Headache & Migraine

There is a significant association between higher interictal burden, disability, and allodynia in patients who sought medical care for migraine, according to recent research published in the journal Headache.

“[T]he burden and impact of migraine on the individual both during and between attacks were identified through supervised machine learning models to be strongly associated with seeking care,” Sait Ashina, MD, of the department of neurology at Harvard Medical School in Boston, and colleagues wrote in their study.

Dr. Ashina and colleagues performed a cross-sectional study of 61,826 patients from the web-based ObserVational survey of the Epidemiology, tReatment and Care Of MigrainE (OVERCOME) study with migraine who visited a primary care, specialty care, or urgent care, or emergency setting for headache between 2018 and 2020.

The patients recruited for OBSERVE were a mean of 41.7 years old and had experienced migraines for an average of 19.0 years; 59.4% had between 0 and 3 average headache days per month, 74.5% were women, 78.8% were White, and 85.4% had health insurance; and they were demographically representative of the US population.

Researchers used a machine learning model, which consisted of random forest and least absolute shrinkage and selection operator (LASSO) algorithms, to identify the relationship between patients who sought care for migraine and 54 different clinical, sociodemographic, and migraine-associated factors, which included age, years with migraine, symptom scores, pain intensity scores, disability score, comorbidities, vomiting, presence and severity of allodynia, and other factors.

The results showed 31,529 patients (51.0%) had an in-person or e-visit encounter with a primary care, specialty care, or urgent care, or emergency care location within 12 months of the survey, and were mostly White (76.5%) women (73.3%) with health insurance (88.9%). Of the patients who sought care, 52.8% had severe interictal burden measured by Migraine Interictal Burden Scale-4 score, compared with 23.1% of patients who did not seek care. Compared with patients who did not seek care, those who did visit a health care setting for migraine had a higher percentage of severe migraine-related disability as measured by the Migraine Disability Assessment Scale (36.7% vs 14.6%) and severe ictal cutaneous allodynia as measured by the Allodynia Symptom Checklist (21.0% vs 7.4%).

In a multivariable logistic regression model analysis, Dr. Ashina and colleagues said the factors most associated with seeking care included severe interictal burden (odds ratio [OR], 2.64; 95% confidence interval [CI], 2.5-2.8), severe migraine-related disability (OR, 2.2; 95% CI, 2.0-2.3), and severe ictal allodynia (OR, 1.7; 95% CI, 1.6-1.8), compared with less severe factors.

The researchers said their results have “significant implications for public health and advocacy efforts.”

“As seen through three decades of epidemiological research in the United States, rates of care-seeking have not improved dramatically over time despite significant additions to scientific knowledge and the therapeutic armamentarium, leaving a significant unmet need. This is also important from a clinical perspective,” they explained. “Health care professionals in primary care and internal medicine most likely see patients with migraine who do not discuss it during visits. This underscores the importance of maintaining vigilance for migraine, especially among those who may experience greater disability, impact, and interictal burden.”
 

Asking the Right Questions

Asked to comment on the research, Robert P. Cowan, MD, a neurologist and professor in the Stanford University School of Medicine department of neurology and neurological sciences in Palo Alto, California, said in an interview that the value of the paper is in what it does not say about the main reasons patients seek care.

“Most clinicians readily acknowledge that the average number of migraine headache days per month is, at best, a weak predictor of which patients seek care and when,” he said.

Dr. Cowan said that most patients are referred to him by other providers, and when he asks them why they did not seek care for migraine sooner, the answer is usually because the migraine was not severe enough or because over-the-counter medication had previously worked for them. He noted that change in frequency is, in his experience, a primary reason why patients will seek care. “[F]or new (or increasing) headache, it is the concern that the headaches are something more ‘serious,’ and once that is ruled out, the conversation often stops,” he said. “For long-standing migraine sufferers, it is the perception that the headache is a ‘fact of life’ and does not rise to the bar of seeking medical advice.”

The questions a survey or a provider asks matters, Dr. Cowan said. “Often, when we ask a patient how many headache (or migraine) days per month, the answer is in single digits. But if we follow-up with a question about the number of headache-free days [per] month, the answer is ‘never’ or ‘hardly ever,’” he explained. “The point here is that what questions a survey (or a provider) asks introduces a clear bias. The use of machine learning instruments, especially when utilizing supervised learning, only reinforces and amplifies the bias of the designers of the categories.”

Epidemiologic studies are interesting but “often ask the wrong questions,” Dr. Cowan said. “I am less worried about the ... 49% of migraine or possible migraine patients who do not seek care and do [not] progress to more disabling ‘chronic’ migraine than I am with identifying the subpopulations of migraine patients who seek care from providers who do not have adequate tools to match patients to the best treatments.”

The authors reported personal and institutional relationships in the form of advisory board memberships, consultancies, employment, honoraria, research support, speakers bureau positions, stock ownership, and teaching services with AbbVie, Aeon, Alder, Allay Lamp, Allergan, Amgen, Axon, Biohaven Pharmaceuticals, Collegium, CoolTech, Currax, Dr. Reddy’s Laboratories (Promius), electroCore, GlaxoSmithKline, Impel NeuroPharma, Informa, Eli Lilly and Company, Lundbeck, Mainistee, Merck, National Headache Foundation, National Institutes of Health, Novartis, Pfizer, Satsuma, Supernus, Percept, Teva, Theranica, UpsherSmith, the US Food and Drug Administration, Vector, Vedanta Research, and Wolff’s Headache. The study was supported by Eli Lilly. Dr. Cowan reports no relevant conflicts of interest.

There is a significant association between higher interictal burden, disability, and allodynia in patients who sought medical care for migraine, according to recent research published in the journal Headache.

“[T]he burden and impact of migraine on the individual both during and between attacks were identified through supervised machine learning models to be strongly associated with seeking care,” Sait Ashina, MD, of the department of neurology at Harvard Medical School in Boston, and colleagues wrote in their study.

Dr. Ashina and colleagues performed a cross-sectional study of 61,826 patients from the web-based ObserVational survey of the Epidemiology, tReatment and Care Of MigrainE (OVERCOME) study with migraine who visited a primary care, specialty care, or urgent care, or emergency setting for headache between 2018 and 2020.

The patients recruited for OBSERVE were a mean of 41.7 years old and had experienced migraines for an average of 19.0 years; 59.4% had between 0 and 3 average headache days per month, 74.5% were women, 78.8% were White, and 85.4% had health insurance; and they were demographically representative of the US population.

Researchers used a machine learning model, which consisted of random forest and least absolute shrinkage and selection operator (LASSO) algorithms, to identify the relationship between patients who sought care for migraine and 54 different clinical, sociodemographic, and migraine-associated factors, which included age, years with migraine, symptom scores, pain intensity scores, disability score, comorbidities, vomiting, presence and severity of allodynia, and other factors.

The results showed 31,529 patients (51.0%) had an in-person or e-visit encounter with a primary care, specialty care, or urgent care, or emergency care location within 12 months of the survey, and were mostly White (76.5%) women (73.3%) with health insurance (88.9%). Of the patients who sought care, 52.8% had severe interictal burden measured by Migraine Interictal Burden Scale-4 score, compared with 23.1% of patients who did not seek care. Compared with patients who did not seek care, those who did visit a health care setting for migraine had a higher percentage of severe migraine-related disability as measured by the Migraine Disability Assessment Scale (36.7% vs 14.6%) and severe ictal cutaneous allodynia as measured by the Allodynia Symptom Checklist (21.0% vs 7.4%).

In a multivariable logistic regression model analysis, Dr. Ashina and colleagues said the factors most associated with seeking care included severe interictal burden (odds ratio [OR], 2.64; 95% confidence interval [CI], 2.5-2.8), severe migraine-related disability (OR, 2.2; 95% CI, 2.0-2.3), and severe ictal allodynia (OR, 1.7; 95% CI, 1.6-1.8), compared with less severe factors.

The researchers said their results have “significant implications for public health and advocacy efforts.”

“As seen through three decades of epidemiological research in the United States, rates of care-seeking have not improved dramatically over time despite significant additions to scientific knowledge and the therapeutic armamentarium, leaving a significant unmet need. This is also important from a clinical perspective,” they explained. “Health care professionals in primary care and internal medicine most likely see patients with migraine who do not discuss it during visits. This underscores the importance of maintaining vigilance for migraine, especially among those who may experience greater disability, impact, and interictal burden.”
 

Asking the Right Questions

Asked to comment on the research, Robert P. Cowan, MD, a neurologist and professor in the Stanford University School of Medicine department of neurology and neurological sciences in Palo Alto, California, said in an interview that the value of the paper is in what it does not say about the main reasons patients seek care.

“Most clinicians readily acknowledge that the average number of migraine headache days per month is, at best, a weak predictor of which patients seek care and when,” he said.

Dr. Cowan said that most patients are referred to him by other providers, and when he asks them why they did not seek care for migraine sooner, the answer is usually because the migraine was not severe enough or because over-the-counter medication had previously worked for them. He noted that change in frequency is, in his experience, a primary reason why patients will seek care. “[F]or new (or increasing) headache, it is the concern that the headaches are something more ‘serious,’ and once that is ruled out, the conversation often stops,” he said. “For long-standing migraine sufferers, it is the perception that the headache is a ‘fact of life’ and does not rise to the bar of seeking medical advice.”

The questions a survey or a provider asks matters, Dr. Cowan said. “Often, when we ask a patient how many headache (or migraine) days per month, the answer is in single digits. But if we follow-up with a question about the number of headache-free days [per] month, the answer is ‘never’ or ‘hardly ever,’” he explained. “The point here is that what questions a survey (or a provider) asks introduces a clear bias. The use of machine learning instruments, especially when utilizing supervised learning, only reinforces and amplifies the bias of the designers of the categories.”

Epidemiologic studies are interesting but “often ask the wrong questions,” Dr. Cowan said. “I am less worried about the ... 49% of migraine or possible migraine patients who do not seek care and do [not] progress to more disabling ‘chronic’ migraine than I am with identifying the subpopulations of migraine patients who seek care from providers who do not have adequate tools to match patients to the best treatments.”

The authors reported personal and institutional relationships in the form of advisory board memberships, consultancies, employment, honoraria, research support, speakers bureau positions, stock ownership, and teaching services with AbbVie, Aeon, Alder, Allay Lamp, Allergan, Amgen, Axon, Biohaven Pharmaceuticals, Collegium, CoolTech, Currax, Dr. Reddy’s Laboratories (Promius), electroCore, GlaxoSmithKline, Impel NeuroPharma, Informa, Eli Lilly and Company, Lundbeck, Mainistee, Merck, National Headache Foundation, National Institutes of Health, Novartis, Pfizer, Satsuma, Supernus, Percept, Teva, Theranica, UpsherSmith, the US Food and Drug Administration, Vector, Vedanta Research, and Wolff’s Headache. The study was supported by Eli Lilly. Dr. Cowan reports no relevant conflicts of interest.

There is a significant association between higher interictal burden, disability, and allodynia in patients who sought medical care for migraine, according to recent research published in the journal Headache.

“[T]he burden and impact of migraine on the individual both during and between attacks were identified through supervised machine learning models to be strongly associated with seeking care,” Sait Ashina, MD, of the department of neurology at Harvard Medical School in Boston, and colleagues wrote in their study.

Dr. Ashina and colleagues performed a cross-sectional study of 61,826 patients from the web-based ObserVational survey of the Epidemiology, tReatment and Care Of MigrainE (OVERCOME) study with migraine who visited a primary care, specialty care, or urgent care, or emergency setting for headache between 2018 and 2020.

The patients recruited for OBSERVE were a mean of 41.7 years old and had experienced migraines for an average of 19.0 years; 59.4% had between 0 and 3 average headache days per month, 74.5% were women, 78.8% were White, and 85.4% had health insurance; and they were demographically representative of the US population.

Researchers used a machine learning model, which consisted of random forest and least absolute shrinkage and selection operator (LASSO) algorithms, to identify the relationship between patients who sought care for migraine and 54 different clinical, sociodemographic, and migraine-associated factors, which included age, years with migraine, symptom scores, pain intensity scores, disability score, comorbidities, vomiting, presence and severity of allodynia, and other factors.

The results showed 31,529 patients (51.0%) had an in-person or e-visit encounter with a primary care, specialty care, or urgent care, or emergency care location within 12 months of the survey, and were mostly White (76.5%) women (73.3%) with health insurance (88.9%). Of the patients who sought care, 52.8% had severe interictal burden measured by Migraine Interictal Burden Scale-4 score, compared with 23.1% of patients who did not seek care. Compared with patients who did not seek care, those who did visit a health care setting for migraine had a higher percentage of severe migraine-related disability as measured by the Migraine Disability Assessment Scale (36.7% vs 14.6%) and severe ictal cutaneous allodynia as measured by the Allodynia Symptom Checklist (21.0% vs 7.4%).

In a multivariable logistic regression model analysis, Dr. Ashina and colleagues said the factors most associated with seeking care included severe interictal burden (odds ratio [OR], 2.64; 95% confidence interval [CI], 2.5-2.8), severe migraine-related disability (OR, 2.2; 95% CI, 2.0-2.3), and severe ictal allodynia (OR, 1.7; 95% CI, 1.6-1.8), compared with less severe factors.

The researchers said their results have “significant implications for public health and advocacy efforts.”

“As seen through three decades of epidemiological research in the United States, rates of care-seeking have not improved dramatically over time despite significant additions to scientific knowledge and the therapeutic armamentarium, leaving a significant unmet need. This is also important from a clinical perspective,” they explained. “Health care professionals in primary care and internal medicine most likely see patients with migraine who do not discuss it during visits. This underscores the importance of maintaining vigilance for migraine, especially among those who may experience greater disability, impact, and interictal burden.”
 

Asking the Right Questions

Asked to comment on the research, Robert P. Cowan, MD, a neurologist and professor in the Stanford University School of Medicine department of neurology and neurological sciences in Palo Alto, California, said in an interview that the value of the paper is in what it does not say about the main reasons patients seek care.

“Most clinicians readily acknowledge that the average number of migraine headache days per month is, at best, a weak predictor of which patients seek care and when,” he said.

Dr. Cowan said that most patients are referred to him by other providers, and when he asks them why they did not seek care for migraine sooner, the answer is usually because the migraine was not severe enough or because over-the-counter medication had previously worked for them. He noted that change in frequency is, in his experience, a primary reason why patients will seek care. “[F]or new (or increasing) headache, it is the concern that the headaches are something more ‘serious,’ and once that is ruled out, the conversation often stops,” he said. “For long-standing migraine sufferers, it is the perception that the headache is a ‘fact of life’ and does not rise to the bar of seeking medical advice.”

The questions a survey or a provider asks matters, Dr. Cowan said. “Often, when we ask a patient how many headache (or migraine) days per month, the answer is in single digits. But if we follow-up with a question about the number of headache-free days [per] month, the answer is ‘never’ or ‘hardly ever,’” he explained. “The point here is that what questions a survey (or a provider) asks introduces a clear bias. The use of machine learning instruments, especially when utilizing supervised learning, only reinforces and amplifies the bias of the designers of the categories.”

Epidemiologic studies are interesting but “often ask the wrong questions,” Dr. Cowan said. “I am less worried about the ... 49% of migraine or possible migraine patients who do not seek care and do [not] progress to more disabling ‘chronic’ migraine than I am with identifying the subpopulations of migraine patients who seek care from providers who do not have adequate tools to match patients to the best treatments.”

The authors reported personal and institutional relationships in the form of advisory board memberships, consultancies, employment, honoraria, research support, speakers bureau positions, stock ownership, and teaching services with AbbVie, Aeon, Alder, Allay Lamp, Allergan, Amgen, Axon, Biohaven Pharmaceuticals, Collegium, CoolTech, Currax, Dr. Reddy’s Laboratories (Promius), electroCore, GlaxoSmithKline, Impel NeuroPharma, Informa, Eli Lilly and Company, Lundbeck, Mainistee, Merck, National Headache Foundation, National Institutes of Health, Novartis, Pfizer, Satsuma, Supernus, Percept, Teva, Theranica, UpsherSmith, the US Food and Drug Administration, Vector, Vedanta Research, and Wolff’s Headache. The study was supported by Eli Lilly. Dr. Cowan reports no relevant conflicts of interest.

Neuropsychiatric symptoms, including nightmares and hallucinatory “daymares,” may be a more important aspect of systemic lupus erythematosus (SLE) than formerly recognized, according to a qualitative mixed methods study published in The Lancet Discovery Science’s eClinicalMedicine. The findings suggested these neuropsychiatric symptoms can sometimes present as prodromal and other times act as an early warning system for a forthcoming flare.

“For clinicians, the key point is to be aware that neurological and psychiatric symptoms are much more common in patients with lupus and other autoimmune systemic rheumatic diseases than previously thought,” lead author Melanie Sloan, PhD, of the Department of Public Health and Primary Care at the University of Cambridge in England, told this news organization.

“If clinicians — and some do already — could all ask about and document these symptoms for each patient, the usual progression of symptoms in a flare can then be monitored, and patients could be supported and treated at an earlier stage,” Dr. Sloan said. “Another key point is to consider systemic autoimmune diseases at an early stage if a patient presents with multiple seemingly unconnected symptoms, which often include both physical and mental health symptoms.”

Alfred Kim, MD, PhD, associate professor of medicine in rheumatology at Washington University School of Medicine in St. Louis, Missouri, noted the difficulty of determining what neuropsychiatric symptoms may be linked to lupus vs those occurring independently or as part of a different condition.

Kim_Alfred_STLOUIS_web.jpg

Study Details

In planning for the study, the researchers first searched the existing literature for studies involving neuropsychiatric symptoms in patients with systemic autoimmune rheumatic diseases (SARDs). “The literature indicated frequent underreporting and misattributions of neuropsychiatric symptoms in SLE and other SARD patients, and clinician-patient discordance in neuropsychiatric symptom attribution,” the authors reported.

During 2022-2023, the researchers conducted two surveys, one with 676 adult patients with SLE and one with 400 clinicians, recruited through social media, online patient support groups, and professional networks. All patients self-reported an SLE diagnosis that the researchers did not independently confirm. The patients were predominantly White (80%) and female (94%), ranging in age from 18 to over 70, with most falling between ages 40 and 69. Most patients lived in the United Kingdom (76%) or Europe (15%).

The clinicians included 51% rheumatologists, 24% psychiatrists, 13% neurologists, 5% rheumatology nurses, 3% primary care physicians, and 7% other clinicians. Nearly half of the clinicians (45%) were from the United Kingdom, with others from the United States or Canada (16%), Europe (17%), Asia (9%), Latin America (8%), Australia or New Zealand (3%), or elsewhere (3%).

The patient surveys asked whether they had experienced any of the 29 neuropsychiatric symptoms. For the symptoms that patients had experienced at least three times in their lives, the survey asked when they first experienced the symptom in relation to their SLE onset or other SLE symptoms: Over a year before, within a year of (on either side), 1-4 years after, or more than 5 years after onset/other symptoms. “Other quantitative data included timings of disrupted dreaming sleep in relation to hallucinations for those patients reporting experiencing these,” the authors wrote.

The researchers also conducted video conference interviews with 50 clinicians, including 20 rheumatologists, and 69 interviews with patients who had a systemic autoimmune rheumatic disease, including 27 patients with SLE. Other conditions among those interviewed included inflammatory arthritis, vasculitis, Sjögren disease, systemic sclerosis, myositis, undifferentiated and mixed connective tissue diseases, and polymyalgia rheumatica. During interviews, the term “daymare” was used to discuss possible hallucinations.
 

Linking Neuropsychiatric Symptoms and Disease

Four themes emerged from the analysis of the surveys and interviews. First, despite many rheumatologists stating that it was an “established theory” that most neuropsychiatric symptoms related to SLE would initially present around the time of diagnosis or disease onset, the findings from patients and interviews with psychiatrists did not align with this theory. The first presentation of each neuropsychiatric symptom only occurred around the onset of other SLE symptoms, about one fifth to one third of the time. In fact, more than half of the patients with SLE who had experienced hallucinations or delusions/paranoia said they occurred more than a year after they first experienced their other SLE symptoms.

Patient experiences differed in terms of whether they believed their neuropsychiatric symptoms were directly related to their SLE or other rheumatic disease. Some did attribute the symptoms, such as hypomania, to their rheumatic illness, while others, such as a patient with major depression, did not see the two as linked.

A second theme focused on pattern recognition of neuropsychiatric symptoms and the onset of a disease flare. “For example, several patients described how they felt that some types of depressive symptoms were directly attributable to active inflammation due to its time of onset and differences in type and intensity compared to their more ‘reactive’ low mood that could be more attributable to a consequence of psychological distress,” the authors wrote. Another common report from patients was experiencing a sudden, intense fatigue that coincided with a flare and differed from other types of fatigue.

Some patients could recognize that a flare was coming because of familiar neuropsychiatric symptoms that acted like an “early warning system.” Often, however, these symptoms “were absent from current diagnostic guidelines and only rarely identified by clinician interviewees as related to SLE/NPSLE,” the authors found. “These neuropsychiatric prodromal symptoms were reported as sometimes preceding the more widely recognized SLE and other SARD symptoms such as joint pain, rashes, and other organ involvement.” These symptoms included sudden changes in mood (usually a lowering but sometimes mania), increased nightmares, a “feeling of unreality,” or increased sensory symptoms.

Other patients, on the other hand, had not considered a link between neuropsychiatric symptoms and their rheumatic disease until the interview, and many of the clinicians, aside from psychiatrists and nurses, said they had little time in clinic to gather information about symptom progression.
 

Nightmares and Daymares

A third theme centered on disrupted dreaming sleep, nightmares, and “daymares” as a prodromal symptom in particular. Some patients had already drawn a connection between an oncoming flare of their disease and these dreaming-related symptoms, while others had not considered a link until the interviews.

“Several SLE patients recounted flares consistently involving the segueing of increasingly vivid and distressing nightmares into distorted reality and daytime hallucinations,” the authors reported. Flare-related nightmares in particular “often involved being attacked, trapped, crushed, or falling.” Patients tended to be more forthcoming about hallucinatory experiences when the term “daymare” was used to describe them, and they often related to the idea of feeling “in-between asleep and awake.”

Only one of the rheumatologists interviewed had considered nightmares as potentially related to SLE flares, and several appeared skeptical about a link but planned to ask their patients about it. Most of the specialists interviewed, meanwhile, said they often discussed sleep disruption with patients.

“There was agreement that recognizing and eliciting these early flare symptoms may improve care and even reduce clinic times by averting flares at any earlier stage, although some rheumatologists were clear that limited appointment times meant that these symptoms would not be prioritized for discussion,” the authors wrote.

Though Dr. Kim acknowledged the possibility of nightmares as prodromal, he noted other ways in which nightmares may be indirectly linked to lupus. “Trauma is a major risk factor for lupus,” Dr. Kim said, with multiple studies showing childhood traumatic experiences and even posttraumatic stress disorder to be risk factors for lupus. “Whether nightmares represent a traumatic event or prior traumatic events is not clear to me, but one could hypothesize that this may be a manifestation of trauma,” Dr. Kim said.

In addition, nightmares represent a sleep disorder that can substantially reduce sleep quality, Dr. Kim said, and poor sleep is also associated with lupus. “One has to wonder whether disruptive dreaming sleep is one of several specific manifestations of poor sleep quality, which then increases the risk of lupus in those patients,” Dr. Kim said.
 

Misattribution of Neuropsychiatric Symptoms

The final theme to emerge from the findings was patients had been misdiagnosed with psychiatric or psychosomatic conditions shortly before getting their rheumatic disease diagnosis. One patient, for example, reported being diagnosed with borderline personality disorder just 6 months before the lupus diagnosis at age 19 and noticed that the symptoms of one “got under control” when the symptoms of the other did.

“Early misattributions of SARD symptoms to primary psychiatric or psychosomatic conditions were frequently reported to have delayed SARD diagnosis and led to future misattributions,” the authors reported. “Whilst some of these misdiagnoses likely reflect the widespread lack of knowledge and limited definitive tests for SLE, it is plausible that some early SLE neurological and/or psychiatric symptoms may represent a neuropsychiatric prodrome for SLE itself.”

Dr. Kim agreed that misattribution of symptoms to other diagnoses is common with lupus and a common reason for delays in diagnosis, even with symptoms that are not neuropsychiatric. The findings in this study broaden “the type of symptoms we need to put on our radar pre-diagnosis,” Dr. Kim said. “We just also have to be aware that these prodromal symptoms are not diagnostic for lupus, though.”

Dr. Sloan cited earlier work in recommending an “ABC” approach to improving clinician-patient relationships: “Availability is being accessible when patients need them, Belief is demonstrating belief and validating patient self-reports of symptoms, and Continuity is when the same clinician sees the same patient each clinic visit to build up a trusting relationship.” She noted the importance of asking about and normalizing the existence of these symptoms with rheumatic diseases.

The research was funded by The Lupus Trust. Three authors reported consultancy, speaker, or advisory fees from Alumis, Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen, MGP, Novartis, Pfizer, Sanofi, UCB, Vifor, and/or Werfen Group. The other authors, including Dr. Sloan, had no industry-related disclosures. Dr. Kim reported research support from AstraZeneca, GlaxoSmithKline, and Novartis; speaking fees from Exagen Diagnostics and GlaxoSmithKline; and consulting fees from AbbVie, Amgen, ANI Pharmaceuticals, AstraZeneca, Atara Bio, Aurinia Pharmaceuticals, Cargo Therapeutics, Exagen Diagnostics, Hinge Bio, GlaxoSmithKline, Kypha, Miltenyi Biotec, Synthekine, and Tectonic Therapeutic.
 

A version of this article appeared on Medscape.com.

Neuropsychiatric symptoms, including nightmares and hallucinatory “daymares,” may be a more important aspect of systemic lupus erythematosus (SLE) than formerly recognized, according to a qualitative mixed methods study published in The Lancet Discovery Science’s eClinicalMedicine. The findings suggested these neuropsychiatric symptoms can sometimes present as prodromal and other times act as an early warning system for a forthcoming flare.

“For clinicians, the key point is to be aware that neurological and psychiatric symptoms are much more common in patients with lupus and other autoimmune systemic rheumatic diseases than previously thought,” lead author Melanie Sloan, PhD, of the Department of Public Health and Primary Care at the University of Cambridge in England, told this news organization.

“If clinicians — and some do already — could all ask about and document these symptoms for each patient, the usual progression of symptoms in a flare can then be monitored, and patients could be supported and treated at an earlier stage,” Dr. Sloan said. “Another key point is to consider systemic autoimmune diseases at an early stage if a patient presents with multiple seemingly unconnected symptoms, which often include both physical and mental health symptoms.”

Alfred Kim, MD, PhD, associate professor of medicine in rheumatology at Washington University School of Medicine in St. Louis, Missouri, noted the difficulty of determining what neuropsychiatric symptoms may be linked to lupus vs those occurring independently or as part of a different condition.

Kim_Alfred_STLOUIS_web.jpg

Study Details

In planning for the study, the researchers first searched the existing literature for studies involving neuropsychiatric symptoms in patients with systemic autoimmune rheumatic diseases (SARDs). “The literature indicated frequent underreporting and misattributions of neuropsychiatric symptoms in SLE and other SARD patients, and clinician-patient discordance in neuropsychiatric symptom attribution,” the authors reported.

During 2022-2023, the researchers conducted two surveys, one with 676 adult patients with SLE and one with 400 clinicians, recruited through social media, online patient support groups, and professional networks. All patients self-reported an SLE diagnosis that the researchers did not independently confirm. The patients were predominantly White (80%) and female (94%), ranging in age from 18 to over 70, with most falling between ages 40 and 69. Most patients lived in the United Kingdom (76%) or Europe (15%).

The clinicians included 51% rheumatologists, 24% psychiatrists, 13% neurologists, 5% rheumatology nurses, 3% primary care physicians, and 7% other clinicians. Nearly half of the clinicians (45%) were from the United Kingdom, with others from the United States or Canada (16%), Europe (17%), Asia (9%), Latin America (8%), Australia or New Zealand (3%), or elsewhere (3%).

The patient surveys asked whether they had experienced any of the 29 neuropsychiatric symptoms. For the symptoms that patients had experienced at least three times in their lives, the survey asked when they first experienced the symptom in relation to their SLE onset or other SLE symptoms: Over a year before, within a year of (on either side), 1-4 years after, or more than 5 years after onset/other symptoms. “Other quantitative data included timings of disrupted dreaming sleep in relation to hallucinations for those patients reporting experiencing these,” the authors wrote.

The researchers also conducted video conference interviews with 50 clinicians, including 20 rheumatologists, and 69 interviews with patients who had a systemic autoimmune rheumatic disease, including 27 patients with SLE. Other conditions among those interviewed included inflammatory arthritis, vasculitis, Sjögren disease, systemic sclerosis, myositis, undifferentiated and mixed connective tissue diseases, and polymyalgia rheumatica. During interviews, the term “daymare” was used to discuss possible hallucinations.
 

Linking Neuropsychiatric Symptoms and Disease

Four themes emerged from the analysis of the surveys and interviews. First, despite many rheumatologists stating that it was an “established theory” that most neuropsychiatric symptoms related to SLE would initially present around the time of diagnosis or disease onset, the findings from patients and interviews with psychiatrists did not align with this theory. The first presentation of each neuropsychiatric symptom only occurred around the onset of other SLE symptoms, about one fifth to one third of the time. In fact, more than half of the patients with SLE who had experienced hallucinations or delusions/paranoia said they occurred more than a year after they first experienced their other SLE symptoms.

Patient experiences differed in terms of whether they believed their neuropsychiatric symptoms were directly related to their SLE or other rheumatic disease. Some did attribute the symptoms, such as hypomania, to their rheumatic illness, while others, such as a patient with major depression, did not see the two as linked.

A second theme focused on pattern recognition of neuropsychiatric symptoms and the onset of a disease flare. “For example, several patients described how they felt that some types of depressive symptoms were directly attributable to active inflammation due to its time of onset and differences in type and intensity compared to their more ‘reactive’ low mood that could be more attributable to a consequence of psychological distress,” the authors wrote. Another common report from patients was experiencing a sudden, intense fatigue that coincided with a flare and differed from other types of fatigue.

Some patients could recognize that a flare was coming because of familiar neuropsychiatric symptoms that acted like an “early warning system.” Often, however, these symptoms “were absent from current diagnostic guidelines and only rarely identified by clinician interviewees as related to SLE/NPSLE,” the authors found. “These neuropsychiatric prodromal symptoms were reported as sometimes preceding the more widely recognized SLE and other SARD symptoms such as joint pain, rashes, and other organ involvement.” These symptoms included sudden changes in mood (usually a lowering but sometimes mania), increased nightmares, a “feeling of unreality,” or increased sensory symptoms.

Other patients, on the other hand, had not considered a link between neuropsychiatric symptoms and their rheumatic disease until the interview, and many of the clinicians, aside from psychiatrists and nurses, said they had little time in clinic to gather information about symptom progression.
 

Nightmares and Daymares

A third theme centered on disrupted dreaming sleep, nightmares, and “daymares” as a prodromal symptom in particular. Some patients had already drawn a connection between an oncoming flare of their disease and these dreaming-related symptoms, while others had not considered a link until the interviews.

“Several SLE patients recounted flares consistently involving the segueing of increasingly vivid and distressing nightmares into distorted reality and daytime hallucinations,” the authors reported. Flare-related nightmares in particular “often involved being attacked, trapped, crushed, or falling.” Patients tended to be more forthcoming about hallucinatory experiences when the term “daymare” was used to describe them, and they often related to the idea of feeling “in-between asleep and awake.”

Only one of the rheumatologists interviewed had considered nightmares as potentially related to SLE flares, and several appeared skeptical about a link but planned to ask their patients about it. Most of the specialists interviewed, meanwhile, said they often discussed sleep disruption with patients.

“There was agreement that recognizing and eliciting these early flare symptoms may improve care and even reduce clinic times by averting flares at any earlier stage, although some rheumatologists were clear that limited appointment times meant that these symptoms would not be prioritized for discussion,” the authors wrote.

Though Dr. Kim acknowledged the possibility of nightmares as prodromal, he noted other ways in which nightmares may be indirectly linked to lupus. “Trauma is a major risk factor for lupus,” Dr. Kim said, with multiple studies showing childhood traumatic experiences and even posttraumatic stress disorder to be risk factors for lupus. “Whether nightmares represent a traumatic event or prior traumatic events is not clear to me, but one could hypothesize that this may be a manifestation of trauma,” Dr. Kim said.

In addition, nightmares represent a sleep disorder that can substantially reduce sleep quality, Dr. Kim said, and poor sleep is also associated with lupus. “One has to wonder whether disruptive dreaming sleep is one of several specific manifestations of poor sleep quality, which then increases the risk of lupus in those patients,” Dr. Kim said.
 

Misattribution of Neuropsychiatric Symptoms

The final theme to emerge from the findings was patients had been misdiagnosed with psychiatric or psychosomatic conditions shortly before getting their rheumatic disease diagnosis. One patient, for example, reported being diagnosed with borderline personality disorder just 6 months before the lupus diagnosis at age 19 and noticed that the symptoms of one “got under control” when the symptoms of the other did.

“Early misattributions of SARD symptoms to primary psychiatric or psychosomatic conditions were frequently reported to have delayed SARD diagnosis and led to future misattributions,” the authors reported. “Whilst some of these misdiagnoses likely reflect the widespread lack of knowledge and limited definitive tests for SLE, it is plausible that some early SLE neurological and/or psychiatric symptoms may represent a neuropsychiatric prodrome for SLE itself.”

Dr. Kim agreed that misattribution of symptoms to other diagnoses is common with lupus and a common reason for delays in diagnosis, even with symptoms that are not neuropsychiatric. The findings in this study broaden “the type of symptoms we need to put on our radar pre-diagnosis,” Dr. Kim said. “We just also have to be aware that these prodromal symptoms are not diagnostic for lupus, though.”

Dr. Sloan cited earlier work in recommending an “ABC” approach to improving clinician-patient relationships: “Availability is being accessible when patients need them, Belief is demonstrating belief and validating patient self-reports of symptoms, and Continuity is when the same clinician sees the same patient each clinic visit to build up a trusting relationship.” She noted the importance of asking about and normalizing the existence of these symptoms with rheumatic diseases.

The research was funded by The Lupus Trust. Three authors reported consultancy, speaker, or advisory fees from Alumis, Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen, MGP, Novartis, Pfizer, Sanofi, UCB, Vifor, and/or Werfen Group. The other authors, including Dr. Sloan, had no industry-related disclosures. Dr. Kim reported research support from AstraZeneca, GlaxoSmithKline, and Novartis; speaking fees from Exagen Diagnostics and GlaxoSmithKline; and consulting fees from AbbVie, Amgen, ANI Pharmaceuticals, AstraZeneca, Atara Bio, Aurinia Pharmaceuticals, Cargo Therapeutics, Exagen Diagnostics, Hinge Bio, GlaxoSmithKline, Kypha, Miltenyi Biotec, Synthekine, and Tectonic Therapeutic.
 

A version of this article appeared on Medscape.com.

Neuropsychiatric symptoms, including nightmares and hallucinatory “daymares,” may be a more important aspect of systemic lupus erythematosus (SLE) than formerly recognized, according to a qualitative mixed methods study published in The Lancet Discovery Science’s eClinicalMedicine. The findings suggested these neuropsychiatric symptoms can sometimes present as prodromal and other times act as an early warning system for a forthcoming flare.

“For clinicians, the key point is to be aware that neurological and psychiatric symptoms are much more common in patients with lupus and other autoimmune systemic rheumatic diseases than previously thought,” lead author Melanie Sloan, PhD, of the Department of Public Health and Primary Care at the University of Cambridge in England, told this news organization.

“If clinicians — and some do already — could all ask about and document these symptoms for each patient, the usual progression of symptoms in a flare can then be monitored, and patients could be supported and treated at an earlier stage,” Dr. Sloan said. “Another key point is to consider systemic autoimmune diseases at an early stage if a patient presents with multiple seemingly unconnected symptoms, which often include both physical and mental health symptoms.”

Alfred Kim, MD, PhD, associate professor of medicine in rheumatology at Washington University School of Medicine in St. Louis, Missouri, noted the difficulty of determining what neuropsychiatric symptoms may be linked to lupus vs those occurring independently or as part of a different condition.

Kim_Alfred_STLOUIS_web.jpg

Study Details

In planning for the study, the researchers first searched the existing literature for studies involving neuropsychiatric symptoms in patients with systemic autoimmune rheumatic diseases (SARDs). “The literature indicated frequent underreporting and misattributions of neuropsychiatric symptoms in SLE and other SARD patients, and clinician-patient discordance in neuropsychiatric symptom attribution,” the authors reported.

During 2022-2023, the researchers conducted two surveys, one with 676 adult patients with SLE and one with 400 clinicians, recruited through social media, online patient support groups, and professional networks. All patients self-reported an SLE diagnosis that the researchers did not independently confirm. The patients were predominantly White (80%) and female (94%), ranging in age from 18 to over 70, with most falling between ages 40 and 69. Most patients lived in the United Kingdom (76%) or Europe (15%).

The clinicians included 51% rheumatologists, 24% psychiatrists, 13% neurologists, 5% rheumatology nurses, 3% primary care physicians, and 7% other clinicians. Nearly half of the clinicians (45%) were from the United Kingdom, with others from the United States or Canada (16%), Europe (17%), Asia (9%), Latin America (8%), Australia or New Zealand (3%), or elsewhere (3%).

The patient surveys asked whether they had experienced any of the 29 neuropsychiatric symptoms. For the symptoms that patients had experienced at least three times in their lives, the survey asked when they first experienced the symptom in relation to their SLE onset or other SLE symptoms: Over a year before, within a year of (on either side), 1-4 years after, or more than 5 years after onset/other symptoms. “Other quantitative data included timings of disrupted dreaming sleep in relation to hallucinations for those patients reporting experiencing these,” the authors wrote.

The researchers also conducted video conference interviews with 50 clinicians, including 20 rheumatologists, and 69 interviews with patients who had a systemic autoimmune rheumatic disease, including 27 patients with SLE. Other conditions among those interviewed included inflammatory arthritis, vasculitis, Sjögren disease, systemic sclerosis, myositis, undifferentiated and mixed connective tissue diseases, and polymyalgia rheumatica. During interviews, the term “daymare” was used to discuss possible hallucinations.
 

Linking Neuropsychiatric Symptoms and Disease

Four themes emerged from the analysis of the surveys and interviews. First, despite many rheumatologists stating that it was an “established theory” that most neuropsychiatric symptoms related to SLE would initially present around the time of diagnosis or disease onset, the findings from patients and interviews with psychiatrists did not align with this theory. The first presentation of each neuropsychiatric symptom only occurred around the onset of other SLE symptoms, about one fifth to one third of the time. In fact, more than half of the patients with SLE who had experienced hallucinations or delusions/paranoia said they occurred more than a year after they first experienced their other SLE symptoms.

Patient experiences differed in terms of whether they believed their neuropsychiatric symptoms were directly related to their SLE or other rheumatic disease. Some did attribute the symptoms, such as hypomania, to their rheumatic illness, while others, such as a patient with major depression, did not see the two as linked.

A second theme focused on pattern recognition of neuropsychiatric symptoms and the onset of a disease flare. “For example, several patients described how they felt that some types of depressive symptoms were directly attributable to active inflammation due to its time of onset and differences in type and intensity compared to their more ‘reactive’ low mood that could be more attributable to a consequence of psychological distress,” the authors wrote. Another common report from patients was experiencing a sudden, intense fatigue that coincided with a flare and differed from other types of fatigue.

Some patients could recognize that a flare was coming because of familiar neuropsychiatric symptoms that acted like an “early warning system.” Often, however, these symptoms “were absent from current diagnostic guidelines and only rarely identified by clinician interviewees as related to SLE/NPSLE,” the authors found. “These neuropsychiatric prodromal symptoms were reported as sometimes preceding the more widely recognized SLE and other SARD symptoms such as joint pain, rashes, and other organ involvement.” These symptoms included sudden changes in mood (usually a lowering but sometimes mania), increased nightmares, a “feeling of unreality,” or increased sensory symptoms.

Other patients, on the other hand, had not considered a link between neuropsychiatric symptoms and their rheumatic disease until the interview, and many of the clinicians, aside from psychiatrists and nurses, said they had little time in clinic to gather information about symptom progression.
 

Nightmares and Daymares

A third theme centered on disrupted dreaming sleep, nightmares, and “daymares” as a prodromal symptom in particular. Some patients had already drawn a connection between an oncoming flare of their disease and these dreaming-related symptoms, while others had not considered a link until the interviews.

“Several SLE patients recounted flares consistently involving the segueing of increasingly vivid and distressing nightmares into distorted reality and daytime hallucinations,” the authors reported. Flare-related nightmares in particular “often involved being attacked, trapped, crushed, or falling.” Patients tended to be more forthcoming about hallucinatory experiences when the term “daymare” was used to describe them, and they often related to the idea of feeling “in-between asleep and awake.”

Only one of the rheumatologists interviewed had considered nightmares as potentially related to SLE flares, and several appeared skeptical about a link but planned to ask their patients about it. Most of the specialists interviewed, meanwhile, said they often discussed sleep disruption with patients.

“There was agreement that recognizing and eliciting these early flare symptoms may improve care and even reduce clinic times by averting flares at any earlier stage, although some rheumatologists were clear that limited appointment times meant that these symptoms would not be prioritized for discussion,” the authors wrote.

Though Dr. Kim acknowledged the possibility of nightmares as prodromal, he noted other ways in which nightmares may be indirectly linked to lupus. “Trauma is a major risk factor for lupus,” Dr. Kim said, with multiple studies showing childhood traumatic experiences and even posttraumatic stress disorder to be risk factors for lupus. “Whether nightmares represent a traumatic event or prior traumatic events is not clear to me, but one could hypothesize that this may be a manifestation of trauma,” Dr. Kim said.

In addition, nightmares represent a sleep disorder that can substantially reduce sleep quality, Dr. Kim said, and poor sleep is also associated with lupus. “One has to wonder whether disruptive dreaming sleep is one of several specific manifestations of poor sleep quality, which then increases the risk of lupus in those patients,” Dr. Kim said.
 

Misattribution of Neuropsychiatric Symptoms

The final theme to emerge from the findings was patients had been misdiagnosed with psychiatric or psychosomatic conditions shortly before getting their rheumatic disease diagnosis. One patient, for example, reported being diagnosed with borderline personality disorder just 6 months before the lupus diagnosis at age 19 and noticed that the symptoms of one “got under control” when the symptoms of the other did.

“Early misattributions of SARD symptoms to primary psychiatric or psychosomatic conditions were frequently reported to have delayed SARD diagnosis and led to future misattributions,” the authors reported. “Whilst some of these misdiagnoses likely reflect the widespread lack of knowledge and limited definitive tests for SLE, it is plausible that some early SLE neurological and/or psychiatric symptoms may represent a neuropsychiatric prodrome for SLE itself.”

Dr. Kim agreed that misattribution of symptoms to other diagnoses is common with lupus and a common reason for delays in diagnosis, even with symptoms that are not neuropsychiatric. The findings in this study broaden “the type of symptoms we need to put on our radar pre-diagnosis,” Dr. Kim said. “We just also have to be aware that these prodromal symptoms are not diagnostic for lupus, though.”

Dr. Sloan cited earlier work in recommending an “ABC” approach to improving clinician-patient relationships: “Availability is being accessible when patients need them, Belief is demonstrating belief and validating patient self-reports of symptoms, and Continuity is when the same clinician sees the same patient each clinic visit to build up a trusting relationship.” She noted the importance of asking about and normalizing the existence of these symptoms with rheumatic diseases.

The research was funded by The Lupus Trust. Three authors reported consultancy, speaker, or advisory fees from Alumis, Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen, MGP, Novartis, Pfizer, Sanofi, UCB, Vifor, and/or Werfen Group. The other authors, including Dr. Sloan, had no industry-related disclosures. Dr. Kim reported research support from AstraZeneca, GlaxoSmithKline, and Novartis; speaking fees from Exagen Diagnostics and GlaxoSmithKline; and consulting fees from AbbVie, Amgen, ANI Pharmaceuticals, AstraZeneca, Atara Bio, Aurinia Pharmaceuticals, Cargo Therapeutics, Exagen Diagnostics, Hinge Bio, GlaxoSmithKline, Kypha, Miltenyi Biotec, Synthekine, and Tectonic Therapeutic.
 

A version of this article appeared on Medscape.com.

heidimoawad_1.jpg

Migraine care requires a comprehensive approach. Identifying and avoiding triggers is a key component of patient-directed self-care. For many migraine patients, preventive therapy can substantially improve their quality of life. Yet, even with the best migraine prevention plan, many patients experience occasional migraines and require therapy for acute symptom relief. When it comes to selecting therapies for acute migraine treatment, criteria include efficacy, fast action, long duration of action, low risk for rebound symptoms, minimal side effects, and patient safety. Prescription therapies and therapies used in a medical setting include new calcitonin gene-related peptide (CGRP) receptor antagonists as well as antihistamines, antiemetics, neuroleptics, and triptans that have been used for years.

A study published in The Journal of Headache and Pain in April 2024 examined migraine symptom relief with the use of Nurtec OTD (rimegepant), one of the recently approved CGRP receptor antagonists. This post hoc subgroup analysis of a large double-blind randomized phase 3 clinical trial included 1075 participants, of whom 538 took 75 mg rimegepant and 537 took placebo to treat a single migraine episode. According to the analysis, rimegepant outperformed placebo on measures of freedom from the most bothersome symptom, pain relief at 2 hours post-dose, ability to function normally at 2 hours post-dose, use of rescue medication within 24 hours post-dose, and sustained pain freedom up to 48 hours post-dose. Treatment-emergent adverse events were assessed using EEG, vital signs, and laboratory tests. There was no notable difference in the incidence of adverse events between the rimegepant group and the placebo group, and no drug-related adverse events were reported.

This result is similar to that of previous studies which have demonstrated the significant efficacy of CGRP receptor blockers on acute migraine symptoms, including pain, bothersome symptoms, and nausea when compared with placebo.¹

A study published in the May 2024 issue of Pediatric Emergency Care examined the efficacy of prochlorperazine monotherapy or prochlorperazine combined with diphenhydramine for the treatment of acute migraine in the pediatric emergency department. This retrospective study included 1683 patients who were treated with either prochlorperazine monotherapy or diphenhydramine co-administered with prochlorperazine. The authors reported that the need for additional therapy, the 72-hour return visit rates, and the admission rates were equal for both groups. They reported that, overall, 13% of the patients required additional therapy, 16.7% were admitted, and 5.3% returned within 72 hours. Extrapyramidal side effects were reported in 2.4% of patients in the prochlorperazine group, while none of the patients in the prochlorperazine/diphenhydramine group reported extrapyramidal side effects. This difference in side-effect incidence should not be interpreted as a protective effect of diphenhydramine but could be an indication that adding diphenhydramine did not increase the risk for extrapyramidal side effects.

A study published in the April 2024 issue of Headache examined the efficacy of parenteral agents on acute migraine in the emergency room setting. The data analysis included 97 studies. The authors examined the efficacy of these medications and various combinations:

• •diphenhydramine (intravenous);
• •trimethobenzamide (intramuscular);
• •granisetron (intravenous);
• •valproate (intravenous);
• •neuroleptics (intravenous):
  • ◦prochlorperazine,
  • ◦chlorpromazine,
  • ◦haloperidol,
  • ◦droperidol,
  • ◦methotrimeprazine; and
• •dihydroergotamine (intravenous, intramuscular, or subcutaneous);
• •ketorolac (intravenous); and
• •magnesium sulfate (intravenous).

Each of these therapies was shown to improve migraine symptoms. According to the authors, "the majority of the parenteral agents commonly available to treat patients with migraine headaches in emergency settings was shown to be effective in providing pain relief." They recommended combination therapy or monotherapy of either neuroleptics or metoclopramide as first-line treatment options for treating acute migraine pain and acknowledged that these therapies carry an increased risk for extrapyramidal side effects.

According to a study published in 2015 in Cephalgia, there were 1.2 million migraine visits to US emergency departments in 2010.² With emerging preventive and acute treatments, it is possible that these numbers could decrease. However, the need for self-administration of acute migraine treatment and for migraine care in the emergency room setting is not likely to go away. The results regarding efficacy and safety of acute migraine therapies are encouraging, as patients who are experiencing migraine need acute therapy for distressing symptoms and do not always have many available options. Patients who can use prescription treatment may need to try a few different therapies before learning which acute migraine treatment is the most effective and which treatment causes the fewest side effects for them personally. Migraine patients who need care in the emergency room can experience speedy and effective relief with most available therapies.

Additional References

1. Pak K, Kim J, Lee GH, et al. Effectiveness of calcitonin gene-related peptide receptor antagonists for migraine treatment: a meta-analysis. Eur Neurol. 2022;85(3):195-201. doi: 10.1159/000521697 Source

2. Friedman BW, West J, Vinson DR, et al. Current management of migraine in US emergency departments: An analysis of the National Hospital Ambulatory Medical Care Survey. Cephalalgia. 2015;35(4):301-309. doi: 10.1177/0333102414539055 Source

heidimoawad_1.jpg

Migraine care requires a comprehensive approach. Identifying and avoiding triggers is a key component of patient-directed self-care. For many migraine patients, preventive therapy can substantially improve their quality of life. Yet, even with the best migraine prevention plan, many patients experience occasional migraines and require therapy for acute symptom relief. When it comes to selecting therapies for acute migraine treatment, criteria include efficacy, fast action, long duration of action, low risk for rebound symptoms, minimal side effects, and patient safety. Prescription therapies and therapies used in a medical setting include new calcitonin gene-related peptide (CGRP) receptor antagonists as well as antihistamines, antiemetics, neuroleptics, and triptans that have been used for years.

A study published in The Journal of Headache and Pain in April 2024 examined migraine symptom relief with the use of Nurtec OTD (rimegepant), one of the recently approved CGRP receptor antagonists. This post hoc subgroup analysis of a large double-blind randomized phase 3 clinical trial included 1075 participants, of whom 538 took 75 mg rimegepant and 537 took placebo to treat a single migraine episode. According to the analysis, rimegepant outperformed placebo on measures of freedom from the most bothersome symptom, pain relief at 2 hours post-dose, ability to function normally at 2 hours post-dose, use of rescue medication within 24 hours post-dose, and sustained pain freedom up to 48 hours post-dose. Treatment-emergent adverse events were assessed using EEG, vital signs, and laboratory tests. There was no notable difference in the incidence of adverse events between the rimegepant group and the placebo group, and no drug-related adverse events were reported.

This result is similar to that of previous studies which have demonstrated the significant efficacy of CGRP receptor blockers on acute migraine symptoms, including pain, bothersome symptoms, and nausea when compared with placebo.¹

A study published in the May 2024 issue of Pediatric Emergency Care examined the efficacy of prochlorperazine monotherapy or prochlorperazine combined with diphenhydramine for the treatment of acute migraine in the pediatric emergency department. This retrospective study included 1683 patients who were treated with either prochlorperazine monotherapy or diphenhydramine co-administered with prochlorperazine. The authors reported that the need for additional therapy, the 72-hour return visit rates, and the admission rates were equal for both groups. They reported that, overall, 13% of the patients required additional therapy, 16.7% were admitted, and 5.3% returned within 72 hours. Extrapyramidal side effects were reported in 2.4% of patients in the prochlorperazine group, while none of the patients in the prochlorperazine/diphenhydramine group reported extrapyramidal side effects. This difference in side-effect incidence should not be interpreted as a protective effect of diphenhydramine but could be an indication that adding diphenhydramine did not increase the risk for extrapyramidal side effects.

A study published in the April 2024 issue of Headache examined the efficacy of parenteral agents on acute migraine in the emergency room setting. The data analysis included 97 studies. The authors examined the efficacy of these medications and various combinations:

• •diphenhydramine (intravenous);
• •trimethobenzamide (intramuscular);
• •granisetron (intravenous);
• •valproate (intravenous);
• •neuroleptics (intravenous):
  • ◦prochlorperazine,
  • ◦chlorpromazine,
  • ◦haloperidol,
  • ◦droperidol,
  • ◦methotrimeprazine; and
• •dihydroergotamine (intravenous, intramuscular, or subcutaneous);
• •ketorolac (intravenous); and
• •magnesium sulfate (intravenous).

Each of these therapies was shown to improve migraine symptoms. According to the authors, "the majority of the parenteral agents commonly available to treat patients with migraine headaches in emergency settings was shown to be effective in providing pain relief." They recommended combination therapy or monotherapy of either neuroleptics or metoclopramide as first-line treatment options for treating acute migraine pain and acknowledged that these therapies carry an increased risk for extrapyramidal side effects.

According to a study published in 2015 in Cephalgia, there were 1.2 million migraine visits to US emergency departments in 2010.² With emerging preventive and acute treatments, it is possible that these numbers could decrease. However, the need for self-administration of acute migraine treatment and for migraine care in the emergency room setting is not likely to go away. The results regarding efficacy and safety of acute migraine therapies are encouraging, as patients who are experiencing migraine need acute therapy for distressing symptoms and do not always have many available options. Patients who can use prescription treatment may need to try a few different therapies before learning which acute migraine treatment is the most effective and which treatment causes the fewest side effects for them personally. Migraine patients who need care in the emergency room can experience speedy and effective relief with most available therapies.

Additional References

1. Pak K, Kim J, Lee GH, et al. Effectiveness of calcitonin gene-related peptide receptor antagonists for migraine treatment: a meta-analysis. Eur Neurol. 2022;85(3):195-201. doi: 10.1159/000521697 Source

2. Friedman BW, West J, Vinson DR, et al. Current management of migraine in US emergency departments: An analysis of the National Hospital Ambulatory Medical Care Survey. Cephalalgia. 2015;35(4):301-309. doi: 10.1177/0333102414539055 Source

heidimoawad_1.jpg

Migraine care requires a comprehensive approach. Identifying and avoiding triggers is a key component of patient-directed self-care. For many migraine patients, preventive therapy can substantially improve their quality of life. Yet, even with the best migraine prevention plan, many patients experience occasional migraines and require therapy for acute symptom relief. When it comes to selecting therapies for acute migraine treatment, criteria include efficacy, fast action, long duration of action, low risk for rebound symptoms, minimal side effects, and patient safety. Prescription therapies and therapies used in a medical setting include new calcitonin gene-related peptide (CGRP) receptor antagonists as well as antihistamines, antiemetics, neuroleptics, and triptans that have been used for years.

A study published in The Journal of Headache and Pain in April 2024 examined migraine symptom relief with the use of Nurtec OTD (rimegepant), one of the recently approved CGRP receptor antagonists. This post hoc subgroup analysis of a large double-blind randomized phase 3 clinical trial included 1075 participants, of whom 538 took 75 mg rimegepant and 537 took placebo to treat a single migraine episode. According to the analysis, rimegepant outperformed placebo on measures of freedom from the most bothersome symptom, pain relief at 2 hours post-dose, ability to function normally at 2 hours post-dose, use of rescue medication within 24 hours post-dose, and sustained pain freedom up to 48 hours post-dose. Treatment-emergent adverse events were assessed using EEG, vital signs, and laboratory tests. There was no notable difference in the incidence of adverse events between the rimegepant group and the placebo group, and no drug-related adverse events were reported.

This result is similar to that of previous studies which have demonstrated the significant efficacy of CGRP receptor blockers on acute migraine symptoms, including pain, bothersome symptoms, and nausea when compared with placebo.¹

A study published in the May 2024 issue of Pediatric Emergency Care examined the efficacy of prochlorperazine monotherapy or prochlorperazine combined with diphenhydramine for the treatment of acute migraine in the pediatric emergency department. This retrospective study included 1683 patients who were treated with either prochlorperazine monotherapy or diphenhydramine co-administered with prochlorperazine. The authors reported that the need for additional therapy, the 72-hour return visit rates, and the admission rates were equal for both groups. They reported that, overall, 13% of the patients required additional therapy, 16.7% were admitted, and 5.3% returned within 72 hours. Extrapyramidal side effects were reported in 2.4% of patients in the prochlorperazine group, while none of the patients in the prochlorperazine/diphenhydramine group reported extrapyramidal side effects. This difference in side-effect incidence should not be interpreted as a protective effect of diphenhydramine but could be an indication that adding diphenhydramine did not increase the risk for extrapyramidal side effects.

A study published in the April 2024 issue of Headache examined the efficacy of parenteral agents on acute migraine in the emergency room setting. The data analysis included 97 studies. The authors examined the efficacy of these medications and various combinations:

• •diphenhydramine (intravenous);
• •trimethobenzamide (intramuscular);
• •granisetron (intravenous);
• •valproate (intravenous);
• •neuroleptics (intravenous):
  • ◦prochlorperazine,
  • ◦chlorpromazine,
  • ◦haloperidol,
  • ◦droperidol,
  • ◦methotrimeprazine; and
• •dihydroergotamine (intravenous, intramuscular, or subcutaneous);
• •ketorolac (intravenous); and
• •magnesium sulfate (intravenous).

Each of these therapies was shown to improve migraine symptoms. According to the authors, "the majority of the parenteral agents commonly available to treat patients with migraine headaches in emergency settings was shown to be effective in providing pain relief." They recommended combination therapy or monotherapy of either neuroleptics or metoclopramide as first-line treatment options for treating acute migraine pain and acknowledged that these therapies carry an increased risk for extrapyramidal side effects.

According to a study published in 2015 in Cephalgia, there were 1.2 million migraine visits to US emergency departments in 2010.² With emerging preventive and acute treatments, it is possible that these numbers could decrease. However, the need for self-administration of acute migraine treatment and for migraine care in the emergency room setting is not likely to go away. The results regarding efficacy and safety of acute migraine therapies are encouraging, as patients who are experiencing migraine need acute therapy for distressing symptoms and do not always have many available options. Patients who can use prescription treatment may need to try a few different therapies before learning which acute migraine treatment is the most effective and which treatment causes the fewest side effects for them personally. Migraine patients who need care in the emergency room can experience speedy and effective relief with most available therapies.

Additional References

1. Pak K, Kim J, Lee GH, et al. Effectiveness of calcitonin gene-related peptide receptor antagonists for migraine treatment: a meta-analysis. Eur Neurol. 2022;85(3):195-201. doi: 10.1159/000521697 Source

2. Friedman BW, West J, Vinson DR, et al. Current management of migraine in US emergency departments: An analysis of the National Hospital Ambulatory Medical Care Survey. Cephalalgia. 2015;35(4):301-309. doi: 10.1177/0333102414539055 Source

Although the prevalence of migraine in the United States has remained stable over the past three decades, migraine-related disability has nearly doubled during that time, a new systematic review showed.

“The disability trend could reflect changes in reporting, study methodology, social, and societal changes, or changes in exacerbating or remediating factors that make migraine more disabling,” wrote lead investigator Fred Cohen, MD, of Center for Headache and Facial Pain, Department of Neurology, Icahn School of Medicine, Mount Sinai, New York City, and colleagues.

The study was published online in Headache.

Researchers conducted a systematic review of population-based US epidemiologic studies focusing on the prevalence and/or burden of migraine, all published before February 2022. Studies on migraine, episodic migraine, and/or chronic migraine were included.

The primary measure of disease burden was the Migraine Disability Assessment Scale (MIDAS), which measures days lost to migraine over a 3-month period in three domains and defines groups with moderate or severe disability (grades III and IV, respectively), using cut-scores.

Of 1609 studies initially reviewed, the researchers included 26 publications from 11 US population-based studies.

For the past 30 years, the prevalence of migraine in the population has remained largely stable, ranging from 12% to 15% in the overall population, from 17% to 19% in women, and from 6% to 7% in men.

In adults overall, chronic migraine prevalence is 0.91% (1.3% in women and 0.5% in men), while in adolescents, the prevalence is 0.8%.

Although prevalence remained roughly the same during the 30 years, the proportion of people with migraine and moderate to severe MIDAS disability (grades III-IV) has trended upward across studies during part of the study period, increasing from 22% in 2005 to 42% in 2018.

Throughout the years studied, a consistently higher proportion of women versus men were assigned MIDAS grades III-IV.

Although researchers said the exact reason for the increase is unknown, possible explanations include changes in study methodology from mailed questionnaires to web surveys or the decline in participation rate in web surveys. It is also possible that people with migraine may be more willing to report disability than they used to be, authors wrote.

Increased MIDAS scores may be attributable to some environmental risk factor that exacerbates migraine without modifying its prevalence, such as worsening air quality, an increase in natural disasters, or increased opioid use for migraine, they added.

The reason for increased moderate to severe disability in women may be attributable to the fact that migraine is “most common in mid-life, a period characterized by familial and work responsibilities, which may engender a higher risk of burden for working women,” authors wrote. The link between migraine attacks and menstrual cycles may also explain observed gender differences in disability.

In general, the most frequently reported burdens associated with migraine included missed work and school and family and social functioning.

It is “surprising that improvements in treatment have not been associated with reductions in disability,” researchers noted.

No financial support was provided for this study. Dr. Cohen serves as an assistant editor for Headache. He has received honoraria from Springer Nature and MedLink Neurology. Other authors’ disclosures are listed on the original paper.
 

A version of this article appeared on Medscape.com.

Although the prevalence of migraine in the United States has remained stable over the past three decades, migraine-related disability has nearly doubled during that time, a new systematic review showed.

“The disability trend could reflect changes in reporting, study methodology, social, and societal changes, or changes in exacerbating or remediating factors that make migraine more disabling,” wrote lead investigator Fred Cohen, MD, of Center for Headache and Facial Pain, Department of Neurology, Icahn School of Medicine, Mount Sinai, New York City, and colleagues.

The study was published online in Headache.

Researchers conducted a systematic review of population-based US epidemiologic studies focusing on the prevalence and/or burden of migraine, all published before February 2022. Studies on migraine, episodic migraine, and/or chronic migraine were included.

The primary measure of disease burden was the Migraine Disability Assessment Scale (MIDAS), which measures days lost to migraine over a 3-month period in three domains and defines groups with moderate or severe disability (grades III and IV, respectively), using cut-scores.

Of 1609 studies initially reviewed, the researchers included 26 publications from 11 US population-based studies.

For the past 30 years, the prevalence of migraine in the population has remained largely stable, ranging from 12% to 15% in the overall population, from 17% to 19% in women, and from 6% to 7% in men.

In adults overall, chronic migraine prevalence is 0.91% (1.3% in women and 0.5% in men), while in adolescents, the prevalence is 0.8%.

Although prevalence remained roughly the same during the 30 years, the proportion of people with migraine and moderate to severe MIDAS disability (grades III-IV) has trended upward across studies during part of the study period, increasing from 22% in 2005 to 42% in 2018.

Throughout the years studied, a consistently higher proportion of women versus men were assigned MIDAS grades III-IV.

Although researchers said the exact reason for the increase is unknown, possible explanations include changes in study methodology from mailed questionnaires to web surveys or the decline in participation rate in web surveys. It is also possible that people with migraine may be more willing to report disability than they used to be, authors wrote.

Increased MIDAS scores may be attributable to some environmental risk factor that exacerbates migraine without modifying its prevalence, such as worsening air quality, an increase in natural disasters, or increased opioid use for migraine, they added.

The reason for increased moderate to severe disability in women may be attributable to the fact that migraine is “most common in mid-life, a period characterized by familial and work responsibilities, which may engender a higher risk of burden for working women,” authors wrote. The link between migraine attacks and menstrual cycles may also explain observed gender differences in disability.

In general, the most frequently reported burdens associated with migraine included missed work and school and family and social functioning.

It is “surprising that improvements in treatment have not been associated with reductions in disability,” researchers noted.

No financial support was provided for this study. Dr. Cohen serves as an assistant editor for Headache. He has received honoraria from Springer Nature and MedLink Neurology. Other authors’ disclosures are listed on the original paper.
 

A version of this article appeared on Medscape.com.

Although the prevalence of migraine in the United States has remained stable over the past three decades, migraine-related disability has nearly doubled during that time, a new systematic review showed.

“The disability trend could reflect changes in reporting, study methodology, social, and societal changes, or changes in exacerbating or remediating factors that make migraine more disabling,” wrote lead investigator Fred Cohen, MD, of Center for Headache and Facial Pain, Department of Neurology, Icahn School of Medicine, Mount Sinai, New York City, and colleagues.

The study was published online in Headache.

Researchers conducted a systematic review of population-based US epidemiologic studies focusing on the prevalence and/or burden of migraine, all published before February 2022. Studies on migraine, episodic migraine, and/or chronic migraine were included.

The primary measure of disease burden was the Migraine Disability Assessment Scale (MIDAS), which measures days lost to migraine over a 3-month period in three domains and defines groups with moderate or severe disability (grades III and IV, respectively), using cut-scores.

Of 1609 studies initially reviewed, the researchers included 26 publications from 11 US population-based studies.

For the past 30 years, the prevalence of migraine in the population has remained largely stable, ranging from 12% to 15% in the overall population, from 17% to 19% in women, and from 6% to 7% in men.

In adults overall, chronic migraine prevalence is 0.91% (1.3% in women and 0.5% in men), while in adolescents, the prevalence is 0.8%.

Although prevalence remained roughly the same during the 30 years, the proportion of people with migraine and moderate to severe MIDAS disability (grades III-IV) has trended upward across studies during part of the study period, increasing from 22% in 2005 to 42% in 2018.

Throughout the years studied, a consistently higher proportion of women versus men were assigned MIDAS grades III-IV.

Although researchers said the exact reason for the increase is unknown, possible explanations include changes in study methodology from mailed questionnaires to web surveys or the decline in participation rate in web surveys. It is also possible that people with migraine may be more willing to report disability than they used to be, authors wrote.

Increased MIDAS scores may be attributable to some environmental risk factor that exacerbates migraine without modifying its prevalence, such as worsening air quality, an increase in natural disasters, or increased opioid use for migraine, they added.

The reason for increased moderate to severe disability in women may be attributable to the fact that migraine is “most common in mid-life, a period characterized by familial and work responsibilities, which may engender a higher risk of burden for working women,” authors wrote. The link between migraine attacks and menstrual cycles may also explain observed gender differences in disability.

In general, the most frequently reported burdens associated with migraine included missed work and school and family and social functioning.

It is “surprising that improvements in treatment have not been associated with reductions in disability,” researchers noted.

No financial support was provided for this study. Dr. Cohen serves as an assistant editor for Headache. He has received honoraria from Springer Nature and MedLink Neurology. Other authors’ disclosures are listed on the original paper.
 

A version of this article appeared on Medscape.com.

Key clinical point: The odds of treatment failure were not increased, and no extrapyramidal adverse events were reported in pediatric patients with migraine when diphenhydramine was coadministered with prochlorperazine in an emergency department (ED) setting.

Major finding: The administration of diphenhydramine plus prochlorperazine vs prochlorperazine alone was not associated with increased odds of additional migraine therapy (P = .347), hospitalization rates (P = .425), and 72-hour return visit rates (P = .271). None of the patients in the diphenhydramine plus prochlorperazine group experienced extrapyramidal adverse events, while 2.4% of patients in prochlorperazine group experienced extrapyramidal adverse events.

Study details: Findings are from a retrospective cohort study that included 1683 pediatric patients with migraine presenting to the ED who received diphenhydramine plus prochlorperazine (n = 1215) or prochlorperazine only (n = 468).

Disclosures: This study did not disclose any funding source. The authors declared no conflicts of interest.

Source: Naeem S, Lozano JM, Ruiz Castaneda AM, Lowe D. Diphenhydramine and migraine treatment failure in pediatric patients receiving prochlorperazine. Pediatr Emerg Care. 2024 (May 9). doi: 10.1097/PEC.0000000000003202 Source

Key clinical point: The odds of treatment failure were not increased, and no extrapyramidal adverse events were reported in pediatric patients with migraine when diphenhydramine was coadministered with prochlorperazine in an emergency department (ED) setting.

Major finding: The administration of diphenhydramine plus prochlorperazine vs prochlorperazine alone was not associated with increased odds of additional migraine therapy (P = .347), hospitalization rates (P = .425), and 72-hour return visit rates (P = .271). None of the patients in the diphenhydramine plus prochlorperazine group experienced extrapyramidal adverse events, while 2.4% of patients in prochlorperazine group experienced extrapyramidal adverse events.

Study details: Findings are from a retrospective cohort study that included 1683 pediatric patients with migraine presenting to the ED who received diphenhydramine plus prochlorperazine (n = 1215) or prochlorperazine only (n = 468).

Disclosures: This study did not disclose any funding source. The authors declared no conflicts of interest.

Source: Naeem S, Lozano JM, Ruiz Castaneda AM, Lowe D. Diphenhydramine and migraine treatment failure in pediatric patients receiving prochlorperazine. Pediatr Emerg Care. 2024 (May 9). doi: 10.1097/PEC.0000000000003202 Source

Key clinical point: The odds of treatment failure were not increased, and no extrapyramidal adverse events were reported in pediatric patients with migraine when diphenhydramine was coadministered with prochlorperazine in an emergency department (ED) setting.

Major finding: The administration of diphenhydramine plus prochlorperazine vs prochlorperazine alone was not associated with increased odds of additional migraine therapy (P = .347), hospitalization rates (P = .425), and 72-hour return visit rates (P = .271). None of the patients in the diphenhydramine plus prochlorperazine group experienced extrapyramidal adverse events, while 2.4% of patients in prochlorperazine group experienced extrapyramidal adverse events.

Study details: Findings are from a retrospective cohort study that included 1683 pediatric patients with migraine presenting to the ED who received diphenhydramine plus prochlorperazine (n = 1215) or prochlorperazine only (n = 468).

Disclosures: This study did not disclose any funding source. The authors declared no conflicts of interest.

Source: Naeem S, Lozano JM, Ruiz Castaneda AM, Lowe D. Diphenhydramine and migraine treatment failure in pediatric patients receiving prochlorperazine. Pediatr Emerg Care. 2024 (May 9). doi: 10.1097/PEC.0000000000003202 Source

Key clinical point: Both cinnarizine and amitriptyline effectively improved migraine symptoms in children and adolescents with migraine, but amitriptyline was a more preferable treatment option since it reduced headache frequency and duration more effectively than cinnarizine.

Major finding: Amitriptyline was more effective than cinnarizine in reducing headache frequency at 4 weeks (mean difference [MD] −8.81 attacks/months; P = .004) and headache duration at 4 (MD −123.0 minutes; P = .017), 8 (MD −110.3 minutes; P = .033), and 12 (MD −123.3 minutes; P = .018) weeks. However, there were no significant differences in headache severity and migraine-related disability between the groups at 4, 8, and 12 weeks (all P > .005).

Study details: Findings are from a randomized, double-blind controlled trial including 43 children with migraine (age 4-17 years) who were randomly assigned to receive cinnarizine (n = 22) and amitriptyline (n = 21).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Olfat M, Hosseinpour S, Masoumi S, et al. A comparative study on prophylactic efficacy of cinnarizine and amitriptyline in childhood migraine: A randomized double-blind clinical trial. Cephalalgia. 2024 (Apr 20). doi: 10.1177/03331024241230963 Source

Key clinical point: Both cinnarizine and amitriptyline effectively improved migraine symptoms in children and adolescents with migraine, but amitriptyline was a more preferable treatment option since it reduced headache frequency and duration more effectively than cinnarizine.

Major finding: Amitriptyline was more effective than cinnarizine in reducing headache frequency at 4 weeks (mean difference [MD] −8.81 attacks/months; P = .004) and headache duration at 4 (MD −123.0 minutes; P = .017), 8 (MD −110.3 minutes; P = .033), and 12 (MD −123.3 minutes; P = .018) weeks. However, there were no significant differences in headache severity and migraine-related disability between the groups at 4, 8, and 12 weeks (all P > .005).

Study details: Findings are from a randomized, double-blind controlled trial including 43 children with migraine (age 4-17 years) who were randomly assigned to receive cinnarizine (n = 22) and amitriptyline (n = 21).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Olfat M, Hosseinpour S, Masoumi S, et al. A comparative study on prophylactic efficacy of cinnarizine and amitriptyline in childhood migraine: A randomized double-blind clinical trial. Cephalalgia. 2024 (Apr 20). doi: 10.1177/03331024241230963 Source

Key clinical point: Both cinnarizine and amitriptyline effectively improved migraine symptoms in children and adolescents with migraine, but amitriptyline was a more preferable treatment option since it reduced headache frequency and duration more effectively than cinnarizine.

Major finding: Amitriptyline was more effective than cinnarizine in reducing headache frequency at 4 weeks (mean difference [MD] −8.81 attacks/months; P = .004) and headache duration at 4 (MD −123.0 minutes; P = .017), 8 (MD −110.3 minutes; P = .033), and 12 (MD −123.3 minutes; P = .018) weeks. However, there were no significant differences in headache severity and migraine-related disability between the groups at 4, 8, and 12 weeks (all P > .005).

Study details: Findings are from a randomized, double-blind controlled trial including 43 children with migraine (age 4-17 years) who were randomly assigned to receive cinnarizine (n = 22) and amitriptyline (n = 21).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Olfat M, Hosseinpour S, Masoumi S, et al. A comparative study on prophylactic efficacy of cinnarizine and amitriptyline in childhood migraine: A randomized double-blind clinical trial. Cephalalgia. 2024 (Apr 20). doi: 10.1177/03331024241230963 Source

Key clinical point: This cross-sectional study demonstrated a significant association between severe headache or migraine and erectile dysfunction (ED) in adult men in the US; however, the results should be interpreted carefully as it did not investigate the effects of depression and anxiety on ED.

Major finding: Presence vs absence of severe headache or migraine was associated with 51% increased risk of ED (adjusted odd ratio 1.51; P = .0036). Age of 40-60 years (P = 0.0292), body mass index < 25 kg/m² (P = .0406) or ≥30 kg/m² (P = .0222), metabolic disorders, such as hypertension (P = .0029), diabetes mellitus (P < .001), and hyperlipidemia (P = .0281), were significant risk factors for ED in those with severe headache or migraine.

Study details: This cross-sectional study included 3117 adult men with (n = 582) and without (n = 2535) history of ED from the US National Health and Nutrition Examination Survey (2001-2 and 2003-4), of whom 16.85% had severe headache or migraine.

Disclosures: This study was funded by National Natural Science Foundation of China. The authors declared no competing interests.

Source: Wu X, Zhang Y, Liu G, et al. Association between severe headache or migraine and erectile dysfunction in American adults: A cross-sectional of data study from the NHANES. Int J Impot Res. 2024 (Apr 12). doi: 10.1038/s41443-024-00867-w Source

Key clinical point: This cross-sectional study demonstrated a significant association between severe headache or migraine and erectile dysfunction (ED) in adult men in the US; however, the results should be interpreted carefully as it did not investigate the effects of depression and anxiety on ED.

Major finding: Presence vs absence of severe headache or migraine was associated with 51% increased risk of ED (adjusted odd ratio 1.51; P = .0036). Age of 40-60 years (P = 0.0292), body mass index < 25 kg/m² (P = .0406) or ≥30 kg/m² (P = .0222), metabolic disorders, such as hypertension (P = .0029), diabetes mellitus (P < .001), and hyperlipidemia (P = .0281), were significant risk factors for ED in those with severe headache or migraine.

Study details: This cross-sectional study included 3117 adult men with (n = 582) and without (n = 2535) history of ED from the US National Health and Nutrition Examination Survey (2001-2 and 2003-4), of whom 16.85% had severe headache or migraine.

Disclosures: This study was funded by National Natural Science Foundation of China. The authors declared no competing interests.

Source: Wu X, Zhang Y, Liu G, et al. Association between severe headache or migraine and erectile dysfunction in American adults: A cross-sectional of data study from the NHANES. Int J Impot Res. 2024 (Apr 12). doi: 10.1038/s41443-024-00867-w Source

Key clinical point: This cross-sectional study demonstrated a significant association between severe headache or migraine and erectile dysfunction (ED) in adult men in the US; however, the results should be interpreted carefully as it did not investigate the effects of depression and anxiety on ED.

Major finding: Presence vs absence of severe headache or migraine was associated with 51% increased risk of ED (adjusted odd ratio 1.51; P = .0036). Age of 40-60 years (P = 0.0292), body mass index < 25 kg/m² (P = .0406) or ≥30 kg/m² (P = .0222), metabolic disorders, such as hypertension (P = .0029), diabetes mellitus (P < .001), and hyperlipidemia (P = .0281), were significant risk factors for ED in those with severe headache or migraine.

Study details: This cross-sectional study included 3117 adult men with (n = 582) and without (n = 2535) history of ED from the US National Health and Nutrition Examination Survey (2001-2 and 2003-4), of whom 16.85% had severe headache or migraine.

Disclosures: This study was funded by National Natural Science Foundation of China. The authors declared no competing interests.

Source: Wu X, Zhang Y, Liu G, et al. Association between severe headache or migraine and erectile dysfunction in American adults: A cross-sectional of data study from the NHANES. Int J Impot Res. 2024 (Apr 12). doi: 10.1038/s41443-024-00867-w Source

Key clinical point: Presence of migraine poses a strong risk for incident venous thromboembolism (VTE), whereas VTE is modest risk factor for the onset of migraine.

Major finding: The risk of developing VTE was significantly higher in patients with vs without migraine (odds ratio [OR] 96.155; P = .004). Conversely, the risk for migraine was modestly higher in patients with vs without VTE (OR 1.002; P = .016).

Study details: This two-sample bidirectional Mendelian randomization study evaluated the causal association between migraine and VTE using single-nucleotide polymorphisms as instrumental variables obtained from large-scale Genome-Wide Association Studies public databases (IEU Open GWAS project, FinnGen).

Disclosures: The study did not disclose any funding. The authors declared no conflicts of interest.

Source: Wang Y, Hu X, Wang X, et al. Exploring the two-way link between migraines and venous thromboembolism: A bidirectional two-sample Mendelian randomization study. Thromb Haemost. 2024 (Apr 24). doi: 10.1055/a-2313-0311 Source

Key clinical point: Presence of migraine poses a strong risk for incident venous thromboembolism (VTE), whereas VTE is modest risk factor for the onset of migraine.

Major finding: The risk of developing VTE was significantly higher in patients with vs without migraine (odds ratio [OR] 96.155; P = .004). Conversely, the risk for migraine was modestly higher in patients with vs without VTE (OR 1.002; P = .016).

Study details: This two-sample bidirectional Mendelian randomization study evaluated the causal association between migraine and VTE using single-nucleotide polymorphisms as instrumental variables obtained from large-scale Genome-Wide Association Studies public databases (IEU Open GWAS project, FinnGen).

Disclosures: The study did not disclose any funding. The authors declared no conflicts of interest.

Source: Wang Y, Hu X, Wang X, et al. Exploring the two-way link between migraines and venous thromboembolism: A bidirectional two-sample Mendelian randomization study. Thromb Haemost. 2024 (Apr 24). doi: 10.1055/a-2313-0311 Source

Key clinical point: Presence of migraine poses a strong risk for incident venous thromboembolism (VTE), whereas VTE is modest risk factor for the onset of migraine.

Major finding: The risk of developing VTE was significantly higher in patients with vs without migraine (odds ratio [OR] 96.155; P = .004). Conversely, the risk for migraine was modestly higher in patients with vs without VTE (OR 1.002; P = .016).

Study details: This two-sample bidirectional Mendelian randomization study evaluated the causal association between migraine and VTE using single-nucleotide polymorphisms as instrumental variables obtained from large-scale Genome-Wide Association Studies public databases (IEU Open GWAS project, FinnGen).

Disclosures: The study did not disclose any funding. The authors declared no conflicts of interest.

Source: Wang Y, Hu X, Wang X, et al. Exploring the two-way link between migraines and venous thromboembolism: A bidirectional two-sample Mendelian randomization study. Thromb Haemost. 2024 (Apr 24). doi: 10.1055/a-2313-0311 Source

Key clinical point: Very low-quality evidence showed that serum pituitary adenylates cyclase–activating polypeptide (PACAP) levels were lower in adults with a longer history of migraine.

Major finding: Serum levels of PACAP were inversely associated with history of migraine duration in adults with migraine (summary r −0.35; P < .01). It was also seen that serum PACAP levels were higher during the ictal vs interictal period in both adults and children with migraine (standardized mean difference 0.41; 95% CI 0.17-0.66).

Study details: Findings are from a meta-analysis of eight observational studies including 674 patients with migraine and 371 control individuals without migraine.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Zhu G, Wang M, Kong F. Blood serum levels of PACAP and migraine onset: A systematic review and meta-analysis of observational studies. Headache. 2024 (Apr 24). doi: 10.1111/head.14711 Source

Key clinical point: Very low-quality evidence showed that serum pituitary adenylates cyclase–activating polypeptide (PACAP) levels were lower in adults with a longer history of migraine.

Major finding: Serum levels of PACAP were inversely associated with history of migraine duration in adults with migraine (summary r −0.35; P < .01). It was also seen that serum PACAP levels were higher during the ictal vs interictal period in both adults and children with migraine (standardized mean difference 0.41; 95% CI 0.17-0.66).

Study details: Findings are from a meta-analysis of eight observational studies including 674 patients with migraine and 371 control individuals without migraine.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Zhu G, Wang M, Kong F. Blood serum levels of PACAP and migraine onset: A systematic review and meta-analysis of observational studies. Headache. 2024 (Apr 24). doi: 10.1111/head.14711 Source

Key clinical point: Very low-quality evidence showed that serum pituitary adenylates cyclase–activating polypeptide (PACAP) levels were lower in adults with a longer history of migraine.

Major finding: Serum levels of PACAP were inversely associated with history of migraine duration in adults with migraine (summary r −0.35; P < .01). It was also seen that serum PACAP levels were higher during the ictal vs interictal period in both adults and children with migraine (standardized mean difference 0.41; 95% CI 0.17-0.66).

Study details: Findings are from a meta-analysis of eight observational studies including 674 patients with migraine and 371 control individuals without migraine.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Zhu G, Wang M, Kong F. Blood serum levels of PACAP and migraine onset: A systematic review and meta-analysis of observational studies. Headache. 2024 (Apr 24). doi: 10.1111/head.14711 Source

Key clinical point: Rimegepant orally disintegrating tablet (ODT) offers pain relief within 2 hours of treatment in adults with migraine, with a tolerable safety profile.

Major finding: At 2 hours post dose, rimegepant was more effective than placebo in providing freedom from pain (risk difference 7.6; P = .0004) and the most bothersome symptom (risk difference 16.2; P < .0001). The overall rates of treatment-emergent adverse events were comparable between the rimegepant and placebo groups (15.2% and 16.4%, respectively).

Study details: This subgroup analysis of a double-blind, randomized, placebo-controlled phase 3 clinical trial included 1075 patients with acute migraine with or without aura (age ≥ 18 years) who were randomly assigned to receive either 75 mg rimegepant ODT (n = 538) or placebo (n = 537).

Disclosures: This study was funded by BioShin, a wholly owned subsidiary of Biohaven Pharmaceuticals, which was acquired by Pfizer. Pfizer provided writing support. Five authors declared being employees or stock owners of Biohaven, BioShin, or Pfizer. The remaining authors declared no conflicts of interest.

Source: Yu S, Guo A, Wang Z, et al. Rimegepant orally disintegrating tablet 75 mg for acute treatment of migraine in adults from China: A subgroup analysis of a double-blind, randomized, placebo-controlled, phase 3 clinical trial. J Headache Pain. 2024;25:57 (Apr 16). Source

Key clinical point: Rimegepant orally disintegrating tablet (ODT) offers pain relief within 2 hours of treatment in adults with migraine, with a tolerable safety profile.

Major finding: At 2 hours post dose, rimegepant was more effective than placebo in providing freedom from pain (risk difference 7.6; P = .0004) and the most bothersome symptom (risk difference 16.2; P < .0001). The overall rates of treatment-emergent adverse events were comparable between the rimegepant and placebo groups (15.2% and 16.4%, respectively).

Study details: This subgroup analysis of a double-blind, randomized, placebo-controlled phase 3 clinical trial included 1075 patients with acute migraine with or without aura (age ≥ 18 years) who were randomly assigned to receive either 75 mg rimegepant ODT (n = 538) or placebo (n = 537).

Disclosures: This study was funded by BioShin, a wholly owned subsidiary of Biohaven Pharmaceuticals, which was acquired by Pfizer. Pfizer provided writing support. Five authors declared being employees or stock owners of Biohaven, BioShin, or Pfizer. The remaining authors declared no conflicts of interest.

Source: Yu S, Guo A, Wang Z, et al. Rimegepant orally disintegrating tablet 75 mg for acute treatment of migraine in adults from China: A subgroup analysis of a double-blind, randomized, placebo-controlled, phase 3 clinical trial. J Headache Pain. 2024;25:57 (Apr 16). Source

Key clinical point: Rimegepant orally disintegrating tablet (ODT) offers pain relief within 2 hours of treatment in adults with migraine, with a tolerable safety profile.

Major finding: At 2 hours post dose, rimegepant was more effective than placebo in providing freedom from pain (risk difference 7.6; P = .0004) and the most bothersome symptom (risk difference 16.2; P < .0001). The overall rates of treatment-emergent adverse events were comparable between the rimegepant and placebo groups (15.2% and 16.4%, respectively).

Study details: This subgroup analysis of a double-blind, randomized, placebo-controlled phase 3 clinical trial included 1075 patients with acute migraine with or without aura (age ≥ 18 years) who were randomly assigned to receive either 75 mg rimegepant ODT (n = 538) or placebo (n = 537).

Disclosures: This study was funded by BioShin, a wholly owned subsidiary of Biohaven Pharmaceuticals, which was acquired by Pfizer. Pfizer provided writing support. Five authors declared being employees or stock owners of Biohaven, BioShin, or Pfizer. The remaining authors declared no conflicts of interest.

Source: Yu S, Guo A, Wang Z, et al. Rimegepant orally disintegrating tablet 75 mg for acute treatment of migraine in adults from China: A subgroup analysis of a double-blind, randomized, placebo-controlled, phase 3 clinical trial. J Headache Pain. 2024;25:57 (Apr 16). Source