronic TTH, which could aid clinicians who are unfamiliar with the therapy or when and how to refer treatment.
“This study provides a more descriptive outline for what type of acupuncture treatment and duration can be effective for patients so doctors can prep patients on what to expect and so doctors can better assess if patients received appropriate acupuncture for their headaches,” said Dr. Bickel, who was not involved with the research.
However, she noted that the acupuncture sites and techniques did not vary during the trial. Although that makes sense for a controlled study, it may not reflect real-world clinical practice, she added.
“The downside is that the study didn’t fully reflect that most acupuncturists in clinical practice would alter treatments during the 20 sessions based on the patient’s response and accompanying symptoms or comorbidities,” Dr. Bickel said.
The study also lacked information on medication overuse headache or patients’ prior history of TTH treatments.
“This could be helpful to understand which patients in clinical practice are most likely to benefit from treatment,” Dr. Bickel said.
Study authors received funding from the Department of Science and Technology of Sichuan Province and the National Natural Science Foundation of China. Dr. Li, Dr. Bickel, and Dr. Vickers report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Migraine-related stigma is common and underappreciated
, new research shows. Results from the OVERCOME population-based survey study, which included more than 59,000 respondents, showed about 32% reported experiencing migraine-related stigma “often” or “very often.”
Even those experiencing only a few headaches per month said they experienced negative attitudes from others about migraine.
“We have been utterly blind to the burden people with migraine experience in terms of how their disease is appreciated by others. It’s time to get busy and address this very stubborn social phenomenon,” said the study’s coinvestigator, Robert E. Shapiro, MD, PhD, professor emeritus, department of neurological sciences, Larner College of Medicine, University of Vermont, Burlington.
The findings were presented at the annual meeting of the American Headache Society.
Population-based research
Stigma is defined as the discounting or discrediting of an individual with a trait that deviates from social norms. To date, there have been no significant population-based studies of how these attitudes affect individuals with migraine.
OVERCOME is a cross-sectional, longitudinal, prospective, web-based survey conducted in a representative sample of the United States population. For this new analysis, researchers pooled data from surveys conducted in 2018, 2019, and 2020.
The analysis included 59,004 respondents (mean age, 41.3 years; 75% women; 70% White) who reported one or more headache or migraine attacks during the previous 12 months and who met criteria for migraine from the International Classification of Headache Disorders. Among the patients, 35% had a college degree, and 89% suffered episodic-type headaches.
Researchers used the following four patient-reported outcome measures:
- Migraine Disability Assessment, which quantifies number of days missed at work, home, or social events over the previous 3 months
- Migraine Interictal Burden Scale–4, which measures burden of migraine between attacks over the previous 4 weeks
- Migraine-Specific Quality of Life Role-Function Restrictive, which assesses the functional effect of migraine on social and work-related activities over the previous 4 weeks
- Migraine-Related Stigma
For the latter, the investigators used two measures – the degree to which others think migraine is used to acquire secondary gain, such as avoiding commitments, and the degree to which others minimize the burden of migraine.
One of the most stigmatizing disorders
Results showed that 31.7% of participants reported experiencing stigmatization from one or both migraine-related stigma categories often or very often – a result Dr. Shapiro characterized as “pretty shocking.”
Participants with chronic headaches, defined as having 15 or more headache days per month, made up 11% of the sample. About 47% of these respondents felt stigma often or very often.
However, even 25% of participants with three or fewer headache days per month reported stigma.
“This is a fundamental tip that we are not really understanding the concerns that drive burden for people living with this disabling disease,” Dr. Shapiro said.
Some previous studies that compared levels of stigmatizing attitudes regarding various diseases showed that migraine is more stigmatized than even epilepsy, a condition “equated with demonic possession in biblical times,” he noted.
One study used machine learning to measure the number of pejorative or negative terms associated with various diseases. “Shockingly, migraine was one of the most stigmatized diseases,” said Dr. Shapiro. “It was as stigmatized as gonorrhea by certain measures.”
Results from the new study showed that, irrespective of the number of headache days experienced per month, there was a threefold increase in interictal burden among those reporting stigma often or very often, compared with those who didn’t report stigma.
Large impact on QoL
“Stigma is a social concept, so maybe it’s not surprising that it would be present whether or not someone is experiencing other symptoms of migraine,” said Dr. Shapiro.
Across all monthly headache days, experiencing more migraine-related stigma was associated with increased disability and decreased quality of life.
Dr. Shapiro noted that when it comes to migraine-specific quality of life, stigma appears to have more of an effect than number of headache days. “That means there are big gaps in our appreciation for what drives the burdens in the patient experience of living with this disabling disease,” he said.
He added that headache’s place within the migraine sphere needs to be reconsidered. “Its singular emphasis has limited our full appreciation of this disease and how we should be paying attention to the things that are important to patients,” he said.
Dr. Shapiro predicts that future clinical trials will include migraine-related stigma as a measure to guide trial enrollment.
In addition, researchers are now digging deeper to try to understand what factors are most likely to drive stigma. “We need to understand why those attitudes are held and who is more likely to hold those attitudes, and that may allow us to develop mitigating strategies to reduce those attitudes,” said Dr. Shapiro.
‘Worrisome’ findings
Commenting on the findings, Deborah Friedman, MD, professor, departments of neurology and of ophthalmology, UT Southwestern Medical Center, Dallas, said the data on stigma were “worrisome.”
Missing social occasions and lost productivity may make migraine more visible to others so perhaps may “provoke stigma or stigmatizing comments or stigmatizing attitudes,” said Dr. Friedman, who was not involved with the research.
She noted that patients with migraine might also have trouble functioning in the workplace. “They may not be able to tolerate the computer screen or smells of perfume at the office and not get accommodation for that,” she said.
In addition to external stigma, which was investigated in the study, individuals with migraine may also experience internal stigma – blaming themselves for their disease, which may make it less likely they will seek care, said Dr. Friedman.
“That’s a huge problem,” she added.
The OVERCOME study is funded by Lilly. Dr. Shapiro has been compensated by Lilly as a research consultant and as a member of the data monitoring committee for clinical trials for galcanezumab, a Lilly pharmaceutical. Dr. Friedman has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows. Results from the OVERCOME population-based survey study, which included more than 59,000 respondents, showed about 32% reported experiencing migraine-related stigma “often” or “very often.”
Even those experiencing only a few headaches per month said they experienced negative attitudes from others about migraine.
“We have been utterly blind to the burden people with migraine experience in terms of how their disease is appreciated by others. It’s time to get busy and address this very stubborn social phenomenon,” said the study’s coinvestigator, Robert E. Shapiro, MD, PhD, professor emeritus, department of neurological sciences, Larner College of Medicine, University of Vermont, Burlington.
The findings were presented at the annual meeting of the American Headache Society.
Population-based research
Stigma is defined as the discounting or discrediting of an individual with a trait that deviates from social norms. To date, there have been no significant population-based studies of how these attitudes affect individuals with migraine.
OVERCOME is a cross-sectional, longitudinal, prospective, web-based survey conducted in a representative sample of the United States population. For this new analysis, researchers pooled data from surveys conducted in 2018, 2019, and 2020.
The analysis included 59,004 respondents (mean age, 41.3 years; 75% women; 70% White) who reported one or more headache or migraine attacks during the previous 12 months and who met criteria for migraine from the International Classification of Headache Disorders. Among the patients, 35% had a college degree, and 89% suffered episodic-type headaches.
Researchers used the following four patient-reported outcome measures:
- Migraine Disability Assessment, which quantifies number of days missed at work, home, or social events over the previous 3 months
- Migraine Interictal Burden Scale–4, which measures burden of migraine between attacks over the previous 4 weeks
- Migraine-Specific Quality of Life Role-Function Restrictive, which assesses the functional effect of migraine on social and work-related activities over the previous 4 weeks
- Migraine-Related Stigma
For the latter, the investigators used two measures – the degree to which others think migraine is used to acquire secondary gain, such as avoiding commitments, and the degree to which others minimize the burden of migraine.
One of the most stigmatizing disorders
Results showed that 31.7% of participants reported experiencing stigmatization from one or both migraine-related stigma categories often or very often – a result Dr. Shapiro characterized as “pretty shocking.”
Participants with chronic headaches, defined as having 15 or more headache days per month, made up 11% of the sample. About 47% of these respondents felt stigma often or very often.
However, even 25% of participants with three or fewer headache days per month reported stigma.
“This is a fundamental tip that we are not really understanding the concerns that drive burden for people living with this disabling disease,” Dr. Shapiro said.
Some previous studies that compared levels of stigmatizing attitudes regarding various diseases showed that migraine is more stigmatized than even epilepsy, a condition “equated with demonic possession in biblical times,” he noted.
One study used machine learning to measure the number of pejorative or negative terms associated with various diseases. “Shockingly, migraine was one of the most stigmatized diseases,” said Dr. Shapiro. “It was as stigmatized as gonorrhea by certain measures.”
Results from the new study showed that, irrespective of the number of headache days experienced per month, there was a threefold increase in interictal burden among those reporting stigma often or very often, compared with those who didn’t report stigma.
Large impact on QoL
“Stigma is a social concept, so maybe it’s not surprising that it would be present whether or not someone is experiencing other symptoms of migraine,” said Dr. Shapiro.
Across all monthly headache days, experiencing more migraine-related stigma was associated with increased disability and decreased quality of life.
Dr. Shapiro noted that when it comes to migraine-specific quality of life, stigma appears to have more of an effect than number of headache days. “That means there are big gaps in our appreciation for what drives the burdens in the patient experience of living with this disabling disease,” he said.
He added that headache’s place within the migraine sphere needs to be reconsidered. “Its singular emphasis has limited our full appreciation of this disease and how we should be paying attention to the things that are important to patients,” he said.
Dr. Shapiro predicts that future clinical trials will include migraine-related stigma as a measure to guide trial enrollment.
In addition, researchers are now digging deeper to try to understand what factors are most likely to drive stigma. “We need to understand why those attitudes are held and who is more likely to hold those attitudes, and that may allow us to develop mitigating strategies to reduce those attitudes,” said Dr. Shapiro.
‘Worrisome’ findings
Commenting on the findings, Deborah Friedman, MD, professor, departments of neurology and of ophthalmology, UT Southwestern Medical Center, Dallas, said the data on stigma were “worrisome.”
Missing social occasions and lost productivity may make migraine more visible to others so perhaps may “provoke stigma or stigmatizing comments or stigmatizing attitudes,” said Dr. Friedman, who was not involved with the research.
She noted that patients with migraine might also have trouble functioning in the workplace. “They may not be able to tolerate the computer screen or smells of perfume at the office and not get accommodation for that,” she said.
In addition to external stigma, which was investigated in the study, individuals with migraine may also experience internal stigma – blaming themselves for their disease, which may make it less likely they will seek care, said Dr. Friedman.
“That’s a huge problem,” she added.
The OVERCOME study is funded by Lilly. Dr. Shapiro has been compensated by Lilly as a research consultant and as a member of the data monitoring committee for clinical trials for galcanezumab, a Lilly pharmaceutical. Dr. Friedman has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows. Results from the OVERCOME population-based survey study, which included more than 59,000 respondents, showed about 32% reported experiencing migraine-related stigma “often” or “very often.”
Even those experiencing only a few headaches per month said they experienced negative attitudes from others about migraine.
“We have been utterly blind to the burden people with migraine experience in terms of how their disease is appreciated by others. It’s time to get busy and address this very stubborn social phenomenon,” said the study’s coinvestigator, Robert E. Shapiro, MD, PhD, professor emeritus, department of neurological sciences, Larner College of Medicine, University of Vermont, Burlington.
The findings were presented at the annual meeting of the American Headache Society.
Population-based research
Stigma is defined as the discounting or discrediting of an individual with a trait that deviates from social norms. To date, there have been no significant population-based studies of how these attitudes affect individuals with migraine.
OVERCOME is a cross-sectional, longitudinal, prospective, web-based survey conducted in a representative sample of the United States population. For this new analysis, researchers pooled data from surveys conducted in 2018, 2019, and 2020.
The analysis included 59,004 respondents (mean age, 41.3 years; 75% women; 70% White) who reported one or more headache or migraine attacks during the previous 12 months and who met criteria for migraine from the International Classification of Headache Disorders. Among the patients, 35% had a college degree, and 89% suffered episodic-type headaches.
Researchers used the following four patient-reported outcome measures:
- Migraine Disability Assessment, which quantifies number of days missed at work, home, or social events over the previous 3 months
- Migraine Interictal Burden Scale–4, which measures burden of migraine between attacks over the previous 4 weeks
- Migraine-Specific Quality of Life Role-Function Restrictive, which assesses the functional effect of migraine on social and work-related activities over the previous 4 weeks
- Migraine-Related Stigma
For the latter, the investigators used two measures – the degree to which others think migraine is used to acquire secondary gain, such as avoiding commitments, and the degree to which others minimize the burden of migraine.
One of the most stigmatizing disorders
Results showed that 31.7% of participants reported experiencing stigmatization from one or both migraine-related stigma categories often or very often – a result Dr. Shapiro characterized as “pretty shocking.”
Participants with chronic headaches, defined as having 15 or more headache days per month, made up 11% of the sample. About 47% of these respondents felt stigma often or very often.
However, even 25% of participants with three or fewer headache days per month reported stigma.
“This is a fundamental tip that we are not really understanding the concerns that drive burden for people living with this disabling disease,” Dr. Shapiro said.
Some previous studies that compared levels of stigmatizing attitudes regarding various diseases showed that migraine is more stigmatized than even epilepsy, a condition “equated with demonic possession in biblical times,” he noted.
One study used machine learning to measure the number of pejorative or negative terms associated with various diseases. “Shockingly, migraine was one of the most stigmatized diseases,” said Dr. Shapiro. “It was as stigmatized as gonorrhea by certain measures.”
Results from the new study showed that, irrespective of the number of headache days experienced per month, there was a threefold increase in interictal burden among those reporting stigma often or very often, compared with those who didn’t report stigma.
Large impact on QoL
“Stigma is a social concept, so maybe it’s not surprising that it would be present whether or not someone is experiencing other symptoms of migraine,” said Dr. Shapiro.
Across all monthly headache days, experiencing more migraine-related stigma was associated with increased disability and decreased quality of life.
Dr. Shapiro noted that when it comes to migraine-specific quality of life, stigma appears to have more of an effect than number of headache days. “That means there are big gaps in our appreciation for what drives the burdens in the patient experience of living with this disabling disease,” he said.
He added that headache’s place within the migraine sphere needs to be reconsidered. “Its singular emphasis has limited our full appreciation of this disease and how we should be paying attention to the things that are important to patients,” he said.
Dr. Shapiro predicts that future clinical trials will include migraine-related stigma as a measure to guide trial enrollment.
In addition, researchers are now digging deeper to try to understand what factors are most likely to drive stigma. “We need to understand why those attitudes are held and who is more likely to hold those attitudes, and that may allow us to develop mitigating strategies to reduce those attitudes,” said Dr. Shapiro.
‘Worrisome’ findings
Commenting on the findings, Deborah Friedman, MD, professor, departments of neurology and of ophthalmology, UT Southwestern Medical Center, Dallas, said the data on stigma were “worrisome.”
Missing social occasions and lost productivity may make migraine more visible to others so perhaps may “provoke stigma or stigmatizing comments or stigmatizing attitudes,” said Dr. Friedman, who was not involved with the research.
She noted that patients with migraine might also have trouble functioning in the workplace. “They may not be able to tolerate the computer screen or smells of perfume at the office and not get accommodation for that,” she said.
In addition to external stigma, which was investigated in the study, individuals with migraine may also experience internal stigma – blaming themselves for their disease, which may make it less likely they will seek care, said Dr. Friedman.
“That’s a huge problem,” she added.
The OVERCOME study is funded by Lilly. Dr. Shapiro has been compensated by Lilly as a research consultant and as a member of the data monitoring committee for clinical trials for galcanezumab, a Lilly pharmaceutical. Dr. Friedman has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AHS 2022
Autoimmune disorder drugs top list of meds linked to headache
DENVER – in a federal side effect database that anyone can contribute to, according to a new study presented at the annual meeting of the American Headache Society.
“Surprising findings included the significant number of immunosuppressants and immunomodulators present in the data,” study lead author Brett Musialowicz, a medical student at Robert Wood Johnson Medical School, New Brunswich, N.J., said in an interview. “Additionally, our data provides evidence that suggests that several medications belonging to these drug classes were less likely to be associated with medication-induced headaches,” raising questions about the mechanism.
Drugs most frequently linked to headaches
The researchers launched their study to better understand headache as a side effect of medication use, Mr. Musialowicz said. They analyzed entries from the Food and Drug Administration’s Adverse Event Reporting System for the period from July 2018 to March 2020 and listed the top 30 most commonly reported medications linked to headaches and their reported odds ratio. According to a website devoted to pharmacovigilance training, ROR refers to “the odds of a certain event occurring with your medicinal product, compared with the odds of the same event occurring with all other medicinal products in the database.”
After generic and brand name data was consolidated, the drug most frequently linked to headaches was apremilast with 8,672 reports, followed by adalimumab (5,357), tofacitinib (4,276), fingolimod (4,123), and etanercept (4,111). These drugs treat autoimmune disorders such as psoriasis, multiple sclerosis, and Crohn’s disease.
The other drugs in the top 15 ranked by frequency are treatments for hepatitis C (4 drugs), pulmonary arterial hypertension (4 drugs), arthritis (1 drug), and asthma (1 drug).
Of the top 30 drugs most frequently linked to headaches, the pulmonary hypertension drug epoprostenol – ranked 23rd – had the highest ROR at 12.8. The next highest were the hepatitis C drugs glecaprevir and pibrentasvir, tied at 10th in the frequency analysis and both with an ROR of 9.4.
“Pulmonary arterial dilators and vasodilators are believed to cause headaches by sensitizing extracranial arteries. Clinical evidence suggests there a vascular component to some types of headache,” Mr. Musialowicz said. “Monoclonal antibodies are suggested to cause headache by means of an immune response. Several monoclonal antibodies are in trials targeting [the calcitonin gene-related peptide] receptor, which is believed to be involved in migraine headache. These trials will help further elucidate the mechanisms of headache and potential drugs to treat these conditions.”
Is the data useful?
Stewart Tepper, MD, a neurologist at Geisel School of Medicine at Dartmouth, Hanover, N.H., who’s familiar with the study findings, discounted the new research in an interview. He noted that any member of the public can contribute to the federal database of adverse effects (drug manufacturers are required to contribute to it), and the data says nothing about denominators.
“It’s not a reasonable way to evaluate adverse effects, to just have everyone and their uncle saying ‘This particular drug did this to me.’ It’s not in any way useful,” he said. However, he added that the database sometimes “gives you a bit of a signal so you can go back and try to get scientifically collected data.”
When asked to respond, study coauthor and neurologist Pengfei (Phil) Zhang, MD, of Robert Wood Johnson Medical School, noted that the FDA created the database “for a reason.” He also noted that the researchers used a statistical analysis technique – ROR – that was invented to adjust for weaknesses in databases.
No study funding is reported. Mr. Musialowicz reported no disclosures. Dr. Zhang has received honorarium from Alder Biopharmaceuticals, Board Vitals, and Fieve Clinical Research. He collaborates with Headache Science Incorporated without receiving financial support, and he has ownership interest in Cymbeline. Another author reports research grant support from the American Epilepsy Society and the New Jersey Health Foundation. Dr. Tepper reported multiple disclosures.
DENVER – in a federal side effect database that anyone can contribute to, according to a new study presented at the annual meeting of the American Headache Society.
“Surprising findings included the significant number of immunosuppressants and immunomodulators present in the data,” study lead author Brett Musialowicz, a medical student at Robert Wood Johnson Medical School, New Brunswich, N.J., said in an interview. “Additionally, our data provides evidence that suggests that several medications belonging to these drug classes were less likely to be associated with medication-induced headaches,” raising questions about the mechanism.
Drugs most frequently linked to headaches
The researchers launched their study to better understand headache as a side effect of medication use, Mr. Musialowicz said. They analyzed entries from the Food and Drug Administration’s Adverse Event Reporting System for the period from July 2018 to March 2020 and listed the top 30 most commonly reported medications linked to headaches and their reported odds ratio. According to a website devoted to pharmacovigilance training, ROR refers to “the odds of a certain event occurring with your medicinal product, compared with the odds of the same event occurring with all other medicinal products in the database.”
After generic and brand name data was consolidated, the drug most frequently linked to headaches was apremilast with 8,672 reports, followed by adalimumab (5,357), tofacitinib (4,276), fingolimod (4,123), and etanercept (4,111). These drugs treat autoimmune disorders such as psoriasis, multiple sclerosis, and Crohn’s disease.
The other drugs in the top 15 ranked by frequency are treatments for hepatitis C (4 drugs), pulmonary arterial hypertension (4 drugs), arthritis (1 drug), and asthma (1 drug).
Of the top 30 drugs most frequently linked to headaches, the pulmonary hypertension drug epoprostenol – ranked 23rd – had the highest ROR at 12.8. The next highest were the hepatitis C drugs glecaprevir and pibrentasvir, tied at 10th in the frequency analysis and both with an ROR of 9.4.
“Pulmonary arterial dilators and vasodilators are believed to cause headaches by sensitizing extracranial arteries. Clinical evidence suggests there a vascular component to some types of headache,” Mr. Musialowicz said. “Monoclonal antibodies are suggested to cause headache by means of an immune response. Several monoclonal antibodies are in trials targeting [the calcitonin gene-related peptide] receptor, which is believed to be involved in migraine headache. These trials will help further elucidate the mechanisms of headache and potential drugs to treat these conditions.”
Is the data useful?
Stewart Tepper, MD, a neurologist at Geisel School of Medicine at Dartmouth, Hanover, N.H., who’s familiar with the study findings, discounted the new research in an interview. He noted that any member of the public can contribute to the federal database of adverse effects (drug manufacturers are required to contribute to it), and the data says nothing about denominators.
“It’s not a reasonable way to evaluate adverse effects, to just have everyone and their uncle saying ‘This particular drug did this to me.’ It’s not in any way useful,” he said. However, he added that the database sometimes “gives you a bit of a signal so you can go back and try to get scientifically collected data.”
When asked to respond, study coauthor and neurologist Pengfei (Phil) Zhang, MD, of Robert Wood Johnson Medical School, noted that the FDA created the database “for a reason.” He also noted that the researchers used a statistical analysis technique – ROR – that was invented to adjust for weaknesses in databases.
No study funding is reported. Mr. Musialowicz reported no disclosures. Dr. Zhang has received honorarium from Alder Biopharmaceuticals, Board Vitals, and Fieve Clinical Research. He collaborates with Headache Science Incorporated without receiving financial support, and he has ownership interest in Cymbeline. Another author reports research grant support from the American Epilepsy Society and the New Jersey Health Foundation. Dr. Tepper reported multiple disclosures.
DENVER – in a federal side effect database that anyone can contribute to, according to a new study presented at the annual meeting of the American Headache Society.
“Surprising findings included the significant number of immunosuppressants and immunomodulators present in the data,” study lead author Brett Musialowicz, a medical student at Robert Wood Johnson Medical School, New Brunswich, N.J., said in an interview. “Additionally, our data provides evidence that suggests that several medications belonging to these drug classes were less likely to be associated with medication-induced headaches,” raising questions about the mechanism.
Drugs most frequently linked to headaches
The researchers launched their study to better understand headache as a side effect of medication use, Mr. Musialowicz said. They analyzed entries from the Food and Drug Administration’s Adverse Event Reporting System for the period from July 2018 to March 2020 and listed the top 30 most commonly reported medications linked to headaches and their reported odds ratio. According to a website devoted to pharmacovigilance training, ROR refers to “the odds of a certain event occurring with your medicinal product, compared with the odds of the same event occurring with all other medicinal products in the database.”
After generic and brand name data was consolidated, the drug most frequently linked to headaches was apremilast with 8,672 reports, followed by adalimumab (5,357), tofacitinib (4,276), fingolimod (4,123), and etanercept (4,111). These drugs treat autoimmune disorders such as psoriasis, multiple sclerosis, and Crohn’s disease.
The other drugs in the top 15 ranked by frequency are treatments for hepatitis C (4 drugs), pulmonary arterial hypertension (4 drugs), arthritis (1 drug), and asthma (1 drug).
Of the top 30 drugs most frequently linked to headaches, the pulmonary hypertension drug epoprostenol – ranked 23rd – had the highest ROR at 12.8. The next highest were the hepatitis C drugs glecaprevir and pibrentasvir, tied at 10th in the frequency analysis and both with an ROR of 9.4.
“Pulmonary arterial dilators and vasodilators are believed to cause headaches by sensitizing extracranial arteries. Clinical evidence suggests there a vascular component to some types of headache,” Mr. Musialowicz said. “Monoclonal antibodies are suggested to cause headache by means of an immune response. Several monoclonal antibodies are in trials targeting [the calcitonin gene-related peptide] receptor, which is believed to be involved in migraine headache. These trials will help further elucidate the mechanisms of headache and potential drugs to treat these conditions.”
Is the data useful?
Stewart Tepper, MD, a neurologist at Geisel School of Medicine at Dartmouth, Hanover, N.H., who’s familiar with the study findings, discounted the new research in an interview. He noted that any member of the public can contribute to the federal database of adverse effects (drug manufacturers are required to contribute to it), and the data says nothing about denominators.
“It’s not a reasonable way to evaluate adverse effects, to just have everyone and their uncle saying ‘This particular drug did this to me.’ It’s not in any way useful,” he said. However, he added that the database sometimes “gives you a bit of a signal so you can go back and try to get scientifically collected data.”
When asked to respond, study coauthor and neurologist Pengfei (Phil) Zhang, MD, of Robert Wood Johnson Medical School, noted that the FDA created the database “for a reason.” He also noted that the researchers used a statistical analysis technique – ROR – that was invented to adjust for weaknesses in databases.
No study funding is reported. Mr. Musialowicz reported no disclosures. Dr. Zhang has received honorarium from Alder Biopharmaceuticals, Board Vitals, and Fieve Clinical Research. He collaborates with Headache Science Incorporated without receiving financial support, and he has ownership interest in Cymbeline. Another author reports research grant support from the American Epilepsy Society and the New Jersey Health Foundation. Dr. Tepper reported multiple disclosures.
AT AHS 2022
Recommended headache treatments get mixed reception in EDs
DENVER – a new study finds. But the use of diphenhydramine (Benadryl) more than doubled even though guidelines caution against it, while recommended drugs such triptans and corticosteroids were rarely prescribed.
From 2007-2010 to 2015-2018, researchers reported at the annual meeting of the American Headache Society, a database reveals that opioid use in headache cases at EDs fell from 54% to 28%. Diphenhydramine use grew from 17% to 36% (both (P < .001). The percentage of cases in which EDs sought neuroimaging stayed stable at about 36%, a number that the study authors described as too high.
“Future studies are warranted to identify strategies to promote evidence-based treatments for headaches and appropriate outpatient referrals for follow-up and to reduce unnecessary neuroimaging orders in EDs,” lead author Seonkyeong Yang, MS, of the University of Florida, Gainesville, said in an interview.
Ms. Yang said researchers launched the study to update previous data in light of changes in opioid prescribing and the 2016 release of American Headache Society guidelines for the treatment of acute migraines in the ED setting. The research was published in the Journal of Clinical Medicine.
Headache treatment in the ED
For the study, researchers analyzed data from the U.S. National Hospital Ambulatory Medical Care survey and focused on adults who had a primary discharge diagnosis of headache.
For the 2015-2018 period, per weighted numbers, the survey encompassed 10.2 million headaches mostly among people younger than 50 (71%), female (73%), and White (73%). Migraines made up 33% of the total, with nonspecified headache accounting for almost all of the remainder (63%).
In 68% of cases, two or more medications were administered in the ED. This number rose to 83% among patients with migraine. But most of the time (54%), no medications were prescribed at discharge.
Among recommended medications, antiemetics – the most commonly used class of drugs in these patients – were prescribed 59% of the time in both 2007-2010 and 2015-2018 (P = .88). Usage of acetaminophens and NSAIDs grew from 37% to 52% over that time period.
Despite recommendations, the use of ergot alkaloids/triptans and corticosteroids remained low (less than 6% of the time).
“Several factors may contribute to the underuse of triptans in EDs, including their cardiovascular contraindications, ED physicians’ unfamiliarity with injectable triptans, higher costs, and treatment failures with triptans before ED visits,” Ms. Yang said. “We observed an upward trend in dexamethasone use over time. However, it was still underutilized. [The corticosteroid was only used 3.5% of the time from 2015-2018.] The 2016 AHS guideline strongly recommends dexamethasone use to prevent migraine recurrence after ED discharge. Identifying patients at high risk of headache recurrence for dexamethasone use may further improve patient outcomes of acute headache management in ED settings.”
Ms. Yang also reported that the use of diphenhydramine grew even though it’s not recommended. “Diphenhydramine is more likely to be used to prevent akathisia, a side effect of some antiemetics [that is, dopamine receptor antagonists] in headache-related ED visits,” she said. “However, the 2016 AHS guideline recommends against diphenhydramine use due to its limited efficacy in relieving headache pain. In addition, there is also conflicting evidence on diphenhydramine’s efficacy in preventing akathisia when coadministered with antiemetics. Diphenhydramine use requires caution due to its sedative effect and abuse potential.”
As for medication combinations, Ms. Yang said “the most broadly used therapy among headache-related ED visits in 2007-2010 was an opioid with an antiemetic (21.0%), which decreased to 6.6% in 2015-2018. Meanwhile, the combined use of acetaminophen/NSAIDs with antiemetic and diphenhydramine increased substantially from 3.9% to 15.7% and became the most prevalent therapy in 2015-2018. Opioid monotherapy use gradually decreased during the study period [from 8.8% to 1.9%].”
Evidence-based treatments underutilized
Commenting on the findings, New York University Langone neurologist and headache researcher Mia Tova Minen, MD, MPH, noted in an interview that AHS guidelines do not indicate acetaminophen/NSAIDs, diphenhydramine, and corticosteroids for the acute treatment of migraine. “The recommended treatments are sumatriptan subcutaneous, IV metoclopramide, and IV prochlorperazine. Steroids can be helpful in the prevention of migraine recurrence but not for the acute treatment of the migraine itself,” she said. “We need to ensure that patients with migraine get the top evidence-based treatments for migraine.”
As for diphenhydramine, she said it “is not a treatment for headache disorders. It does not have proven efficacy. It is sometimes given to reduce side effects of more acute treatments of headache, but it can make patients fatigued and keep them in the ED longer.”
Overuse of neuroimaging
Ms. Yang also highlighted study data about the frequency of neuroimaging. “Understandably, ED physicians do not want to miss any life-threatening secondary headaches like stroke,” she said. “However, other factors also contribute to the overuse of neuroimaging in headache-related ED visits: patient demands, financial incentives, a busy ED practice where clinical evaluation is replaced by tests, and ED physicians’ unfamiliarity with ICHD-3 diagnostic criteria for primary headache disorders. There is still much room for improvement in neuroimaging use for headaches in ED settings.”
For her part, Dr. Minen said scans are often performed reflexively and can be overused. “A CT scan is really only good in the case of acute trauma to rule out a fracture or a bleed or if there are signs of an emergent neurologic emergency like herniation or if a MRI is contraindicated. An MRI of the brain is typically the best test to examine brain tissue, though sometimes vessel imaging is also warranted. In the case of no red flags and a normal neurologic exam, the use of neuroimaging is low yield.”
The research has no funding. Ms. Yang and two other authors disclosed research funding from Merck. Dr. Minen reports no disclosures.
DENVER – a new study finds. But the use of diphenhydramine (Benadryl) more than doubled even though guidelines caution against it, while recommended drugs such triptans and corticosteroids were rarely prescribed.
From 2007-2010 to 2015-2018, researchers reported at the annual meeting of the American Headache Society, a database reveals that opioid use in headache cases at EDs fell from 54% to 28%. Diphenhydramine use grew from 17% to 36% (both (P < .001). The percentage of cases in which EDs sought neuroimaging stayed stable at about 36%, a number that the study authors described as too high.
“Future studies are warranted to identify strategies to promote evidence-based treatments for headaches and appropriate outpatient referrals for follow-up and to reduce unnecessary neuroimaging orders in EDs,” lead author Seonkyeong Yang, MS, of the University of Florida, Gainesville, said in an interview.
Ms. Yang said researchers launched the study to update previous data in light of changes in opioid prescribing and the 2016 release of American Headache Society guidelines for the treatment of acute migraines in the ED setting. The research was published in the Journal of Clinical Medicine.
Headache treatment in the ED
For the study, researchers analyzed data from the U.S. National Hospital Ambulatory Medical Care survey and focused on adults who had a primary discharge diagnosis of headache.
For the 2015-2018 period, per weighted numbers, the survey encompassed 10.2 million headaches mostly among people younger than 50 (71%), female (73%), and White (73%). Migraines made up 33% of the total, with nonspecified headache accounting for almost all of the remainder (63%).
In 68% of cases, two or more medications were administered in the ED. This number rose to 83% among patients with migraine. But most of the time (54%), no medications were prescribed at discharge.
Among recommended medications, antiemetics – the most commonly used class of drugs in these patients – were prescribed 59% of the time in both 2007-2010 and 2015-2018 (P = .88). Usage of acetaminophens and NSAIDs grew from 37% to 52% over that time period.
Despite recommendations, the use of ergot alkaloids/triptans and corticosteroids remained low (less than 6% of the time).
“Several factors may contribute to the underuse of triptans in EDs, including their cardiovascular contraindications, ED physicians’ unfamiliarity with injectable triptans, higher costs, and treatment failures with triptans before ED visits,” Ms. Yang said. “We observed an upward trend in dexamethasone use over time. However, it was still underutilized. [The corticosteroid was only used 3.5% of the time from 2015-2018.] The 2016 AHS guideline strongly recommends dexamethasone use to prevent migraine recurrence after ED discharge. Identifying patients at high risk of headache recurrence for dexamethasone use may further improve patient outcomes of acute headache management in ED settings.”
Ms. Yang also reported that the use of diphenhydramine grew even though it’s not recommended. “Diphenhydramine is more likely to be used to prevent akathisia, a side effect of some antiemetics [that is, dopamine receptor antagonists] in headache-related ED visits,” she said. “However, the 2016 AHS guideline recommends against diphenhydramine use due to its limited efficacy in relieving headache pain. In addition, there is also conflicting evidence on diphenhydramine’s efficacy in preventing akathisia when coadministered with antiemetics. Diphenhydramine use requires caution due to its sedative effect and abuse potential.”
As for medication combinations, Ms. Yang said “the most broadly used therapy among headache-related ED visits in 2007-2010 was an opioid with an antiemetic (21.0%), which decreased to 6.6% in 2015-2018. Meanwhile, the combined use of acetaminophen/NSAIDs with antiemetic and diphenhydramine increased substantially from 3.9% to 15.7% and became the most prevalent therapy in 2015-2018. Opioid monotherapy use gradually decreased during the study period [from 8.8% to 1.9%].”
Evidence-based treatments underutilized
Commenting on the findings, New York University Langone neurologist and headache researcher Mia Tova Minen, MD, MPH, noted in an interview that AHS guidelines do not indicate acetaminophen/NSAIDs, diphenhydramine, and corticosteroids for the acute treatment of migraine. “The recommended treatments are sumatriptan subcutaneous, IV metoclopramide, and IV prochlorperazine. Steroids can be helpful in the prevention of migraine recurrence but not for the acute treatment of the migraine itself,” she said. “We need to ensure that patients with migraine get the top evidence-based treatments for migraine.”
As for diphenhydramine, she said it “is not a treatment for headache disorders. It does not have proven efficacy. It is sometimes given to reduce side effects of more acute treatments of headache, but it can make patients fatigued and keep them in the ED longer.”
Overuse of neuroimaging
Ms. Yang also highlighted study data about the frequency of neuroimaging. “Understandably, ED physicians do not want to miss any life-threatening secondary headaches like stroke,” she said. “However, other factors also contribute to the overuse of neuroimaging in headache-related ED visits: patient demands, financial incentives, a busy ED practice where clinical evaluation is replaced by tests, and ED physicians’ unfamiliarity with ICHD-3 diagnostic criteria for primary headache disorders. There is still much room for improvement in neuroimaging use for headaches in ED settings.”
For her part, Dr. Minen said scans are often performed reflexively and can be overused. “A CT scan is really only good in the case of acute trauma to rule out a fracture or a bleed or if there are signs of an emergent neurologic emergency like herniation or if a MRI is contraindicated. An MRI of the brain is typically the best test to examine brain tissue, though sometimes vessel imaging is also warranted. In the case of no red flags and a normal neurologic exam, the use of neuroimaging is low yield.”
The research has no funding. Ms. Yang and two other authors disclosed research funding from Merck. Dr. Minen reports no disclosures.
DENVER – a new study finds. But the use of diphenhydramine (Benadryl) more than doubled even though guidelines caution against it, while recommended drugs such triptans and corticosteroids were rarely prescribed.
From 2007-2010 to 2015-2018, researchers reported at the annual meeting of the American Headache Society, a database reveals that opioid use in headache cases at EDs fell from 54% to 28%. Diphenhydramine use grew from 17% to 36% (both (P < .001). The percentage of cases in which EDs sought neuroimaging stayed stable at about 36%, a number that the study authors described as too high.
“Future studies are warranted to identify strategies to promote evidence-based treatments for headaches and appropriate outpatient referrals for follow-up and to reduce unnecessary neuroimaging orders in EDs,” lead author Seonkyeong Yang, MS, of the University of Florida, Gainesville, said in an interview.
Ms. Yang said researchers launched the study to update previous data in light of changes in opioid prescribing and the 2016 release of American Headache Society guidelines for the treatment of acute migraines in the ED setting. The research was published in the Journal of Clinical Medicine.
Headache treatment in the ED
For the study, researchers analyzed data from the U.S. National Hospital Ambulatory Medical Care survey and focused on adults who had a primary discharge diagnosis of headache.
For the 2015-2018 period, per weighted numbers, the survey encompassed 10.2 million headaches mostly among people younger than 50 (71%), female (73%), and White (73%). Migraines made up 33% of the total, with nonspecified headache accounting for almost all of the remainder (63%).
In 68% of cases, two or more medications were administered in the ED. This number rose to 83% among patients with migraine. But most of the time (54%), no medications were prescribed at discharge.
Among recommended medications, antiemetics – the most commonly used class of drugs in these patients – were prescribed 59% of the time in both 2007-2010 and 2015-2018 (P = .88). Usage of acetaminophens and NSAIDs grew from 37% to 52% over that time period.
Despite recommendations, the use of ergot alkaloids/triptans and corticosteroids remained low (less than 6% of the time).
“Several factors may contribute to the underuse of triptans in EDs, including their cardiovascular contraindications, ED physicians’ unfamiliarity with injectable triptans, higher costs, and treatment failures with triptans before ED visits,” Ms. Yang said. “We observed an upward trend in dexamethasone use over time. However, it was still underutilized. [The corticosteroid was only used 3.5% of the time from 2015-2018.] The 2016 AHS guideline strongly recommends dexamethasone use to prevent migraine recurrence after ED discharge. Identifying patients at high risk of headache recurrence for dexamethasone use may further improve patient outcomes of acute headache management in ED settings.”
Ms. Yang also reported that the use of diphenhydramine grew even though it’s not recommended. “Diphenhydramine is more likely to be used to prevent akathisia, a side effect of some antiemetics [that is, dopamine receptor antagonists] in headache-related ED visits,” she said. “However, the 2016 AHS guideline recommends against diphenhydramine use due to its limited efficacy in relieving headache pain. In addition, there is also conflicting evidence on diphenhydramine’s efficacy in preventing akathisia when coadministered with antiemetics. Diphenhydramine use requires caution due to its sedative effect and abuse potential.”
As for medication combinations, Ms. Yang said “the most broadly used therapy among headache-related ED visits in 2007-2010 was an opioid with an antiemetic (21.0%), which decreased to 6.6% in 2015-2018. Meanwhile, the combined use of acetaminophen/NSAIDs with antiemetic and diphenhydramine increased substantially from 3.9% to 15.7% and became the most prevalent therapy in 2015-2018. Opioid monotherapy use gradually decreased during the study period [from 8.8% to 1.9%].”
Evidence-based treatments underutilized
Commenting on the findings, New York University Langone neurologist and headache researcher Mia Tova Minen, MD, MPH, noted in an interview that AHS guidelines do not indicate acetaminophen/NSAIDs, diphenhydramine, and corticosteroids for the acute treatment of migraine. “The recommended treatments are sumatriptan subcutaneous, IV metoclopramide, and IV prochlorperazine. Steroids can be helpful in the prevention of migraine recurrence but not for the acute treatment of the migraine itself,” she said. “We need to ensure that patients with migraine get the top evidence-based treatments for migraine.”
As for diphenhydramine, she said it “is not a treatment for headache disorders. It does not have proven efficacy. It is sometimes given to reduce side effects of more acute treatments of headache, but it can make patients fatigued and keep them in the ED longer.”
Overuse of neuroimaging
Ms. Yang also highlighted study data about the frequency of neuroimaging. “Understandably, ED physicians do not want to miss any life-threatening secondary headaches like stroke,” she said. “However, other factors also contribute to the overuse of neuroimaging in headache-related ED visits: patient demands, financial incentives, a busy ED practice where clinical evaluation is replaced by tests, and ED physicians’ unfamiliarity with ICHD-3 diagnostic criteria for primary headache disorders. There is still much room for improvement in neuroimaging use for headaches in ED settings.”
For her part, Dr. Minen said scans are often performed reflexively and can be overused. “A CT scan is really only good in the case of acute trauma to rule out a fracture or a bleed or if there are signs of an emergent neurologic emergency like herniation or if a MRI is contraindicated. An MRI of the brain is typically the best test to examine brain tissue, though sometimes vessel imaging is also warranted. In the case of no red flags and a normal neurologic exam, the use of neuroimaging is low yield.”
The research has no funding. Ms. Yang and two other authors disclosed research funding from Merck. Dr. Minen reports no disclosures.
AT AHS 2022
Bariatric surgery can be a tool to relieve migraine
DENVER – , a neurologist told colleagues at the annual meeting of the American Headache Society. “There’s evidence-based medicine to support bariatric surgery, a lot of it, and the outcomes are actually pretty good,” said Jennifer McVige, MD, MA, of Dent Neurologic Institute in Buffalo, N.Y.
As Dr. McVige noted, research has linked obesity to migraine even after adjustment for comorbidities. A 2007 analysis of a survey of 30,215 participants, for example, found that “the proportion of subjects with severe headache pain increased with BMI, doubling in the morbidly obese relative to the normally weighted (odds ratio [OR] = 1.9).” And a 2011 study of 3,733 pregnant women found that risk of migraine increased in line with level of obesity: “obese women had a 1.48-fold increased odds of migraine (OR = 1.48; 95% confidence interval [CI], 1.12-1.96). Severely obese (OR = 2.07; 95% CI, 1.27-3.39) and morbidly obese (OR = 2.75; 95% CI, 1.60-4.70) had the highest odds of migraines.”
The link between obesity and headaches is unclear, she said, but there are hints at possible factors. For one, calcitonin gene-related peptide (CGRP) is increased in people with obesity and is an important factor in migraines. Additionally, nausea is quite common in people with migraine, suggesting a possible gut-brain interaction – or not.
“Nausea is associated with a lot of the medicines that we give patients with migraine. Is it the nausea that’s associated with the migraine medicine, or is nausea occurring at the end of the migraine?” she asked. “That’s always been kind of a conundrum for us.”
Whatever the case, she said, bariatric surgery appears to be helpful for patients with headache. Some studies have been small, but a 2021 analysis of 1,680 patients with migraine found that 55% experienced remission with no need for medication at 180 days post surgery. Women, older patients, and those taking more migraine medications were less likely to reach remission.
Research also suggests that bariatric surgery can relieve headache symptoms in patients with idiopathic intracranial hypertension.
Dr. McVige cautioned, however, that medical professionals must take special care when they talk to patients about their weight. “I’ve learned from conversations with my patients that they don’t like hearing ‘obese,’ or ‘fat,’ or ‘diet,’ or ‘losing weight.’ What they do like is ‘maybe we could try to find ways to be more healthy, to help your body to look the way that you would like it to look in the future. Let me help you. Maybe we can talk about nutrition. Maybe we can talk about exercise. Let’s talk about energy. Let’s talk about those types of things.’”
Unfortunately, there’s little research into how to have these conversations, Dr. McVige said. Still, “we need to be the first people to come forward and say, ‘This is a tough topic for me to talk about too. It makes me uncomfortable as well. I know you’re uncomfortable, but I have to talk to you because I care about you as a patient.’”
She also advised colleagues to not bring up weight right out of the gate. “It’s easier to say some of those things after you develop a relationship,” she said, “when they know you care about them.”
Dr. McVige reported multiple disclosures related to research funding and speaker fees.
DENVER – , a neurologist told colleagues at the annual meeting of the American Headache Society. “There’s evidence-based medicine to support bariatric surgery, a lot of it, and the outcomes are actually pretty good,” said Jennifer McVige, MD, MA, of Dent Neurologic Institute in Buffalo, N.Y.
As Dr. McVige noted, research has linked obesity to migraine even after adjustment for comorbidities. A 2007 analysis of a survey of 30,215 participants, for example, found that “the proportion of subjects with severe headache pain increased with BMI, doubling in the morbidly obese relative to the normally weighted (odds ratio [OR] = 1.9).” And a 2011 study of 3,733 pregnant women found that risk of migraine increased in line with level of obesity: “obese women had a 1.48-fold increased odds of migraine (OR = 1.48; 95% confidence interval [CI], 1.12-1.96). Severely obese (OR = 2.07; 95% CI, 1.27-3.39) and morbidly obese (OR = 2.75; 95% CI, 1.60-4.70) had the highest odds of migraines.”
The link between obesity and headaches is unclear, she said, but there are hints at possible factors. For one, calcitonin gene-related peptide (CGRP) is increased in people with obesity and is an important factor in migraines. Additionally, nausea is quite common in people with migraine, suggesting a possible gut-brain interaction – or not.
“Nausea is associated with a lot of the medicines that we give patients with migraine. Is it the nausea that’s associated with the migraine medicine, or is nausea occurring at the end of the migraine?” she asked. “That’s always been kind of a conundrum for us.”
Whatever the case, she said, bariatric surgery appears to be helpful for patients with headache. Some studies have been small, but a 2021 analysis of 1,680 patients with migraine found that 55% experienced remission with no need for medication at 180 days post surgery. Women, older patients, and those taking more migraine medications were less likely to reach remission.
Research also suggests that bariatric surgery can relieve headache symptoms in patients with idiopathic intracranial hypertension.
Dr. McVige cautioned, however, that medical professionals must take special care when they talk to patients about their weight. “I’ve learned from conversations with my patients that they don’t like hearing ‘obese,’ or ‘fat,’ or ‘diet,’ or ‘losing weight.’ What they do like is ‘maybe we could try to find ways to be more healthy, to help your body to look the way that you would like it to look in the future. Let me help you. Maybe we can talk about nutrition. Maybe we can talk about exercise. Let’s talk about energy. Let’s talk about those types of things.’”
Unfortunately, there’s little research into how to have these conversations, Dr. McVige said. Still, “we need to be the first people to come forward and say, ‘This is a tough topic for me to talk about too. It makes me uncomfortable as well. I know you’re uncomfortable, but I have to talk to you because I care about you as a patient.’”
She also advised colleagues to not bring up weight right out of the gate. “It’s easier to say some of those things after you develop a relationship,” she said, “when they know you care about them.”
Dr. McVige reported multiple disclosures related to research funding and speaker fees.
DENVER – , a neurologist told colleagues at the annual meeting of the American Headache Society. “There’s evidence-based medicine to support bariatric surgery, a lot of it, and the outcomes are actually pretty good,” said Jennifer McVige, MD, MA, of Dent Neurologic Institute in Buffalo, N.Y.
As Dr. McVige noted, research has linked obesity to migraine even after adjustment for comorbidities. A 2007 analysis of a survey of 30,215 participants, for example, found that “the proportion of subjects with severe headache pain increased with BMI, doubling in the morbidly obese relative to the normally weighted (odds ratio [OR] = 1.9).” And a 2011 study of 3,733 pregnant women found that risk of migraine increased in line with level of obesity: “obese women had a 1.48-fold increased odds of migraine (OR = 1.48; 95% confidence interval [CI], 1.12-1.96). Severely obese (OR = 2.07; 95% CI, 1.27-3.39) and morbidly obese (OR = 2.75; 95% CI, 1.60-4.70) had the highest odds of migraines.”
The link between obesity and headaches is unclear, she said, but there are hints at possible factors. For one, calcitonin gene-related peptide (CGRP) is increased in people with obesity and is an important factor in migraines. Additionally, nausea is quite common in people with migraine, suggesting a possible gut-brain interaction – or not.
“Nausea is associated with a lot of the medicines that we give patients with migraine. Is it the nausea that’s associated with the migraine medicine, or is nausea occurring at the end of the migraine?” she asked. “That’s always been kind of a conundrum for us.”
Whatever the case, she said, bariatric surgery appears to be helpful for patients with headache. Some studies have been small, but a 2021 analysis of 1,680 patients with migraine found that 55% experienced remission with no need for medication at 180 days post surgery. Women, older patients, and those taking more migraine medications were less likely to reach remission.
Research also suggests that bariatric surgery can relieve headache symptoms in patients with idiopathic intracranial hypertension.
Dr. McVige cautioned, however, that medical professionals must take special care when they talk to patients about their weight. “I’ve learned from conversations with my patients that they don’t like hearing ‘obese,’ or ‘fat,’ or ‘diet,’ or ‘losing weight.’ What they do like is ‘maybe we could try to find ways to be more healthy, to help your body to look the way that you would like it to look in the future. Let me help you. Maybe we can talk about nutrition. Maybe we can talk about exercise. Let’s talk about energy. Let’s talk about those types of things.’”
Unfortunately, there’s little research into how to have these conversations, Dr. McVige said. Still, “we need to be the first people to come forward and say, ‘This is a tough topic for me to talk about too. It makes me uncomfortable as well. I know you’re uncomfortable, but I have to talk to you because I care about you as a patient.’”
She also advised colleagues to not bring up weight right out of the gate. “It’s easier to say some of those things after you develop a relationship,” she said, “when they know you care about them.”
Dr. McVige reported multiple disclosures related to research funding and speaker fees.
AT AHS 2022
Psychedelic drugs ‘truly have potential’ in headache care
DENVER – Psychedelics such as psilocybin “truly have the potential to transform how we treat a number of neuropsychiatric diseases, including headaches,” a neuropharmacologist told colleagues at the annual meeting of the American Headache Society.
However, Bryan Roth, MD, PhD, professor of pharmacology at the University of North Carolina at Chapel Hill, also offered a major cautionary note: There have been no randomized, phase 3 trials of psychedelics, and he bluntly said that “I do not recommend the use of psychedelics for any medical condition.”
The potential disease-altering powers of psychedelics have received a tremendous amount of research and media attention over the past several years. A landmark randomized, double-blind study released in 2016 triggered much of the interest, Dr. Roth said, when it suggested that high-dose psilocybin significantly lowered levels of depressed mood/anxiety in patients with life-threatening cancer. At 6 months, 80% of patients who took the dose reported moderate or greater improvement in well-being/life satisfaction.
“You have the potential – unprecedented in psychiatry – that a single dose of a therapeutic agent may induce a rapid, robust, and sustained antidepressant action,” he said. Also of note: The “vast majority” of subjects say their encounter with a psychedelic was “one of the most meaningful experiences of their lives.”
Dr. Roth said his own research suggests that psychedelics cause a “huge increase” in the asynchronous firing of neurons. “Noise is being injected into the system and is interpreted by the brain or the mind, which always likes to make a story about what’s going on. The story it makes up is idiosyncratic to every person and memorable for reasons that are not understood.”
Now, Dr. Roth said, he and colleagues are working to “create drugs that have this potential remarkable therapeutic efficacy in psychiatric and neurologic disorders without the psychedelic effects.” A $27 million grant from the Defense Advanced Research Projects Agency is providing support for their efforts, he said.
For the moment, he said, there’s no way to know if “the psychedelic experience is essential to the therapeutic action of these drugs. But it’s a testable hypothesis.”
As he noted, a tiny 2010 study of 2-bromo-lysergic acid diethylamide (LSD), which doesn’t cause hallucinations, showed promise as a treatment for cluster headaches.
For now, Dr. Roth said, his lab is synthesizing and testing new compounds that interact with the crucial 5-HT2A receptor.
Additional research
In another presentation at the AHS annual meeting, neurologist Emmanuelle A. D. Schindler, MD, PhD, of Yale School of Medicine, highlighted her 2021 study of an exploratory double-blind, placebo-controlled, cross-over study of psilocybin versus placebo for migraine headache. A single oral dose of the drug, the researchers found, reduced headache frequency and pain over 2 weeks. The study is small, with just 10 subjects, and multiple exclusion criteria.
She also revealed preliminary findings from an ongoing randomized, double-blind, placebo-controlled study of psilocybin versus placebo in cluster headaches. In 14 subjects, a psilocybin pulse was linked to fewer cluster attacks over 3 weeks, although the effect wasn’t statistically significant. However, there was a statistically significant reduction over 8 weeks in patients with chronic headache.
Dr. Schindler noted that “with these early studies, we only looked out to 2 weeks for migraine, and we only looked out to 2 months for cluster.” There are multiple other limitations, she acknowledged. “We have to do a lot more research and consider safety as well.”
However, “there is a really unique capacity for lasting effects after limited dosing,” she added, and the studies do show reductions in headache burden “that do not correlate with acute psychedelic effects.”
Moving forward, Dr. Roth cautioned that while U.S. states are allowing the use of psychedelics for medical purposes, “we don’t know if they ultimately are therapeutic. And we have strong reason to believe that microdosing or chronic dosing of these compounds is ultimately going to be deleterious to the health of our patients.”
Dr. Roth did not provide disclosure information. Dr. Schindler discloses research funding (Ceruvia Lifesciences, Wallace Research Foundation, Clusterbusters, Department of Veterans Affairs), serves on advisory boards (Ceruvia Lifesciences, Clusterbusters), and has a patent.
DENVER – Psychedelics such as psilocybin “truly have the potential to transform how we treat a number of neuropsychiatric diseases, including headaches,” a neuropharmacologist told colleagues at the annual meeting of the American Headache Society.
However, Bryan Roth, MD, PhD, professor of pharmacology at the University of North Carolina at Chapel Hill, also offered a major cautionary note: There have been no randomized, phase 3 trials of psychedelics, and he bluntly said that “I do not recommend the use of psychedelics for any medical condition.”
The potential disease-altering powers of psychedelics have received a tremendous amount of research and media attention over the past several years. A landmark randomized, double-blind study released in 2016 triggered much of the interest, Dr. Roth said, when it suggested that high-dose psilocybin significantly lowered levels of depressed mood/anxiety in patients with life-threatening cancer. At 6 months, 80% of patients who took the dose reported moderate or greater improvement in well-being/life satisfaction.
“You have the potential – unprecedented in psychiatry – that a single dose of a therapeutic agent may induce a rapid, robust, and sustained antidepressant action,” he said. Also of note: The “vast majority” of subjects say their encounter with a psychedelic was “one of the most meaningful experiences of their lives.”
Dr. Roth said his own research suggests that psychedelics cause a “huge increase” in the asynchronous firing of neurons. “Noise is being injected into the system and is interpreted by the brain or the mind, which always likes to make a story about what’s going on. The story it makes up is idiosyncratic to every person and memorable for reasons that are not understood.”
Now, Dr. Roth said, he and colleagues are working to “create drugs that have this potential remarkable therapeutic efficacy in psychiatric and neurologic disorders without the psychedelic effects.” A $27 million grant from the Defense Advanced Research Projects Agency is providing support for their efforts, he said.
For the moment, he said, there’s no way to know if “the psychedelic experience is essential to the therapeutic action of these drugs. But it’s a testable hypothesis.”
As he noted, a tiny 2010 study of 2-bromo-lysergic acid diethylamide (LSD), which doesn’t cause hallucinations, showed promise as a treatment for cluster headaches.
For now, Dr. Roth said, his lab is synthesizing and testing new compounds that interact with the crucial 5-HT2A receptor.
Additional research
In another presentation at the AHS annual meeting, neurologist Emmanuelle A. D. Schindler, MD, PhD, of Yale School of Medicine, highlighted her 2021 study of an exploratory double-blind, placebo-controlled, cross-over study of psilocybin versus placebo for migraine headache. A single oral dose of the drug, the researchers found, reduced headache frequency and pain over 2 weeks. The study is small, with just 10 subjects, and multiple exclusion criteria.
She also revealed preliminary findings from an ongoing randomized, double-blind, placebo-controlled study of psilocybin versus placebo in cluster headaches. In 14 subjects, a psilocybin pulse was linked to fewer cluster attacks over 3 weeks, although the effect wasn’t statistically significant. However, there was a statistically significant reduction over 8 weeks in patients with chronic headache.
Dr. Schindler noted that “with these early studies, we only looked out to 2 weeks for migraine, and we only looked out to 2 months for cluster.” There are multiple other limitations, she acknowledged. “We have to do a lot more research and consider safety as well.”
However, “there is a really unique capacity for lasting effects after limited dosing,” she added, and the studies do show reductions in headache burden “that do not correlate with acute psychedelic effects.”
Moving forward, Dr. Roth cautioned that while U.S. states are allowing the use of psychedelics for medical purposes, “we don’t know if they ultimately are therapeutic. And we have strong reason to believe that microdosing or chronic dosing of these compounds is ultimately going to be deleterious to the health of our patients.”
Dr. Roth did not provide disclosure information. Dr. Schindler discloses research funding (Ceruvia Lifesciences, Wallace Research Foundation, Clusterbusters, Department of Veterans Affairs), serves on advisory boards (Ceruvia Lifesciences, Clusterbusters), and has a patent.
DENVER – Psychedelics such as psilocybin “truly have the potential to transform how we treat a number of neuropsychiatric diseases, including headaches,” a neuropharmacologist told colleagues at the annual meeting of the American Headache Society.
However, Bryan Roth, MD, PhD, professor of pharmacology at the University of North Carolina at Chapel Hill, also offered a major cautionary note: There have been no randomized, phase 3 trials of psychedelics, and he bluntly said that “I do not recommend the use of psychedelics for any medical condition.”
The potential disease-altering powers of psychedelics have received a tremendous amount of research and media attention over the past several years. A landmark randomized, double-blind study released in 2016 triggered much of the interest, Dr. Roth said, when it suggested that high-dose psilocybin significantly lowered levels of depressed mood/anxiety in patients with life-threatening cancer. At 6 months, 80% of patients who took the dose reported moderate or greater improvement in well-being/life satisfaction.
“You have the potential – unprecedented in psychiatry – that a single dose of a therapeutic agent may induce a rapid, robust, and sustained antidepressant action,” he said. Also of note: The “vast majority” of subjects say their encounter with a psychedelic was “one of the most meaningful experiences of their lives.”
Dr. Roth said his own research suggests that psychedelics cause a “huge increase” in the asynchronous firing of neurons. “Noise is being injected into the system and is interpreted by the brain or the mind, which always likes to make a story about what’s going on. The story it makes up is idiosyncratic to every person and memorable for reasons that are not understood.”
Now, Dr. Roth said, he and colleagues are working to “create drugs that have this potential remarkable therapeutic efficacy in psychiatric and neurologic disorders without the psychedelic effects.” A $27 million grant from the Defense Advanced Research Projects Agency is providing support for their efforts, he said.
For the moment, he said, there’s no way to know if “the psychedelic experience is essential to the therapeutic action of these drugs. But it’s a testable hypothesis.”
As he noted, a tiny 2010 study of 2-bromo-lysergic acid diethylamide (LSD), which doesn’t cause hallucinations, showed promise as a treatment for cluster headaches.
For now, Dr. Roth said, his lab is synthesizing and testing new compounds that interact with the crucial 5-HT2A receptor.
Additional research
In another presentation at the AHS annual meeting, neurologist Emmanuelle A. D. Schindler, MD, PhD, of Yale School of Medicine, highlighted her 2021 study of an exploratory double-blind, placebo-controlled, cross-over study of psilocybin versus placebo for migraine headache. A single oral dose of the drug, the researchers found, reduced headache frequency and pain over 2 weeks. The study is small, with just 10 subjects, and multiple exclusion criteria.
She also revealed preliminary findings from an ongoing randomized, double-blind, placebo-controlled study of psilocybin versus placebo in cluster headaches. In 14 subjects, a psilocybin pulse was linked to fewer cluster attacks over 3 weeks, although the effect wasn’t statistically significant. However, there was a statistically significant reduction over 8 weeks in patients with chronic headache.
Dr. Schindler noted that “with these early studies, we only looked out to 2 weeks for migraine, and we only looked out to 2 months for cluster.” There are multiple other limitations, she acknowledged. “We have to do a lot more research and consider safety as well.”
However, “there is a really unique capacity for lasting effects after limited dosing,” she added, and the studies do show reductions in headache burden “that do not correlate with acute psychedelic effects.”
Moving forward, Dr. Roth cautioned that while U.S. states are allowing the use of psychedelics for medical purposes, “we don’t know if they ultimately are therapeutic. And we have strong reason to believe that microdosing or chronic dosing of these compounds is ultimately going to be deleterious to the health of our patients.”
Dr. Roth did not provide disclosure information. Dr. Schindler discloses research funding (Ceruvia Lifesciences, Wallace Research Foundation, Clusterbusters, Department of Veterans Affairs), serves on advisory boards (Ceruvia Lifesciences, Clusterbusters), and has a patent.
FROM AHS 2022
Findings raise questions about migraine and sleep
CHARLOTTE, N.C. – What may be the largest case-based study of patients with migraine and sleep-disordered breathing to date has found that, counter to prevailing thought, they may not be at higher risk of having obstructive sleep apnea (OSA) than nonmigraine patients, although further prospective studies are needed to validate that finding.
“This in no way for me changes the fact that, for patients that complain of headaches, sleep apnea remains to be something that should be considered as possible cause of their headaches,” neurologist and Cleveland Clinic postdoctoral fellow Eric Gruenthal, MD, said in an interview after he presented his results at the annual meeting of the Associated Professional Sleep Societies.
The study suggested that patients with migraine may have an OSA risk that “may be a little lower” than their nonmigraine counterparts, Dr. Gruenthal said. “But we have really yet to determine whether that’s true or not.”
Large case-based study
The retrospective case study included 4,783 migraine cases from the Cleveland Clinic electronic health record database who were case matched on a 1:3 basis with 14,287 controls. Patients with migraine had an average age of 47.5 years (±13.3) and body mass index of 33.7 kg/m2 (±8.6), and 76.4% were White. All patients had polysomnography (PSG) at a Cleveland Clinic facility from 1998 to 2021.
The analysis evaluated the collected data in two domains: sleep architecture, consisting of arousal index (AI), total sleep time (TST) and percentage of sleep stage time; and sleep-disordered breathing, including apnea hypopnea index (AHI) and mean oxygen saturation. The key findings of the migraine patients versus controls include:
- Lower AI, 19.6 (95% confidence interval, 12.8-30.9) versus 22.6 (95% CI, 14.7-34.9; P < .001).
- Shorter TST, 359 (95% CI, 307-421) versus 363 (95% CI, 306-432.5) minutes (P = .01).
- With regard to sleep stage, the percentage of N2 sleep was higher, 67.8% (95% CI, 59.6%-75.6%) versus 67% (95% CI, 58.4%-74.8%; P < .001); but the percentage of REM was lower at 16.7% (95% CI, 10%-22%) versus 17% (95% CI, 11.1%-22.2%; P = .012).
- Lower AHI, 7.4 (95% CI, 2.6-17) versus 9.5 (95% CI, 3.7-22.1, P < .001).
- Higher mean oxygen saturation, 93.7 (±2.4) versus 93.3% (±2.6; P < .001).
“Also,” Dr. Gruenthal added, “we found that the percentage of sleep time with oxygen saturation below 90% was lower among patients with migraine, at 1.3% versus 2.4%” (P < .001).
A unique profile?
The goal of the study was to determine whether migraine patients would have a unique PSG profile, Dr. Gruenthal said. “We were trying to overcome some of the limitations of previous studies, most notably those that use small sample sizes, and in some cases a lack of controls.”
The findings that migraine patients would have higher AI and elevated AHI ran counter to the study’s hypotheses, but fell in line with the expectation that they would have reduced TST, Dr. Gruenthal said.
Patients with migraine “may, in fact, exhibit a lower burden of sleep-disordered breathing, and that’s based on our findings such as the lower AHI and decreased burden of hypoxemia,” he said. “We theorized that this may be related to patients with migraine having a unique CGRP [calcitonin gene-related peptide] and serotonin physiology.” He noted that previously published research has shown that sleep CGRP and serotonin have a central role in causing arousal in response to rising CO2 levels during sleep, which can occur during apneas and hypopneas.
Dr. Gruenthal noted that the researchers are still analyzing the findings. “We theorized that possible indication bias may be present in our study,” he said. “It may be the case that patients with migraine are more likely to get their PSG done because of their headache and not for things like snoring and witnessed apneas, which may be more predictive of significant sleep apnea.” They’re also evaluating the “question of medicine confounding.”
Dr. Gruenthal added that “the big unanswered question out there is, if you have a patient with migraine who also has sleep apnea, by treating the sleep apnea will that improve their migraine?”
More questions than answers
Commenting on the study, Donald Bliwise, PhD, professor of neurology at Emory Sleep Center, Atlanta, said the study findings shouldn’t change how clinicians approach migraine in relation to sleep.
“It’s a case series, it’s retrospective,” said Dr. Bliwise, who was not involved in the study. “It’s the largest study that I know of that has ever looked at the diagnosis of migraine in relation to polysomnographic measures of sleep, but it’s imprecise to the extent that migraine is a clinical diagnosis, so not everyone that carries the diagnosis of migraine has the diagnosis made by a neurologist.”
The study raises more questions than it answers, he said, “but that’s not necessarily a bad thing. I think we need more prospective studies.” Those studies should be more granular in how they analyze sleep in migraine patients “Since migraine is an intermittent event, and sleep quality and length, and percentage of REM sleep and even sleep apnea can vary from night to night, it would be fascinating to look at headaches over a month in relation to sleep over a month.”
Dr. Gruenthal and Dr. Bliwise have no disclosures. The Association of Migraine Disorders provided funding for the study.
CHARLOTTE, N.C. – What may be the largest case-based study of patients with migraine and sleep-disordered breathing to date has found that, counter to prevailing thought, they may not be at higher risk of having obstructive sleep apnea (OSA) than nonmigraine patients, although further prospective studies are needed to validate that finding.
“This in no way for me changes the fact that, for patients that complain of headaches, sleep apnea remains to be something that should be considered as possible cause of their headaches,” neurologist and Cleveland Clinic postdoctoral fellow Eric Gruenthal, MD, said in an interview after he presented his results at the annual meeting of the Associated Professional Sleep Societies.
The study suggested that patients with migraine may have an OSA risk that “may be a little lower” than their nonmigraine counterparts, Dr. Gruenthal said. “But we have really yet to determine whether that’s true or not.”
Large case-based study
The retrospective case study included 4,783 migraine cases from the Cleveland Clinic electronic health record database who were case matched on a 1:3 basis with 14,287 controls. Patients with migraine had an average age of 47.5 years (±13.3) and body mass index of 33.7 kg/m2 (±8.6), and 76.4% were White. All patients had polysomnography (PSG) at a Cleveland Clinic facility from 1998 to 2021.
The analysis evaluated the collected data in two domains: sleep architecture, consisting of arousal index (AI), total sleep time (TST) and percentage of sleep stage time; and sleep-disordered breathing, including apnea hypopnea index (AHI) and mean oxygen saturation. The key findings of the migraine patients versus controls include:
- Lower AI, 19.6 (95% confidence interval, 12.8-30.9) versus 22.6 (95% CI, 14.7-34.9; P < .001).
- Shorter TST, 359 (95% CI, 307-421) versus 363 (95% CI, 306-432.5) minutes (P = .01).
- With regard to sleep stage, the percentage of N2 sleep was higher, 67.8% (95% CI, 59.6%-75.6%) versus 67% (95% CI, 58.4%-74.8%; P < .001); but the percentage of REM was lower at 16.7% (95% CI, 10%-22%) versus 17% (95% CI, 11.1%-22.2%; P = .012).
- Lower AHI, 7.4 (95% CI, 2.6-17) versus 9.5 (95% CI, 3.7-22.1, P < .001).
- Higher mean oxygen saturation, 93.7 (±2.4) versus 93.3% (±2.6; P < .001).
“Also,” Dr. Gruenthal added, “we found that the percentage of sleep time with oxygen saturation below 90% was lower among patients with migraine, at 1.3% versus 2.4%” (P < .001).
A unique profile?
The goal of the study was to determine whether migraine patients would have a unique PSG profile, Dr. Gruenthal said. “We were trying to overcome some of the limitations of previous studies, most notably those that use small sample sizes, and in some cases a lack of controls.”
The findings that migraine patients would have higher AI and elevated AHI ran counter to the study’s hypotheses, but fell in line with the expectation that they would have reduced TST, Dr. Gruenthal said.
Patients with migraine “may, in fact, exhibit a lower burden of sleep-disordered breathing, and that’s based on our findings such as the lower AHI and decreased burden of hypoxemia,” he said. “We theorized that this may be related to patients with migraine having a unique CGRP [calcitonin gene-related peptide] and serotonin physiology.” He noted that previously published research has shown that sleep CGRP and serotonin have a central role in causing arousal in response to rising CO2 levels during sleep, which can occur during apneas and hypopneas.
Dr. Gruenthal noted that the researchers are still analyzing the findings. “We theorized that possible indication bias may be present in our study,” he said. “It may be the case that patients with migraine are more likely to get their PSG done because of their headache and not for things like snoring and witnessed apneas, which may be more predictive of significant sleep apnea.” They’re also evaluating the “question of medicine confounding.”
Dr. Gruenthal added that “the big unanswered question out there is, if you have a patient with migraine who also has sleep apnea, by treating the sleep apnea will that improve their migraine?”
More questions than answers
Commenting on the study, Donald Bliwise, PhD, professor of neurology at Emory Sleep Center, Atlanta, said the study findings shouldn’t change how clinicians approach migraine in relation to sleep.
“It’s a case series, it’s retrospective,” said Dr. Bliwise, who was not involved in the study. “It’s the largest study that I know of that has ever looked at the diagnosis of migraine in relation to polysomnographic measures of sleep, but it’s imprecise to the extent that migraine is a clinical diagnosis, so not everyone that carries the diagnosis of migraine has the diagnosis made by a neurologist.”
The study raises more questions than it answers, he said, “but that’s not necessarily a bad thing. I think we need more prospective studies.” Those studies should be more granular in how they analyze sleep in migraine patients “Since migraine is an intermittent event, and sleep quality and length, and percentage of REM sleep and even sleep apnea can vary from night to night, it would be fascinating to look at headaches over a month in relation to sleep over a month.”
Dr. Gruenthal and Dr. Bliwise have no disclosures. The Association of Migraine Disorders provided funding for the study.
CHARLOTTE, N.C. – What may be the largest case-based study of patients with migraine and sleep-disordered breathing to date has found that, counter to prevailing thought, they may not be at higher risk of having obstructive sleep apnea (OSA) than nonmigraine patients, although further prospective studies are needed to validate that finding.
“This in no way for me changes the fact that, for patients that complain of headaches, sleep apnea remains to be something that should be considered as possible cause of their headaches,” neurologist and Cleveland Clinic postdoctoral fellow Eric Gruenthal, MD, said in an interview after he presented his results at the annual meeting of the Associated Professional Sleep Societies.
The study suggested that patients with migraine may have an OSA risk that “may be a little lower” than their nonmigraine counterparts, Dr. Gruenthal said. “But we have really yet to determine whether that’s true or not.”
Large case-based study
The retrospective case study included 4,783 migraine cases from the Cleveland Clinic electronic health record database who were case matched on a 1:3 basis with 14,287 controls. Patients with migraine had an average age of 47.5 years (±13.3) and body mass index of 33.7 kg/m2 (±8.6), and 76.4% were White. All patients had polysomnography (PSG) at a Cleveland Clinic facility from 1998 to 2021.
The analysis evaluated the collected data in two domains: sleep architecture, consisting of arousal index (AI), total sleep time (TST) and percentage of sleep stage time; and sleep-disordered breathing, including apnea hypopnea index (AHI) and mean oxygen saturation. The key findings of the migraine patients versus controls include:
- Lower AI, 19.6 (95% confidence interval, 12.8-30.9) versus 22.6 (95% CI, 14.7-34.9; P < .001).
- Shorter TST, 359 (95% CI, 307-421) versus 363 (95% CI, 306-432.5) minutes (P = .01).
- With regard to sleep stage, the percentage of N2 sleep was higher, 67.8% (95% CI, 59.6%-75.6%) versus 67% (95% CI, 58.4%-74.8%; P < .001); but the percentage of REM was lower at 16.7% (95% CI, 10%-22%) versus 17% (95% CI, 11.1%-22.2%; P = .012).
- Lower AHI, 7.4 (95% CI, 2.6-17) versus 9.5 (95% CI, 3.7-22.1, P < .001).
- Higher mean oxygen saturation, 93.7 (±2.4) versus 93.3% (±2.6; P < .001).
“Also,” Dr. Gruenthal added, “we found that the percentage of sleep time with oxygen saturation below 90% was lower among patients with migraine, at 1.3% versus 2.4%” (P < .001).
A unique profile?
The goal of the study was to determine whether migraine patients would have a unique PSG profile, Dr. Gruenthal said. “We were trying to overcome some of the limitations of previous studies, most notably those that use small sample sizes, and in some cases a lack of controls.”
The findings that migraine patients would have higher AI and elevated AHI ran counter to the study’s hypotheses, but fell in line with the expectation that they would have reduced TST, Dr. Gruenthal said.
Patients with migraine “may, in fact, exhibit a lower burden of sleep-disordered breathing, and that’s based on our findings such as the lower AHI and decreased burden of hypoxemia,” he said. “We theorized that this may be related to patients with migraine having a unique CGRP [calcitonin gene-related peptide] and serotonin physiology.” He noted that previously published research has shown that sleep CGRP and serotonin have a central role in causing arousal in response to rising CO2 levels during sleep, which can occur during apneas and hypopneas.
Dr. Gruenthal noted that the researchers are still analyzing the findings. “We theorized that possible indication bias may be present in our study,” he said. “It may be the case that patients with migraine are more likely to get their PSG done because of their headache and not for things like snoring and witnessed apneas, which may be more predictive of significant sleep apnea.” They’re also evaluating the “question of medicine confounding.”
Dr. Gruenthal added that “the big unanswered question out there is, if you have a patient with migraine who also has sleep apnea, by treating the sleep apnea will that improve their migraine?”
More questions than answers
Commenting on the study, Donald Bliwise, PhD, professor of neurology at Emory Sleep Center, Atlanta, said the study findings shouldn’t change how clinicians approach migraine in relation to sleep.
“It’s a case series, it’s retrospective,” said Dr. Bliwise, who was not involved in the study. “It’s the largest study that I know of that has ever looked at the diagnosis of migraine in relation to polysomnographic measures of sleep, but it’s imprecise to the extent that migraine is a clinical diagnosis, so not everyone that carries the diagnosis of migraine has the diagnosis made by a neurologist.”
The study raises more questions than it answers, he said, “but that’s not necessarily a bad thing. I think we need more prospective studies.” Those studies should be more granular in how they analyze sleep in migraine patients “Since migraine is an intermittent event, and sleep quality and length, and percentage of REM sleep and even sleep apnea can vary from night to night, it would be fascinating to look at headaches over a month in relation to sleep over a month.”
Dr. Gruenthal and Dr. Bliwise have no disclosures. The Association of Migraine Disorders provided funding for the study.
AT SLEEP 2022
The Slow, Long Search for Migraine’s Headwaters
Dr. Messoud Ashina is a Professor of Neurology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. He is Director of the Human Migraine Research Unit at the Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup. He serves an associate editor for Cephalalgia, Journal of Headache and Pain, and Brain.
Dr. Faisal Mohammad Amin is an Associate Professor, Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, University of Copenhagen, Denmark. He is an associate editor for Headache Medicine and is President of the Danish Headache Society.
Dr. Ashina reports that he has received fees and grants from and/or has served as a principal trial investigator for AbbVie, Amgen, Eli Lilly, Lundbeck Pharmaceuticals, Lundbeck Foundation, Novartis, Novo Nordisk Foundation, and Teva.
Dr. Amin reports that he has worked as a consultant, speaker, and/or primary investigator Eli Lilly, Lundbeck, Novartis, and Teva. Both authors have reported that they have no ownership interest nor own any stocks in a pharmaceutical company.
Since the time of the Neanderthals, humankind has looked for ways to rid the brain of migraine headache. There is evidence that trepanation–removing a portion of bone from the skull–was performed on Neolithic skulls. Did it work for that poor individual? We will never know.
What is known is that the often circuitous hunt for effective treatments has taken centuries. And while this search led to the successful introduction of calcitonin gene-related peptides (CGRPs) a few years ago, the search is nowhere near finished, as efforts to pinpoint the source of migraine continue, as does the search for other possible therapies.
The nearly 39 million people with migraine in the United States would be grateful; they often experience a perplexing, frustrating, and unsatisfactory search for a pain-free existence. Migraine is estimated to cost more than $20 million per year in direct medical expenses and lost productivity in the United States. People with migraine, meanwhile, face the prospect of significant disability. More than 8 in every 10 participants in the American Migraine Study had at least some headache-related disability. More than half said their pain has caused severe impairment.
The search to find relief for these patients is focused on understanding the pathophysiology of migraine. Approaches include in vitro application of mediators, direct electrical stimulation of trigeminal neurons in vivo, administration of vasoactive substances in vivo, and introduction of exogenous pain-inducing substances in vivo. In 2021, investigators at AstraZeneca and the University of Arizona College of Medicine described their development of an injury-free murine model to be used to study migraine-like pain. Animal research has led to a few interventional studies involving new and existing medications.
How the field has evolved from using a chisel to make a cranial hole to using magnetic resonance imaging and other technologies to examine the trigeminovascular system’s role in the pathophysiology of migraine headache is a tale worth telling.
From crocodiles to nitroglycerin to allergies
The search for an effective remedy for migraine has proved to be torturously slow. In addition to trepanation, another procedure thought to have been used during prehistoric times involved a religious ritual whereby a clay crocodile was attached tightly with a strip of linen to an individual’s head. Though the gods were credited if the headache pain receded, relief likely came from the resulting compression on the scalp. Centuries later, in the Middle Ages, treatments included soaking bandages in drugs and then applying them to the head or mixing elixirs with vinegar (which opened scalp pores) and opium (which traveled into the scalp through the open pores).
The Persian scholar Ibn Sina (980-1032), also known as Avicenna, postulated that the pain could emanate from the bones that comprise the skull or within the parenchyma or from veins and arteries outside the cranium. The medicinal plants he investigated for the treatment of migraine have components that resonate today: antineuroinflammatory agents, analgesics, and even cyclooxegenase-2 inhibitors.
Six hundred years later, English physician Thomas Willis discussed how the vascular system perpetrated migraine, and in the next century, Erasmus Darwin, Charles’ grandfather, proposed that individuals with migraine be spun around so that blood from the head would be forced down toward the feet. In the 1800s, English physician Edward Liveing abandoned vascular theory, instead proposing that migraine resulted from discharges of the central nervous system.
British neurologist William Gowers thought migraine could be a derangement of neurons, but ultimately wrote in his Manual of Diseases (p. 852) that, “When all has been that can be, mystery still envelops the mechanism of migraine.” Gowers advocated continuous treatment with drugs to minimize the frequency of attacks, as well as treating the attacks themselves. His preferred treatments were nitroglycerin in alcohol, combined with other agents, as well as marijuana. His choice of nitroglycerin is an interesting one, given that modern medicine considers nitroglycerin an important neurochemical in migraine initiation.
The concept of neuronal involvement retained support into the 20th century, solidified by German physician Paul Ehrlich’s Nobel Prize–winning work involving immunology and brain receptors. In the 1920s, thoughts turned to allergy as the source of migraine, as an association between migraine, asthma, and urticaria emerged, but this connection was eventually proved to be incidental, not causal.
In the 1930s, the vascular theory again was vogue -- aided by studies performed by US physician Harold G. Wolff. His work, the first to assess headache in a laboratory setting, along with observations about changes in vasculature and evolving treatment, appeared to support the vascular nature of headache. In the 1940s and 1950s, psychosomatic disorders crept into the mix of possible causes. Some categorized migraine as a so-called stress disease.
Puzzles and irony
In 1979, Moskowitz and colleagues introduced a new hypothesis focused on the importance of the neuropeptide-containing trigeminal nerve. CGRP is stored in vesicles in sensory nerve terminals, where it is released along with the vasodilating peptide, substance P, when the trigeminal nerve is activated.
At about the same time, researchers in England were working on a discovery with ancestral roots going back hundreds of years. In the 18th century, scientists learned that rye ergot was a constrictor of blood vessels. In time, ergot became ergotamine and hence more valuable because it could reduce vascular headaches. But the adverse effects, prominent in those with cardiovascular disease, kept researchers in the lab.
So, while Moskowitz and colleagues were focused on CGRPs, Humphrey et al were focused on a receptor they found in cranial blood vessels that came to be called serotonin (5-HT1B). An agonist soon followed. In 1991, sumatriptan became available in Europe, and 2 years later, it was available in the United States. But sumatriptan is for acute care treatment, not a preventive therapy. It was Moskowitz’s work that led to studies demonstrating that antisera could neutralize CGRP and substance P.
For those with chronic migraine, preventive therapy was exactly what they needed because, while the triptans helped, they were insufficient for many. In a 2-year longitudinal analysis conducted in Italy involving 82,446 individuals prescribed at least 1 triptan, 31,515 had an unmet medical need in migraine (3.1 per 1000 patients).
In February 2022, a team of researchers published the results of a genome-wide association study involving over 100,000 cases. The results were 125 risk loci linked to migraine within the vascular and central nervous systems, thereby firmly establishing that the pathophysiology of migraine exists in neurovascular mechanisms.
The fact that it has taken technology to prove that migraine exists and that it is organically rooted is obviously satisfying but also frustrating. For centuries, people with migraine were considered to have caused their own illness or were exaggerating the pain.
In March 2022, a large German population-based study found that people with migraine still struggled with bias, stigma, and undermedication. Fifty-four percent said they were not seeing a physician for their migraine, and 33% said they had not received information on medication overuse risks.
With captured images of what happens inside the brains of these patients during an attack, now the focus can be on helping them and not questioning the validity of their reported symptoms.
Coming next month, a discussion about migraine therapies.
Dr. Messoud Ashina is a Professor of Neurology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. He is Director of the Human Migraine Research Unit at the Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup. He serves an associate editor for Cephalalgia, Journal of Headache and Pain, and Brain.
Dr. Faisal Mohammad Amin is an Associate Professor, Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, University of Copenhagen, Denmark. He is an associate editor for Headache Medicine and is President of the Danish Headache Society.
Dr. Ashina reports that he has received fees and grants from and/or has served as a principal trial investigator for AbbVie, Amgen, Eli Lilly, Lundbeck Pharmaceuticals, Lundbeck Foundation, Novartis, Novo Nordisk Foundation, and Teva.
Dr. Amin reports that he has worked as a consultant, speaker, and/or primary investigator Eli Lilly, Lundbeck, Novartis, and Teva. Both authors have reported that they have no ownership interest nor own any stocks in a pharmaceutical company.
Since the time of the Neanderthals, humankind has looked for ways to rid the brain of migraine headache. There is evidence that trepanation–removing a portion of bone from the skull–was performed on Neolithic skulls. Did it work for that poor individual? We will never know.
What is known is that the often circuitous hunt for effective treatments has taken centuries. And while this search led to the successful introduction of calcitonin gene-related peptides (CGRPs) a few years ago, the search is nowhere near finished, as efforts to pinpoint the source of migraine continue, as does the search for other possible therapies.
The nearly 39 million people with migraine in the United States would be grateful; they often experience a perplexing, frustrating, and unsatisfactory search for a pain-free existence. Migraine is estimated to cost more than $20 million per year in direct medical expenses and lost productivity in the United States. People with migraine, meanwhile, face the prospect of significant disability. More than 8 in every 10 participants in the American Migraine Study had at least some headache-related disability. More than half said their pain has caused severe impairment.
The search to find relief for these patients is focused on understanding the pathophysiology of migraine. Approaches include in vitro application of mediators, direct electrical stimulation of trigeminal neurons in vivo, administration of vasoactive substances in vivo, and introduction of exogenous pain-inducing substances in vivo. In 2021, investigators at AstraZeneca and the University of Arizona College of Medicine described their development of an injury-free murine model to be used to study migraine-like pain. Animal research has led to a few interventional studies involving new and existing medications.
How the field has evolved from using a chisel to make a cranial hole to using magnetic resonance imaging and other technologies to examine the trigeminovascular system’s role in the pathophysiology of migraine headache is a tale worth telling.
From crocodiles to nitroglycerin to allergies
The search for an effective remedy for migraine has proved to be torturously slow. In addition to trepanation, another procedure thought to have been used during prehistoric times involved a religious ritual whereby a clay crocodile was attached tightly with a strip of linen to an individual’s head. Though the gods were credited if the headache pain receded, relief likely came from the resulting compression on the scalp. Centuries later, in the Middle Ages, treatments included soaking bandages in drugs and then applying them to the head or mixing elixirs with vinegar (which opened scalp pores) and opium (which traveled into the scalp through the open pores).
The Persian scholar Ibn Sina (980-1032), also known as Avicenna, postulated that the pain could emanate from the bones that comprise the skull or within the parenchyma or from veins and arteries outside the cranium. The medicinal plants he investigated for the treatment of migraine have components that resonate today: antineuroinflammatory agents, analgesics, and even cyclooxegenase-2 inhibitors.
Six hundred years later, English physician Thomas Willis discussed how the vascular system perpetrated migraine, and in the next century, Erasmus Darwin, Charles’ grandfather, proposed that individuals with migraine be spun around so that blood from the head would be forced down toward the feet. In the 1800s, English physician Edward Liveing abandoned vascular theory, instead proposing that migraine resulted from discharges of the central nervous system.
British neurologist William Gowers thought migraine could be a derangement of neurons, but ultimately wrote in his Manual of Diseases (p. 852) that, “When all has been that can be, mystery still envelops the mechanism of migraine.” Gowers advocated continuous treatment with drugs to minimize the frequency of attacks, as well as treating the attacks themselves. His preferred treatments were nitroglycerin in alcohol, combined with other agents, as well as marijuana. His choice of nitroglycerin is an interesting one, given that modern medicine considers nitroglycerin an important neurochemical in migraine initiation.
The concept of neuronal involvement retained support into the 20th century, solidified by German physician Paul Ehrlich’s Nobel Prize–winning work involving immunology and brain receptors. In the 1920s, thoughts turned to allergy as the source of migraine, as an association between migraine, asthma, and urticaria emerged, but this connection was eventually proved to be incidental, not causal.
In the 1930s, the vascular theory again was vogue -- aided by studies performed by US physician Harold G. Wolff. His work, the first to assess headache in a laboratory setting, along with observations about changes in vasculature and evolving treatment, appeared to support the vascular nature of headache. In the 1940s and 1950s, psychosomatic disorders crept into the mix of possible causes. Some categorized migraine as a so-called stress disease.
Puzzles and irony
In 1979, Moskowitz and colleagues introduced a new hypothesis focused on the importance of the neuropeptide-containing trigeminal nerve. CGRP is stored in vesicles in sensory nerve terminals, where it is released along with the vasodilating peptide, substance P, when the trigeminal nerve is activated.
At about the same time, researchers in England were working on a discovery with ancestral roots going back hundreds of years. In the 18th century, scientists learned that rye ergot was a constrictor of blood vessels. In time, ergot became ergotamine and hence more valuable because it could reduce vascular headaches. But the adverse effects, prominent in those with cardiovascular disease, kept researchers in the lab.
So, while Moskowitz and colleagues were focused on CGRPs, Humphrey et al were focused on a receptor they found in cranial blood vessels that came to be called serotonin (5-HT1B). An agonist soon followed. In 1991, sumatriptan became available in Europe, and 2 years later, it was available in the United States. But sumatriptan is for acute care treatment, not a preventive therapy. It was Moskowitz’s work that led to studies demonstrating that antisera could neutralize CGRP and substance P.
For those with chronic migraine, preventive therapy was exactly what they needed because, while the triptans helped, they were insufficient for many. In a 2-year longitudinal analysis conducted in Italy involving 82,446 individuals prescribed at least 1 triptan, 31,515 had an unmet medical need in migraine (3.1 per 1000 patients).
In February 2022, a team of researchers published the results of a genome-wide association study involving over 100,000 cases. The results were 125 risk loci linked to migraine within the vascular and central nervous systems, thereby firmly establishing that the pathophysiology of migraine exists in neurovascular mechanisms.
The fact that it has taken technology to prove that migraine exists and that it is organically rooted is obviously satisfying but also frustrating. For centuries, people with migraine were considered to have caused their own illness or were exaggerating the pain.
In March 2022, a large German population-based study found that people with migraine still struggled with bias, stigma, and undermedication. Fifty-four percent said they were not seeing a physician for their migraine, and 33% said they had not received information on medication overuse risks.
With captured images of what happens inside the brains of these patients during an attack, now the focus can be on helping them and not questioning the validity of their reported symptoms.
Coming next month, a discussion about migraine therapies.
Dr. Messoud Ashina is a Professor of Neurology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. He is Director of the Human Migraine Research Unit at the Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup. He serves an associate editor for Cephalalgia, Journal of Headache and Pain, and Brain.
Dr. Faisal Mohammad Amin is an Associate Professor, Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, University of Copenhagen, Denmark. He is an associate editor for Headache Medicine and is President of the Danish Headache Society.
Dr. Ashina reports that he has received fees and grants from and/or has served as a principal trial investigator for AbbVie, Amgen, Eli Lilly, Lundbeck Pharmaceuticals, Lundbeck Foundation, Novartis, Novo Nordisk Foundation, and Teva.
Dr. Amin reports that he has worked as a consultant, speaker, and/or primary investigator Eli Lilly, Lundbeck, Novartis, and Teva. Both authors have reported that they have no ownership interest nor own any stocks in a pharmaceutical company.
Since the time of the Neanderthals, humankind has looked for ways to rid the brain of migraine headache. There is evidence that trepanation–removing a portion of bone from the skull–was performed on Neolithic skulls. Did it work for that poor individual? We will never know.
What is known is that the often circuitous hunt for effective treatments has taken centuries. And while this search led to the successful introduction of calcitonin gene-related peptides (CGRPs) a few years ago, the search is nowhere near finished, as efforts to pinpoint the source of migraine continue, as does the search for other possible therapies.
The nearly 39 million people with migraine in the United States would be grateful; they often experience a perplexing, frustrating, and unsatisfactory search for a pain-free existence. Migraine is estimated to cost more than $20 million per year in direct medical expenses and lost productivity in the United States. People with migraine, meanwhile, face the prospect of significant disability. More than 8 in every 10 participants in the American Migraine Study had at least some headache-related disability. More than half said their pain has caused severe impairment.
The search to find relief for these patients is focused on understanding the pathophysiology of migraine. Approaches include in vitro application of mediators, direct electrical stimulation of trigeminal neurons in vivo, administration of vasoactive substances in vivo, and introduction of exogenous pain-inducing substances in vivo. In 2021, investigators at AstraZeneca and the University of Arizona College of Medicine described their development of an injury-free murine model to be used to study migraine-like pain. Animal research has led to a few interventional studies involving new and existing medications.
How the field has evolved from using a chisel to make a cranial hole to using magnetic resonance imaging and other technologies to examine the trigeminovascular system’s role in the pathophysiology of migraine headache is a tale worth telling.
From crocodiles to nitroglycerin to allergies
The search for an effective remedy for migraine has proved to be torturously slow. In addition to trepanation, another procedure thought to have been used during prehistoric times involved a religious ritual whereby a clay crocodile was attached tightly with a strip of linen to an individual’s head. Though the gods were credited if the headache pain receded, relief likely came from the resulting compression on the scalp. Centuries later, in the Middle Ages, treatments included soaking bandages in drugs and then applying them to the head or mixing elixirs with vinegar (which opened scalp pores) and opium (which traveled into the scalp through the open pores).
The Persian scholar Ibn Sina (980-1032), also known as Avicenna, postulated that the pain could emanate from the bones that comprise the skull or within the parenchyma or from veins and arteries outside the cranium. The medicinal plants he investigated for the treatment of migraine have components that resonate today: antineuroinflammatory agents, analgesics, and even cyclooxegenase-2 inhibitors.
Six hundred years later, English physician Thomas Willis discussed how the vascular system perpetrated migraine, and in the next century, Erasmus Darwin, Charles’ grandfather, proposed that individuals with migraine be spun around so that blood from the head would be forced down toward the feet. In the 1800s, English physician Edward Liveing abandoned vascular theory, instead proposing that migraine resulted from discharges of the central nervous system.
British neurologist William Gowers thought migraine could be a derangement of neurons, but ultimately wrote in his Manual of Diseases (p. 852) that, “When all has been that can be, mystery still envelops the mechanism of migraine.” Gowers advocated continuous treatment with drugs to minimize the frequency of attacks, as well as treating the attacks themselves. His preferred treatments were nitroglycerin in alcohol, combined with other agents, as well as marijuana. His choice of nitroglycerin is an interesting one, given that modern medicine considers nitroglycerin an important neurochemical in migraine initiation.
The concept of neuronal involvement retained support into the 20th century, solidified by German physician Paul Ehrlich’s Nobel Prize–winning work involving immunology and brain receptors. In the 1920s, thoughts turned to allergy as the source of migraine, as an association between migraine, asthma, and urticaria emerged, but this connection was eventually proved to be incidental, not causal.
In the 1930s, the vascular theory again was vogue -- aided by studies performed by US physician Harold G. Wolff. His work, the first to assess headache in a laboratory setting, along with observations about changes in vasculature and evolving treatment, appeared to support the vascular nature of headache. In the 1940s and 1950s, psychosomatic disorders crept into the mix of possible causes. Some categorized migraine as a so-called stress disease.
Puzzles and irony
In 1979, Moskowitz and colleagues introduced a new hypothesis focused on the importance of the neuropeptide-containing trigeminal nerve. CGRP is stored in vesicles in sensory nerve terminals, where it is released along with the vasodilating peptide, substance P, when the trigeminal nerve is activated.
At about the same time, researchers in England were working on a discovery with ancestral roots going back hundreds of years. In the 18th century, scientists learned that rye ergot was a constrictor of blood vessels. In time, ergot became ergotamine and hence more valuable because it could reduce vascular headaches. But the adverse effects, prominent in those with cardiovascular disease, kept researchers in the lab.
So, while Moskowitz and colleagues were focused on CGRPs, Humphrey et al were focused on a receptor they found in cranial blood vessels that came to be called serotonin (5-HT1B). An agonist soon followed. In 1991, sumatriptan became available in Europe, and 2 years later, it was available in the United States. But sumatriptan is for acute care treatment, not a preventive therapy. It was Moskowitz’s work that led to studies demonstrating that antisera could neutralize CGRP and substance P.
For those with chronic migraine, preventive therapy was exactly what they needed because, while the triptans helped, they were insufficient for many. In a 2-year longitudinal analysis conducted in Italy involving 82,446 individuals prescribed at least 1 triptan, 31,515 had an unmet medical need in migraine (3.1 per 1000 patients).
In February 2022, a team of researchers published the results of a genome-wide association study involving over 100,000 cases. The results were 125 risk loci linked to migraine within the vascular and central nervous systems, thereby firmly establishing that the pathophysiology of migraine exists in neurovascular mechanisms.
The fact that it has taken technology to prove that migraine exists and that it is organically rooted is obviously satisfying but also frustrating. For centuries, people with migraine were considered to have caused their own illness or were exaggerating the pain.
In March 2022, a large German population-based study found that people with migraine still struggled with bias, stigma, and undermedication. Fifty-four percent said they were not seeing a physician for their migraine, and 33% said they had not received information on medication overuse risks.
With captured images of what happens inside the brains of these patients during an attack, now the focus can be on helping them and not questioning the validity of their reported symptoms.
Coming next month, a discussion about migraine therapies.
Clinical Edge Journal Scan Commentary: Migraine June 2022
Many of our patients with refractory migraine do not respond to first-line acute or preventive treatments, and, almost by definition, first- and second-line treatments have failed in the majority of patients on calcitonin gene-related peptide (CGRP) antagonist medications. Three studies this month highlight the efficacy of CGRP monoclonal antibody (mAb) and small-molecule medications in this population specifically.
After an initial first dose of a CGRP mAb treatment, many patients ask whether a suboptimal response necessitates switching to another agent or whether a second (or third) dose should be given first. Eptinezumab is an intravenously administered mAb that is repeated every 12 weeks. Schim and colleagues present post hoc data for patients who initially had a minimally beneficial response to eptinezumab and received a second dose at week 13.
The authors define a suboptimal response as having less then a 50% decrease in monthly migraine days after 12 weeks. There were two pooled samples of patients — those who received 100 mg eptinezumab and those who received a 300 mg dose. Approximately 45% of patients in the pivotal trials of eptinezumab (PROMISE-1 and -2) were considered suboptimal responders, and 33%-37% of those suboptimal responders had a more than 50% decrease of their monthly migraine days after a second dose (week 24).
Further analysis determined predictive factors that favored a second dose response. The most prominent (and arguably most obvious) predictive factor was a favorable response after the first dose; the greater percent change in monthly migraine days after the first dose was proportional to the response after the second dose. Change in the Headache Impact Test (HIT-6) disability score after the first dose was also seen to be a strong predictive factor for improvement after the second dose.
When we discuss continuation of medications with our patients, especially when they have a suboptimal response, we should first keep in mind the degree of improvement that the patient initially had. There can be benefit from further treatment with the same medication; however, if the response truly was minimal, it may be better to consider another treatment option.
Practically every patient taking a preventive medication is taking at least one acute medication as well. Even the best preventive medication is not a guarantee that further exacerbations will not occur, and our patients will still need some acute treatment option even when their preventive medications are very effective. The study by Ambrosini and colleagues specifically shows how effective a preventive medication can be, specifically in allowing the patient to use fewer acute medications over time in a population of patients who have been resistant to two to four treatments.
Galcanezumab is a once-monthly mAb for the prevention of migraine. The authors of this study compared the acute use of medications for migraine in both the randomized and open-label stages of a study assessing treatment-refractory patients. A total of 462 patients were enrolled who were all resistant to two to four standard-of-care migraine-preventive medications that had been stopped either because of lack of efficacy or tolerance. The double-blind stage lasted 3 months; the open-label stage lasted another 3 months.
The treatment group was seen to use significantly fewer acute medications after just the first month and continued to improve through month 3. In the open-label phase, a similar improvement was noted in patients transitioning from placebo. In addition to acute medication use, emergency department use for migraine treatment was decreased significantly as well, by more than two thirds in month 3.
Migraine prevention will always remain the key ingredient for improvement for patients with higher frequencies of migraine, and adequate prevention will allow for the lower use of acute medications, and for less healthcare system use in general.
Most practitioners recommend migraine-specific medications for the acute treatment of migraine. Since the advent of sumatriptan, this has usually meant a triptan medication. However, a significant percentage of the population (up to 44% in one study) are either intolerant to, contraindicated for, or respond insufficiently to triptan medications. This can either be due to a strong triptan side effect (worsened nausea; tightness/soreness of the muscles of the chest, shoulders, and neck), having cardiovascular risk factors, or not responding adequately 2 hours after treatment. The study by Lipton and colleagues specifically assessed the efficacy of ubrogepant in this population.
Ubrogepant is a small-molecule CGRP antagonist for the acute treatment of migraine. Although somewhat controversial, most practitioners use ubrogepant in patients with some cardiovascular risk, a situation where they would be more likely to avoid the use of triptans. The study authors pooled post hoc data from the pivotal ubrogepant trials (ACHIEVE-1 and -2) to isolate patients with insufficient response to triptans, and their primary outcome was improvement in function 2 hours after medication dose.
Participants in the pivotal trials were separated into three groups: triptan responders, triptan insufficient responders, and triptan-naive patients. Triptan response was defined as achieving pain freedom 2 hours after medication dose. Both those who had an insufficient response and those who no longer use the triptan owing to intolerance or contraindications were included in the group with insufficient triptan response. Function improvement was defined as the primary outcome on the basis of a 4-point response scale (0 = no disability, 1 = mildly impaired, 2 = moderately impaired, 3 = severely impaired). In addition, patients were asked to report scores of satisfaction with the medication (yes or no) at 2 and 24 hours and their impression of overall change at 2 hours using a 7-point scale.
The population group of triptan insufficient responders (451 patients) had significant improvement in the primary outcome functional disability at 2, 4, and 7 hours after receipt of medications, but there was no statistical difference at 1 hour. This was similar when comparing those with intolerance to triptans, insufficient response to triptans, or contraindications for triptans. The secondary outcomes of satisfaction and global impression of change were also statistically improved in the insufficient-responders group. No additional tolerance issues or adverse events were noted in this group either.
It would certainly be worth considering the use of a gepant acute medication, such as ubrogepant, in patients who are intolerant to or inadequately treated by triptan medications. There still is much to learn about cardiovascular risk and the use of CGRP antagonists, and although no adverse events were noted, more data may be necessary to widely prescribe this class in higher-risk patients.
Many of our patients with refractory migraine do not respond to first-line acute or preventive treatments, and, almost by definition, first- and second-line treatments have failed in the majority of patients on calcitonin gene-related peptide (CGRP) antagonist medications. Three studies this month highlight the efficacy of CGRP monoclonal antibody (mAb) and small-molecule medications in this population specifically.
After an initial first dose of a CGRP mAb treatment, many patients ask whether a suboptimal response necessitates switching to another agent or whether a second (or third) dose should be given first. Eptinezumab is an intravenously administered mAb that is repeated every 12 weeks. Schim and colleagues present post hoc data for patients who initially had a minimally beneficial response to eptinezumab and received a second dose at week 13.
The authors define a suboptimal response as having less then a 50% decrease in monthly migraine days after 12 weeks. There were two pooled samples of patients — those who received 100 mg eptinezumab and those who received a 300 mg dose. Approximately 45% of patients in the pivotal trials of eptinezumab (PROMISE-1 and -2) were considered suboptimal responders, and 33%-37% of those suboptimal responders had a more than 50% decrease of their monthly migraine days after a second dose (week 24).
Further analysis determined predictive factors that favored a second dose response. The most prominent (and arguably most obvious) predictive factor was a favorable response after the first dose; the greater percent change in monthly migraine days after the first dose was proportional to the response after the second dose. Change in the Headache Impact Test (HIT-6) disability score after the first dose was also seen to be a strong predictive factor for improvement after the second dose.
When we discuss continuation of medications with our patients, especially when they have a suboptimal response, we should first keep in mind the degree of improvement that the patient initially had. There can be benefit from further treatment with the same medication; however, if the response truly was minimal, it may be better to consider another treatment option.
Practically every patient taking a preventive medication is taking at least one acute medication as well. Even the best preventive medication is not a guarantee that further exacerbations will not occur, and our patients will still need some acute treatment option even when their preventive medications are very effective. The study by Ambrosini and colleagues specifically shows how effective a preventive medication can be, specifically in allowing the patient to use fewer acute medications over time in a population of patients who have been resistant to two to four treatments.
Galcanezumab is a once-monthly mAb for the prevention of migraine. The authors of this study compared the acute use of medications for migraine in both the randomized and open-label stages of a study assessing treatment-refractory patients. A total of 462 patients were enrolled who were all resistant to two to four standard-of-care migraine-preventive medications that had been stopped either because of lack of efficacy or tolerance. The double-blind stage lasted 3 months; the open-label stage lasted another 3 months.
The treatment group was seen to use significantly fewer acute medications after just the first month and continued to improve through month 3. In the open-label phase, a similar improvement was noted in patients transitioning from placebo. In addition to acute medication use, emergency department use for migraine treatment was decreased significantly as well, by more than two thirds in month 3.
Migraine prevention will always remain the key ingredient for improvement for patients with higher frequencies of migraine, and adequate prevention will allow for the lower use of acute medications, and for less healthcare system use in general.
Most practitioners recommend migraine-specific medications for the acute treatment of migraine. Since the advent of sumatriptan, this has usually meant a triptan medication. However, a significant percentage of the population (up to 44% in one study) are either intolerant to, contraindicated for, or respond insufficiently to triptan medications. This can either be due to a strong triptan side effect (worsened nausea; tightness/soreness of the muscles of the chest, shoulders, and neck), having cardiovascular risk factors, or not responding adequately 2 hours after treatment. The study by Lipton and colleagues specifically assessed the efficacy of ubrogepant in this population.
Ubrogepant is a small-molecule CGRP antagonist for the acute treatment of migraine. Although somewhat controversial, most practitioners use ubrogepant in patients with some cardiovascular risk, a situation where they would be more likely to avoid the use of triptans. The study authors pooled post hoc data from the pivotal ubrogepant trials (ACHIEVE-1 and -2) to isolate patients with insufficient response to triptans, and their primary outcome was improvement in function 2 hours after medication dose.
Participants in the pivotal trials were separated into three groups: triptan responders, triptan insufficient responders, and triptan-naive patients. Triptan response was defined as achieving pain freedom 2 hours after medication dose. Both those who had an insufficient response and those who no longer use the triptan owing to intolerance or contraindications were included in the group with insufficient triptan response. Function improvement was defined as the primary outcome on the basis of a 4-point response scale (0 = no disability, 1 = mildly impaired, 2 = moderately impaired, 3 = severely impaired). In addition, patients were asked to report scores of satisfaction with the medication (yes or no) at 2 and 24 hours and their impression of overall change at 2 hours using a 7-point scale.
The population group of triptan insufficient responders (451 patients) had significant improvement in the primary outcome functional disability at 2, 4, and 7 hours after receipt of medications, but there was no statistical difference at 1 hour. This was similar when comparing those with intolerance to triptans, insufficient response to triptans, or contraindications for triptans. The secondary outcomes of satisfaction and global impression of change were also statistically improved in the insufficient-responders group. No additional tolerance issues or adverse events were noted in this group either.
It would certainly be worth considering the use of a gepant acute medication, such as ubrogepant, in patients who are intolerant to or inadequately treated by triptan medications. There still is much to learn about cardiovascular risk and the use of CGRP antagonists, and although no adverse events were noted, more data may be necessary to widely prescribe this class in higher-risk patients.
Many of our patients with refractory migraine do not respond to first-line acute or preventive treatments, and, almost by definition, first- and second-line treatments have failed in the majority of patients on calcitonin gene-related peptide (CGRP) antagonist medications. Three studies this month highlight the efficacy of CGRP monoclonal antibody (mAb) and small-molecule medications in this population specifically.
After an initial first dose of a CGRP mAb treatment, many patients ask whether a suboptimal response necessitates switching to another agent or whether a second (or third) dose should be given first. Eptinezumab is an intravenously administered mAb that is repeated every 12 weeks. Schim and colleagues present post hoc data for patients who initially had a minimally beneficial response to eptinezumab and received a second dose at week 13.
The authors define a suboptimal response as having less then a 50% decrease in monthly migraine days after 12 weeks. There were two pooled samples of patients — those who received 100 mg eptinezumab and those who received a 300 mg dose. Approximately 45% of patients in the pivotal trials of eptinezumab (PROMISE-1 and -2) were considered suboptimal responders, and 33%-37% of those suboptimal responders had a more than 50% decrease of their monthly migraine days after a second dose (week 24).
Further analysis determined predictive factors that favored a second dose response. The most prominent (and arguably most obvious) predictive factor was a favorable response after the first dose; the greater percent change in monthly migraine days after the first dose was proportional to the response after the second dose. Change in the Headache Impact Test (HIT-6) disability score after the first dose was also seen to be a strong predictive factor for improvement after the second dose.
When we discuss continuation of medications with our patients, especially when they have a suboptimal response, we should first keep in mind the degree of improvement that the patient initially had. There can be benefit from further treatment with the same medication; however, if the response truly was minimal, it may be better to consider another treatment option.
Practically every patient taking a preventive medication is taking at least one acute medication as well. Even the best preventive medication is not a guarantee that further exacerbations will not occur, and our patients will still need some acute treatment option even when their preventive medications are very effective. The study by Ambrosini and colleagues specifically shows how effective a preventive medication can be, specifically in allowing the patient to use fewer acute medications over time in a population of patients who have been resistant to two to four treatments.
Galcanezumab is a once-monthly mAb for the prevention of migraine. The authors of this study compared the acute use of medications for migraine in both the randomized and open-label stages of a study assessing treatment-refractory patients. A total of 462 patients were enrolled who were all resistant to two to four standard-of-care migraine-preventive medications that had been stopped either because of lack of efficacy or tolerance. The double-blind stage lasted 3 months; the open-label stage lasted another 3 months.
The treatment group was seen to use significantly fewer acute medications after just the first month and continued to improve through month 3. In the open-label phase, a similar improvement was noted in patients transitioning from placebo. In addition to acute medication use, emergency department use for migraine treatment was decreased significantly as well, by more than two thirds in month 3.
Migraine prevention will always remain the key ingredient for improvement for patients with higher frequencies of migraine, and adequate prevention will allow for the lower use of acute medications, and for less healthcare system use in general.
Most practitioners recommend migraine-specific medications for the acute treatment of migraine. Since the advent of sumatriptan, this has usually meant a triptan medication. However, a significant percentage of the population (up to 44% in one study) are either intolerant to, contraindicated for, or respond insufficiently to triptan medications. This can either be due to a strong triptan side effect (worsened nausea; tightness/soreness of the muscles of the chest, shoulders, and neck), having cardiovascular risk factors, or not responding adequately 2 hours after treatment. The study by Lipton and colleagues specifically assessed the efficacy of ubrogepant in this population.
Ubrogepant is a small-molecule CGRP antagonist for the acute treatment of migraine. Although somewhat controversial, most practitioners use ubrogepant in patients with some cardiovascular risk, a situation where they would be more likely to avoid the use of triptans. The study authors pooled post hoc data from the pivotal ubrogepant trials (ACHIEVE-1 and -2) to isolate patients with insufficient response to triptans, and their primary outcome was improvement in function 2 hours after medication dose.
Participants in the pivotal trials were separated into three groups: triptan responders, triptan insufficient responders, and triptan-naive patients. Triptan response was defined as achieving pain freedom 2 hours after medication dose. Both those who had an insufficient response and those who no longer use the triptan owing to intolerance or contraindications were included in the group with insufficient triptan response. Function improvement was defined as the primary outcome on the basis of a 4-point response scale (0 = no disability, 1 = mildly impaired, 2 = moderately impaired, 3 = severely impaired). In addition, patients were asked to report scores of satisfaction with the medication (yes or no) at 2 and 24 hours and their impression of overall change at 2 hours using a 7-point scale.
The population group of triptan insufficient responders (451 patients) had significant improvement in the primary outcome functional disability at 2, 4, and 7 hours after receipt of medications, but there was no statistical difference at 1 hour. This was similar when comparing those with intolerance to triptans, insufficient response to triptans, or contraindications for triptans. The secondary outcomes of satisfaction and global impression of change were also statistically improved in the insufficient-responders group. No additional tolerance issues or adverse events were noted in this group either.
It would certainly be worth considering the use of a gepant acute medication, such as ubrogepant, in patients who are intolerant to or inadequately treated by triptan medications. There still is much to learn about cardiovascular risk and the use of CGRP antagonists, and although no adverse events were noted, more data may be necessary to widely prescribe this class in higher-risk patients.
Attention deficit hyperactivity disorder increases the risk for migraine in children and adolescents
Key clinical point: The prevalence of migraine is higher in children and adolescents with attention deficit hyperactivity disorder (ADHD) vs those without.
Major finding: The risk of developing migraine was significantly higher in patients with ADHD than in matched controls (adjusted hazard ratio [aHR] 1.92; 95% CI 1.64-2.31) with the risk being prominent in children (aHR 2.01; 95% CI 1.63-2.49) and adolescents (aHR 1.94; 95% CI 1.35-2.79) but not in young adults with ADHD.
Study details: This was a nationwide longitudinal case-cohort study including 81,441 patients (including children, adolescents, and young adults aged 3-11, 12-17, and 18-29 years, respectively) with ADHD and 81,441 matched controls without ADHD.
Disclosures: The study was supported by grants from Taipei Veterans General Hospital; Kaohsiung Veterans General Hospital; Yen Tjing Ling Medical Foundation; and the Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.
Source: Hsu T-W et al. Attention deficit hyperactivity disorder and risk of migraine: A nationwide longitudinal study. Headache. 2022 (May 6). Doi: 10.1111/head.14306
Key clinical point: The prevalence of migraine is higher in children and adolescents with attention deficit hyperactivity disorder (ADHD) vs those without.
Major finding: The risk of developing migraine was significantly higher in patients with ADHD than in matched controls (adjusted hazard ratio [aHR] 1.92; 95% CI 1.64-2.31) with the risk being prominent in children (aHR 2.01; 95% CI 1.63-2.49) and adolescents (aHR 1.94; 95% CI 1.35-2.79) but not in young adults with ADHD.
Study details: This was a nationwide longitudinal case-cohort study including 81,441 patients (including children, adolescents, and young adults aged 3-11, 12-17, and 18-29 years, respectively) with ADHD and 81,441 matched controls without ADHD.
Disclosures: The study was supported by grants from Taipei Veterans General Hospital; Kaohsiung Veterans General Hospital; Yen Tjing Ling Medical Foundation; and the Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.
Source: Hsu T-W et al. Attention deficit hyperactivity disorder and risk of migraine: A nationwide longitudinal study. Headache. 2022 (May 6). Doi: 10.1111/head.14306
Key clinical point: The prevalence of migraine is higher in children and adolescents with attention deficit hyperactivity disorder (ADHD) vs those without.
Major finding: The risk of developing migraine was significantly higher in patients with ADHD than in matched controls (adjusted hazard ratio [aHR] 1.92; 95% CI 1.64-2.31) with the risk being prominent in children (aHR 2.01; 95% CI 1.63-2.49) and adolescents (aHR 1.94; 95% CI 1.35-2.79) but not in young adults with ADHD.
Study details: This was a nationwide longitudinal case-cohort study including 81,441 patients (including children, adolescents, and young adults aged 3-11, 12-17, and 18-29 years, respectively) with ADHD and 81,441 matched controls without ADHD.
Disclosures: The study was supported by grants from Taipei Veterans General Hospital; Kaohsiung Veterans General Hospital; Yen Tjing Ling Medical Foundation; and the Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.
Source: Hsu T-W et al. Attention deficit hyperactivity disorder and risk of migraine: A nationwide longitudinal study. Headache. 2022 (May 6). Doi: 10.1111/head.14306