Headache & Migraine

As we move further into the 21st century, technology continues to revolutionize various facets of our lives. Healthcare is a prime example. Advances in technology have dramatically reshaped the way we develop medications, diagnose diseases, and enhance patient care. The rise of artificial intelligence (AI) and the widespread adoption of digital health technologies have marked a significant milestone in improving the quality of care. AI, with its ability to leverage algorithms, deep learning, and machine learning to process data, make decisions, and perform tasks autonomously, is becoming an integral part of modern society. It is embedded in various technologies that we rely on daily, from smartphones and smart home devices to content recommendations on streaming services and social media platforms.

In healthcare, AI has applications in numerous fields, such as radiology. AI streamlines processes such as organizing patient appointments, optimizing radiation protocols for safety and efficiency, and enhancing the documentation process through advanced image analysis. AI technology plays an integral role in imaging tasks like image enhancement, lesion detection, and precise measurement. In difficult-to-interpret radiologic studies, such as some mammography images, it can be a crucial aid to the radiologist. Additionally, the use of AI has significantly improved remote patient monitoring that enables healthcare professionals to monitor and assess patient conditions without needing in-person visits. Remote patient monitoring gained prominence during the COVID-19 pandemic and continues to be a valuable tool in post pandemic care. Study results have highlighted that AI-driven ambient dictation tools have increased provider engagement with patients during consultations while reducing the time spent documenting in electronic health records.

Like many other medical specialties, headache medicine also uses AI. Most prominently, AI has been used in models and engines in assisting with headache diagnoses. A noteworthy example of AI in headache medicine is the development of an online, computer-based diagnostic engine (CDE) by Rapoport et al, called BonTriage. This tool is designed to diagnose headaches by employing a rule set based on the International Classification of Headache Disorders-3 (ICHD-3) criteria for primary headache disorders while also evaluating secondary headaches and medication overuse headaches. By leveraging machine learning, the CDE has the potential to streamline the diagnostic process, reducing the number of questions needed to reach a diagnosis and making the experience more efficient. This information can then be printed as a PDF file and taken by the patient to a healthcare professional for further discussion, fostering a more accurate, fluid, and conversational consultation.

A study was conducted to evaluate the accuracy of the CDE. Participants were randomly assigned to 1 of 2 sequences: (1) using the CDE followed by a structured standard interview with a headache specialist using the same ICHD-3 criteria or (2) starting with the structured standard interview followed by the CDE. The results demonstrated nearly perfect agreement in diagnosing migraine and probable migraine between the CDE and structured standard interview (κ = 0.82, 95% CI: 0.74, 0.90). The CDE demonstrated a diagnostic accuracy of 91.6% (95% CI: 86.9%, 95.0%), a sensitivity rate of 89.0% (95% CI: 82.5%, 93.7%), and a specificity rate of 97.0% (95% CI: 89.5%, 99.6%).

A diagnostic engine such as this can save time that clinicians spend on documentation and allow more time for discussion with the patient. For instance, a patient can take the printout received from the CDE to an appointment; the printout gives a detailed history plus information about social and psychological issues, a list of medications taken, and results of previous testing. The CDE system was originally designed to help patients see a specialist in the environment of a nationwide lack of headache specialists. There are currently 45 million patients with headaches who are seeking treatment with only around 550 certified headache specialists in the United States. The CDE printed information can help a patient obtain a consultation from a clinician quickly and start evaluation and treatment earlier. This expert online consultation is currently free of charge.

Kwon et al developed a machine learning–based model designed to automatically classify headache disorders using data from a questionnaire. Their model was able to predict diagnoses for conditions such as migraine, tension-type headaches, trigeminal autonomic cephalalgia, epicranial headache, and thunderclap headaches. The model was trained on data from 2162 patients, all diagnosed by headache specialists, and achieved an overall accuracy of 81%, with a sensitivity of 88% and a specificity of 95% for diagnosing migraines. However, the model’s performance was less robust when applied to other headache disorders.

Katsuki et al developed an AI model to help non specialists accurately diagnose headaches. This model analyzed 17 variables and was trained on data from 2800 patients, with additional testing and refinement using data from another 200 patients. To evaluate its effectiveness, 2 groups of non-headache specialists each assessed 50 patients: 1 group relied solely on their expertise, while the other used the AI model. The group without AI assistance achieved an overall accuracy of 46% (κ = 0.21), while the group using the AI model significantly improved, reaching an overall accuracy of 83.2% (κ = 0.68).

Building on their work with AI for diagnosing headaches, Katsuki et al conducted a study using a smartphone application that tracked user-reported headache events alongside local weather data. The AI model revealed that lower barometric pressure, higher humidity, and increased rainfall were linked to the onset of headache attacks. The application also identified triggers for headaches in specific weather patterns, such as a drop in barometric pressure noted 6 hours before headache onset. The application of AI in monitoring weather changes could be crucial, especially given concerns that the rising frequency of severe weather events due to climate change may be exacerbating the severity and burden of migraine. Additionally, recent post hoc analyses of fremanezumab clinical trials have provided further evidence that weather changes can trigger headaches.

Rapoport and colleagues have also developed an application called Migraine Mentor, which accurately tracks headaches, triggers, health data, and response to medication on a smartphone. The patient spends 3 minutes a day answering a few questions about their day and whether they had a headache or took any medication. At 1 or 2 months, Migraine Mentor can generate a detailed report with data and current trends that is sent to the patient, which the patient can then share with the clinician. The application also reminds patients when to document data and take medication.

However, although the use of AI in headache medicine appears promising, caution must be exercised to ensure proper results and information are disseminated. One rapidly expanding application of AI is the widely popular ChatGPT. ChatGPT, which stands for generative pretraining transformer, is a type of large language model (LLM). An LLM is a deep learning algorithm designed to recognize, translate, predict, summarize, and generate text responses based on a given prompt. This model is trained on an extensive dataset that includes a diverse array of books, articles, and websites, exposing it to various language structures and styles. This training enables ChatGPT to generate responses that closely mimic human communication. LLMs are being used more and more in medicine to assist with generating patient documentation and educational materials.

However, Dr Fred Cohen published a perspective piece detailing how LLMs (such as ChatGPT) can produce misleading and inaccurate answers. In his example, he tasked ChatGPT to describe the epidemiology of migraines in penguins; the AI model generated a well-written and highly believable manuscript titled, “Migraine Under the Ice: Understanding Headaches in Antarctica's Feathered Friends.” The manuscript highlights that migraines are more prevalent in male penguins compared to females, with the peak age of onset occurring between 4 and 5 years. Additionally, emperor and king penguins are identified as being more susceptible to developing migraines compared to other penguin species. The paper was fictitious (as no studies on migraine in penguins have been written to date), exemplifying that these models can produce nonfactual materials.

For years, technological advancements have been reshaping many aspects of life, and medicine is no exception. AI has been successfully applied to streamline medical documentation, develop new drug targets, and deepen our understanding of various diseases. The field of headache medicine now also uses AI. Recent developments show significant promise, with AI aiding in the diagnosis of migraine and other headache disorders. AI models have even been used in the identification of potential drug targets for migraine treatment. Although there are still limitations to overcome, the future of AI in headache medicine appears bright.

If you would like to read more about Dr. Cohen’s work on AI and migraine, please visit fredcohenmd.com or TikTok @fredcohenmd. 

As we move further into the 21st century, technology continues to revolutionize various facets of our lives. Healthcare is a prime example. Advances in technology have dramatically reshaped the way we develop medications, diagnose diseases, and enhance patient care. The rise of artificial intelligence (AI) and the widespread adoption of digital health technologies have marked a significant milestone in improving the quality of care. AI, with its ability to leverage algorithms, deep learning, and machine learning to process data, make decisions, and perform tasks autonomously, is becoming an integral part of modern society. It is embedded in various technologies that we rely on daily, from smartphones and smart home devices to content recommendations on streaming services and social media platforms.

In healthcare, AI has applications in numerous fields, such as radiology. AI streamlines processes such as organizing patient appointments, optimizing radiation protocols for safety and efficiency, and enhancing the documentation process through advanced image analysis. AI technology plays an integral role in imaging tasks like image enhancement, lesion detection, and precise measurement. In difficult-to-interpret radiologic studies, such as some mammography images, it can be a crucial aid to the radiologist. Additionally, the use of AI has significantly improved remote patient monitoring that enables healthcare professionals to monitor and assess patient conditions without needing in-person visits. Remote patient monitoring gained prominence during the COVID-19 pandemic and continues to be a valuable tool in post pandemic care. Study results have highlighted that AI-driven ambient dictation tools have increased provider engagement with patients during consultations while reducing the time spent documenting in electronic health records.

Like many other medical specialties, headache medicine also uses AI. Most prominently, AI has been used in models and engines in assisting with headache diagnoses. A noteworthy example of AI in headache medicine is the development of an online, computer-based diagnostic engine (CDE) by Rapoport et al, called BonTriage. This tool is designed to diagnose headaches by employing a rule set based on the International Classification of Headache Disorders-3 (ICHD-3) criteria for primary headache disorders while also evaluating secondary headaches and medication overuse headaches. By leveraging machine learning, the CDE has the potential to streamline the diagnostic process, reducing the number of questions needed to reach a diagnosis and making the experience more efficient. This information can then be printed as a PDF file and taken by the patient to a healthcare professional for further discussion, fostering a more accurate, fluid, and conversational consultation.

A study was conducted to evaluate the accuracy of the CDE. Participants were randomly assigned to 1 of 2 sequences: (1) using the CDE followed by a structured standard interview with a headache specialist using the same ICHD-3 criteria or (2) starting with the structured standard interview followed by the CDE. The results demonstrated nearly perfect agreement in diagnosing migraine and probable migraine between the CDE and structured standard interview (κ = 0.82, 95% CI: 0.74, 0.90). The CDE demonstrated a diagnostic accuracy of 91.6% (95% CI: 86.9%, 95.0%), a sensitivity rate of 89.0% (95% CI: 82.5%, 93.7%), and a specificity rate of 97.0% (95% CI: 89.5%, 99.6%).

A diagnostic engine such as this can save time that clinicians spend on documentation and allow more time for discussion with the patient. For instance, a patient can take the printout received from the CDE to an appointment; the printout gives a detailed history plus information about social and psychological issues, a list of medications taken, and results of previous testing. The CDE system was originally designed to help patients see a specialist in the environment of a nationwide lack of headache specialists. There are currently 45 million patients with headaches who are seeking treatment with only around 550 certified headache specialists in the United States. The CDE printed information can help a patient obtain a consultation from a clinician quickly and start evaluation and treatment earlier. This expert online consultation is currently free of charge.

Kwon et al developed a machine learning–based model designed to automatically classify headache disorders using data from a questionnaire. Their model was able to predict diagnoses for conditions such as migraine, tension-type headaches, trigeminal autonomic cephalalgia, epicranial headache, and thunderclap headaches. The model was trained on data from 2162 patients, all diagnosed by headache specialists, and achieved an overall accuracy of 81%, with a sensitivity of 88% and a specificity of 95% for diagnosing migraines. However, the model’s performance was less robust when applied to other headache disorders.

Katsuki et al developed an AI model to help non specialists accurately diagnose headaches. This model analyzed 17 variables and was trained on data from 2800 patients, with additional testing and refinement using data from another 200 patients. To evaluate its effectiveness, 2 groups of non-headache specialists each assessed 50 patients: 1 group relied solely on their expertise, while the other used the AI model. The group without AI assistance achieved an overall accuracy of 46% (κ = 0.21), while the group using the AI model significantly improved, reaching an overall accuracy of 83.2% (κ = 0.68).

Building on their work with AI for diagnosing headaches, Katsuki et al conducted a study using a smartphone application that tracked user-reported headache events alongside local weather data. The AI model revealed that lower barometric pressure, higher humidity, and increased rainfall were linked to the onset of headache attacks. The application also identified triggers for headaches in specific weather patterns, such as a drop in barometric pressure noted 6 hours before headache onset. The application of AI in monitoring weather changes could be crucial, especially given concerns that the rising frequency of severe weather events due to climate change may be exacerbating the severity and burden of migraine. Additionally, recent post hoc analyses of fremanezumab clinical trials have provided further evidence that weather changes can trigger headaches.

Rapoport and colleagues have also developed an application called Migraine Mentor, which accurately tracks headaches, triggers, health data, and response to medication on a smartphone. The patient spends 3 minutes a day answering a few questions about their day and whether they had a headache or took any medication. At 1 or 2 months, Migraine Mentor can generate a detailed report with data and current trends that is sent to the patient, which the patient can then share with the clinician. The application also reminds patients when to document data and take medication.

However, although the use of AI in headache medicine appears promising, caution must be exercised to ensure proper results and information are disseminated. One rapidly expanding application of AI is the widely popular ChatGPT. ChatGPT, which stands for generative pretraining transformer, is a type of large language model (LLM). An LLM is a deep learning algorithm designed to recognize, translate, predict, summarize, and generate text responses based on a given prompt. This model is trained on an extensive dataset that includes a diverse array of books, articles, and websites, exposing it to various language structures and styles. This training enables ChatGPT to generate responses that closely mimic human communication. LLMs are being used more and more in medicine to assist with generating patient documentation and educational materials.

However, Dr Fred Cohen published a perspective piece detailing how LLMs (such as ChatGPT) can produce misleading and inaccurate answers. In his example, he tasked ChatGPT to describe the epidemiology of migraines in penguins; the AI model generated a well-written and highly believable manuscript titled, “Migraine Under the Ice: Understanding Headaches in Antarctica's Feathered Friends.” The manuscript highlights that migraines are more prevalent in male penguins compared to females, with the peak age of onset occurring between 4 and 5 years. Additionally, emperor and king penguins are identified as being more susceptible to developing migraines compared to other penguin species. The paper was fictitious (as no studies on migraine in penguins have been written to date), exemplifying that these models can produce nonfactual materials.

For years, technological advancements have been reshaping many aspects of life, and medicine is no exception. AI has been successfully applied to streamline medical documentation, develop new drug targets, and deepen our understanding of various diseases. The field of headache medicine now also uses AI. Recent developments show significant promise, with AI aiding in the diagnosis of migraine and other headache disorders. AI models have even been used in the identification of potential drug targets for migraine treatment. Although there are still limitations to overcome, the future of AI in headache medicine appears bright.

If you would like to read more about Dr. Cohen’s work on AI and migraine, please visit fredcohenmd.com or TikTok @fredcohenmd. 

As we move further into the 21st century, technology continues to revolutionize various facets of our lives. Healthcare is a prime example. Advances in technology have dramatically reshaped the way we develop medications, diagnose diseases, and enhance patient care. The rise of artificial intelligence (AI) and the widespread adoption of digital health technologies have marked a significant milestone in improving the quality of care. AI, with its ability to leverage algorithms, deep learning, and machine learning to process data, make decisions, and perform tasks autonomously, is becoming an integral part of modern society. It is embedded in various technologies that we rely on daily, from smartphones and smart home devices to content recommendations on streaming services and social media platforms.

In healthcare, AI has applications in numerous fields, such as radiology. AI streamlines processes such as organizing patient appointments, optimizing radiation protocols for safety and efficiency, and enhancing the documentation process through advanced image analysis. AI technology plays an integral role in imaging tasks like image enhancement, lesion detection, and precise measurement. In difficult-to-interpret radiologic studies, such as some mammography images, it can be a crucial aid to the radiologist. Additionally, the use of AI has significantly improved remote patient monitoring that enables healthcare professionals to monitor and assess patient conditions without needing in-person visits. Remote patient monitoring gained prominence during the COVID-19 pandemic and continues to be a valuable tool in post pandemic care. Study results have highlighted that AI-driven ambient dictation tools have increased provider engagement with patients during consultations while reducing the time spent documenting in electronic health records.

Like many other medical specialties, headache medicine also uses AI. Most prominently, AI has been used in models and engines in assisting with headache diagnoses. A noteworthy example of AI in headache medicine is the development of an online, computer-based diagnostic engine (CDE) by Rapoport et al, called BonTriage. This tool is designed to diagnose headaches by employing a rule set based on the International Classification of Headache Disorders-3 (ICHD-3) criteria for primary headache disorders while also evaluating secondary headaches and medication overuse headaches. By leveraging machine learning, the CDE has the potential to streamline the diagnostic process, reducing the number of questions needed to reach a diagnosis and making the experience more efficient. This information can then be printed as a PDF file and taken by the patient to a healthcare professional for further discussion, fostering a more accurate, fluid, and conversational consultation.

A study was conducted to evaluate the accuracy of the CDE. Participants were randomly assigned to 1 of 2 sequences: (1) using the CDE followed by a structured standard interview with a headache specialist using the same ICHD-3 criteria or (2) starting with the structured standard interview followed by the CDE. The results demonstrated nearly perfect agreement in diagnosing migraine and probable migraine between the CDE and structured standard interview (κ = 0.82, 95% CI: 0.74, 0.90). The CDE demonstrated a diagnostic accuracy of 91.6% (95% CI: 86.9%, 95.0%), a sensitivity rate of 89.0% (95% CI: 82.5%, 93.7%), and a specificity rate of 97.0% (95% CI: 89.5%, 99.6%).

A diagnostic engine such as this can save time that clinicians spend on documentation and allow more time for discussion with the patient. For instance, a patient can take the printout received from the CDE to an appointment; the printout gives a detailed history plus information about social and psychological issues, a list of medications taken, and results of previous testing. The CDE system was originally designed to help patients see a specialist in the environment of a nationwide lack of headache specialists. There are currently 45 million patients with headaches who are seeking treatment with only around 550 certified headache specialists in the United States. The CDE printed information can help a patient obtain a consultation from a clinician quickly and start evaluation and treatment earlier. This expert online consultation is currently free of charge.

Kwon et al developed a machine learning–based model designed to automatically classify headache disorders using data from a questionnaire. Their model was able to predict diagnoses for conditions such as migraine, tension-type headaches, trigeminal autonomic cephalalgia, epicranial headache, and thunderclap headaches. The model was trained on data from 2162 patients, all diagnosed by headache specialists, and achieved an overall accuracy of 81%, with a sensitivity of 88% and a specificity of 95% for diagnosing migraines. However, the model’s performance was less robust when applied to other headache disorders.

Katsuki et al developed an AI model to help non specialists accurately diagnose headaches. This model analyzed 17 variables and was trained on data from 2800 patients, with additional testing and refinement using data from another 200 patients. To evaluate its effectiveness, 2 groups of non-headache specialists each assessed 50 patients: 1 group relied solely on their expertise, while the other used the AI model. The group without AI assistance achieved an overall accuracy of 46% (κ = 0.21), while the group using the AI model significantly improved, reaching an overall accuracy of 83.2% (κ = 0.68).

Building on their work with AI for diagnosing headaches, Katsuki et al conducted a study using a smartphone application that tracked user-reported headache events alongside local weather data. The AI model revealed that lower barometric pressure, higher humidity, and increased rainfall were linked to the onset of headache attacks. The application also identified triggers for headaches in specific weather patterns, such as a drop in barometric pressure noted 6 hours before headache onset. The application of AI in monitoring weather changes could be crucial, especially given concerns that the rising frequency of severe weather events due to climate change may be exacerbating the severity and burden of migraine. Additionally, recent post hoc analyses of fremanezumab clinical trials have provided further evidence that weather changes can trigger headaches.

Rapoport and colleagues have also developed an application called Migraine Mentor, which accurately tracks headaches, triggers, health data, and response to medication on a smartphone. The patient spends 3 minutes a day answering a few questions about their day and whether they had a headache or took any medication. At 1 or 2 months, Migraine Mentor can generate a detailed report with data and current trends that is sent to the patient, which the patient can then share with the clinician. The application also reminds patients when to document data and take medication.

However, although the use of AI in headache medicine appears promising, caution must be exercised to ensure proper results and information are disseminated. One rapidly expanding application of AI is the widely popular ChatGPT. ChatGPT, which stands for generative pretraining transformer, is a type of large language model (LLM). An LLM is a deep learning algorithm designed to recognize, translate, predict, summarize, and generate text responses based on a given prompt. This model is trained on an extensive dataset that includes a diverse array of books, articles, and websites, exposing it to various language structures and styles. This training enables ChatGPT to generate responses that closely mimic human communication. LLMs are being used more and more in medicine to assist with generating patient documentation and educational materials.

However, Dr Fred Cohen published a perspective piece detailing how LLMs (such as ChatGPT) can produce misleading and inaccurate answers. In his example, he tasked ChatGPT to describe the epidemiology of migraines in penguins; the AI model generated a well-written and highly believable manuscript titled, “Migraine Under the Ice: Understanding Headaches in Antarctica's Feathered Friends.” The manuscript highlights that migraines are more prevalent in male penguins compared to females, with the peak age of onset occurring between 4 and 5 years. Additionally, emperor and king penguins are identified as being more susceptible to developing migraines compared to other penguin species. The paper was fictitious (as no studies on migraine in penguins have been written to date), exemplifying that these models can produce nonfactual materials.

For years, technological advancements have been reshaping many aspects of life, and medicine is no exception. AI has been successfully applied to streamline medical documentation, develop new drug targets, and deepen our understanding of various diseases. The field of headache medicine now also uses AI. Recent developments show significant promise, with AI aiding in the diagnosis of migraine and other headache disorders. AI models have even been used in the identification of potential drug targets for migraine treatment. Although there are still limitations to overcome, the future of AI in headache medicine appears bright.

If you would like to read more about Dr. Cohen’s work on AI and migraine, please visit fredcohenmd.com or TikTok @fredcohenmd. 

Four triptans are more effective for acute migraine than newer, more expensive medications for this headache type, new research suggested.

Results of a large systematic review and meta-analysis showed that eletriptan, rizatriptan, sumatriptan, and zolmitriptan were more effective than lasmiditan, rimegepant, and ubrogepant, which investigators found were as effective as nonsteroidal anti-inflammatory drugs (NSAIDs).

International guidelines generally endorse NSAIDs as the first-line treatment for migraine and recommend triptans for moderate to severe episodes or when the response to NSAIDs is insufficient.

However, based on the study’s findings, these four triptans should be considered the treatment of choice for migraine, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry at the University of Oxford in England and director of the Oxford Health Clinical Research Facility, told a press briefing.

The investigators added that these particular triptans should be “included in the WHO [World Health Organization] List of Essential Medicines to promote global accessibility and uniform standards of care.”

The study was published online in The BMJ.
 

Filling the Knowledge Gap

To date, almost all migraine studies have compared migraine drugs with placebo, so there’s a knowledge gap, said Dr. Cipriani. As a result, “there’s no clear consensus among experts and guidelines about which specific drug classes should be prescribed initially, and this is a clinical problem.”

The researchers pointed out that, in recent years, lasmiditan and gepants have been introduced as further treatment options, especially for patients in whom triptans are contraindicated because of their potential vasoconstrictive effects and higher risk for ischemic events.

The analysis included 137 double-blind, randomized, controlled trials that were primarily sponsored by the pharmaceutical industry. It included 89,445 adult outpatients with migraine (mean age, 40.3 years; 85.6% women).

Only drugs licensed for migraine or headache that are recommended in at least one country were included. Researchers divided these 17 drugs into five categories: Antipyretics (paracetamol), ditans (lasmiditan), gepants (rimegepant and ubrogepant), NSAIDs (acetylsalicylic acid, celecoxib, diclofenac potassium, ibuprofen, naproxen sodium, and phenazone), and triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan).

The study’s primary outcomes were freedom from pain at 2 hours and at 2-24 hours, without the use of rescue drugs.

Investigators used sumatriptan as the reference intervention because it is the most commonly prescribed migraine drug and is included in the WHO Model Lists of Essential Medicines.

The study showed all active interventions were better than placebo for pain freedom at 2 hours; with the exception of paracetamol and naratriptan, all were better for sustained pain freedom from 2 to 24 hours.

When the active interventions were compared with each other, eletriptan outperformed other drugs for achieving pain freedom at 2 hours. It was followed by rizatriptan, sumatriptan, and zolmitriptan (odds ratio [OR], 1.35-3.01). For sustained pain freedom up to 24 hours, the most efficacious interventions were eletriptan (OR, 1.41-2.73) and ibuprofen (OR, 3.16-4.82).

As for secondary efficacy outcomes, in head-to-head comparisons, eletriptan was superior to nearly all other active interventions for pain relief at 2 hours and for the use of rescue drugs.

As for adverse events, dizziness was more commonly associated with lasmiditan, eletriptan, sumatriptan, and zolmitriptan, while fatigue and sedation occurred more frequently with eletriptan and lasmiditan. Nausea was more often associated with lasmiditan, sumatriptan, zolmitriptan, and ubrogepant. Eletriptan was the only intervention most frequently associated with chest pain or discomfort.
 

Need to Update Guidelines?

Considering the new results, Dr. Cipriani and study coauthor Messoud Ashina, MD, PhD, professor of neurology, University of Copenhagen in Denmark, said clinical guidelines for acute migraine management should be updated.

While triptans are contraindicated in patients with vascular disease, the researchers noted that “cerebrovascular events may present primarily as migraine-like headaches, and misdiagnosis of transient ischemic attack and minor stroke as migraine is not rare.”

Recently, lasmiditan, rimegepant, and ubrogepant — which are not associated with vasoconstrictive effects — have been promoted as alternatives in patients for whom triptans are contraindicated or not tolerated. But the high costs of these drugs put them out of reach for some patients, the investigators noted.

Triptans are widely underutilized, Dr. Ashina noted during the press briefing. Current use ranges from 17% to 22% in the United States and from 3% to 22.5% in Europe.

The investigators said that triptans have been shown to be superior and should be promoted globally, adding that the limited access and substantial underutilization of these medications are “missed opportunities to offer more effective treatments.”

The new results underscore the importance of head-to-head trials, which is the gold standard, said Dr. Cipriani.

The investigators noted that the study’s main limitation was the quality of the data, which was deemed to be low, or very low, for most comparisons. Other potential limitations included lack of individual patient data; exclusion of combination drugs; inclusion of only oral treatments; and not considering type of oral formulation, consistency in response across migraine episodes, or cost-effectiveness.

The study also did not cover important clinical issues that might inform treatment decision-making, including drug overuse headache or potential withdrawal symptoms. And the authors were unable to quantify some outcomes, such as global functioning.
 

‘Best Profile’?

Reached for comment, Neurologist Nina Riggins, MD, PhD, Headache Center of Excellence, Palo Alto VA Medical Center in California, praised the authors for a “great job” of bringing attention to the topic.

However, she noted that the investigators’ characterization of the four triptans as having the “best profile” for acute migraine gave her pause.

“Calling triptans the medication with the ‘best profile’ might be not applicable in many cases,” she said. For example, those who need acute medication more than two to three times a week in addition to those with cardiovascular contraindications to triptans may fall outside of that category.

Dr. Riggins said that “it makes sense” that longer-acting triptans like frovatriptan and naratriptan may not rank highly for efficacy within the first 2 hours. However, these agents likely offer a superior therapeutic profile in specific contexts, such as menstrual-related migraine.

In addition, while triptans are known to cause medication overuse headache, this may not be the case with gepants, she noted.

In a release from the Science Media Center, a nonprofit organization promoting voices and views of the scientific community, Eloísa Rubio-Beltrán, PhD, research associate with The Migraine Trust at the Wolfson Sensory, Pain and Regeneration Centre, King’s College London in England, said the findings should affect migraine treatment guidelines.

“As the study highlights, due to their high efficacy and low cost, triptans should be the first-line treatment option for the acute treatment of migraine. These results should inform treatment guidelines and support the inclusion of the best performing triptans into the List of Essential Medicines, to optimize treatment, allowing patients to access more efficacious options,” said Dr. Rubio-Beltrán.

It is also important to note that gepants and ditans were developed to offer alternatives for patients who show no improvement from triptans, she added.

She pointed out that these medications were not developed as a substitute for triptans, but rather to expand the number of treatment options for migraine.

“Nonetheless,” she added, “this study highlights the need for further research on the pathophysiology of migraine, which will allow the discovery of novel targets, and thus, novel treatments options that will benefit all patient populations.”

The study was funded by the NIHR Oxford Health Biomedical Research Centre and the Lundbeck Foundation. Dr. Cipriani reported receiving research, educational, and consultancy fees from Italian Network for Pediatric Clinical Trials, Fondazione Cariplo, Lundbeck, and Angelini Pharma. Dr. Ashina is a consultant, speaker, or scientific adviser for AbbVie, Amgen, AstraZeneca, Eli Lilly, GSK, Lundbeck, Novartis, Pfizer, and Teva; is the past president of the International Headache Society; and an associate editor of The Journal of Headache and Pain and Brain. Dr. Riggins has consulted for Gerson Lehrman Group; participated in compensated work with AcademicCME and Association of Migraine Disorders; was a principal investigator on research with electroCore, Theranica, and Eli Lilly; serves on advisory boards for Theranica, Teva, Lundbeck, Amneal Pharmaceuticals, NeurologyLive, and Miles for Migraine; and is a project advisor for Clinical Awareness Initiative with Clinical Neurological Society of America. Dr. Rubio-Beltrán reported serving as a junior editorial board member of The Journal of Headache and Pain and a junior representative of the International Headache Society; receiving research support from The Migraine Trust, Eli Lilly, CoLucid Pharmaceuticals, Amgen, Novartis, and Kallyope; and receiving travel support from CoLucid Pharmaceuticals, Allergan, and Novartis.

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

Four triptans are more effective for acute migraine than newer, more expensive medications for this headache type, new research suggested.

Results of a large systematic review and meta-analysis showed that eletriptan, rizatriptan, sumatriptan, and zolmitriptan were more effective than lasmiditan, rimegepant, and ubrogepant, which investigators found were as effective as nonsteroidal anti-inflammatory drugs (NSAIDs).

International guidelines generally endorse NSAIDs as the first-line treatment for migraine and recommend triptans for moderate to severe episodes or when the response to NSAIDs is insufficient.

However, based on the study’s findings, these four triptans should be considered the treatment of choice for migraine, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry at the University of Oxford in England and director of the Oxford Health Clinical Research Facility, told a press briefing.

The investigators added that these particular triptans should be “included in the WHO [World Health Organization] List of Essential Medicines to promote global accessibility and uniform standards of care.”

The study was published online in The BMJ.
 

Filling the Knowledge Gap

To date, almost all migraine studies have compared migraine drugs with placebo, so there’s a knowledge gap, said Dr. Cipriani. As a result, “there’s no clear consensus among experts and guidelines about which specific drug classes should be prescribed initially, and this is a clinical problem.”

The researchers pointed out that, in recent years, lasmiditan and gepants have been introduced as further treatment options, especially for patients in whom triptans are contraindicated because of their potential vasoconstrictive effects and higher risk for ischemic events.

The analysis included 137 double-blind, randomized, controlled trials that were primarily sponsored by the pharmaceutical industry. It included 89,445 adult outpatients with migraine (mean age, 40.3 years; 85.6% women).

Only drugs licensed for migraine or headache that are recommended in at least one country were included. Researchers divided these 17 drugs into five categories: Antipyretics (paracetamol), ditans (lasmiditan), gepants (rimegepant and ubrogepant), NSAIDs (acetylsalicylic acid, celecoxib, diclofenac potassium, ibuprofen, naproxen sodium, and phenazone), and triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan).

The study’s primary outcomes were freedom from pain at 2 hours and at 2-24 hours, without the use of rescue drugs.

Investigators used sumatriptan as the reference intervention because it is the most commonly prescribed migraine drug and is included in the WHO Model Lists of Essential Medicines.

The study showed all active interventions were better than placebo for pain freedom at 2 hours; with the exception of paracetamol and naratriptan, all were better for sustained pain freedom from 2 to 24 hours.

When the active interventions were compared with each other, eletriptan outperformed other drugs for achieving pain freedom at 2 hours. It was followed by rizatriptan, sumatriptan, and zolmitriptan (odds ratio [OR], 1.35-3.01). For sustained pain freedom up to 24 hours, the most efficacious interventions were eletriptan (OR, 1.41-2.73) and ibuprofen (OR, 3.16-4.82).

As for secondary efficacy outcomes, in head-to-head comparisons, eletriptan was superior to nearly all other active interventions for pain relief at 2 hours and for the use of rescue drugs.

As for adverse events, dizziness was more commonly associated with lasmiditan, eletriptan, sumatriptan, and zolmitriptan, while fatigue and sedation occurred more frequently with eletriptan and lasmiditan. Nausea was more often associated with lasmiditan, sumatriptan, zolmitriptan, and ubrogepant. Eletriptan was the only intervention most frequently associated with chest pain or discomfort.
 

Need to Update Guidelines?

Considering the new results, Dr. Cipriani and study coauthor Messoud Ashina, MD, PhD, professor of neurology, University of Copenhagen in Denmark, said clinical guidelines for acute migraine management should be updated.

While triptans are contraindicated in patients with vascular disease, the researchers noted that “cerebrovascular events may present primarily as migraine-like headaches, and misdiagnosis of transient ischemic attack and minor stroke as migraine is not rare.”

Recently, lasmiditan, rimegepant, and ubrogepant — which are not associated with vasoconstrictive effects — have been promoted as alternatives in patients for whom triptans are contraindicated or not tolerated. But the high costs of these drugs put them out of reach for some patients, the investigators noted.

Triptans are widely underutilized, Dr. Ashina noted during the press briefing. Current use ranges from 17% to 22% in the United States and from 3% to 22.5% in Europe.

The investigators said that triptans have been shown to be superior and should be promoted globally, adding that the limited access and substantial underutilization of these medications are “missed opportunities to offer more effective treatments.”

The new results underscore the importance of head-to-head trials, which is the gold standard, said Dr. Cipriani.

The investigators noted that the study’s main limitation was the quality of the data, which was deemed to be low, or very low, for most comparisons. Other potential limitations included lack of individual patient data; exclusion of combination drugs; inclusion of only oral treatments; and not considering type of oral formulation, consistency in response across migraine episodes, or cost-effectiveness.

The study also did not cover important clinical issues that might inform treatment decision-making, including drug overuse headache or potential withdrawal symptoms. And the authors were unable to quantify some outcomes, such as global functioning.
 

‘Best Profile’?

Reached for comment, Neurologist Nina Riggins, MD, PhD, Headache Center of Excellence, Palo Alto VA Medical Center in California, praised the authors for a “great job” of bringing attention to the topic.

However, she noted that the investigators’ characterization of the four triptans as having the “best profile” for acute migraine gave her pause.

“Calling triptans the medication with the ‘best profile’ might be not applicable in many cases,” she said. For example, those who need acute medication more than two to three times a week in addition to those with cardiovascular contraindications to triptans may fall outside of that category.

Dr. Riggins said that “it makes sense” that longer-acting triptans like frovatriptan and naratriptan may not rank highly for efficacy within the first 2 hours. However, these agents likely offer a superior therapeutic profile in specific contexts, such as menstrual-related migraine.

In addition, while triptans are known to cause medication overuse headache, this may not be the case with gepants, she noted.

In a release from the Science Media Center, a nonprofit organization promoting voices and views of the scientific community, Eloísa Rubio-Beltrán, PhD, research associate with The Migraine Trust at the Wolfson Sensory, Pain and Regeneration Centre, King’s College London in England, said the findings should affect migraine treatment guidelines.

“As the study highlights, due to their high efficacy and low cost, triptans should be the first-line treatment option for the acute treatment of migraine. These results should inform treatment guidelines and support the inclusion of the best performing triptans into the List of Essential Medicines, to optimize treatment, allowing patients to access more efficacious options,” said Dr. Rubio-Beltrán.

It is also important to note that gepants and ditans were developed to offer alternatives for patients who show no improvement from triptans, she added.

She pointed out that these medications were not developed as a substitute for triptans, but rather to expand the number of treatment options for migraine.

“Nonetheless,” she added, “this study highlights the need for further research on the pathophysiology of migraine, which will allow the discovery of novel targets, and thus, novel treatments options that will benefit all patient populations.”

The study was funded by the NIHR Oxford Health Biomedical Research Centre and the Lundbeck Foundation. Dr. Cipriani reported receiving research, educational, and consultancy fees from Italian Network for Pediatric Clinical Trials, Fondazione Cariplo, Lundbeck, and Angelini Pharma. Dr. Ashina is a consultant, speaker, or scientific adviser for AbbVie, Amgen, AstraZeneca, Eli Lilly, GSK, Lundbeck, Novartis, Pfizer, and Teva; is the past president of the International Headache Society; and an associate editor of The Journal of Headache and Pain and Brain. Dr. Riggins has consulted for Gerson Lehrman Group; participated in compensated work with AcademicCME and Association of Migraine Disorders; was a principal investigator on research with electroCore, Theranica, and Eli Lilly; serves on advisory boards for Theranica, Teva, Lundbeck, Amneal Pharmaceuticals, NeurologyLive, and Miles for Migraine; and is a project advisor for Clinical Awareness Initiative with Clinical Neurological Society of America. Dr. Rubio-Beltrán reported serving as a junior editorial board member of The Journal of Headache and Pain and a junior representative of the International Headache Society; receiving research support from The Migraine Trust, Eli Lilly, CoLucid Pharmaceuticals, Amgen, Novartis, and Kallyope; and receiving travel support from CoLucid Pharmaceuticals, Allergan, and Novartis.

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

Four triptans are more effective for acute migraine than newer, more expensive medications for this headache type, new research suggested.

Results of a large systematic review and meta-analysis showed that eletriptan, rizatriptan, sumatriptan, and zolmitriptan were more effective than lasmiditan, rimegepant, and ubrogepant, which investigators found were as effective as nonsteroidal anti-inflammatory drugs (NSAIDs).

International guidelines generally endorse NSAIDs as the first-line treatment for migraine and recommend triptans for moderate to severe episodes or when the response to NSAIDs is insufficient.

However, based on the study’s findings, these four triptans should be considered the treatment of choice for migraine, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry at the University of Oxford in England and director of the Oxford Health Clinical Research Facility, told a press briefing.

The investigators added that these particular triptans should be “included in the WHO [World Health Organization] List of Essential Medicines to promote global accessibility and uniform standards of care.”

The study was published online in The BMJ.
 

Filling the Knowledge Gap

To date, almost all migraine studies have compared migraine drugs with placebo, so there’s a knowledge gap, said Dr. Cipriani. As a result, “there’s no clear consensus among experts and guidelines about which specific drug classes should be prescribed initially, and this is a clinical problem.”

The researchers pointed out that, in recent years, lasmiditan and gepants have been introduced as further treatment options, especially for patients in whom triptans are contraindicated because of their potential vasoconstrictive effects and higher risk for ischemic events.

The analysis included 137 double-blind, randomized, controlled trials that were primarily sponsored by the pharmaceutical industry. It included 89,445 adult outpatients with migraine (mean age, 40.3 years; 85.6% women).

Only drugs licensed for migraine or headache that are recommended in at least one country were included. Researchers divided these 17 drugs into five categories: Antipyretics (paracetamol), ditans (lasmiditan), gepants (rimegepant and ubrogepant), NSAIDs (acetylsalicylic acid, celecoxib, diclofenac potassium, ibuprofen, naproxen sodium, and phenazone), and triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan).

The study’s primary outcomes were freedom from pain at 2 hours and at 2-24 hours, without the use of rescue drugs.

Investigators used sumatriptan as the reference intervention because it is the most commonly prescribed migraine drug and is included in the WHO Model Lists of Essential Medicines.

The study showed all active interventions were better than placebo for pain freedom at 2 hours; with the exception of paracetamol and naratriptan, all were better for sustained pain freedom from 2 to 24 hours.

When the active interventions were compared with each other, eletriptan outperformed other drugs for achieving pain freedom at 2 hours. It was followed by rizatriptan, sumatriptan, and zolmitriptan (odds ratio [OR], 1.35-3.01). For sustained pain freedom up to 24 hours, the most efficacious interventions were eletriptan (OR, 1.41-2.73) and ibuprofen (OR, 3.16-4.82).

As for secondary efficacy outcomes, in head-to-head comparisons, eletriptan was superior to nearly all other active interventions for pain relief at 2 hours and for the use of rescue drugs.

As for adverse events, dizziness was more commonly associated with lasmiditan, eletriptan, sumatriptan, and zolmitriptan, while fatigue and sedation occurred more frequently with eletriptan and lasmiditan. Nausea was more often associated with lasmiditan, sumatriptan, zolmitriptan, and ubrogepant. Eletriptan was the only intervention most frequently associated with chest pain or discomfort.
 

Need to Update Guidelines?

Considering the new results, Dr. Cipriani and study coauthor Messoud Ashina, MD, PhD, professor of neurology, University of Copenhagen in Denmark, said clinical guidelines for acute migraine management should be updated.

While triptans are contraindicated in patients with vascular disease, the researchers noted that “cerebrovascular events may present primarily as migraine-like headaches, and misdiagnosis of transient ischemic attack and minor stroke as migraine is not rare.”

Recently, lasmiditan, rimegepant, and ubrogepant — which are not associated with vasoconstrictive effects — have been promoted as alternatives in patients for whom triptans are contraindicated or not tolerated. But the high costs of these drugs put them out of reach for some patients, the investigators noted.

Triptans are widely underutilized, Dr. Ashina noted during the press briefing. Current use ranges from 17% to 22% in the United States and from 3% to 22.5% in Europe.

The investigators said that triptans have been shown to be superior and should be promoted globally, adding that the limited access and substantial underutilization of these medications are “missed opportunities to offer more effective treatments.”

The new results underscore the importance of head-to-head trials, which is the gold standard, said Dr. Cipriani.

The investigators noted that the study’s main limitation was the quality of the data, which was deemed to be low, or very low, for most comparisons. Other potential limitations included lack of individual patient data; exclusion of combination drugs; inclusion of only oral treatments; and not considering type of oral formulation, consistency in response across migraine episodes, or cost-effectiveness.

The study also did not cover important clinical issues that might inform treatment decision-making, including drug overuse headache or potential withdrawal symptoms. And the authors were unable to quantify some outcomes, such as global functioning.
 

‘Best Profile’?

Reached for comment, Neurologist Nina Riggins, MD, PhD, Headache Center of Excellence, Palo Alto VA Medical Center in California, praised the authors for a “great job” of bringing attention to the topic.

However, she noted that the investigators’ characterization of the four triptans as having the “best profile” for acute migraine gave her pause.

“Calling triptans the medication with the ‘best profile’ might be not applicable in many cases,” she said. For example, those who need acute medication more than two to three times a week in addition to those with cardiovascular contraindications to triptans may fall outside of that category.

Dr. Riggins said that “it makes sense” that longer-acting triptans like frovatriptan and naratriptan may not rank highly for efficacy within the first 2 hours. However, these agents likely offer a superior therapeutic profile in specific contexts, such as menstrual-related migraine.

In addition, while triptans are known to cause medication overuse headache, this may not be the case with gepants, she noted.

In a release from the Science Media Center, a nonprofit organization promoting voices and views of the scientific community, Eloísa Rubio-Beltrán, PhD, research associate with The Migraine Trust at the Wolfson Sensory, Pain and Regeneration Centre, King’s College London in England, said the findings should affect migraine treatment guidelines.

“As the study highlights, due to their high efficacy and low cost, triptans should be the first-line treatment option for the acute treatment of migraine. These results should inform treatment guidelines and support the inclusion of the best performing triptans into the List of Essential Medicines, to optimize treatment, allowing patients to access more efficacious options,” said Dr. Rubio-Beltrán.

It is also important to note that gepants and ditans were developed to offer alternatives for patients who show no improvement from triptans, she added.

She pointed out that these medications were not developed as a substitute for triptans, but rather to expand the number of treatment options for migraine.

“Nonetheless,” she added, “this study highlights the need for further research on the pathophysiology of migraine, which will allow the discovery of novel targets, and thus, novel treatments options that will benefit all patient populations.”

The study was funded by the NIHR Oxford Health Biomedical Research Centre and the Lundbeck Foundation. Dr. Cipriani reported receiving research, educational, and consultancy fees from Italian Network for Pediatric Clinical Trials, Fondazione Cariplo, Lundbeck, and Angelini Pharma. Dr. Ashina is a consultant, speaker, or scientific adviser for AbbVie, Amgen, AstraZeneca, Eli Lilly, GSK, Lundbeck, Novartis, Pfizer, and Teva; is the past president of the International Headache Society; and an associate editor of The Journal of Headache and Pain and Brain. Dr. Riggins has consulted for Gerson Lehrman Group; participated in compensated work with AcademicCME and Association of Migraine Disorders; was a principal investigator on research with electroCore, Theranica, and Eli Lilly; serves on advisory boards for Theranica, Teva, Lundbeck, Amneal Pharmaceuticals, NeurologyLive, and Miles for Migraine; and is a project advisor for Clinical Awareness Initiative with Clinical Neurological Society of America. Dr. Rubio-Beltrán reported serving as a junior editorial board member of The Journal of Headache and Pain and a junior representative of the International Headache Society; receiving research support from The Migraine Trust, Eli Lilly, CoLucid Pharmaceuticals, Amgen, Novartis, and Kallyope; and receiving travel support from CoLucid Pharmaceuticals, Allergan, and Novartis.

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

Key clinical point: Although valsartan is not typically used for migraine treatment, it was found to reduce migraine frequency and severity as effectively as propranolol, and in some instances, more effectively.

Major findings: Valsartan vs propranolol significantly reduced the mean score of migraine frequency and severity (1.82 vs 2.39; P = .042), and a lower rate of grade 3 headaches (0% vs 7.14%; P = .029) and a lower Headache Index score (1.41 vs 3.22; P = .048) in patients with migraine. Conversely, propranolol was more effective than valsartan in lowering the Headache Unit Index score (0.06 vs 0.13; P = .025).

Study details: This double-blind trial included 56 adult patients with migraine who were randomly assigned to receive propranolol (20 mg twice daily) or valsartan (40 mg once daily) for 12 weeks.

Disclosure: This study was supported by a grant from Urmia University of Medical Sciences. The authors declared no conflicts of interest.

Source: Mosarrezaii A, Tahazadeh D, Soleimantabar H, Panahi P. Comparison of the efficacy of propranolol versus valsartan in the prevention of migraine: A randomized controlled trial. Pain Manag Nurs. 2024 (Aug 13). doi: 10.1016/j.pmn.2024.07.001 Source

Key clinical point: Although valsartan is not typically used for migraine treatment, it was found to reduce migraine frequency and severity as effectively as propranolol, and in some instances, more effectively.

Major findings: Valsartan vs propranolol significantly reduced the mean score of migraine frequency and severity (1.82 vs 2.39; P = .042), and a lower rate of grade 3 headaches (0% vs 7.14%; P = .029) and a lower Headache Index score (1.41 vs 3.22; P = .048) in patients with migraine. Conversely, propranolol was more effective than valsartan in lowering the Headache Unit Index score (0.06 vs 0.13; P = .025).

Study details: This double-blind trial included 56 adult patients with migraine who were randomly assigned to receive propranolol (20 mg twice daily) or valsartan (40 mg once daily) for 12 weeks.

Disclosure: This study was supported by a grant from Urmia University of Medical Sciences. The authors declared no conflicts of interest.

Source: Mosarrezaii A, Tahazadeh D, Soleimantabar H, Panahi P. Comparison of the efficacy of propranolol versus valsartan in the prevention of migraine: A randomized controlled trial. Pain Manag Nurs. 2024 (Aug 13). doi: 10.1016/j.pmn.2024.07.001 Source

Key clinical point: Although valsartan is not typically used for migraine treatment, it was found to reduce migraine frequency and severity as effectively as propranolol, and in some instances, more effectively.

Major findings: Valsartan vs propranolol significantly reduced the mean score of migraine frequency and severity (1.82 vs 2.39; P = .042), and a lower rate of grade 3 headaches (0% vs 7.14%; P = .029) and a lower Headache Index score (1.41 vs 3.22; P = .048) in patients with migraine. Conversely, propranolol was more effective than valsartan in lowering the Headache Unit Index score (0.06 vs 0.13; P = .025).

Study details: This double-blind trial included 56 adult patients with migraine who were randomly assigned to receive propranolol (20 mg twice daily) or valsartan (40 mg once daily) for 12 weeks.

Disclosure: This study was supported by a grant from Urmia University of Medical Sciences. The authors declared no conflicts of interest.

Source: Mosarrezaii A, Tahazadeh D, Soleimantabar H, Panahi P. Comparison of the efficacy of propranolol versus valsartan in the prevention of migraine: A randomized controlled trial. Pain Manag Nurs. 2024 (Aug 13). doi: 10.1016/j.pmn.2024.07.001 Source

Key clinical point: Migraine may have a protective effect against some cardiovascular diseases, such as coronary artery disease (CAD) and ischemic stroke, in this Mendelian randomization (MR) analysis, with coronary atherosclerosis (CA) and myocardial infarction (MI), reducing the risk for migraine in reverse MR analysis.

Major findings: Genetically predicted risk of migraine was associated with a lower risk for CAD (odds ratio [OR] 0.881; P = .023) and ischemic stroke (OR 0.912; P = .006). Reciprocally, CA (OR 0.865; P = .001) and MI (OR 0.798; P = .012) were associated with a lower risk for migraine.

Study details: This bidirectional MR study analyzed the causal effect of migraine on CVD using data from 873,341 and 554,569 individuals, and the causal effect of CVD on migraine using data from 484,598 and 463,010 individuals, using large-scale Genome-Wide Association Study databases.

Disclosure: The study was supported by the National Natural Science Foundation of China, and others. The authors reported no conflicts of interest.

Source: Duan X, Du X, Zheng G, et al. Causality between migraine and cardiovascular disease: A bidirectional Mendelian randomization study. J Headache Pain. 2024;25:130 (Aug 13). doi: 10.1186/s10194-024-01836-w Source

Key clinical point: Migraine may have a protective effect against some cardiovascular diseases, such as coronary artery disease (CAD) and ischemic stroke, in this Mendelian randomization (MR) analysis, with coronary atherosclerosis (CA) and myocardial infarction (MI), reducing the risk for migraine in reverse MR analysis.

Major findings: Genetically predicted risk of migraine was associated with a lower risk for CAD (odds ratio [OR] 0.881; P = .023) and ischemic stroke (OR 0.912; P = .006). Reciprocally, CA (OR 0.865; P = .001) and MI (OR 0.798; P = .012) were associated with a lower risk for migraine.

Study details: This bidirectional MR study analyzed the causal effect of migraine on CVD using data from 873,341 and 554,569 individuals, and the causal effect of CVD on migraine using data from 484,598 and 463,010 individuals, using large-scale Genome-Wide Association Study databases.

Disclosure: The study was supported by the National Natural Science Foundation of China, and others. The authors reported no conflicts of interest.

Source: Duan X, Du X, Zheng G, et al. Causality between migraine and cardiovascular disease: A bidirectional Mendelian randomization study. J Headache Pain. 2024;25:130 (Aug 13). doi: 10.1186/s10194-024-01836-w Source

Key clinical point: Migraine may have a protective effect against some cardiovascular diseases, such as coronary artery disease (CAD) and ischemic stroke, in this Mendelian randomization (MR) analysis, with coronary atherosclerosis (CA) and myocardial infarction (MI), reducing the risk for migraine in reverse MR analysis.

Major findings: Genetically predicted risk of migraine was associated with a lower risk for CAD (odds ratio [OR] 0.881; P = .023) and ischemic stroke (OR 0.912; P = .006). Reciprocally, CA (OR 0.865; P = .001) and MI (OR 0.798; P = .012) were associated with a lower risk for migraine.

Study details: This bidirectional MR study analyzed the causal effect of migraine on CVD using data from 873,341 and 554,569 individuals, and the causal effect of CVD on migraine using data from 484,598 and 463,010 individuals, using large-scale Genome-Wide Association Study databases.

Disclosure: The study was supported by the National Natural Science Foundation of China, and others. The authors reported no conflicts of interest.

Source: Duan X, Du X, Zheng G, et al. Causality between migraine and cardiovascular disease: A bidirectional Mendelian randomization study. J Headache Pain. 2024;25:130 (Aug 13). doi: 10.1186/s10194-024-01836-w Source

Key clinical point: Administration of monthly or quarterly fremanezumab reduced acute medication use and alleviated migraine-associated symptoms in patients with episodic migraine (EM).

Major findings: Fremanezumab, administered monthly vs placebo significantly reduced the acute medication use for headaches (–2.98 vs –0.01; P < .001) and number of days with nausea or vomiting (–1.59 vs –0.66; P = .023) in the first month after initial dosage, with continued benefits till months 2 and 3. Fremanezumab, administered quarterly, also yielded promising outcomes.

Study details: Findings are from an exploratory endpoint analysis of a phase 2b/3 randomized trial including patients with EM who were randomly assigned to receive either monthly fremanezumab (n =  121), quarterly fremanezumab (n =  119), or placebo (n =  117) in monthly intervals.

Disclosures: This study was funded by Otsuka Pharmaceutical Co., Ltd. Five authors declared being full-time employees of Otsuka Pharmaceutical Co., Ltd. Other authors declared having other ties with various sources, including Otsuka Pharmaceutical Co., Ltd.

Source: Tatsumoto M, Ishida M, Iba K, et al. Effects of fremanezumab on migraine-associated symptoms and medication use in Japanese and Korean patients with episodic migraine: Exploratory endpoint analysis of a multicenter, randomized, double-blind, placebo-controlled trial. Headache. 2024 (Sept 2). doi: 10.1111/head.14810 Source

Key clinical point: Administration of monthly or quarterly fremanezumab reduced acute medication use and alleviated migraine-associated symptoms in patients with episodic migraine (EM).

Major findings: Fremanezumab, administered monthly vs placebo significantly reduced the acute medication use for headaches (–2.98 vs –0.01; P < .001) and number of days with nausea or vomiting (–1.59 vs –0.66; P = .023) in the first month after initial dosage, with continued benefits till months 2 and 3. Fremanezumab, administered quarterly, also yielded promising outcomes.

Study details: Findings are from an exploratory endpoint analysis of a phase 2b/3 randomized trial including patients with EM who were randomly assigned to receive either monthly fremanezumab (n =  121), quarterly fremanezumab (n =  119), or placebo (n =  117) in monthly intervals.

Disclosures: This study was funded by Otsuka Pharmaceutical Co., Ltd. Five authors declared being full-time employees of Otsuka Pharmaceutical Co., Ltd. Other authors declared having other ties with various sources, including Otsuka Pharmaceutical Co., Ltd.

Source: Tatsumoto M, Ishida M, Iba K, et al. Effects of fremanezumab on migraine-associated symptoms and medication use in Japanese and Korean patients with episodic migraine: Exploratory endpoint analysis of a multicenter, randomized, double-blind, placebo-controlled trial. Headache. 2024 (Sept 2). doi: 10.1111/head.14810 Source

Key clinical point: Administration of monthly or quarterly fremanezumab reduced acute medication use and alleviated migraine-associated symptoms in patients with episodic migraine (EM).

Major findings: Fremanezumab, administered monthly vs placebo significantly reduced the acute medication use for headaches (–2.98 vs –0.01; P < .001) and number of days with nausea or vomiting (–1.59 vs –0.66; P = .023) in the first month after initial dosage, with continued benefits till months 2 and 3. Fremanezumab, administered quarterly, also yielded promising outcomes.

Study details: Findings are from an exploratory endpoint analysis of a phase 2b/3 randomized trial including patients with EM who were randomly assigned to receive either monthly fremanezumab (n =  121), quarterly fremanezumab (n =  119), or placebo (n =  117) in monthly intervals.

Disclosures: This study was funded by Otsuka Pharmaceutical Co., Ltd. Five authors declared being full-time employees of Otsuka Pharmaceutical Co., Ltd. Other authors declared having other ties with various sources, including Otsuka Pharmaceutical Co., Ltd.

Source: Tatsumoto M, Ishida M, Iba K, et al. Effects of fremanezumab on migraine-associated symptoms and medication use in Japanese and Korean patients with episodic migraine: Exploratory endpoint analysis of a multicenter, randomized, double-blind, placebo-controlled trial. Headache. 2024 (Sept 2). doi: 10.1111/head.14810 Source

Key clinical point: Eicosapentaenoic acid (EPA), used with standard prophylactic pharmacotherapy, significantly reduced migraine headache days (MHD) and migraine attacks in patients with chronic migraine (CM).

Major findings: The score relating to headache impact was significantly lower in the EPA vs placebo group at weeks 4 (P = .017) and 8 (P = .042). At 8 weeks, EPA treatment led to a greater reduction in mean MHD (−9.76 vs −4.60; P < .001) and mean number of attacks per month (3 vs 4; P = .012) than placebo. In the EPA group, only three patients experienced nausea and gastrointestinal upset.

Study details: This randomized controlled trial included 60 adult patients with CM who received 1000 mg EPA or placebo twice daily for 8 weeks and continued their first-line preventive pharmacotherapy throughout the trial.

Disclosure: The study was supported by the research committee of Shahid Beheshti University of Medical Sciences, Iran. The authors declared no conflicts of interest.

Source: Mohammadnezhad G, Assarzadegan F, Koosha M, Esmaily H. Eicosapentaenoic acid versus placebo as adjunctive therapy in chronic migraine: A randomized controlled trial. Headache. 2024 (Sept 2). doi: 10.1111/head.14808  Source

Key clinical point: Eicosapentaenoic acid (EPA), used with standard prophylactic pharmacotherapy, significantly reduced migraine headache days (MHD) and migraine attacks in patients with chronic migraine (CM).

Major findings: The score relating to headache impact was significantly lower in the EPA vs placebo group at weeks 4 (P = .017) and 8 (P = .042). At 8 weeks, EPA treatment led to a greater reduction in mean MHD (−9.76 vs −4.60; P < .001) and mean number of attacks per month (3 vs 4; P = .012) than placebo. In the EPA group, only three patients experienced nausea and gastrointestinal upset.

Study details: This randomized controlled trial included 60 adult patients with CM who received 1000 mg EPA or placebo twice daily for 8 weeks and continued their first-line preventive pharmacotherapy throughout the trial.

Disclosure: The study was supported by the research committee of Shahid Beheshti University of Medical Sciences, Iran. The authors declared no conflicts of interest.

Source: Mohammadnezhad G, Assarzadegan F, Koosha M, Esmaily H. Eicosapentaenoic acid versus placebo as adjunctive therapy in chronic migraine: A randomized controlled trial. Headache. 2024 (Sept 2). doi: 10.1111/head.14808  Source

Key clinical point: Eicosapentaenoic acid (EPA), used with standard prophylactic pharmacotherapy, significantly reduced migraine headache days (MHD) and migraine attacks in patients with chronic migraine (CM).

Major findings: The score relating to headache impact was significantly lower in the EPA vs placebo group at weeks 4 (P = .017) and 8 (P = .042). At 8 weeks, EPA treatment led to a greater reduction in mean MHD (−9.76 vs −4.60; P < .001) and mean number of attacks per month (3 vs 4; P = .012) than placebo. In the EPA group, only three patients experienced nausea and gastrointestinal upset.

Study details: This randomized controlled trial included 60 adult patients with CM who received 1000 mg EPA or placebo twice daily for 8 weeks and continued their first-line preventive pharmacotherapy throughout the trial.

Disclosure: The study was supported by the research committee of Shahid Beheshti University of Medical Sciences, Iran. The authors declared no conflicts of interest.

Source: Mohammadnezhad G, Assarzadegan F, Koosha M, Esmaily H. Eicosapentaenoic acid versus placebo as adjunctive therapy in chronic migraine: A randomized controlled trial. Headache. 2024 (Sept 2). doi: 10.1111/head.14808  Source

Key clinical point: Zavegepant nasal spray, administered as needed for up to eight doses per month, demonstrated long-term safety in the acute treatment of migraine over 1 year.

Major finding: The most common adverse events (AE), reported in ≥5% patients receiving zavegepant, were dysgeusia, nasal discomfort, COVID-19, nausea, nasal congestion, throat irritation, and back pain. In the 1-year period, only 6.8% patients discontinued treatment due to AE; dysgeusia was the most common cause, accounting for 1.5% of discontinuations. No deaths were reported.

Study details: This phase 2/3, open-label safety study included 603 adults with moderate to severe migraine who had a history of 2 to 8 moderate to severe attacks per month and were treated with intranasal 10 mg zavegepant daily for 1 year.

Disclosures: This study was funded by Biohaven Pharmaceuticals. Some authors declared being employees of or holding stocks of or stock options in Biohaven Pharmaceuticals. Some others declared having ties with various sources, including Biohaven Pharmaceuticals.

Source: Mullin K, Croop R, Mosher L, et al. Long-term safety of zavegepant nasal spray for acute treatment of migraine: A phase 2/3 open-label study. Cephalalgia. 2024 (Aug 30). doi: 10.1177/033310242412594 Source

Key clinical point: Zavegepant nasal spray, administered as needed for up to eight doses per month, demonstrated long-term safety in the acute treatment of migraine over 1 year.

Major finding: The most common adverse events (AE), reported in ≥5% patients receiving zavegepant, were dysgeusia, nasal discomfort, COVID-19, nausea, nasal congestion, throat irritation, and back pain. In the 1-year period, only 6.8% patients discontinued treatment due to AE; dysgeusia was the most common cause, accounting for 1.5% of discontinuations. No deaths were reported.

Study details: This phase 2/3, open-label safety study included 603 adults with moderate to severe migraine who had a history of 2 to 8 moderate to severe attacks per month and were treated with intranasal 10 mg zavegepant daily for 1 year.

Disclosures: This study was funded by Biohaven Pharmaceuticals. Some authors declared being employees of or holding stocks of or stock options in Biohaven Pharmaceuticals. Some others declared having ties with various sources, including Biohaven Pharmaceuticals.

Source: Mullin K, Croop R, Mosher L, et al. Long-term safety of zavegepant nasal spray for acute treatment of migraine: A phase 2/3 open-label study. Cephalalgia. 2024 (Aug 30). doi: 10.1177/033310242412594 Source

Key clinical point: Zavegepant nasal spray, administered as needed for up to eight doses per month, demonstrated long-term safety in the acute treatment of migraine over 1 year.

Major finding: The most common adverse events (AE), reported in ≥5% patients receiving zavegepant, were dysgeusia, nasal discomfort, COVID-19, nausea, nasal congestion, throat irritation, and back pain. In the 1-year period, only 6.8% patients discontinued treatment due to AE; dysgeusia was the most common cause, accounting for 1.5% of discontinuations. No deaths were reported.

Study details: This phase 2/3, open-label safety study included 603 adults with moderate to severe migraine who had a history of 2 to 8 moderate to severe attacks per month and were treated with intranasal 10 mg zavegepant daily for 1 year.

Disclosures: This study was funded by Biohaven Pharmaceuticals. Some authors declared being employees of or holding stocks of or stock options in Biohaven Pharmaceuticals. Some others declared having ties with various sources, including Biohaven Pharmaceuticals.

Source: Mullin K, Croop R, Mosher L, et al. Long-term safety of zavegepant nasal spray for acute treatment of migraine: A phase 2/3 open-label study. Cephalalgia. 2024 (Aug 30). doi: 10.1177/033310242412594 Source

Key clinical point: Women with either migraine or gestational diabetes mellitus (GDM) faced an increased long-term risk for developing major adverse cardiovascular and cerebrovascular events (MACCE) at a premature age (≤60 years), with the risk being significantly higher among those with both conditions.

Major findings: Women with migraine or GDM had a significantly higher 20-year risk for premature MACCE than women without these conditions (adjusted hazard ratio [aHR] 1.65; 95% CI 1.49-1.82 for migraine and aHR 1.64; 95% CI 1.37-1.96 for GDM). The risk was highest among women with both migraine and GDM (aHR 2.35; 95% CI 1.03-5.36).

Study details: This population-based longitudinal cohort study included 1,390,451 women, of which 56,811 had migraine, 24,700 had GDM, 1484 had both migraine and GDM, and 1,307,456 women had neither migraine nor GDM.

Disclosure: The study was funded by Aarhus University. The authors declared no conflicts of interest.

Source: Fuglsang CH, Pedersen L, Schmidt M, et al. The combined impact of migraine and gestational diabetes on long-term risk of premature myocardial infarction and stroke: A population-based cohort study. Headache. 2024 (Aug 28). doi: 10.1111/head.14821 Source

Key clinical point: Women with either migraine or gestational diabetes mellitus (GDM) faced an increased long-term risk for developing major adverse cardiovascular and cerebrovascular events (MACCE) at a premature age (≤60 years), with the risk being significantly higher among those with both conditions.

Major findings: Women with migraine or GDM had a significantly higher 20-year risk for premature MACCE than women without these conditions (adjusted hazard ratio [aHR] 1.65; 95% CI 1.49-1.82 for migraine and aHR 1.64; 95% CI 1.37-1.96 for GDM). The risk was highest among women with both migraine and GDM (aHR 2.35; 95% CI 1.03-5.36).

Study details: This population-based longitudinal cohort study included 1,390,451 women, of which 56,811 had migraine, 24,700 had GDM, 1484 had both migraine and GDM, and 1,307,456 women had neither migraine nor GDM.

Disclosure: The study was funded by Aarhus University. The authors declared no conflicts of interest.

Source: Fuglsang CH, Pedersen L, Schmidt M, et al. The combined impact of migraine and gestational diabetes on long-term risk of premature myocardial infarction and stroke: A population-based cohort study. Headache. 2024 (Aug 28). doi: 10.1111/head.14821 Source

Key clinical point: Women with either migraine or gestational diabetes mellitus (GDM) faced an increased long-term risk for developing major adverse cardiovascular and cerebrovascular events (MACCE) at a premature age (≤60 years), with the risk being significantly higher among those with both conditions.

Major findings: Women with migraine or GDM had a significantly higher 20-year risk for premature MACCE than women without these conditions (adjusted hazard ratio [aHR] 1.65; 95% CI 1.49-1.82 for migraine and aHR 1.64; 95% CI 1.37-1.96 for GDM). The risk was highest among women with both migraine and GDM (aHR 2.35; 95% CI 1.03-5.36).

Study details: This population-based longitudinal cohort study included 1,390,451 women, of which 56,811 had migraine, 24,700 had GDM, 1484 had both migraine and GDM, and 1,307,456 women had neither migraine nor GDM.

Disclosure: The study was funded by Aarhus University. The authors declared no conflicts of interest.

Source: Fuglsang CH, Pedersen L, Schmidt M, et al. The combined impact of migraine and gestational diabetes on long-term risk of premature myocardial infarction and stroke: A population-based cohort study. Headache. 2024 (Aug 28). doi: 10.1111/head.14821 Source

Key clinical point: Patients with migraine experienced considerable neck pain–related disability, with the effect being more prominent among patients with chronic vs episodic migraine.

Major findings: Patients with migraine reported a mean Neck Disability Index (NDI) score of 16.2, indicative of moderate disability. The NDI scores were 12.1 points higher among patients with migraine vs control individuals without headache (P < .001) and 5.5 points higher among patients with chronic vs episodic migraine (P < .001).

Study details: Findings are from a meta-analysis of 33 observational studies including patients with migraine, patients with tension-type headache, and healthy individuals without headache.

Disclosure: The study did not receive any funding. Four authors declared receiving personal fees or honoraria for consultation from or having other ties with various sources; others declared no conflicts of interest.

Source: Al-Khazali HM, Al-Sayegh Z, Younis S, et al. Systematic review and meta-analysis of Neck Disability Index and Numeric Pain Rating Scale in patients with migraine and tension-type headache. Cephalalgia. 2024 (Aug 28). doi: 10.1177/033310242412742 Source

Key clinical point: Patients with migraine experienced considerable neck pain–related disability, with the effect being more prominent among patients with chronic vs episodic migraine.

Major findings: Patients with migraine reported a mean Neck Disability Index (NDI) score of 16.2, indicative of moderate disability. The NDI scores were 12.1 points higher among patients with migraine vs control individuals without headache (P < .001) and 5.5 points higher among patients with chronic vs episodic migraine (P < .001).

Study details: Findings are from a meta-analysis of 33 observational studies including patients with migraine, patients with tension-type headache, and healthy individuals without headache.

Disclosure: The study did not receive any funding. Four authors declared receiving personal fees or honoraria for consultation from or having other ties with various sources; others declared no conflicts of interest.

Source: Al-Khazali HM, Al-Sayegh Z, Younis S, et al. Systematic review and meta-analysis of Neck Disability Index and Numeric Pain Rating Scale in patients with migraine and tension-type headache. Cephalalgia. 2024 (Aug 28). doi: 10.1177/033310242412742 Source

Key clinical point: Patients with migraine experienced considerable neck pain–related disability, with the effect being more prominent among patients with chronic vs episodic migraine.

Major findings: Patients with migraine reported a mean Neck Disability Index (NDI) score of 16.2, indicative of moderate disability. The NDI scores were 12.1 points higher among patients with migraine vs control individuals without headache (P < .001) and 5.5 points higher among patients with chronic vs episodic migraine (P < .001).

Study details: Findings are from a meta-analysis of 33 observational studies including patients with migraine, patients with tension-type headache, and healthy individuals without headache.

Disclosure: The study did not receive any funding. Four authors declared receiving personal fees or honoraria for consultation from or having other ties with various sources; others declared no conflicts of interest.

Source: Al-Khazali HM, Al-Sayegh Z, Younis S, et al. Systematic review and meta-analysis of Neck Disability Index and Numeric Pain Rating Scale in patients with migraine and tension-type headache. Cephalalgia. 2024 (Aug 28). doi: 10.1177/033310242412742 Source

Key clinical point: When administered during the prodrome, ubrogepant was more effective than placebo in improving normal functioning, reducing activity limitations, and increasing treatment satisfaction in patients with acute migraine.

Major findings: A significantly higher proportion of patients were able to function normally as early as 2 hours after receiving ubrogepant vs placebo (odds ratio [OR] 1.76; P = .0001), with the effects being sustained through 24 hours. The patients also experienced reduced activity limitations (OR 2.07; P < .0001) and greater treatment satisfaction (OR 2.32; P < .0001) at 24 hours after receiving ubrogepant vs placebo.

Study details: This PRODROME trial included 477 adult patients with acute migraine who were randomly assigned to receive either placebo followed by 100 mg ubrogepant for the first and second prodrome events, respectively, or vice versa.

Disclosure: The study was funded by AbbVie. Seven authors reported being employees of AbbVie and may hold stock in the company. Other authors declared having other ties with various sources, including AbbVie.

Source: Lipton RB, Harriott AM, Ma JY, et al. Effect of ubrogepant on patient-reported outcomes when administered during the migraine prodrome: Results from the randomized PRODROME trial. Neurology. 2024;103(6):e209745 (Aug 28). doi: 10.1212/WNL.00000000002097 Source

Key clinical point: When administered during the prodrome, ubrogepant was more effective than placebo in improving normal functioning, reducing activity limitations, and increasing treatment satisfaction in patients with acute migraine.

Major findings: A significantly higher proportion of patients were able to function normally as early as 2 hours after receiving ubrogepant vs placebo (odds ratio [OR] 1.76; P = .0001), with the effects being sustained through 24 hours. The patients also experienced reduced activity limitations (OR 2.07; P < .0001) and greater treatment satisfaction (OR 2.32; P < .0001) at 24 hours after receiving ubrogepant vs placebo.

Study details: This PRODROME trial included 477 adult patients with acute migraine who were randomly assigned to receive either placebo followed by 100 mg ubrogepant for the first and second prodrome events, respectively, or vice versa.

Disclosure: The study was funded by AbbVie. Seven authors reported being employees of AbbVie and may hold stock in the company. Other authors declared having other ties with various sources, including AbbVie.

Source: Lipton RB, Harriott AM, Ma JY, et al. Effect of ubrogepant on patient-reported outcomes when administered during the migraine prodrome: Results from the randomized PRODROME trial. Neurology. 2024;103(6):e209745 (Aug 28). doi: 10.1212/WNL.00000000002097 Source

Key clinical point: When administered during the prodrome, ubrogepant was more effective than placebo in improving normal functioning, reducing activity limitations, and increasing treatment satisfaction in patients with acute migraine.

Major findings: A significantly higher proportion of patients were able to function normally as early as 2 hours after receiving ubrogepant vs placebo (odds ratio [OR] 1.76; P = .0001), with the effects being sustained through 24 hours. The patients also experienced reduced activity limitations (OR 2.07; P < .0001) and greater treatment satisfaction (OR 2.32; P < .0001) at 24 hours after receiving ubrogepant vs placebo.

Study details: This PRODROME trial included 477 adult patients with acute migraine who were randomly assigned to receive either placebo followed by 100 mg ubrogepant for the first and second prodrome events, respectively, or vice versa.

Disclosure: The study was funded by AbbVie. Seven authors reported being employees of AbbVie and may hold stock in the company. Other authors declared having other ties with various sources, including AbbVie.

Source: Lipton RB, Harriott AM, Ma JY, et al. Effect of ubrogepant on patient-reported outcomes when administered during the migraine prodrome: Results from the randomized PRODROME trial. Neurology. 2024;103(6):e209745 (Aug 28). doi: 10.1212/WNL.00000000002097 Source