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Commentary: Refractory chronic migraine treatment, July 2023
Calcitonin gene-related peptide (CGRP) antagonist medications have revolutionized migraine therapy since being introduced in 2018. The initial preventive trials for monoclonal antibodies (mAb) excluded older adults, with a cutoff in all studies at age 65 years. Long-term safety studies have not revealed signals for concern related to vascular or other adverse events. The study by Muñoz-Vendrell and colleagues investigated the efficacy of CGRP mAb in treatment-refractory older adults.
This was an observational retrospective study in participants older than 65 years that had previously used three or more prior migraine preventives unsuccessfully. The primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and acute medication frequency as well as improvement in patient reported outcomes.
A total of 162 participants were followed at 18 different headache centers throughout Spain. All patients had at least 8 headache days per month and had been treated unsuccessfully with three prior medications for migraine prevention, one of which was botulinum toxin. The median age was 68 years, and over 80% had chronic migraine. The reduction in mean headache days was 10 days per month; 72% continued to use their CGRP mAb after using it for 6 months. Participants were compared relative to medication overuse but no significant differences were found between those who overused medication and others.
This study highlights the efficacy of CGRP medications in those outside of the initially studied population. Other preventive medications may be contraindicated in this population, but CGRP antagonists do appear to be safe and effective options for older adults.
Opiate medications are typically considered inappropriate as an acute treatment for migraine. Even infrequent use of opiate medications has been shown to be associated with worse migraine outcomes, specifically higher frequency and a higher likelihood to convert from episodic to chronic migraine. Van Welie and colleagues performed a cross-sectional questionnaire-based study assessing levels of opioid use in patients with migraine.
Participants were selected from the Leiden Headache Center and fit the diagnostic criteria of migraine. They were given an e-questionnaire to determine their use of these opiates: buprenorphine, fentanyl, hydromorphone, morphine, oxycodone, tapentadol, and tramadol (codeine was not included in this list). Patients were separately divided between chronic and episodic migraine groups. The primary outcome was assessing for current acute treatment of migraine with an opiate; secondary outcomes were association of chronicity of migraine and likelihood of medication overuse with opiate use.
Only approximately 1.8% of participants reported that they currently use an opiate for acute migraine treatment; 12.5% reported that they previously have used an opiate and 25.7% reported using an opiate for another pain condition. Tramadol was the most commonly used opiate medication, followed by oxycodone and morphine; 2.4% of patients reported that their opiate use was not prescribed by their doctor. Primary care doctors were the most common prescribers of the opiate medications; 16% of the time, patients were told that it was a preventive treatment for migraine. Opiate use was more frequent in patients with a diagnosis of chronic migraine, and the duration of use was greater.
Opiate medications remain a poor acute choice of treatment for migraine, and this study shows a correlation between higher opiate use and chronic migraine. There are many other acute medications now available for migraine, many of them migraine-specific treatments, such as triptans, gepants, and ditans. This research again shows that opiates should be avoided if at all possible for migraine.
Patients with medication overuse headache are more likely to be treatment-refractory, and the addition of acute medications often can be less effective if they remain on the overused medication. There has been a long-standing debate whether it is best to wean medications first or start a preventive initially when faced with medication overuse. The CGRP antagonists may be one of the better preventive options in this situation, and one mAb (fremenezumab) reported positive data in a small medication overuse trial. The study by Guerzoni and colleagues investigated the effectiveness of galcanezumab in chronic migraine with medication overuse.
This was a prospective trial conducted at the University Hospital of Modena. A total of 78 patients with a diagnosis of chronic migraine and medication overuse were enrolled for 15 months, with follow-up every 3 months. At each follow-up appointment, they completed a questionnaire asking them details about: mean migraine days per month, mean number of painkillers taken per month, mean days per month taking a painkiller, average migraine severity, and the Headache Impact Test (HIT-6) and Migraine Disability Assessment (MIDAS) questions. Patients were given the standard-dosing regimen of glacanezumab for migraine and were not blinded; this was an open-label study.
The mean migraine days per month were significantly reduced after 3, 6, 9, and 12 months. The amount of painkillers used per month and days of painkillers per month both reduced significantly as well. Migraine-related disability on HIT-6 and MIDAS were all reduced significantly as well. The most significant improvement long-term was noted in patients who improved the most during the initial 3 months of treatment.
The debate regarding the best treatment for patients with medication overuse will continue, but this study highlights the effectiveness of CGRP mAb use in this population. Patients were able to decrease the use of acute medications without a strict wean off of their previous medication. Ideally, a similar study should also be done for additional mAb and oral CGRP antagonists.
Calcitonin gene-related peptide (CGRP) antagonist medications have revolutionized migraine therapy since being introduced in 2018. The initial preventive trials for monoclonal antibodies (mAb) excluded older adults, with a cutoff in all studies at age 65 years. Long-term safety studies have not revealed signals for concern related to vascular or other adverse events. The study by Muñoz-Vendrell and colleagues investigated the efficacy of CGRP mAb in treatment-refractory older adults.
This was an observational retrospective study in participants older than 65 years that had previously used three or more prior migraine preventives unsuccessfully. The primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and acute medication frequency as well as improvement in patient reported outcomes.
A total of 162 participants were followed at 18 different headache centers throughout Spain. All patients had at least 8 headache days per month and had been treated unsuccessfully with three prior medications for migraine prevention, one of which was botulinum toxin. The median age was 68 years, and over 80% had chronic migraine. The reduction in mean headache days was 10 days per month; 72% continued to use their CGRP mAb after using it for 6 months. Participants were compared relative to medication overuse but no significant differences were found between those who overused medication and others.
This study highlights the efficacy of CGRP medications in those outside of the initially studied population. Other preventive medications may be contraindicated in this population, but CGRP antagonists do appear to be safe and effective options for older adults.
Opiate medications are typically considered inappropriate as an acute treatment for migraine. Even infrequent use of opiate medications has been shown to be associated with worse migraine outcomes, specifically higher frequency and a higher likelihood to convert from episodic to chronic migraine. Van Welie and colleagues performed a cross-sectional questionnaire-based study assessing levels of opioid use in patients with migraine.
Participants were selected from the Leiden Headache Center and fit the diagnostic criteria of migraine. They were given an e-questionnaire to determine their use of these opiates: buprenorphine, fentanyl, hydromorphone, morphine, oxycodone, tapentadol, and tramadol (codeine was not included in this list). Patients were separately divided between chronic and episodic migraine groups. The primary outcome was assessing for current acute treatment of migraine with an opiate; secondary outcomes were association of chronicity of migraine and likelihood of medication overuse with opiate use.
Only approximately 1.8% of participants reported that they currently use an opiate for acute migraine treatment; 12.5% reported that they previously have used an opiate and 25.7% reported using an opiate for another pain condition. Tramadol was the most commonly used opiate medication, followed by oxycodone and morphine; 2.4% of patients reported that their opiate use was not prescribed by their doctor. Primary care doctors were the most common prescribers of the opiate medications; 16% of the time, patients were told that it was a preventive treatment for migraine. Opiate use was more frequent in patients with a diagnosis of chronic migraine, and the duration of use was greater.
Opiate medications remain a poor acute choice of treatment for migraine, and this study shows a correlation between higher opiate use and chronic migraine. There are many other acute medications now available for migraine, many of them migraine-specific treatments, such as triptans, gepants, and ditans. This research again shows that opiates should be avoided if at all possible for migraine.
Patients with medication overuse headache are more likely to be treatment-refractory, and the addition of acute medications often can be less effective if they remain on the overused medication. There has been a long-standing debate whether it is best to wean medications first or start a preventive initially when faced with medication overuse. The CGRP antagonists may be one of the better preventive options in this situation, and one mAb (fremenezumab) reported positive data in a small medication overuse trial. The study by Guerzoni and colleagues investigated the effectiveness of galcanezumab in chronic migraine with medication overuse.
This was a prospective trial conducted at the University Hospital of Modena. A total of 78 patients with a diagnosis of chronic migraine and medication overuse were enrolled for 15 months, with follow-up every 3 months. At each follow-up appointment, they completed a questionnaire asking them details about: mean migraine days per month, mean number of painkillers taken per month, mean days per month taking a painkiller, average migraine severity, and the Headache Impact Test (HIT-6) and Migraine Disability Assessment (MIDAS) questions. Patients were given the standard-dosing regimen of glacanezumab for migraine and were not blinded; this was an open-label study.
The mean migraine days per month were significantly reduced after 3, 6, 9, and 12 months. The amount of painkillers used per month and days of painkillers per month both reduced significantly as well. Migraine-related disability on HIT-6 and MIDAS were all reduced significantly as well. The most significant improvement long-term was noted in patients who improved the most during the initial 3 months of treatment.
The debate regarding the best treatment for patients with medication overuse will continue, but this study highlights the effectiveness of CGRP mAb use in this population. Patients were able to decrease the use of acute medications without a strict wean off of their previous medication. Ideally, a similar study should also be done for additional mAb and oral CGRP antagonists.
Calcitonin gene-related peptide (CGRP) antagonist medications have revolutionized migraine therapy since being introduced in 2018. The initial preventive trials for monoclonal antibodies (mAb) excluded older adults, with a cutoff in all studies at age 65 years. Long-term safety studies have not revealed signals for concern related to vascular or other adverse events. The study by Muñoz-Vendrell and colleagues investigated the efficacy of CGRP mAb in treatment-refractory older adults.
This was an observational retrospective study in participants older than 65 years that had previously used three or more prior migraine preventives unsuccessfully. The primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and acute medication frequency as well as improvement in patient reported outcomes.
A total of 162 participants were followed at 18 different headache centers throughout Spain. All patients had at least 8 headache days per month and had been treated unsuccessfully with three prior medications for migraine prevention, one of which was botulinum toxin. The median age was 68 years, and over 80% had chronic migraine. The reduction in mean headache days was 10 days per month; 72% continued to use their CGRP mAb after using it for 6 months. Participants were compared relative to medication overuse but no significant differences were found between those who overused medication and others.
This study highlights the efficacy of CGRP medications in those outside of the initially studied population. Other preventive medications may be contraindicated in this population, but CGRP antagonists do appear to be safe and effective options for older adults.
Opiate medications are typically considered inappropriate as an acute treatment for migraine. Even infrequent use of opiate medications has been shown to be associated with worse migraine outcomes, specifically higher frequency and a higher likelihood to convert from episodic to chronic migraine. Van Welie and colleagues performed a cross-sectional questionnaire-based study assessing levels of opioid use in patients with migraine.
Participants were selected from the Leiden Headache Center and fit the diagnostic criteria of migraine. They were given an e-questionnaire to determine their use of these opiates: buprenorphine, fentanyl, hydromorphone, morphine, oxycodone, tapentadol, and tramadol (codeine was not included in this list). Patients were separately divided between chronic and episodic migraine groups. The primary outcome was assessing for current acute treatment of migraine with an opiate; secondary outcomes were association of chronicity of migraine and likelihood of medication overuse with opiate use.
Only approximately 1.8% of participants reported that they currently use an opiate for acute migraine treatment; 12.5% reported that they previously have used an opiate and 25.7% reported using an opiate for another pain condition. Tramadol was the most commonly used opiate medication, followed by oxycodone and morphine; 2.4% of patients reported that their opiate use was not prescribed by their doctor. Primary care doctors were the most common prescribers of the opiate medications; 16% of the time, patients were told that it was a preventive treatment for migraine. Opiate use was more frequent in patients with a diagnosis of chronic migraine, and the duration of use was greater.
Opiate medications remain a poor acute choice of treatment for migraine, and this study shows a correlation between higher opiate use and chronic migraine. There are many other acute medications now available for migraine, many of them migraine-specific treatments, such as triptans, gepants, and ditans. This research again shows that opiates should be avoided if at all possible for migraine.
Patients with medication overuse headache are more likely to be treatment-refractory, and the addition of acute medications often can be less effective if they remain on the overused medication. There has been a long-standing debate whether it is best to wean medications first or start a preventive initially when faced with medication overuse. The CGRP antagonists may be one of the better preventive options in this situation, and one mAb (fremenezumab) reported positive data in a small medication overuse trial. The study by Guerzoni and colleagues investigated the effectiveness of galcanezumab in chronic migraine with medication overuse.
This was a prospective trial conducted at the University Hospital of Modena. A total of 78 patients with a diagnosis of chronic migraine and medication overuse were enrolled for 15 months, with follow-up every 3 months. At each follow-up appointment, they completed a questionnaire asking them details about: mean migraine days per month, mean number of painkillers taken per month, mean days per month taking a painkiller, average migraine severity, and the Headache Impact Test (HIT-6) and Migraine Disability Assessment (MIDAS) questions. Patients were given the standard-dosing regimen of glacanezumab for migraine and were not blinded; this was an open-label study.
The mean migraine days per month were significantly reduced after 3, 6, 9, and 12 months. The amount of painkillers used per month and days of painkillers per month both reduced significantly as well. Migraine-related disability on HIT-6 and MIDAS were all reduced significantly as well. The most significant improvement long-term was noted in patients who improved the most during the initial 3 months of treatment.
The debate regarding the best treatment for patients with medication overuse will continue, but this study highlights the effectiveness of CGRP mAb use in this population. Patients were able to decrease the use of acute medications without a strict wean off of their previous medication. Ideally, a similar study should also be done for additional mAb and oral CGRP antagonists.
What is the proper treatment for posttraumatic headache? Expert debate
AUSTIN, TEX – There are no guidelines available, nor is there much quality evidence to support one decision or another, according to two experts who debated the question at the annual meeting of the American Headache Society.
Early treatment
Frank Conidi, DO, spoke first, and pointed out the need to define both early treatment and the condition being treated. Is it early-treatment abortive, is it preventative, and if the patient has a concussion, is it a mild traumatic brain injury (TBI), or severe TBI?
The majority of patients with posttraumatic headache will meet criteria for migraine or probable migraine. “It can be anywhere from 58% to upwards of 90%. And if you see these patients, it makes sense, because posttraumatic headache patients are disabled by their headaches,” said Dr. Conidi, director of the Florida Center for Headache and Sports Neurology.
He argued for early treatment to reduce chronification. “We know that if headaches are left untreated, they’re going to start to spiral up and become daily. This leads to the development of peripheral and central sensitization and lowers the threshold for further migraine attacks,” said Dr. Conidi.
He noted that patients with posttraumatic headache often have comorbidities such as sleep issues, neck pain, or posttraumatic stress disorder, all of which are risk factors for chronification. Treatment does not necessarily mean medication, however. “The mainstay of posttraumatic headache treatment is actually physical and cognitive activity to tolerance. And what I call the 20/5 rule: 20 minutes of physical activity with 5-minute chill breaks. In addition, we use light sub-aerobic exercise 3 to 5 days out in concussion, [which] has been shown to improve concussion recovery time,” he said.
Dr. Conidi suggested treatment of triggers, such as neck issues and whiplash symptoms. “Probably the best treatment I’ve ever seen, and I published on this, are pericranial nerve blocks. Pericranial nerve blocks work wonderfully. If you’re going to block the pericranial nerves, block them all, not just the occipital. Block the trigeminal branches. I’ve actually been able to locate a little two-and-a-half-inch plastic Luer-lock catheter that I can hook on a 1-cc syringe with viscous lidocaine, and I can do sphenopalatine ganglion blocks on all my patients now for under 25 cents. So we’ve been combining the nerve blocks, and we’ve been using them early. Oftentimes the patients won’t have any further headaches, especially if it’s [after] a concussion,” he said.
With respect to concussion-related posttraumatic headache, he summed up: “We’re aggressive early. We’re using intervention. We’re layering our treatment. We’re using medications: prednisone, NSAIDS, and now we have gepants. We’ve been having good success with using gepants,” he said.
Treatment of TBI patients is broadly similar, with the main difference being that neurologists typically won’t see such patients early on as they may be in rehab facilities or hospitals for extended periods. “You may not be getting [to see] them for 1 or 2 months. In that case, you want to educate your neurosurgery and your [physical medicine and rehabilitation] colleagues on the treatment.
Finally, he described work that his group has done in using stimulants for posttraumatic headache. “Stimulants not only treat the cognitive symptoms, but they give the patient cognitive reserve and we find that it gets the patient through the day so they actually have less headaches. It’s a form of prevention. I know there are shortages nationally of both Adderall and Ritalin, but we have had excellent results in our posttraumatic patients using these types of medications,” said Dr. Conidi.
Delayed treatment
Amaal J. Starling, MD, offered a counterargument, but she narrowed the question down to whether preventive treatment should be used within one and a half months of the injury, which she defined as early treatment. Her argument against early preventive treatment centered around the core value of beneficence – to act for the benefit of the patient, and avoid harm.
She discussed the natural history of posttraumatic headache, which is largely self-limited. For example, an NCAA study that found 88% of concussions had symptom resolution within 1 week, and 86% of posttraumatic headache resolved within 1 week. “If individuals routinely are having a self-limited course, there is no need for early treatment with a preventive treatment option because the majority of posttraumatic headache is resolving within that one-and-a-half-month postinjury threshold. The better recommendation, as provided in evidence from Dr. Conidi’s presentation, is to provide supportive care, including acute medications or acute treatment options like nerve blocks for acute pain relief and symptom relief,” said Dr. Starling, associate professor of neurology at Mayo Clinic in Scottsdale, Ariz.
Dr. Starling expressed concern that preventive medications could lead to worsening of comorbidities. For example, posttraumatic headache is often associated with autonomic dysfunction and visual vestibular dysfunction. The former commonly occurs with concussion and is similar to postural orthostatic tachycardia syndrome (POTS), and the second most common symptom of POTS is headache, according to Dr. Starling. Posttraumatic POTS is treated similarly to idiopathic POTS, with a nonpharmacologic approach. One element of POTS management is to withdraw exacerbating medications such as beta-blockers, tricyclic antidepressants, and SNRIs. “These look strikingly similar to some of the headache preventive medications that we might consider for somebody, and so the concern is early preventive treatment with these medications to treat the posttraumatic headache may actually worsen some of these comorbidities that are present in our posttraumatic headache patients. We have to be careful about potentially exacerbating comorbidities with early preventive treatment,” she said.
Prevention medications for headache can also worsen visual vestibular dysfunction, such as dizziness. There are some data suggesting that vestibular rehabilitation and vision therapy can improve dizziness, but also headache. “We all know that many of our preventive medications for headache could potentially exacerbate visual vestibular symptoms, so we have to be careful about that. So again, first do no harm. Posttraumatic POTS is common and causes headache. Posttraumatic vestibular dysfunction is common and causes headache. Instead of initiating a headache preventive medication early, we recommend to identify these comorbidities and provide targeted treatment. Treatment of these comorbidities may, in and of itself, improve the headache. We also we have to be careful because some preventive medications may worsen the comorbidities,” said Dr. Starling.
Areas of agreement
Dr. Conidi agreed that preventative treatment is less likely to be needed for concussion patients, but said that TBI patients are more likely to require it to prevent chronification. Dr. Starling agreed that chronification is an important concern, but she noted that many posttraumatic headache patients are athletes, and preventative medications can also lead to issues that might interfere with return to play, such as decreased sweating, or weight gain or loss. This is complicated by the fact that titration and weaning periods can be long. “We have to be very careful about these medications’ side effects, especially when we don’t have the evidence to demonstrate that it is worth the potential risk of being put on these medications,” she said.
The debate led Catherin Chong, PhD, to ask about the state of the field. “There’s a posttraumatic headache special interest section here [at AHS 2023], and the question that really is coming up at every meeting is, is there some coherence in the field? Is it too early or is it time for a position statement?” asked Dr. Chong, a career scientist at Mayo Clinic (Phoenix). Dr. Chong comoderated the debate and ensuing discussion.
Dr. Starling felt it’s too early for a position statement, but a scoping review could identify research questions that could lead to a position statement. “I’m really excited about the work that’s being done to identify the cohort of individuals with acute posttraumatic headache that may chronify to persistent posttraumatic headache so that we can minimize the risk of exposing the large cohort that’s going to be likely self-limited to a treatment option. Then we can identify those individuals where that risk is worth it because they’re the ones that could lead to chronification. Figuring out if that’s looking at levels of allodynia or other factors that can [help identify those at most risk] would be important,” she said.
Dr. Conidi agreed with the need for more information on the parameters to be studied, but he expressed the belief that any position statement would be a consensus statement. “It’s not going to have any hard evidence behind it, but I do think we need [a position statement]. Even in the general neurology world, there’s a huge lack of understanding of how to treat these patients,” he said.
Dr. Conidi did not make any disclosures. Dr. Starling has consulted for AbbVie, Allergan, Amgen, Axsome Therapeutics, Everyday Health, Lundbeck, Med-IQ, Medscape, Neurolief, Satsuma, and WebMD. Dr. Chong has no relevant financial disclosures.
AUSTIN, TEX – There are no guidelines available, nor is there much quality evidence to support one decision or another, according to two experts who debated the question at the annual meeting of the American Headache Society.
Early treatment
Frank Conidi, DO, spoke first, and pointed out the need to define both early treatment and the condition being treated. Is it early-treatment abortive, is it preventative, and if the patient has a concussion, is it a mild traumatic brain injury (TBI), or severe TBI?
The majority of patients with posttraumatic headache will meet criteria for migraine or probable migraine. “It can be anywhere from 58% to upwards of 90%. And if you see these patients, it makes sense, because posttraumatic headache patients are disabled by their headaches,” said Dr. Conidi, director of the Florida Center for Headache and Sports Neurology.
He argued for early treatment to reduce chronification. “We know that if headaches are left untreated, they’re going to start to spiral up and become daily. This leads to the development of peripheral and central sensitization and lowers the threshold for further migraine attacks,” said Dr. Conidi.
He noted that patients with posttraumatic headache often have comorbidities such as sleep issues, neck pain, or posttraumatic stress disorder, all of which are risk factors for chronification. Treatment does not necessarily mean medication, however. “The mainstay of posttraumatic headache treatment is actually physical and cognitive activity to tolerance. And what I call the 20/5 rule: 20 minutes of physical activity with 5-minute chill breaks. In addition, we use light sub-aerobic exercise 3 to 5 days out in concussion, [which] has been shown to improve concussion recovery time,” he said.
Dr. Conidi suggested treatment of triggers, such as neck issues and whiplash symptoms. “Probably the best treatment I’ve ever seen, and I published on this, are pericranial nerve blocks. Pericranial nerve blocks work wonderfully. If you’re going to block the pericranial nerves, block them all, not just the occipital. Block the trigeminal branches. I’ve actually been able to locate a little two-and-a-half-inch plastic Luer-lock catheter that I can hook on a 1-cc syringe with viscous lidocaine, and I can do sphenopalatine ganglion blocks on all my patients now for under 25 cents. So we’ve been combining the nerve blocks, and we’ve been using them early. Oftentimes the patients won’t have any further headaches, especially if it’s [after] a concussion,” he said.
With respect to concussion-related posttraumatic headache, he summed up: “We’re aggressive early. We’re using intervention. We’re layering our treatment. We’re using medications: prednisone, NSAIDS, and now we have gepants. We’ve been having good success with using gepants,” he said.
Treatment of TBI patients is broadly similar, with the main difference being that neurologists typically won’t see such patients early on as they may be in rehab facilities or hospitals for extended periods. “You may not be getting [to see] them for 1 or 2 months. In that case, you want to educate your neurosurgery and your [physical medicine and rehabilitation] colleagues on the treatment.
Finally, he described work that his group has done in using stimulants for posttraumatic headache. “Stimulants not only treat the cognitive symptoms, but they give the patient cognitive reserve and we find that it gets the patient through the day so they actually have less headaches. It’s a form of prevention. I know there are shortages nationally of both Adderall and Ritalin, but we have had excellent results in our posttraumatic patients using these types of medications,” said Dr. Conidi.
Delayed treatment
Amaal J. Starling, MD, offered a counterargument, but she narrowed the question down to whether preventive treatment should be used within one and a half months of the injury, which she defined as early treatment. Her argument against early preventive treatment centered around the core value of beneficence – to act for the benefit of the patient, and avoid harm.
She discussed the natural history of posttraumatic headache, which is largely self-limited. For example, an NCAA study that found 88% of concussions had symptom resolution within 1 week, and 86% of posttraumatic headache resolved within 1 week. “If individuals routinely are having a self-limited course, there is no need for early treatment with a preventive treatment option because the majority of posttraumatic headache is resolving within that one-and-a-half-month postinjury threshold. The better recommendation, as provided in evidence from Dr. Conidi’s presentation, is to provide supportive care, including acute medications or acute treatment options like nerve blocks for acute pain relief and symptom relief,” said Dr. Starling, associate professor of neurology at Mayo Clinic in Scottsdale, Ariz.
Dr. Starling expressed concern that preventive medications could lead to worsening of comorbidities. For example, posttraumatic headache is often associated with autonomic dysfunction and visual vestibular dysfunction. The former commonly occurs with concussion and is similar to postural orthostatic tachycardia syndrome (POTS), and the second most common symptom of POTS is headache, according to Dr. Starling. Posttraumatic POTS is treated similarly to idiopathic POTS, with a nonpharmacologic approach. One element of POTS management is to withdraw exacerbating medications such as beta-blockers, tricyclic antidepressants, and SNRIs. “These look strikingly similar to some of the headache preventive medications that we might consider for somebody, and so the concern is early preventive treatment with these medications to treat the posttraumatic headache may actually worsen some of these comorbidities that are present in our posttraumatic headache patients. We have to be careful about potentially exacerbating comorbidities with early preventive treatment,” she said.
Prevention medications for headache can also worsen visual vestibular dysfunction, such as dizziness. There are some data suggesting that vestibular rehabilitation and vision therapy can improve dizziness, but also headache. “We all know that many of our preventive medications for headache could potentially exacerbate visual vestibular symptoms, so we have to be careful about that. So again, first do no harm. Posttraumatic POTS is common and causes headache. Posttraumatic vestibular dysfunction is common and causes headache. Instead of initiating a headache preventive medication early, we recommend to identify these comorbidities and provide targeted treatment. Treatment of these comorbidities may, in and of itself, improve the headache. We also we have to be careful because some preventive medications may worsen the comorbidities,” said Dr. Starling.
Areas of agreement
Dr. Conidi agreed that preventative treatment is less likely to be needed for concussion patients, but said that TBI patients are more likely to require it to prevent chronification. Dr. Starling agreed that chronification is an important concern, but she noted that many posttraumatic headache patients are athletes, and preventative medications can also lead to issues that might interfere with return to play, such as decreased sweating, or weight gain or loss. This is complicated by the fact that titration and weaning periods can be long. “We have to be very careful about these medications’ side effects, especially when we don’t have the evidence to demonstrate that it is worth the potential risk of being put on these medications,” she said.
The debate led Catherin Chong, PhD, to ask about the state of the field. “There’s a posttraumatic headache special interest section here [at AHS 2023], and the question that really is coming up at every meeting is, is there some coherence in the field? Is it too early or is it time for a position statement?” asked Dr. Chong, a career scientist at Mayo Clinic (Phoenix). Dr. Chong comoderated the debate and ensuing discussion.
Dr. Starling felt it’s too early for a position statement, but a scoping review could identify research questions that could lead to a position statement. “I’m really excited about the work that’s being done to identify the cohort of individuals with acute posttraumatic headache that may chronify to persistent posttraumatic headache so that we can minimize the risk of exposing the large cohort that’s going to be likely self-limited to a treatment option. Then we can identify those individuals where that risk is worth it because they’re the ones that could lead to chronification. Figuring out if that’s looking at levels of allodynia or other factors that can [help identify those at most risk] would be important,” she said.
Dr. Conidi agreed with the need for more information on the parameters to be studied, but he expressed the belief that any position statement would be a consensus statement. “It’s not going to have any hard evidence behind it, but I do think we need [a position statement]. Even in the general neurology world, there’s a huge lack of understanding of how to treat these patients,” he said.
Dr. Conidi did not make any disclosures. Dr. Starling has consulted for AbbVie, Allergan, Amgen, Axsome Therapeutics, Everyday Health, Lundbeck, Med-IQ, Medscape, Neurolief, Satsuma, and WebMD. Dr. Chong has no relevant financial disclosures.
AUSTIN, TEX – There are no guidelines available, nor is there much quality evidence to support one decision or another, according to two experts who debated the question at the annual meeting of the American Headache Society.
Early treatment
Frank Conidi, DO, spoke first, and pointed out the need to define both early treatment and the condition being treated. Is it early-treatment abortive, is it preventative, and if the patient has a concussion, is it a mild traumatic brain injury (TBI), or severe TBI?
The majority of patients with posttraumatic headache will meet criteria for migraine or probable migraine. “It can be anywhere from 58% to upwards of 90%. And if you see these patients, it makes sense, because posttraumatic headache patients are disabled by their headaches,” said Dr. Conidi, director of the Florida Center for Headache and Sports Neurology.
He argued for early treatment to reduce chronification. “We know that if headaches are left untreated, they’re going to start to spiral up and become daily. This leads to the development of peripheral and central sensitization and lowers the threshold for further migraine attacks,” said Dr. Conidi.
He noted that patients with posttraumatic headache often have comorbidities such as sleep issues, neck pain, or posttraumatic stress disorder, all of which are risk factors for chronification. Treatment does not necessarily mean medication, however. “The mainstay of posttraumatic headache treatment is actually physical and cognitive activity to tolerance. And what I call the 20/5 rule: 20 minutes of physical activity with 5-minute chill breaks. In addition, we use light sub-aerobic exercise 3 to 5 days out in concussion, [which] has been shown to improve concussion recovery time,” he said.
Dr. Conidi suggested treatment of triggers, such as neck issues and whiplash symptoms. “Probably the best treatment I’ve ever seen, and I published on this, are pericranial nerve blocks. Pericranial nerve blocks work wonderfully. If you’re going to block the pericranial nerves, block them all, not just the occipital. Block the trigeminal branches. I’ve actually been able to locate a little two-and-a-half-inch plastic Luer-lock catheter that I can hook on a 1-cc syringe with viscous lidocaine, and I can do sphenopalatine ganglion blocks on all my patients now for under 25 cents. So we’ve been combining the nerve blocks, and we’ve been using them early. Oftentimes the patients won’t have any further headaches, especially if it’s [after] a concussion,” he said.
With respect to concussion-related posttraumatic headache, he summed up: “We’re aggressive early. We’re using intervention. We’re layering our treatment. We’re using medications: prednisone, NSAIDS, and now we have gepants. We’ve been having good success with using gepants,” he said.
Treatment of TBI patients is broadly similar, with the main difference being that neurologists typically won’t see such patients early on as they may be in rehab facilities or hospitals for extended periods. “You may not be getting [to see] them for 1 or 2 months. In that case, you want to educate your neurosurgery and your [physical medicine and rehabilitation] colleagues on the treatment.
Finally, he described work that his group has done in using stimulants for posttraumatic headache. “Stimulants not only treat the cognitive symptoms, but they give the patient cognitive reserve and we find that it gets the patient through the day so they actually have less headaches. It’s a form of prevention. I know there are shortages nationally of both Adderall and Ritalin, but we have had excellent results in our posttraumatic patients using these types of medications,” said Dr. Conidi.
Delayed treatment
Amaal J. Starling, MD, offered a counterargument, but she narrowed the question down to whether preventive treatment should be used within one and a half months of the injury, which she defined as early treatment. Her argument against early preventive treatment centered around the core value of beneficence – to act for the benefit of the patient, and avoid harm.
She discussed the natural history of posttraumatic headache, which is largely self-limited. For example, an NCAA study that found 88% of concussions had symptom resolution within 1 week, and 86% of posttraumatic headache resolved within 1 week. “If individuals routinely are having a self-limited course, there is no need for early treatment with a preventive treatment option because the majority of posttraumatic headache is resolving within that one-and-a-half-month postinjury threshold. The better recommendation, as provided in evidence from Dr. Conidi’s presentation, is to provide supportive care, including acute medications or acute treatment options like nerve blocks for acute pain relief and symptom relief,” said Dr. Starling, associate professor of neurology at Mayo Clinic in Scottsdale, Ariz.
Dr. Starling expressed concern that preventive medications could lead to worsening of comorbidities. For example, posttraumatic headache is often associated with autonomic dysfunction and visual vestibular dysfunction. The former commonly occurs with concussion and is similar to postural orthostatic tachycardia syndrome (POTS), and the second most common symptom of POTS is headache, according to Dr. Starling. Posttraumatic POTS is treated similarly to idiopathic POTS, with a nonpharmacologic approach. One element of POTS management is to withdraw exacerbating medications such as beta-blockers, tricyclic antidepressants, and SNRIs. “These look strikingly similar to some of the headache preventive medications that we might consider for somebody, and so the concern is early preventive treatment with these medications to treat the posttraumatic headache may actually worsen some of these comorbidities that are present in our posttraumatic headache patients. We have to be careful about potentially exacerbating comorbidities with early preventive treatment,” she said.
Prevention medications for headache can also worsen visual vestibular dysfunction, such as dizziness. There are some data suggesting that vestibular rehabilitation and vision therapy can improve dizziness, but also headache. “We all know that many of our preventive medications for headache could potentially exacerbate visual vestibular symptoms, so we have to be careful about that. So again, first do no harm. Posttraumatic POTS is common and causes headache. Posttraumatic vestibular dysfunction is common and causes headache. Instead of initiating a headache preventive medication early, we recommend to identify these comorbidities and provide targeted treatment. Treatment of these comorbidities may, in and of itself, improve the headache. We also we have to be careful because some preventive medications may worsen the comorbidities,” said Dr. Starling.
Areas of agreement
Dr. Conidi agreed that preventative treatment is less likely to be needed for concussion patients, but said that TBI patients are more likely to require it to prevent chronification. Dr. Starling agreed that chronification is an important concern, but she noted that many posttraumatic headache patients are athletes, and preventative medications can also lead to issues that might interfere with return to play, such as decreased sweating, or weight gain or loss. This is complicated by the fact that titration and weaning periods can be long. “We have to be very careful about these medications’ side effects, especially when we don’t have the evidence to demonstrate that it is worth the potential risk of being put on these medications,” she said.
The debate led Catherin Chong, PhD, to ask about the state of the field. “There’s a posttraumatic headache special interest section here [at AHS 2023], and the question that really is coming up at every meeting is, is there some coherence in the field? Is it too early or is it time for a position statement?” asked Dr. Chong, a career scientist at Mayo Clinic (Phoenix). Dr. Chong comoderated the debate and ensuing discussion.
Dr. Starling felt it’s too early for a position statement, but a scoping review could identify research questions that could lead to a position statement. “I’m really excited about the work that’s being done to identify the cohort of individuals with acute posttraumatic headache that may chronify to persistent posttraumatic headache so that we can minimize the risk of exposing the large cohort that’s going to be likely self-limited to a treatment option. Then we can identify those individuals where that risk is worth it because they’re the ones that could lead to chronification. Figuring out if that’s looking at levels of allodynia or other factors that can [help identify those at most risk] would be important,” she said.
Dr. Conidi agreed with the need for more information on the parameters to be studied, but he expressed the belief that any position statement would be a consensus statement. “It’s not going to have any hard evidence behind it, but I do think we need [a position statement]. Even in the general neurology world, there’s a huge lack of understanding of how to treat these patients,” he said.
Dr. Conidi did not make any disclosures. Dr. Starling has consulted for AbbVie, Allergan, Amgen, Axsome Therapeutics, Everyday Health, Lundbeck, Med-IQ, Medscape, Neurolief, Satsuma, and WebMD. Dr. Chong has no relevant financial disclosures.
AT AHS 2023
Prodrome treatment with ubrogepant prevents migraines
AUSTIN, TEX – , according to results from a new randomized, crossover study. Researchers took pains to identify migraineurs who could predict an ensuing headache 75% of the time based on prodromal symptoms. Those who could make such predictions were allowed into the randomized study.
Patients are quite good at predicting ensuing headaches when encouraged to do so, according to Peter J. Goadsby, MBBS, MD, PhD, who presented the study findings at the annual meeting of the American Headache Society.
“I find it quite useful to ask patients about these [symptoms]: Have you got cognitive clouding? Do you pass more urine? Have you got mood change? Do you feel fatigue? Associated with the attack, is how I phrase it. Get them first into the idea of thinking about the symptoms, and then get them to think about when they’re occurring. Certainly with things like brain fog, many patients will tell you that it happens. If you ask them whether they’re 100% [certain] when that’s happening, they will tell you [they’re] not. This is part of taking a history and building a relationship with the patient,” Dr. Goadsby, professor of neurology at the University of California, Los Angeles, said during the Q&A after his presentation.
‘Significant’ finding
“This is a significant finding because what patients really want is not to develop their headache and no medication has been shown to prevent a headache during the prodrome,” said Alan M. Rapoport, MD, a board certified neurologist and headache expert, as well as clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews. Successful treatment during the prodrome treatment could eliminate the need for use of preventive medication, which might decrease the patient’s adverse effects, he said.
Session comoderator Jason J. Sico, MD, took note of the patient experience during the prodrome period. “One of many noteworthy things is the large percentage of people that reported disability during prodrome before the headache. I just find that staggering, though not surprising to many of us,” he said during the session. Dr. Sico is associate professor of neurology and internal medicine at Yale University, New Haven, Conn.
Dr. Rapoport and Dr. Sico were not involved in the study.
Probing the prodrome
The study included a 60-day screening period, which had to include between 3 and 16 recorded prodrome events. Headaches had to occur within 1-6 hours in at least 75% of prodrome events. Study subjects were then randomized to 100 mg ubrogepant or placebo for up to 60 days. After their first prodrome event, they entered a 7-day washout period, and then crossed over to the other group until they experienced a second prodrome event.
During the screening period, 81.5% of prodromal events identified by patients were followed by a headache within 1-6 hours of onset. Nearly 10% of the time headache occurred in 1 hour or less, 81.5% between 1 and 6 hours, and 4.5% between 6 and 24 hours after prodrome. Commonly reported prodromal symptoms included sensitivity to light (57.2%), fatigue (50.1%), neck pain (41.9%), sensitivity to sound (33.9%), and dizziness (27.8%).
The study included 247 patients in the first sequence, and 233 in the second sequence. Patient characteristics were similar in both. Ubrogepant treatment led to a greater absence of moderate- or severe-intensity headache within 24 hours of the dose (45.5% vs. 28.6% headache-free; odds ratio [OR], 2.09; P < .0001). They were also more likely to report normal functioning over 24 hours (OR, 1.66; P < .0001) and to have absence of headache within 24 hours (23.7% vs. 13.9%; OR, 1.93; P < .0001).
Between 73% and 75% of participants reported at least mild functional disability before taking medication. Two hours after a dose, ubrogepant led to a higher rate of normal functioning (37.0% vs. 26.1%; P < .001). Ubrogepant had a similar positive effect on sensitivity to light, fatigue, neck pain, sensitivity to sound, and dizziness. Adverse events were higher during ubrogepant treatment (13.2% vs. 9.1%), and included nausea, dizziness, fatigue, and somnolence, all of which were mild. “One is really scraping the barrel [to identify adverse events]. There were no serious adverse events,” said Dr. Goadsby.
A unique result?
One questioner asked if other medications used during the prodrome might yield similar results. Dr. Goadsby expressed doubt. “I think the evidence for other treatments is not terribly good. The triptan evidence is really poor. There is no randomized, placebo-controlled trial of a triptan explicitly in promontory symptomatology. There are randomized placebo controlled trials of triptans during the aura phase. The best one was the injected sumatriptan study, and it failed. So, as far as I can see from the randomized-controlled data, triptans don’t do this, and we don’t have good data for nonsteroidals and other therapies,” said Dr. Goadsby.
The researchers showed that you could treat a patient in advance of the headache to actually prevent the headache a significant number of times; it also reduced the prodromal events and it got patients back to normal functioning to a greater extent.
Dr. Goadsby was asked how many patients are typically able to identify prodrome periods on their own. He estimated that about one in three can do it initially. “I think if you teach people how to do this, it becomes very common. I would say four out of five people in my practice are able to talk about this, but you have to introduce the topic. They’ve had [prodrome symptoms], but they haven’t thought about it for a while. This is one of the things where headache doctors can offer real benefit in helping educate patients,” said Dr. Goadsby.
Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. He is editor-in-chief of Neurology Reviews and on the Editorial Board of CNS Drugs. Dr. Goadsby has financial ties to Amgen, Eli Lilly, Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Biohaven Pharmaceuticals Inc., Dr. Reddy’s Laboratories, Electrocore, eNeura, Massachusetts Medical Society, MedicoLegal work, Novartis, Oxford University Press, Teva Pharmaceuticals, Trigemina, Up-to-Date, and Wolters Kluwer. He has a patent for headache assigned to eNeura without fee.
AUSTIN, TEX – , according to results from a new randomized, crossover study. Researchers took pains to identify migraineurs who could predict an ensuing headache 75% of the time based on prodromal symptoms. Those who could make such predictions were allowed into the randomized study.
Patients are quite good at predicting ensuing headaches when encouraged to do so, according to Peter J. Goadsby, MBBS, MD, PhD, who presented the study findings at the annual meeting of the American Headache Society.
“I find it quite useful to ask patients about these [symptoms]: Have you got cognitive clouding? Do you pass more urine? Have you got mood change? Do you feel fatigue? Associated with the attack, is how I phrase it. Get them first into the idea of thinking about the symptoms, and then get them to think about when they’re occurring. Certainly with things like brain fog, many patients will tell you that it happens. If you ask them whether they’re 100% [certain] when that’s happening, they will tell you [they’re] not. This is part of taking a history and building a relationship with the patient,” Dr. Goadsby, professor of neurology at the University of California, Los Angeles, said during the Q&A after his presentation.
‘Significant’ finding
“This is a significant finding because what patients really want is not to develop their headache and no medication has been shown to prevent a headache during the prodrome,” said Alan M. Rapoport, MD, a board certified neurologist and headache expert, as well as clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews. Successful treatment during the prodrome treatment could eliminate the need for use of preventive medication, which might decrease the patient’s adverse effects, he said.
Session comoderator Jason J. Sico, MD, took note of the patient experience during the prodrome period. “One of many noteworthy things is the large percentage of people that reported disability during prodrome before the headache. I just find that staggering, though not surprising to many of us,” he said during the session. Dr. Sico is associate professor of neurology and internal medicine at Yale University, New Haven, Conn.
Dr. Rapoport and Dr. Sico were not involved in the study.
Probing the prodrome
The study included a 60-day screening period, which had to include between 3 and 16 recorded prodrome events. Headaches had to occur within 1-6 hours in at least 75% of prodrome events. Study subjects were then randomized to 100 mg ubrogepant or placebo for up to 60 days. After their first prodrome event, they entered a 7-day washout period, and then crossed over to the other group until they experienced a second prodrome event.
During the screening period, 81.5% of prodromal events identified by patients were followed by a headache within 1-6 hours of onset. Nearly 10% of the time headache occurred in 1 hour or less, 81.5% between 1 and 6 hours, and 4.5% between 6 and 24 hours after prodrome. Commonly reported prodromal symptoms included sensitivity to light (57.2%), fatigue (50.1%), neck pain (41.9%), sensitivity to sound (33.9%), and dizziness (27.8%).
The study included 247 patients in the first sequence, and 233 in the second sequence. Patient characteristics were similar in both. Ubrogepant treatment led to a greater absence of moderate- or severe-intensity headache within 24 hours of the dose (45.5% vs. 28.6% headache-free; odds ratio [OR], 2.09; P < .0001). They were also more likely to report normal functioning over 24 hours (OR, 1.66; P < .0001) and to have absence of headache within 24 hours (23.7% vs. 13.9%; OR, 1.93; P < .0001).
Between 73% and 75% of participants reported at least mild functional disability before taking medication. Two hours after a dose, ubrogepant led to a higher rate of normal functioning (37.0% vs. 26.1%; P < .001). Ubrogepant had a similar positive effect on sensitivity to light, fatigue, neck pain, sensitivity to sound, and dizziness. Adverse events were higher during ubrogepant treatment (13.2% vs. 9.1%), and included nausea, dizziness, fatigue, and somnolence, all of which were mild. “One is really scraping the barrel [to identify adverse events]. There were no serious adverse events,” said Dr. Goadsby.
A unique result?
One questioner asked if other medications used during the prodrome might yield similar results. Dr. Goadsby expressed doubt. “I think the evidence for other treatments is not terribly good. The triptan evidence is really poor. There is no randomized, placebo-controlled trial of a triptan explicitly in promontory symptomatology. There are randomized placebo controlled trials of triptans during the aura phase. The best one was the injected sumatriptan study, and it failed. So, as far as I can see from the randomized-controlled data, triptans don’t do this, and we don’t have good data for nonsteroidals and other therapies,” said Dr. Goadsby.
The researchers showed that you could treat a patient in advance of the headache to actually prevent the headache a significant number of times; it also reduced the prodromal events and it got patients back to normal functioning to a greater extent.
Dr. Goadsby was asked how many patients are typically able to identify prodrome periods on their own. He estimated that about one in three can do it initially. “I think if you teach people how to do this, it becomes very common. I would say four out of five people in my practice are able to talk about this, but you have to introduce the topic. They’ve had [prodrome symptoms], but they haven’t thought about it for a while. This is one of the things where headache doctors can offer real benefit in helping educate patients,” said Dr. Goadsby.
Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. He is editor-in-chief of Neurology Reviews and on the Editorial Board of CNS Drugs. Dr. Goadsby has financial ties to Amgen, Eli Lilly, Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Biohaven Pharmaceuticals Inc., Dr. Reddy’s Laboratories, Electrocore, eNeura, Massachusetts Medical Society, MedicoLegal work, Novartis, Oxford University Press, Teva Pharmaceuticals, Trigemina, Up-to-Date, and Wolters Kluwer. He has a patent for headache assigned to eNeura without fee.
AUSTIN, TEX – , according to results from a new randomized, crossover study. Researchers took pains to identify migraineurs who could predict an ensuing headache 75% of the time based on prodromal symptoms. Those who could make such predictions were allowed into the randomized study.
Patients are quite good at predicting ensuing headaches when encouraged to do so, according to Peter J. Goadsby, MBBS, MD, PhD, who presented the study findings at the annual meeting of the American Headache Society.
“I find it quite useful to ask patients about these [symptoms]: Have you got cognitive clouding? Do you pass more urine? Have you got mood change? Do you feel fatigue? Associated with the attack, is how I phrase it. Get them first into the idea of thinking about the symptoms, and then get them to think about when they’re occurring. Certainly with things like brain fog, many patients will tell you that it happens. If you ask them whether they’re 100% [certain] when that’s happening, they will tell you [they’re] not. This is part of taking a history and building a relationship with the patient,” Dr. Goadsby, professor of neurology at the University of California, Los Angeles, said during the Q&A after his presentation.
‘Significant’ finding
“This is a significant finding because what patients really want is not to develop their headache and no medication has been shown to prevent a headache during the prodrome,” said Alan M. Rapoport, MD, a board certified neurologist and headache expert, as well as clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews. Successful treatment during the prodrome treatment could eliminate the need for use of preventive medication, which might decrease the patient’s adverse effects, he said.
Session comoderator Jason J. Sico, MD, took note of the patient experience during the prodrome period. “One of many noteworthy things is the large percentage of people that reported disability during prodrome before the headache. I just find that staggering, though not surprising to many of us,” he said during the session. Dr. Sico is associate professor of neurology and internal medicine at Yale University, New Haven, Conn.
Dr. Rapoport and Dr. Sico were not involved in the study.
Probing the prodrome
The study included a 60-day screening period, which had to include between 3 and 16 recorded prodrome events. Headaches had to occur within 1-6 hours in at least 75% of prodrome events. Study subjects were then randomized to 100 mg ubrogepant or placebo for up to 60 days. After their first prodrome event, they entered a 7-day washout period, and then crossed over to the other group until they experienced a second prodrome event.
During the screening period, 81.5% of prodromal events identified by patients were followed by a headache within 1-6 hours of onset. Nearly 10% of the time headache occurred in 1 hour or less, 81.5% between 1 and 6 hours, and 4.5% between 6 and 24 hours after prodrome. Commonly reported prodromal symptoms included sensitivity to light (57.2%), fatigue (50.1%), neck pain (41.9%), sensitivity to sound (33.9%), and dizziness (27.8%).
The study included 247 patients in the first sequence, and 233 in the second sequence. Patient characteristics were similar in both. Ubrogepant treatment led to a greater absence of moderate- or severe-intensity headache within 24 hours of the dose (45.5% vs. 28.6% headache-free; odds ratio [OR], 2.09; P < .0001). They were also more likely to report normal functioning over 24 hours (OR, 1.66; P < .0001) and to have absence of headache within 24 hours (23.7% vs. 13.9%; OR, 1.93; P < .0001).
Between 73% and 75% of participants reported at least mild functional disability before taking medication. Two hours after a dose, ubrogepant led to a higher rate of normal functioning (37.0% vs. 26.1%; P < .001). Ubrogepant had a similar positive effect on sensitivity to light, fatigue, neck pain, sensitivity to sound, and dizziness. Adverse events were higher during ubrogepant treatment (13.2% vs. 9.1%), and included nausea, dizziness, fatigue, and somnolence, all of which were mild. “One is really scraping the barrel [to identify adverse events]. There were no serious adverse events,” said Dr. Goadsby.
A unique result?
One questioner asked if other medications used during the prodrome might yield similar results. Dr. Goadsby expressed doubt. “I think the evidence for other treatments is not terribly good. The triptan evidence is really poor. There is no randomized, placebo-controlled trial of a triptan explicitly in promontory symptomatology. There are randomized placebo controlled trials of triptans during the aura phase. The best one was the injected sumatriptan study, and it failed. So, as far as I can see from the randomized-controlled data, triptans don’t do this, and we don’t have good data for nonsteroidals and other therapies,” said Dr. Goadsby.
The researchers showed that you could treat a patient in advance of the headache to actually prevent the headache a significant number of times; it also reduced the prodromal events and it got patients back to normal functioning to a greater extent.
Dr. Goadsby was asked how many patients are typically able to identify prodrome periods on their own. He estimated that about one in three can do it initially. “I think if you teach people how to do this, it becomes very common. I would say four out of five people in my practice are able to talk about this, but you have to introduce the topic. They’ve had [prodrome symptoms], but they haven’t thought about it for a while. This is one of the things where headache doctors can offer real benefit in helping educate patients,” said Dr. Goadsby.
Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. He is editor-in-chief of Neurology Reviews and on the Editorial Board of CNS Drugs. Dr. Goadsby has financial ties to Amgen, Eli Lilly, Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Biohaven Pharmaceuticals Inc., Dr. Reddy’s Laboratories, Electrocore, eNeura, Massachusetts Medical Society, MedicoLegal work, Novartis, Oxford University Press, Teva Pharmaceuticals, Trigemina, Up-to-Date, and Wolters Kluwer. He has a patent for headache assigned to eNeura without fee.
FROM AHS 2023
Migraine treatment with rimegepant linked to reduced barbiturate use
AUSTIN – , according to a real-world analysis. Butalbital is the only commonly prescribed short-acting barbiturate in the United States, according to Noah Rosen, MD, who presented the study at the annual meeting of the American Headache Society.
Despite its effectiveness, the drug carries a risk of abuse as well as neurologic side effects, and has also been linked to an increase in medication overuse headache, which in turn can affect quality of life and lead to more disability and health care costs. “Although acute treatment recommendations supported by AHS discourage the use of barbiturates for the acute treatment of migraine, butalbital and associated medications are still widely prescribed, so effective, low-risk novel abortive and preventive therapies that have potential barbiturate-sparing characteristics do have the potential to help people with migraine,” said Dr. Rosen during his presentation. He is the program director of neurology at Hofstra Northwell Health, Hempstead, N.Y.
His group previously showed an association between rimegepant initiation and a reduction in opioid use in another real-world analysis.
The present study retrospectively analyzed data from 34,486 patients drawn from the U.S.-based Longitudinal Access and Adjudication Data (LAAD) produced by IQVIA, which is an anonymized integrated commercial medical and prescription claims database. The period studied was between November 2015 and November 2022. The median age was 47 and 89% were female. Eligibility criteria included the presence of at least 6 months of baseline data before exposure to rimegepant and at least 6 months of follow-up, at least two rimegepant refills, and at least one butalbital prescription during the baseline period.
During the baseline period, the mean number of milligrams of butalbital dispensed was 1,012, and this dropped to 742 during follow-up (–26.7%). The mean number of butalbital prescription fills dropped from 0.47 to 0.32 (–32.0%). About half of patients (49.4%) had no butalbital refills after starting rimegepant. The researchers also examined triptan use and found no difference. “We saw that it actually made no significant difference with the deflection from baseline or discontinuation if they had been given a triptan or not. This seemed to concur with my own experiences with triptan use and not affecting barbiturate dosing,” said Dr. Rosen.
‘Good news’
The results are good news, according to Jason Sico, MD, who comoderated the session. “I remember being a PGY-2 neurology resident and hearing a lecture from Stew Tepper [now professor of medicine at Geisel School of Medicine at Dartmouth, Hanover, N.H.] that fiorinal and fioricet were the F words of headache medicine, so it’s really great to see a modality that could lower barbiturate use,” said Dr. Sico, who is an associate professor of neurology and internal medicine at Yale University, New Haven, Conn.
Dr. Rosen responded: “I don’t mean to malign a single chemical, because fioricet has provided many people treatment over time, but with the introduction of newer options, we would hope to see a trend toward that use.”
A listener on the virtual platform asked whether the decline in barbiturate use could be due to education by the provider on the dangers of barbiturate use when rimegepant was prescribed. “This is one of those big limitations of claims data analysis is we can speculate what the influence or the cause is, because this type of data analysis does not show causation. There are many different things that could influence the discontinuation. Education is a huge one, although you would hope that if somebody is prescribed butalbital on a regular basis, that there’s some physician contact or education that’s part of that as well. But it’s possible it plays a role,” said Dr. Rosen.
Any strategy to reduce butalbital use in migraine is important
Alan Rapoport, MD, who attended the session, was also asked to comment on the study. “Butalbital-containing medications can help headache pain but have not been approved by the FDA for a migraine indication. They can also decrease anxiety in the migraine patient, but if used frequently, they cause dependency. When used too often, butalbital-containing medications are major causes of medication overuse headache. They’re often used with other acute care medications such as triptans and over-the-counter products, and combinations of these drugs can be even more of a problem because one only needs to use any of these medicines in combination for 10 days a month or more, for at least 3 months, for a doctor to diagnose a patient with medication overuse headache. So any attempt and success to reduce the frequency of taking butalbital-containing medication is important. That can be done by counseling the patient to take fewer tablets per month, but this often does not work. This study shows a good success rate in reducing the use of these medications by treating the patient with rimegepant 75 mg ODT given once every other day. This dose has been approved by the FDA for prevention in migraine, but has not previously been shown as a treatment for overuse of butalbital or medication. Previous studies have shown that rimegepant reduced migraine days per month and the use of acute care medications monthly. It this study, rimegepant decreases the number of butalbital-containing medications taken,” said Dr. Rapoport, who is a clinical professor of neurology at the University of California, Los Angeles, and editor in chief of Neurology Reviews.
Dr. Rosen has financial ties to Allergan/Abbvie, Amgen, BioHaven, Eli Lilly, Lundbeck, Novartis, Supernus, and Teva. Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureaus of AbbVie, Dr. Reddy’s, Impel, Pfizer, and Teva Pharmaceutical Industries. He is editor in chief of Neurology Reviews and on the editorial board of CNS Drugs.
AUSTIN – , according to a real-world analysis. Butalbital is the only commonly prescribed short-acting barbiturate in the United States, according to Noah Rosen, MD, who presented the study at the annual meeting of the American Headache Society.
Despite its effectiveness, the drug carries a risk of abuse as well as neurologic side effects, and has also been linked to an increase in medication overuse headache, which in turn can affect quality of life and lead to more disability and health care costs. “Although acute treatment recommendations supported by AHS discourage the use of barbiturates for the acute treatment of migraine, butalbital and associated medications are still widely prescribed, so effective, low-risk novel abortive and preventive therapies that have potential barbiturate-sparing characteristics do have the potential to help people with migraine,” said Dr. Rosen during his presentation. He is the program director of neurology at Hofstra Northwell Health, Hempstead, N.Y.
His group previously showed an association between rimegepant initiation and a reduction in opioid use in another real-world analysis.
The present study retrospectively analyzed data from 34,486 patients drawn from the U.S.-based Longitudinal Access and Adjudication Data (LAAD) produced by IQVIA, which is an anonymized integrated commercial medical and prescription claims database. The period studied was between November 2015 and November 2022. The median age was 47 and 89% were female. Eligibility criteria included the presence of at least 6 months of baseline data before exposure to rimegepant and at least 6 months of follow-up, at least two rimegepant refills, and at least one butalbital prescription during the baseline period.
During the baseline period, the mean number of milligrams of butalbital dispensed was 1,012, and this dropped to 742 during follow-up (–26.7%). The mean number of butalbital prescription fills dropped from 0.47 to 0.32 (–32.0%). About half of patients (49.4%) had no butalbital refills after starting rimegepant. The researchers also examined triptan use and found no difference. “We saw that it actually made no significant difference with the deflection from baseline or discontinuation if they had been given a triptan or not. This seemed to concur with my own experiences with triptan use and not affecting barbiturate dosing,” said Dr. Rosen.
‘Good news’
The results are good news, according to Jason Sico, MD, who comoderated the session. “I remember being a PGY-2 neurology resident and hearing a lecture from Stew Tepper [now professor of medicine at Geisel School of Medicine at Dartmouth, Hanover, N.H.] that fiorinal and fioricet were the F words of headache medicine, so it’s really great to see a modality that could lower barbiturate use,” said Dr. Sico, who is an associate professor of neurology and internal medicine at Yale University, New Haven, Conn.
Dr. Rosen responded: “I don’t mean to malign a single chemical, because fioricet has provided many people treatment over time, but with the introduction of newer options, we would hope to see a trend toward that use.”
A listener on the virtual platform asked whether the decline in barbiturate use could be due to education by the provider on the dangers of barbiturate use when rimegepant was prescribed. “This is one of those big limitations of claims data analysis is we can speculate what the influence or the cause is, because this type of data analysis does not show causation. There are many different things that could influence the discontinuation. Education is a huge one, although you would hope that if somebody is prescribed butalbital on a regular basis, that there’s some physician contact or education that’s part of that as well. But it’s possible it plays a role,” said Dr. Rosen.
Any strategy to reduce butalbital use in migraine is important
Alan Rapoport, MD, who attended the session, was also asked to comment on the study. “Butalbital-containing medications can help headache pain but have not been approved by the FDA for a migraine indication. They can also decrease anxiety in the migraine patient, but if used frequently, they cause dependency. When used too often, butalbital-containing medications are major causes of medication overuse headache. They’re often used with other acute care medications such as triptans and over-the-counter products, and combinations of these drugs can be even more of a problem because one only needs to use any of these medicines in combination for 10 days a month or more, for at least 3 months, for a doctor to diagnose a patient with medication overuse headache. So any attempt and success to reduce the frequency of taking butalbital-containing medication is important. That can be done by counseling the patient to take fewer tablets per month, but this often does not work. This study shows a good success rate in reducing the use of these medications by treating the patient with rimegepant 75 mg ODT given once every other day. This dose has been approved by the FDA for prevention in migraine, but has not previously been shown as a treatment for overuse of butalbital or medication. Previous studies have shown that rimegepant reduced migraine days per month and the use of acute care medications monthly. It this study, rimegepant decreases the number of butalbital-containing medications taken,” said Dr. Rapoport, who is a clinical professor of neurology at the University of California, Los Angeles, and editor in chief of Neurology Reviews.
Dr. Rosen has financial ties to Allergan/Abbvie, Amgen, BioHaven, Eli Lilly, Lundbeck, Novartis, Supernus, and Teva. Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureaus of AbbVie, Dr. Reddy’s, Impel, Pfizer, and Teva Pharmaceutical Industries. He is editor in chief of Neurology Reviews and on the editorial board of CNS Drugs.
AUSTIN – , according to a real-world analysis. Butalbital is the only commonly prescribed short-acting barbiturate in the United States, according to Noah Rosen, MD, who presented the study at the annual meeting of the American Headache Society.
Despite its effectiveness, the drug carries a risk of abuse as well as neurologic side effects, and has also been linked to an increase in medication overuse headache, which in turn can affect quality of life and lead to more disability and health care costs. “Although acute treatment recommendations supported by AHS discourage the use of barbiturates for the acute treatment of migraine, butalbital and associated medications are still widely prescribed, so effective, low-risk novel abortive and preventive therapies that have potential barbiturate-sparing characteristics do have the potential to help people with migraine,” said Dr. Rosen during his presentation. He is the program director of neurology at Hofstra Northwell Health, Hempstead, N.Y.
His group previously showed an association between rimegepant initiation and a reduction in opioid use in another real-world analysis.
The present study retrospectively analyzed data from 34,486 patients drawn from the U.S.-based Longitudinal Access and Adjudication Data (LAAD) produced by IQVIA, which is an anonymized integrated commercial medical and prescription claims database. The period studied was between November 2015 and November 2022. The median age was 47 and 89% were female. Eligibility criteria included the presence of at least 6 months of baseline data before exposure to rimegepant and at least 6 months of follow-up, at least two rimegepant refills, and at least one butalbital prescription during the baseline period.
During the baseline period, the mean number of milligrams of butalbital dispensed was 1,012, and this dropped to 742 during follow-up (–26.7%). The mean number of butalbital prescription fills dropped from 0.47 to 0.32 (–32.0%). About half of patients (49.4%) had no butalbital refills after starting rimegepant. The researchers also examined triptan use and found no difference. “We saw that it actually made no significant difference with the deflection from baseline or discontinuation if they had been given a triptan or not. This seemed to concur with my own experiences with triptan use and not affecting barbiturate dosing,” said Dr. Rosen.
‘Good news’
The results are good news, according to Jason Sico, MD, who comoderated the session. “I remember being a PGY-2 neurology resident and hearing a lecture from Stew Tepper [now professor of medicine at Geisel School of Medicine at Dartmouth, Hanover, N.H.] that fiorinal and fioricet were the F words of headache medicine, so it’s really great to see a modality that could lower barbiturate use,” said Dr. Sico, who is an associate professor of neurology and internal medicine at Yale University, New Haven, Conn.
Dr. Rosen responded: “I don’t mean to malign a single chemical, because fioricet has provided many people treatment over time, but with the introduction of newer options, we would hope to see a trend toward that use.”
A listener on the virtual platform asked whether the decline in barbiturate use could be due to education by the provider on the dangers of barbiturate use when rimegepant was prescribed. “This is one of those big limitations of claims data analysis is we can speculate what the influence or the cause is, because this type of data analysis does not show causation. There are many different things that could influence the discontinuation. Education is a huge one, although you would hope that if somebody is prescribed butalbital on a regular basis, that there’s some physician contact or education that’s part of that as well. But it’s possible it plays a role,” said Dr. Rosen.
Any strategy to reduce butalbital use in migraine is important
Alan Rapoport, MD, who attended the session, was also asked to comment on the study. “Butalbital-containing medications can help headache pain but have not been approved by the FDA for a migraine indication. They can also decrease anxiety in the migraine patient, but if used frequently, they cause dependency. When used too often, butalbital-containing medications are major causes of medication overuse headache. They’re often used with other acute care medications such as triptans and over-the-counter products, and combinations of these drugs can be even more of a problem because one only needs to use any of these medicines in combination for 10 days a month or more, for at least 3 months, for a doctor to diagnose a patient with medication overuse headache. So any attempt and success to reduce the frequency of taking butalbital-containing medication is important. That can be done by counseling the patient to take fewer tablets per month, but this often does not work. This study shows a good success rate in reducing the use of these medications by treating the patient with rimegepant 75 mg ODT given once every other day. This dose has been approved by the FDA for prevention in migraine, but has not previously been shown as a treatment for overuse of butalbital or medication. Previous studies have shown that rimegepant reduced migraine days per month and the use of acute care medications monthly. It this study, rimegepant decreases the number of butalbital-containing medications taken,” said Dr. Rapoport, who is a clinical professor of neurology at the University of California, Los Angeles, and editor in chief of Neurology Reviews.
Dr. Rosen has financial ties to Allergan/Abbvie, Amgen, BioHaven, Eli Lilly, Lundbeck, Novartis, Supernus, and Teva. Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureaus of AbbVie, Dr. Reddy’s, Impel, Pfizer, and Teva Pharmaceutical Industries. He is editor in chief of Neurology Reviews and on the editorial board of CNS Drugs.
FROM AHS 2023
Safety first: Regulations
The word “regulations” gets a mixed response.
This is common in all industries, and certainly pharmaceuticals. On any given day there are stories on industry news sites about disputes between companies and regulatory agencies.
I’d agree that some regulation is needed. The history of pharmacy has had both remarkable successes – and failures.
Let’s look at migraines, since that’s in my field. The calcitonin gene-related peptide (CGRP) drugs have been a remarkable breakthrough, certainly the biggest one since the triptans in 1992. There are currently seven on the market for both prevention and abortive use. They’re effective and (to date) pretty safe.
But it wasn’t always that way. Look back just 14 years ago to 2009, when the first promising CGRP agent (MK-3207) had its development halted because of hepatic abnormalities. It’s cousin telcagepant (MK-0974) came to a similar end 2 years later.
Without regulations in place (and the potential for lawsuits) these might have made it to market, bringing migraine relief to some and potentially serious liver damage to others. So Merck made the right decision to axe them. Researchers learned from the experience, went back to the drawing board, and developed the current generation of far-safer drugs.
This came into sharp focus in another industry recently, when the eyes of the world were on the north Atlantic. A small tourist submarine imploded and killed five people. During the inevitable media coverage it came out that the submarine hadn’t been certified for safety by any of the agencies that handle such things, falling into a gray area in international waters where inspections aren’t required.
This isn’t to say it wasn’t safe – it had made several dives before – but obviously not safe enough. While I didn’t know the late Stockton Rush (the owner/designer) it sounds like he viewed regulations as stifling innovation, and in one interview said “at some point, safety is just pure waste.” He ignored warnings from several sides about the submersible’s ability to handle deep ocean pressure and the inevitable wear and tear repeated dives will have on the hull.
I understand there’s a margin of luck, too. Bad things can happen to any of us – or any company. Some things can’t be clearly foreseen. Some drugs don’t start to show problems until they’re on the market and reach a certain number of prescriptions.
But there’s a reason we have regulations. Pretty much every government has, going back to the Roman Empire, covering numerous things. In a perfect world we wouldn’t need them.
But people are far from perfect. And the consequences can be terrible.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
The word “regulations” gets a mixed response.
This is common in all industries, and certainly pharmaceuticals. On any given day there are stories on industry news sites about disputes between companies and regulatory agencies.
I’d agree that some regulation is needed. The history of pharmacy has had both remarkable successes – and failures.
Let’s look at migraines, since that’s in my field. The calcitonin gene-related peptide (CGRP) drugs have been a remarkable breakthrough, certainly the biggest one since the triptans in 1992. There are currently seven on the market for both prevention and abortive use. They’re effective and (to date) pretty safe.
But it wasn’t always that way. Look back just 14 years ago to 2009, when the first promising CGRP agent (MK-3207) had its development halted because of hepatic abnormalities. It’s cousin telcagepant (MK-0974) came to a similar end 2 years later.
Without regulations in place (and the potential for lawsuits) these might have made it to market, bringing migraine relief to some and potentially serious liver damage to others. So Merck made the right decision to axe them. Researchers learned from the experience, went back to the drawing board, and developed the current generation of far-safer drugs.
This came into sharp focus in another industry recently, when the eyes of the world were on the north Atlantic. A small tourist submarine imploded and killed five people. During the inevitable media coverage it came out that the submarine hadn’t been certified for safety by any of the agencies that handle such things, falling into a gray area in international waters where inspections aren’t required.
This isn’t to say it wasn’t safe – it had made several dives before – but obviously not safe enough. While I didn’t know the late Stockton Rush (the owner/designer) it sounds like he viewed regulations as stifling innovation, and in one interview said “at some point, safety is just pure waste.” He ignored warnings from several sides about the submersible’s ability to handle deep ocean pressure and the inevitable wear and tear repeated dives will have on the hull.
I understand there’s a margin of luck, too. Bad things can happen to any of us – or any company. Some things can’t be clearly foreseen. Some drugs don’t start to show problems until they’re on the market and reach a certain number of prescriptions.
But there’s a reason we have regulations. Pretty much every government has, going back to the Roman Empire, covering numerous things. In a perfect world we wouldn’t need them.
But people are far from perfect. And the consequences can be terrible.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
The word “regulations” gets a mixed response.
This is common in all industries, and certainly pharmaceuticals. On any given day there are stories on industry news sites about disputes between companies and regulatory agencies.
I’d agree that some regulation is needed. The history of pharmacy has had both remarkable successes – and failures.
Let’s look at migraines, since that’s in my field. The calcitonin gene-related peptide (CGRP) drugs have been a remarkable breakthrough, certainly the biggest one since the triptans in 1992. There are currently seven on the market for both prevention and abortive use. They’re effective and (to date) pretty safe.
But it wasn’t always that way. Look back just 14 years ago to 2009, when the first promising CGRP agent (MK-3207) had its development halted because of hepatic abnormalities. It’s cousin telcagepant (MK-0974) came to a similar end 2 years later.
Without regulations in place (and the potential for lawsuits) these might have made it to market, bringing migraine relief to some and potentially serious liver damage to others. So Merck made the right decision to axe them. Researchers learned from the experience, went back to the drawing board, and developed the current generation of far-safer drugs.
This came into sharp focus in another industry recently, when the eyes of the world were on the north Atlantic. A small tourist submarine imploded and killed five people. During the inevitable media coverage it came out that the submarine hadn’t been certified for safety by any of the agencies that handle such things, falling into a gray area in international waters where inspections aren’t required.
This isn’t to say it wasn’t safe – it had made several dives before – but obviously not safe enough. While I didn’t know the late Stockton Rush (the owner/designer) it sounds like he viewed regulations as stifling innovation, and in one interview said “at some point, safety is just pure waste.” He ignored warnings from several sides about the submersible’s ability to handle deep ocean pressure and the inevitable wear and tear repeated dives will have on the hull.
I understand there’s a margin of luck, too. Bad things can happen to any of us – or any company. Some things can’t be clearly foreseen. Some drugs don’t start to show problems until they’re on the market and reach a certain number of prescriptions.
But there’s a reason we have regulations. Pretty much every government has, going back to the Roman Empire, covering numerous things. In a perfect world we wouldn’t need them.
But people are far from perfect. And the consequences can be terrible.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Anti-CGRP monoclonal antibody offers relief from migraine and comorbid depression
AUSTIN, TEX. – , new research shows.
Patients with both conditions who were randomly assigned to receive fremanezumab showed a statistically significant reduction in both the 17-item Hamilton Depression Rating Scale (HAMD-17) and the nine-criteria Patient Health Questionnaire (PHQ-9) scores, compared with matched controls who received placebo.
The results from the UNITE trial were presented at the annual meeting of the American Headache Society.
Long-standing questions
“It’s been well known for a long time that migraine is comorbid with a number of illnesses, and one of the most common is depression,” said study investigator Richard B. Lipton, a professor of neurology at Albert Einstein College of Medicine and the director of the Montefiore Headache Center, New York.
“Do you treat the depression? Do you treat the migraine? Do you independently treat both? Those have been long-standing questions for clinicians,” Dr. Lipton said.
Investigators randomly assigned 330 adults with migraine who were diagnosed with moderate-to-severe MDD (defined as a PHQ-9 score of 10 or greater) to receive 225 mg subcutaneous monthly fremanezumab (n = 164) or placebo (n = 166) for 12 weeks.
The trial continued as an open-label trial for another 12 weeks.
During the double-blind phase of the study, the mean change from baseline in the HAMD-17 score with placebo was –4.6 at week 8 and –5.4 at week 12, compared with –6.0 with fremanezumab at week 8 (P = .0205) and –6.7 at week 12 (P = .0228).
The change from baseline in PHQ-9 total score at week 8 was –5.8 for placebo and –7.1 for fremanezumab (P = .0283). At week 12, the change was –6.3 for placebo versus –7.8 for fremanezumab (P = .0108). These reductions were maintained throughout the open-label period of the trial.
The beneficial effect on depression and migraine demonstrated in the study is interesting on several levels, Dr. Lipton said.
“One, it tells us that if the patient has migraine and depression and you treat with fremanezumab, both disorders get better to a statistically significant degree. That’s critically important,” he said.
“The other thing, and this is actually what I find most interesting about this study, is that fremanezumab doesn’t get into the brain. There are many antimigraine therapies that do, so you can treat a patient with migraine and depression with a tricyclic antidepressant.”
“It may make the migraine better and the depression better, but you don’t know if the benefit in depression comes from the improvement in migraine, because of course the antidepressant works for both conditions. Maybe there are people who would disagree with this, but my interpretation [of the trial results] is that the depression got better because the migraine got better,” he added.
The link between migraine and depression is well established, Dr. Lipton added. Longitudinal studies have shown that people with depression but without migraine develop migraine at increased rates, compared with people with no depression. Conversely, people with migraine but no depression develop depression at increased rates.
“Both disorders may have a common substrate, but I also think many forms of chronic pain lead to depression, and that’s the part we’re making better,” he said.
If fremanezumab has this dual effect on migraine and depression, it is possible that other anti-CGRP drugs will have a similar effect, Dr. Lipton said.
“Honestly, my hope is that other companies that make effective drugs will do similar studies to see if other monoclonal antibodies that target CGRP have the same effect. My guess is that all of them work but until the studies are done, I’m going to use fremanezumab, the one that has been studied, in my patients.”
He added that depression is an important comorbidity of migraine and represents a huge challenge for clinicians. “A lot of headache patients want to know what to do about comorbid anxiety or comorbid depression. I run a headache center in a specialty practice, and when people come in with migraine, they almost always come in with migraine and depression or anxiety or another pain disorder, or something else, and one of the great challenges in the practice is managing these comorbidities,” he said.
A bidirectional relationship
The overlap between migraine and depression and anxiety has been known for quite a while, agreed Elizabeth W. Loder, MD, MPH, vice chair of academic affairs, department of neurology, Brigham and Women’s Hospital, and professor of neurology at Harvard Medical School, both in Boston.
“I think the relationship is generally viewed as bidirectional and causality is uncertain. I still do not think I would assume that any drug that reduces migraine would reduce depression,” said Dr. Loder.
However, she added, the fremanezumab study data are interesting. “The effects of any drug on depression could be due to improvement of migraine or it could be due to some other effect of the treatment on depression. That is what makes these results so intriguing. If the findings are borne out by other studies, it could mean that these treatments would be preferred to those older ones in patients with depression,” Dr. Loder said.
Also commenting on the findings, Huma Sheikh, MD, CEO of NY Neurology Medicine PC, said the study is important because it confirms the strong association between migraine and depression. “Both conditions have similar underlying neurobiological pathophysiologies, and if you are impacting one area in the brain with the CGRP inhibitors, you might also be targeting some of the receptors or pathways that are involved in depression,” Dr. Sheikh said.
The study was funded by Teva Pharmaceuticals. Dr. Lipton reported financial relationships with Teva and multiple other pharmaceutical companies. Dr. Loder and Dr. Sheikh have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AUSTIN, TEX. – , new research shows.
Patients with both conditions who were randomly assigned to receive fremanezumab showed a statistically significant reduction in both the 17-item Hamilton Depression Rating Scale (HAMD-17) and the nine-criteria Patient Health Questionnaire (PHQ-9) scores, compared with matched controls who received placebo.
The results from the UNITE trial were presented at the annual meeting of the American Headache Society.
Long-standing questions
“It’s been well known for a long time that migraine is comorbid with a number of illnesses, and one of the most common is depression,” said study investigator Richard B. Lipton, a professor of neurology at Albert Einstein College of Medicine and the director of the Montefiore Headache Center, New York.
“Do you treat the depression? Do you treat the migraine? Do you independently treat both? Those have been long-standing questions for clinicians,” Dr. Lipton said.
Investigators randomly assigned 330 adults with migraine who were diagnosed with moderate-to-severe MDD (defined as a PHQ-9 score of 10 or greater) to receive 225 mg subcutaneous monthly fremanezumab (n = 164) or placebo (n = 166) for 12 weeks.
The trial continued as an open-label trial for another 12 weeks.
During the double-blind phase of the study, the mean change from baseline in the HAMD-17 score with placebo was –4.6 at week 8 and –5.4 at week 12, compared with –6.0 with fremanezumab at week 8 (P = .0205) and –6.7 at week 12 (P = .0228).
The change from baseline in PHQ-9 total score at week 8 was –5.8 for placebo and –7.1 for fremanezumab (P = .0283). At week 12, the change was –6.3 for placebo versus –7.8 for fremanezumab (P = .0108). These reductions were maintained throughout the open-label period of the trial.
The beneficial effect on depression and migraine demonstrated in the study is interesting on several levels, Dr. Lipton said.
“One, it tells us that if the patient has migraine and depression and you treat with fremanezumab, both disorders get better to a statistically significant degree. That’s critically important,” he said.
“The other thing, and this is actually what I find most interesting about this study, is that fremanezumab doesn’t get into the brain. There are many antimigraine therapies that do, so you can treat a patient with migraine and depression with a tricyclic antidepressant.”
“It may make the migraine better and the depression better, but you don’t know if the benefit in depression comes from the improvement in migraine, because of course the antidepressant works for both conditions. Maybe there are people who would disagree with this, but my interpretation [of the trial results] is that the depression got better because the migraine got better,” he added.
The link between migraine and depression is well established, Dr. Lipton added. Longitudinal studies have shown that people with depression but without migraine develop migraine at increased rates, compared with people with no depression. Conversely, people with migraine but no depression develop depression at increased rates.
“Both disorders may have a common substrate, but I also think many forms of chronic pain lead to depression, and that’s the part we’re making better,” he said.
If fremanezumab has this dual effect on migraine and depression, it is possible that other anti-CGRP drugs will have a similar effect, Dr. Lipton said.
“Honestly, my hope is that other companies that make effective drugs will do similar studies to see if other monoclonal antibodies that target CGRP have the same effect. My guess is that all of them work but until the studies are done, I’m going to use fremanezumab, the one that has been studied, in my patients.”
He added that depression is an important comorbidity of migraine and represents a huge challenge for clinicians. “A lot of headache patients want to know what to do about comorbid anxiety or comorbid depression. I run a headache center in a specialty practice, and when people come in with migraine, they almost always come in with migraine and depression or anxiety or another pain disorder, or something else, and one of the great challenges in the practice is managing these comorbidities,” he said.
A bidirectional relationship
The overlap between migraine and depression and anxiety has been known for quite a while, agreed Elizabeth W. Loder, MD, MPH, vice chair of academic affairs, department of neurology, Brigham and Women’s Hospital, and professor of neurology at Harvard Medical School, both in Boston.
“I think the relationship is generally viewed as bidirectional and causality is uncertain. I still do not think I would assume that any drug that reduces migraine would reduce depression,” said Dr. Loder.
However, she added, the fremanezumab study data are interesting. “The effects of any drug on depression could be due to improvement of migraine or it could be due to some other effect of the treatment on depression. That is what makes these results so intriguing. If the findings are borne out by other studies, it could mean that these treatments would be preferred to those older ones in patients with depression,” Dr. Loder said.
Also commenting on the findings, Huma Sheikh, MD, CEO of NY Neurology Medicine PC, said the study is important because it confirms the strong association between migraine and depression. “Both conditions have similar underlying neurobiological pathophysiologies, and if you are impacting one area in the brain with the CGRP inhibitors, you might also be targeting some of the receptors or pathways that are involved in depression,” Dr. Sheikh said.
The study was funded by Teva Pharmaceuticals. Dr. Lipton reported financial relationships with Teva and multiple other pharmaceutical companies. Dr. Loder and Dr. Sheikh have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AUSTIN, TEX. – , new research shows.
Patients with both conditions who were randomly assigned to receive fremanezumab showed a statistically significant reduction in both the 17-item Hamilton Depression Rating Scale (HAMD-17) and the nine-criteria Patient Health Questionnaire (PHQ-9) scores, compared with matched controls who received placebo.
The results from the UNITE trial were presented at the annual meeting of the American Headache Society.
Long-standing questions
“It’s been well known for a long time that migraine is comorbid with a number of illnesses, and one of the most common is depression,” said study investigator Richard B. Lipton, a professor of neurology at Albert Einstein College of Medicine and the director of the Montefiore Headache Center, New York.
“Do you treat the depression? Do you treat the migraine? Do you independently treat both? Those have been long-standing questions for clinicians,” Dr. Lipton said.
Investigators randomly assigned 330 adults with migraine who were diagnosed with moderate-to-severe MDD (defined as a PHQ-9 score of 10 or greater) to receive 225 mg subcutaneous monthly fremanezumab (n = 164) or placebo (n = 166) for 12 weeks.
The trial continued as an open-label trial for another 12 weeks.
During the double-blind phase of the study, the mean change from baseline in the HAMD-17 score with placebo was –4.6 at week 8 and –5.4 at week 12, compared with –6.0 with fremanezumab at week 8 (P = .0205) and –6.7 at week 12 (P = .0228).
The change from baseline in PHQ-9 total score at week 8 was –5.8 for placebo and –7.1 for fremanezumab (P = .0283). At week 12, the change was –6.3 for placebo versus –7.8 for fremanezumab (P = .0108). These reductions were maintained throughout the open-label period of the trial.
The beneficial effect on depression and migraine demonstrated in the study is interesting on several levels, Dr. Lipton said.
“One, it tells us that if the patient has migraine and depression and you treat with fremanezumab, both disorders get better to a statistically significant degree. That’s critically important,” he said.
“The other thing, and this is actually what I find most interesting about this study, is that fremanezumab doesn’t get into the brain. There are many antimigraine therapies that do, so you can treat a patient with migraine and depression with a tricyclic antidepressant.”
“It may make the migraine better and the depression better, but you don’t know if the benefit in depression comes from the improvement in migraine, because of course the antidepressant works for both conditions. Maybe there are people who would disagree with this, but my interpretation [of the trial results] is that the depression got better because the migraine got better,” he added.
The link between migraine and depression is well established, Dr. Lipton added. Longitudinal studies have shown that people with depression but without migraine develop migraine at increased rates, compared with people with no depression. Conversely, people with migraine but no depression develop depression at increased rates.
“Both disorders may have a common substrate, but I also think many forms of chronic pain lead to depression, and that’s the part we’re making better,” he said.
If fremanezumab has this dual effect on migraine and depression, it is possible that other anti-CGRP drugs will have a similar effect, Dr. Lipton said.
“Honestly, my hope is that other companies that make effective drugs will do similar studies to see if other monoclonal antibodies that target CGRP have the same effect. My guess is that all of them work but until the studies are done, I’m going to use fremanezumab, the one that has been studied, in my patients.”
He added that depression is an important comorbidity of migraine and represents a huge challenge for clinicians. “A lot of headache patients want to know what to do about comorbid anxiety or comorbid depression. I run a headache center in a specialty practice, and when people come in with migraine, they almost always come in with migraine and depression or anxiety or another pain disorder, or something else, and one of the great challenges in the practice is managing these comorbidities,” he said.
A bidirectional relationship
The overlap between migraine and depression and anxiety has been known for quite a while, agreed Elizabeth W. Loder, MD, MPH, vice chair of academic affairs, department of neurology, Brigham and Women’s Hospital, and professor of neurology at Harvard Medical School, both in Boston.
“I think the relationship is generally viewed as bidirectional and causality is uncertain. I still do not think I would assume that any drug that reduces migraine would reduce depression,” said Dr. Loder.
However, she added, the fremanezumab study data are interesting. “The effects of any drug on depression could be due to improvement of migraine or it could be due to some other effect of the treatment on depression. That is what makes these results so intriguing. If the findings are borne out by other studies, it could mean that these treatments would be preferred to those older ones in patients with depression,” Dr. Loder said.
Also commenting on the findings, Huma Sheikh, MD, CEO of NY Neurology Medicine PC, said the study is important because it confirms the strong association between migraine and depression. “Both conditions have similar underlying neurobiological pathophysiologies, and if you are impacting one area in the brain with the CGRP inhibitors, you might also be targeting some of the receptors or pathways that are involved in depression,” Dr. Sheikh said.
The study was funded by Teva Pharmaceuticals. Dr. Lipton reported financial relationships with Teva and multiple other pharmaceutical companies. Dr. Loder and Dr. Sheikh have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT AHS 2023
Can a puff of cool air up the nose stop acute migraine?
AUSTIN, TEX. – , according to the results of a small study. Most patients reported relief of their symptoms after receiving 15 minutes of transnasal evaporative cooling, without any need for rescue medication.
The cooling may modulate the sphenopalatine ganglion, a large ganglion implicated in migraine, said lead author Larry Charleston IV, MD, director of the headache and facial pain division, and professor of neurology at Michigan State University, East Lansing.
“The transnasal evaporative cooling device cools by blowing dry, ambient air across the nasal turbinates and may work by neuromodulation via the sphenopalatine ganglion for migraine,” Dr. Charleston said.
The findings were presented at the annual meeting of the American Headache Society.
A ‘cool’ approach to migraine treatment
“Everyone who has migraine disease needs abortive treatment,” Dr. Charleston said. “There is a need for safe and effective acute treatment for migraine. As we understand more about the pathophysiology of migraine, we learn that peripheral input plays a role in migraine disease.
“I was excited to learn of the device and to learn how we might take advantage of our knowledge of the sphenopalatine ganglia in the treatment of migraine, and was very enthusiastic to be involved in researching a nonpharmacological treatment to abort migraine attacks,” he said. “I thought this approach to migraine treatment was really ‘cool.’ ”
Twenty-four patients who met diagnostic criteria for episodic migraine with or without aura were randomized to receive 15 minutes of cooling induced by the CoolStat Transnasal Thermal Regulating Device (CoolTech LLC), or to a sham treatment with a CoolStat sham device.
Participants receiving active treatment were further randomized to receive one of the following flow rates: 24 liters per minute (LPM; n = 6 patients), 18 LPM (n = 9 patients), and 6 LPM (n = 9 patients).
All patients were instructed to get to their headache clinic during a migraine attack to start treatment.
The researchers looked at pain levels and most bothersome symptoms at baseline, and then at 2 and 24 hours after treatment. The primary endpoint was pain relief at 2 hours. Other endpoints included tolerability, relief from most bothersome symptoms, and freedom from pain at 2 hours.
The results showed that 88% (8/9 patients) of the 6-LPM group reported pain relief at 2 hours. Of these, 44% (4/9) reported being pain free at 2 hours, all without need for rescue medication. Similarly, pain relief at 2 hours occurred in 44% (4/9) of patients in the 18-LPM group, and in 50% (3/6) of the patients in the 24-LPM group.
No participants in the 18-LPM or the 24-LPM groups reported pain freedom at 2 hours.
Most bothersome symptoms were reduced. Response was greater with 6-LPM treatment. At 2 hours, 77% (7/9) of patients in the 6-LPM group reported relief of their symptoms, followed by 66% (6/9) of the 18-LPM group and 50% (3/6) of the 24-LPM group.
However, nasal discomfort was a bothersome adverse effect, Dr. Charleston noted. The rate of nasal discomfort occurred in all groups but was lower in the 6-LPM group.
Moderate intranasal discomfort during treatment was reported by 11% of the 6-LPM group, compared with 33% (3/9) in the 18-LPM group and 83% (5/6) in the 24-LPM group.
However, the study was terminated due to insufficient subject accrual rate.
“Originally, 87 participants were recruited and consented. It may have been challenging for some to come in to study clinic sites for the study treatment at the onset of their migraine attacks. The next iteration of the treatment device is a more portable model and study treatment may be used at home. This will likely be more convenient and enhance study participation,” Dr. Charleston said.
The data in the current study will help inform dose ranging analyses in future studies, to optimize efficacy and increase tolerability, he added.
The findings are promising and merit further assessment in a larger study with a sham control group, said Richard B. Lipton, MD, Edwin S. Lowe Professor and vice chair of neurology, and director of the Montefiore Headache Center, Albert Einstein College of Medicine, New York.
“Charleston et al. report that the lowest flow dose (6 liters per minute) was most effective, with a 2-hour pain-relief rate of 88% and a 2-hour pain-free rate of 50%, but, though these rates of pain relief and pain freedom are high, caution in interpretation is required,” Dr. Lipton said.
“The sample size is very modest with only nine patients in the 6-liter-per-minute treatment arm. In addition, the study lacks results from the group that got the sham device, making it difficult to contextualize the findings,” Dr. Lipton said.
He added that it is unusual for higher doses to be less effective but that may be because air flow higher than 6 LPM is irritating to the nasal mucosa during migraine attacks.
Always a need for effective nonpharmaceuticals
Also commenting on this study, Nina Riggins, MD, director of the Headache Center at the University of California, San Diego, said she found the novel device “exciting and really clever.
“I really enjoyed reviewing this abstract because I am a big fan of sphenopalatine ganglion block in the palatine ganglion. When we do those, we basically apply numbing medication to decrease the sensation and discharges coming from this group of neural cells in order to decrease pain,” Dr. Riggins said. “The procedure is very well tolerated and usually sphenopalatine ganglion blocks are used in patients when we do not want any side effects, such as in pregnant and postpartum women.”
The novel technique has the potential to have fewer side effects than those of oral medications, she said. “For example, the triptans are effective drugs but they constrict the blood vessels and we don’t want to use them in people with heart disease or history of stroke. This is where these potentially safer devices can play an important role. We can have more options to offer our patients,” Dr. Riggins said.
“I am super excited and looking forward to see what will come out of future research. I am really grateful that the authors are looking into new neuromodulation devices which can be so useful,” she said.
Migraine is the second leading cause of disability worldwide, Dr. Riggins noted. “It peaks in the years when people are most productive and affects families and communities. Medications are good, of course, but now with these novel devices, these are wonderful areas for research. Also now, we can offer so much more to people with migraine and other headache disorders,” she said.
“When I started in the field, I remember we were very limited in resources, and now, it’s just so wonderful.”
The study was sponsored by CoolTech Corp LLC. Dr. Charleston reports financial relationships with Allergan/AbbVie, Amgen, Amneal, Biohaven, Haleon, Linpharma, Satsuma, and Teva, and that he has received CME honoraria from the American Headache Society and the American Academy of Neurology. Dr. Lipton reports financial relationships with multiple pharmaceutical companies. Dr. Riggins reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AUSTIN, TEX. – , according to the results of a small study. Most patients reported relief of their symptoms after receiving 15 minutes of transnasal evaporative cooling, without any need for rescue medication.
The cooling may modulate the sphenopalatine ganglion, a large ganglion implicated in migraine, said lead author Larry Charleston IV, MD, director of the headache and facial pain division, and professor of neurology at Michigan State University, East Lansing.
“The transnasal evaporative cooling device cools by blowing dry, ambient air across the nasal turbinates and may work by neuromodulation via the sphenopalatine ganglion for migraine,” Dr. Charleston said.
The findings were presented at the annual meeting of the American Headache Society.
A ‘cool’ approach to migraine treatment
“Everyone who has migraine disease needs abortive treatment,” Dr. Charleston said. “There is a need for safe and effective acute treatment for migraine. As we understand more about the pathophysiology of migraine, we learn that peripheral input plays a role in migraine disease.
“I was excited to learn of the device and to learn how we might take advantage of our knowledge of the sphenopalatine ganglia in the treatment of migraine, and was very enthusiastic to be involved in researching a nonpharmacological treatment to abort migraine attacks,” he said. “I thought this approach to migraine treatment was really ‘cool.’ ”
Twenty-four patients who met diagnostic criteria for episodic migraine with or without aura were randomized to receive 15 minutes of cooling induced by the CoolStat Transnasal Thermal Regulating Device (CoolTech LLC), or to a sham treatment with a CoolStat sham device.
Participants receiving active treatment were further randomized to receive one of the following flow rates: 24 liters per minute (LPM; n = 6 patients), 18 LPM (n = 9 patients), and 6 LPM (n = 9 patients).
All patients were instructed to get to their headache clinic during a migraine attack to start treatment.
The researchers looked at pain levels and most bothersome symptoms at baseline, and then at 2 and 24 hours after treatment. The primary endpoint was pain relief at 2 hours. Other endpoints included tolerability, relief from most bothersome symptoms, and freedom from pain at 2 hours.
The results showed that 88% (8/9 patients) of the 6-LPM group reported pain relief at 2 hours. Of these, 44% (4/9) reported being pain free at 2 hours, all without need for rescue medication. Similarly, pain relief at 2 hours occurred in 44% (4/9) of patients in the 18-LPM group, and in 50% (3/6) of the patients in the 24-LPM group.
No participants in the 18-LPM or the 24-LPM groups reported pain freedom at 2 hours.
Most bothersome symptoms were reduced. Response was greater with 6-LPM treatment. At 2 hours, 77% (7/9) of patients in the 6-LPM group reported relief of their symptoms, followed by 66% (6/9) of the 18-LPM group and 50% (3/6) of the 24-LPM group.
However, nasal discomfort was a bothersome adverse effect, Dr. Charleston noted. The rate of nasal discomfort occurred in all groups but was lower in the 6-LPM group.
Moderate intranasal discomfort during treatment was reported by 11% of the 6-LPM group, compared with 33% (3/9) in the 18-LPM group and 83% (5/6) in the 24-LPM group.
However, the study was terminated due to insufficient subject accrual rate.
“Originally, 87 participants were recruited and consented. It may have been challenging for some to come in to study clinic sites for the study treatment at the onset of their migraine attacks. The next iteration of the treatment device is a more portable model and study treatment may be used at home. This will likely be more convenient and enhance study participation,” Dr. Charleston said.
The data in the current study will help inform dose ranging analyses in future studies, to optimize efficacy and increase tolerability, he added.
The findings are promising and merit further assessment in a larger study with a sham control group, said Richard B. Lipton, MD, Edwin S. Lowe Professor and vice chair of neurology, and director of the Montefiore Headache Center, Albert Einstein College of Medicine, New York.
“Charleston et al. report that the lowest flow dose (6 liters per minute) was most effective, with a 2-hour pain-relief rate of 88% and a 2-hour pain-free rate of 50%, but, though these rates of pain relief and pain freedom are high, caution in interpretation is required,” Dr. Lipton said.
“The sample size is very modest with only nine patients in the 6-liter-per-minute treatment arm. In addition, the study lacks results from the group that got the sham device, making it difficult to contextualize the findings,” Dr. Lipton said.
He added that it is unusual for higher doses to be less effective but that may be because air flow higher than 6 LPM is irritating to the nasal mucosa during migraine attacks.
Always a need for effective nonpharmaceuticals
Also commenting on this study, Nina Riggins, MD, director of the Headache Center at the University of California, San Diego, said she found the novel device “exciting and really clever.
“I really enjoyed reviewing this abstract because I am a big fan of sphenopalatine ganglion block in the palatine ganglion. When we do those, we basically apply numbing medication to decrease the sensation and discharges coming from this group of neural cells in order to decrease pain,” Dr. Riggins said. “The procedure is very well tolerated and usually sphenopalatine ganglion blocks are used in patients when we do not want any side effects, such as in pregnant and postpartum women.”
The novel technique has the potential to have fewer side effects than those of oral medications, she said. “For example, the triptans are effective drugs but they constrict the blood vessels and we don’t want to use them in people with heart disease or history of stroke. This is where these potentially safer devices can play an important role. We can have more options to offer our patients,” Dr. Riggins said.
“I am super excited and looking forward to see what will come out of future research. I am really grateful that the authors are looking into new neuromodulation devices which can be so useful,” she said.
Migraine is the second leading cause of disability worldwide, Dr. Riggins noted. “It peaks in the years when people are most productive and affects families and communities. Medications are good, of course, but now with these novel devices, these are wonderful areas for research. Also now, we can offer so much more to people with migraine and other headache disorders,” she said.
“When I started in the field, I remember we were very limited in resources, and now, it’s just so wonderful.”
The study was sponsored by CoolTech Corp LLC. Dr. Charleston reports financial relationships with Allergan/AbbVie, Amgen, Amneal, Biohaven, Haleon, Linpharma, Satsuma, and Teva, and that he has received CME honoraria from the American Headache Society and the American Academy of Neurology. Dr. Lipton reports financial relationships with multiple pharmaceutical companies. Dr. Riggins reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AUSTIN, TEX. – , according to the results of a small study. Most patients reported relief of their symptoms after receiving 15 minutes of transnasal evaporative cooling, without any need for rescue medication.
The cooling may modulate the sphenopalatine ganglion, a large ganglion implicated in migraine, said lead author Larry Charleston IV, MD, director of the headache and facial pain division, and professor of neurology at Michigan State University, East Lansing.
“The transnasal evaporative cooling device cools by blowing dry, ambient air across the nasal turbinates and may work by neuromodulation via the sphenopalatine ganglion for migraine,” Dr. Charleston said.
The findings were presented at the annual meeting of the American Headache Society.
A ‘cool’ approach to migraine treatment
“Everyone who has migraine disease needs abortive treatment,” Dr. Charleston said. “There is a need for safe and effective acute treatment for migraine. As we understand more about the pathophysiology of migraine, we learn that peripheral input plays a role in migraine disease.
“I was excited to learn of the device and to learn how we might take advantage of our knowledge of the sphenopalatine ganglia in the treatment of migraine, and was very enthusiastic to be involved in researching a nonpharmacological treatment to abort migraine attacks,” he said. “I thought this approach to migraine treatment was really ‘cool.’ ”
Twenty-four patients who met diagnostic criteria for episodic migraine with or without aura were randomized to receive 15 minutes of cooling induced by the CoolStat Transnasal Thermal Regulating Device (CoolTech LLC), or to a sham treatment with a CoolStat sham device.
Participants receiving active treatment were further randomized to receive one of the following flow rates: 24 liters per minute (LPM; n = 6 patients), 18 LPM (n = 9 patients), and 6 LPM (n = 9 patients).
All patients were instructed to get to their headache clinic during a migraine attack to start treatment.
The researchers looked at pain levels and most bothersome symptoms at baseline, and then at 2 and 24 hours after treatment. The primary endpoint was pain relief at 2 hours. Other endpoints included tolerability, relief from most bothersome symptoms, and freedom from pain at 2 hours.
The results showed that 88% (8/9 patients) of the 6-LPM group reported pain relief at 2 hours. Of these, 44% (4/9) reported being pain free at 2 hours, all without need for rescue medication. Similarly, pain relief at 2 hours occurred in 44% (4/9) of patients in the 18-LPM group, and in 50% (3/6) of the patients in the 24-LPM group.
No participants in the 18-LPM or the 24-LPM groups reported pain freedom at 2 hours.
Most bothersome symptoms were reduced. Response was greater with 6-LPM treatment. At 2 hours, 77% (7/9) of patients in the 6-LPM group reported relief of their symptoms, followed by 66% (6/9) of the 18-LPM group and 50% (3/6) of the 24-LPM group.
However, nasal discomfort was a bothersome adverse effect, Dr. Charleston noted. The rate of nasal discomfort occurred in all groups but was lower in the 6-LPM group.
Moderate intranasal discomfort during treatment was reported by 11% of the 6-LPM group, compared with 33% (3/9) in the 18-LPM group and 83% (5/6) in the 24-LPM group.
However, the study was terminated due to insufficient subject accrual rate.
“Originally, 87 participants were recruited and consented. It may have been challenging for some to come in to study clinic sites for the study treatment at the onset of their migraine attacks. The next iteration of the treatment device is a more portable model and study treatment may be used at home. This will likely be more convenient and enhance study participation,” Dr. Charleston said.
The data in the current study will help inform dose ranging analyses in future studies, to optimize efficacy and increase tolerability, he added.
The findings are promising and merit further assessment in a larger study with a sham control group, said Richard B. Lipton, MD, Edwin S. Lowe Professor and vice chair of neurology, and director of the Montefiore Headache Center, Albert Einstein College of Medicine, New York.
“Charleston et al. report that the lowest flow dose (6 liters per minute) was most effective, with a 2-hour pain-relief rate of 88% and a 2-hour pain-free rate of 50%, but, though these rates of pain relief and pain freedom are high, caution in interpretation is required,” Dr. Lipton said.
“The sample size is very modest with only nine patients in the 6-liter-per-minute treatment arm. In addition, the study lacks results from the group that got the sham device, making it difficult to contextualize the findings,” Dr. Lipton said.
He added that it is unusual for higher doses to be less effective but that may be because air flow higher than 6 LPM is irritating to the nasal mucosa during migraine attacks.
Always a need for effective nonpharmaceuticals
Also commenting on this study, Nina Riggins, MD, director of the Headache Center at the University of California, San Diego, said she found the novel device “exciting and really clever.
“I really enjoyed reviewing this abstract because I am a big fan of sphenopalatine ganglion block in the palatine ganglion. When we do those, we basically apply numbing medication to decrease the sensation and discharges coming from this group of neural cells in order to decrease pain,” Dr. Riggins said. “The procedure is very well tolerated and usually sphenopalatine ganglion blocks are used in patients when we do not want any side effects, such as in pregnant and postpartum women.”
The novel technique has the potential to have fewer side effects than those of oral medications, she said. “For example, the triptans are effective drugs but they constrict the blood vessels and we don’t want to use them in people with heart disease or history of stroke. This is where these potentially safer devices can play an important role. We can have more options to offer our patients,” Dr. Riggins said.
“I am super excited and looking forward to see what will come out of future research. I am really grateful that the authors are looking into new neuromodulation devices which can be so useful,” she said.
Migraine is the second leading cause of disability worldwide, Dr. Riggins noted. “It peaks in the years when people are most productive and affects families and communities. Medications are good, of course, but now with these novel devices, these are wonderful areas for research. Also now, we can offer so much more to people with migraine and other headache disorders,” she said.
“When I started in the field, I remember we were very limited in resources, and now, it’s just so wonderful.”
The study was sponsored by CoolTech Corp LLC. Dr. Charleston reports financial relationships with Allergan/AbbVie, Amgen, Amneal, Biohaven, Haleon, Linpharma, Satsuma, and Teva, and that he has received CME honoraria from the American Headache Society and the American Academy of Neurology. Dr. Lipton reports financial relationships with multiple pharmaceutical companies. Dr. Riggins reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
At ASH 2023
Migraine device expands treatment possibilities
AUSTIN, TEX – Migraine treatment and prevention is challenging in any population, but some present even more difficulties. Pregnant women and pediatric patients are two such groups where physicians and patients may be hesitant to use drugs.
Neuromodulation devices are proven alternatives to medical interventions, and the remote electrical neuromodulation device Nerivio (Theranica) was cleared by the Food and Drug Administration for acute treatment of migraine patients aged 12 and over in 2021. In March 2023, the agency expanded the clearance to include prevention of migration in adolescents aged 12 and over as well as adults.
Two studies presented at the annual meeting of the American Headache Society showed The latter study yielded similar findings to adults and was used by FDA in its decision to expand the device’s indication in adolescents in 2023, according to Teshamae Monteith, MD, who presented the study at a poster session.
The device, worn on the arm, allows the user to modulate the intensity of the stimulation so that it activates nociceptive pain receptors, but not in a painful way. “Each [patient] raises the intensity until it feels strong, yet comfortable, and when that happens, they activate the nociceptive receptors and the arm sends a signal all the way back up to the brainstem, where the pain control area is. Activating it causes the release of neurotransmitters that inhibit pain. That inhibition is a global pain inhibition mechanism, which causes inhibition of the migraine pain, and also the symptoms associated with migraine like photophobia and vomiting,” said Alit Stark-Inbar, PhD, who presented the study of treatment of pregnant women during a poster session.
Declining treatment days over time in adolescents
Dr. Monteith’s team studied high-frequency remote electrical neuromodulation device use in adolescents who had migraine on 10 days or more per month. They also required at least three treatment days in months 2 and 3 to control for the possibility that patients might stop using the device because they couldn’t afford it or for some reason other than efficacy or because their migraines went away.
The study included 83 adolescents aged 12-17 (mean, 15.9 years, 89% female). In the first month of use, the mean number of migraine treatment days was 12.6, which dropped to 9.0 in month 2 (P < .001), and 7.4 in month 3 (P < .001 from month 2). At 2 hours after treatment, 61.9% had pain relief, 24.5% had freedom from pain, 67.4% had functional disability relief, and 41.3% had functional disability freedom.
“It parallels the findings of the randomized, sham-controlled study in adults. The safety profile was excellent with just one person complaining of minor discomfort of the arm that resolved after treatment. The combination of the exceedingly safe profile and the likelihood of efficacy based on using monthly migraine treatment days as a proxy, the FDA decided to clear this for an adolescent indication,” said Dr. Monteith, associate professor of clinical neurology and chief of the headache division at the University of Miami.
The device design is convenient, according to Dr. Monteith. “The arm is just an easy place to stimulate. It’s a wearable device, and it’s 45 minutes [of treatment] and it’s app controlled. You know adolescents like their technology. They can track their symptoms here, and there’s some biobehavioral power to this because they can do biobehavioral exercises in addition to receiving the simulation,” she said.
The fact that the device is discrete is also an advantage for adolescents in school. “You have to go to the nurse to get your medication versus a device, you can just put it on, it’s easy, no one sees it, and no one’s making fun of you,” said Dr. Monteith.
Advantages for adolescents
The device offers a useful alternative to medication, according to Alan M. Rapoport, MD, who was asked for comment on the adolescent study. “I’d rather not give medication and certainly not preventive medication to an adolescent,” he said. He noted that over-the-counter acute care migraine medications such as aspirin or acetaminophen and combination medications with caffeine, as well as prescription medications such as triptans, “all have possible side effects, and when used to an increased extent can even cause medication overuse headache, increasing the severity and frequency of headache and migraine days per month,” Dr. Rapoport said. Using an effective device with almost no side effects is preferable to any of these acute care medications, especially if there are several headaches a month,” he said. Some newer medications that block calcitonin gene-related peptide might be quite effective when they are approved for adolescents, and should have few adverse events, he added.
In the past, Dr. Rapoport has favored biofeedback training for acute and especially preventive treatment of migraine in adolescents. “[Remote electrical neuromodulation] seems to do just as well, children enjoy it, and it’s easier for a patient to do at home,” said Dr. Rapoport.
Biofeedback training is usually taught to patients by a PhD psychologist. Once the patients have been on the biofeedback equipment and learn the techniques, they can practice on their own at home without equipment. “This new device treatment using Nerivio for acute care and prevention of migraine in adults and children 12 and older, where they can easily apply the device in almost any situation, whether they are at home or possibly even in school or out and about, looks very promising,” said Dr. Rapoport. It is quite effective and has almost no adverse events, which is what you really want, especially for adolescents,” he said.
Also asked to comment on the study of remote electrical neuromodulation use in adolescents, Abraham Avi Ashkenazi, MD, director of the Headache Clinic at Shaare Zedek Medical Center in Jerusalem, who attended the session, was enthusiastic, and said he has begun using it in his own practice. “It shows that remote electrical neuromodulation can not only be effective for the acute migraine attack, but also has a potential preventive effect on future migraine attacks. [This] actually makes sense, because we know that the more migraine attacks a person has, the more likely they are to progress to a more chronic form of the disease,” he said in an interview.
Asked what distinguishes REN from other neuromodulation therapies such as vagus nerve stimulation or transcranial magnetic stimulation (TMS), Dr. Ashkenazi said: “It’s just a different way of modulating the brain system via a different mechanism. In both ways, though, the advantage is that there are literally no adverse effects, as opposed to drug treatment.”
An alternative during pregnancy
Adolescents aren’t the only population where there is reluctance to use medication. Physicians have been prescribing the device for pregnant women, who are reluctant to take medication due to concerns effects on the fetus. However, pregnant women were not included in the pivotal studies. “They expect it to be safe. This study was done in order to validate that assumption. We reached out to women who either used the device during pregnancy or women from the same database who started it using afterwards, but did not use it during the pregnancy,” said Dr. Stark-Inbar, vice president of medical information at Theranica.
The study included 140 women, 59 in the remote electrical neuromodulation device group and 81 controls. The primary endpoint was gestational age, which was 38 weeks and 5 days in the remote electrical neuromodulation device group and 39 weeks among controls (P = .150). There were no significant between-group differences with respect to newborn birth weight, miscarriage rate, preterm birth rate, birth defect rate, developmental milestone rate, or emergency department visit rate.
Dr. Monteith and Dr. Ashkenazi have no relevant financial disclosures. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. Dr. Rapoport is the editor-in-chief of Neurology Reviews and on the editorial board of CNS Drugs.
AUSTIN, TEX – Migraine treatment and prevention is challenging in any population, but some present even more difficulties. Pregnant women and pediatric patients are two such groups where physicians and patients may be hesitant to use drugs.
Neuromodulation devices are proven alternatives to medical interventions, and the remote electrical neuromodulation device Nerivio (Theranica) was cleared by the Food and Drug Administration for acute treatment of migraine patients aged 12 and over in 2021. In March 2023, the agency expanded the clearance to include prevention of migration in adolescents aged 12 and over as well as adults.
Two studies presented at the annual meeting of the American Headache Society showed The latter study yielded similar findings to adults and was used by FDA in its decision to expand the device’s indication in adolescents in 2023, according to Teshamae Monteith, MD, who presented the study at a poster session.
The device, worn on the arm, allows the user to modulate the intensity of the stimulation so that it activates nociceptive pain receptors, but not in a painful way. “Each [patient] raises the intensity until it feels strong, yet comfortable, and when that happens, they activate the nociceptive receptors and the arm sends a signal all the way back up to the brainstem, where the pain control area is. Activating it causes the release of neurotransmitters that inhibit pain. That inhibition is a global pain inhibition mechanism, which causes inhibition of the migraine pain, and also the symptoms associated with migraine like photophobia and vomiting,” said Alit Stark-Inbar, PhD, who presented the study of treatment of pregnant women during a poster session.
Declining treatment days over time in adolescents
Dr. Monteith’s team studied high-frequency remote electrical neuromodulation device use in adolescents who had migraine on 10 days or more per month. They also required at least three treatment days in months 2 and 3 to control for the possibility that patients might stop using the device because they couldn’t afford it or for some reason other than efficacy or because their migraines went away.
The study included 83 adolescents aged 12-17 (mean, 15.9 years, 89% female). In the first month of use, the mean number of migraine treatment days was 12.6, which dropped to 9.0 in month 2 (P < .001), and 7.4 in month 3 (P < .001 from month 2). At 2 hours after treatment, 61.9% had pain relief, 24.5% had freedom from pain, 67.4% had functional disability relief, and 41.3% had functional disability freedom.
“It parallels the findings of the randomized, sham-controlled study in adults. The safety profile was excellent with just one person complaining of minor discomfort of the arm that resolved after treatment. The combination of the exceedingly safe profile and the likelihood of efficacy based on using monthly migraine treatment days as a proxy, the FDA decided to clear this for an adolescent indication,” said Dr. Monteith, associate professor of clinical neurology and chief of the headache division at the University of Miami.
The device design is convenient, according to Dr. Monteith. “The arm is just an easy place to stimulate. It’s a wearable device, and it’s 45 minutes [of treatment] and it’s app controlled. You know adolescents like their technology. They can track their symptoms here, and there’s some biobehavioral power to this because they can do biobehavioral exercises in addition to receiving the simulation,” she said.
The fact that the device is discrete is also an advantage for adolescents in school. “You have to go to the nurse to get your medication versus a device, you can just put it on, it’s easy, no one sees it, and no one’s making fun of you,” said Dr. Monteith.
Advantages for adolescents
The device offers a useful alternative to medication, according to Alan M. Rapoport, MD, who was asked for comment on the adolescent study. “I’d rather not give medication and certainly not preventive medication to an adolescent,” he said. He noted that over-the-counter acute care migraine medications such as aspirin or acetaminophen and combination medications with caffeine, as well as prescription medications such as triptans, “all have possible side effects, and when used to an increased extent can even cause medication overuse headache, increasing the severity and frequency of headache and migraine days per month,” Dr. Rapoport said. Using an effective device with almost no side effects is preferable to any of these acute care medications, especially if there are several headaches a month,” he said. Some newer medications that block calcitonin gene-related peptide might be quite effective when they are approved for adolescents, and should have few adverse events, he added.
In the past, Dr. Rapoport has favored biofeedback training for acute and especially preventive treatment of migraine in adolescents. “[Remote electrical neuromodulation] seems to do just as well, children enjoy it, and it’s easier for a patient to do at home,” said Dr. Rapoport.
Biofeedback training is usually taught to patients by a PhD psychologist. Once the patients have been on the biofeedback equipment and learn the techniques, they can practice on their own at home without equipment. “This new device treatment using Nerivio for acute care and prevention of migraine in adults and children 12 and older, where they can easily apply the device in almost any situation, whether they are at home or possibly even in school or out and about, looks very promising,” said Dr. Rapoport. It is quite effective and has almost no adverse events, which is what you really want, especially for adolescents,” he said.
Also asked to comment on the study of remote electrical neuromodulation use in adolescents, Abraham Avi Ashkenazi, MD, director of the Headache Clinic at Shaare Zedek Medical Center in Jerusalem, who attended the session, was enthusiastic, and said he has begun using it in his own practice. “It shows that remote electrical neuromodulation can not only be effective for the acute migraine attack, but also has a potential preventive effect on future migraine attacks. [This] actually makes sense, because we know that the more migraine attacks a person has, the more likely they are to progress to a more chronic form of the disease,” he said in an interview.
Asked what distinguishes REN from other neuromodulation therapies such as vagus nerve stimulation or transcranial magnetic stimulation (TMS), Dr. Ashkenazi said: “It’s just a different way of modulating the brain system via a different mechanism. In both ways, though, the advantage is that there are literally no adverse effects, as opposed to drug treatment.”
An alternative during pregnancy
Adolescents aren’t the only population where there is reluctance to use medication. Physicians have been prescribing the device for pregnant women, who are reluctant to take medication due to concerns effects on the fetus. However, pregnant women were not included in the pivotal studies. “They expect it to be safe. This study was done in order to validate that assumption. We reached out to women who either used the device during pregnancy or women from the same database who started it using afterwards, but did not use it during the pregnancy,” said Dr. Stark-Inbar, vice president of medical information at Theranica.
The study included 140 women, 59 in the remote electrical neuromodulation device group and 81 controls. The primary endpoint was gestational age, which was 38 weeks and 5 days in the remote electrical neuromodulation device group and 39 weeks among controls (P = .150). There were no significant between-group differences with respect to newborn birth weight, miscarriage rate, preterm birth rate, birth defect rate, developmental milestone rate, or emergency department visit rate.
Dr. Monteith and Dr. Ashkenazi have no relevant financial disclosures. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. Dr. Rapoport is the editor-in-chief of Neurology Reviews and on the editorial board of CNS Drugs.
AUSTIN, TEX – Migraine treatment and prevention is challenging in any population, but some present even more difficulties. Pregnant women and pediatric patients are two such groups where physicians and patients may be hesitant to use drugs.
Neuromodulation devices are proven alternatives to medical interventions, and the remote electrical neuromodulation device Nerivio (Theranica) was cleared by the Food and Drug Administration for acute treatment of migraine patients aged 12 and over in 2021. In March 2023, the agency expanded the clearance to include prevention of migration in adolescents aged 12 and over as well as adults.
Two studies presented at the annual meeting of the American Headache Society showed The latter study yielded similar findings to adults and was used by FDA in its decision to expand the device’s indication in adolescents in 2023, according to Teshamae Monteith, MD, who presented the study at a poster session.
The device, worn on the arm, allows the user to modulate the intensity of the stimulation so that it activates nociceptive pain receptors, but not in a painful way. “Each [patient] raises the intensity until it feels strong, yet comfortable, and when that happens, they activate the nociceptive receptors and the arm sends a signal all the way back up to the brainstem, where the pain control area is. Activating it causes the release of neurotransmitters that inhibit pain. That inhibition is a global pain inhibition mechanism, which causes inhibition of the migraine pain, and also the symptoms associated with migraine like photophobia and vomiting,” said Alit Stark-Inbar, PhD, who presented the study of treatment of pregnant women during a poster session.
Declining treatment days over time in adolescents
Dr. Monteith’s team studied high-frequency remote electrical neuromodulation device use in adolescents who had migraine on 10 days or more per month. They also required at least three treatment days in months 2 and 3 to control for the possibility that patients might stop using the device because they couldn’t afford it or for some reason other than efficacy or because their migraines went away.
The study included 83 adolescents aged 12-17 (mean, 15.9 years, 89% female). In the first month of use, the mean number of migraine treatment days was 12.6, which dropped to 9.0 in month 2 (P < .001), and 7.4 in month 3 (P < .001 from month 2). At 2 hours after treatment, 61.9% had pain relief, 24.5% had freedom from pain, 67.4% had functional disability relief, and 41.3% had functional disability freedom.
“It parallels the findings of the randomized, sham-controlled study in adults. The safety profile was excellent with just one person complaining of minor discomfort of the arm that resolved after treatment. The combination of the exceedingly safe profile and the likelihood of efficacy based on using monthly migraine treatment days as a proxy, the FDA decided to clear this for an adolescent indication,” said Dr. Monteith, associate professor of clinical neurology and chief of the headache division at the University of Miami.
The device design is convenient, according to Dr. Monteith. “The arm is just an easy place to stimulate. It’s a wearable device, and it’s 45 minutes [of treatment] and it’s app controlled. You know adolescents like their technology. They can track their symptoms here, and there’s some biobehavioral power to this because they can do biobehavioral exercises in addition to receiving the simulation,” she said.
The fact that the device is discrete is also an advantage for adolescents in school. “You have to go to the nurse to get your medication versus a device, you can just put it on, it’s easy, no one sees it, and no one’s making fun of you,” said Dr. Monteith.
Advantages for adolescents
The device offers a useful alternative to medication, according to Alan M. Rapoport, MD, who was asked for comment on the adolescent study. “I’d rather not give medication and certainly not preventive medication to an adolescent,” he said. He noted that over-the-counter acute care migraine medications such as aspirin or acetaminophen and combination medications with caffeine, as well as prescription medications such as triptans, “all have possible side effects, and when used to an increased extent can even cause medication overuse headache, increasing the severity and frequency of headache and migraine days per month,” Dr. Rapoport said. Using an effective device with almost no side effects is preferable to any of these acute care medications, especially if there are several headaches a month,” he said. Some newer medications that block calcitonin gene-related peptide might be quite effective when they are approved for adolescents, and should have few adverse events, he added.
In the past, Dr. Rapoport has favored biofeedback training for acute and especially preventive treatment of migraine in adolescents. “[Remote electrical neuromodulation] seems to do just as well, children enjoy it, and it’s easier for a patient to do at home,” said Dr. Rapoport.
Biofeedback training is usually taught to patients by a PhD psychologist. Once the patients have been on the biofeedback equipment and learn the techniques, they can practice on their own at home without equipment. “This new device treatment using Nerivio for acute care and prevention of migraine in adults and children 12 and older, where they can easily apply the device in almost any situation, whether they are at home or possibly even in school or out and about, looks very promising,” said Dr. Rapoport. It is quite effective and has almost no adverse events, which is what you really want, especially for adolescents,” he said.
Also asked to comment on the study of remote electrical neuromodulation use in adolescents, Abraham Avi Ashkenazi, MD, director of the Headache Clinic at Shaare Zedek Medical Center in Jerusalem, who attended the session, was enthusiastic, and said he has begun using it in his own practice. “It shows that remote electrical neuromodulation can not only be effective for the acute migraine attack, but also has a potential preventive effect on future migraine attacks. [This] actually makes sense, because we know that the more migraine attacks a person has, the more likely they are to progress to a more chronic form of the disease,” he said in an interview.
Asked what distinguishes REN from other neuromodulation therapies such as vagus nerve stimulation or transcranial magnetic stimulation (TMS), Dr. Ashkenazi said: “It’s just a different way of modulating the brain system via a different mechanism. In both ways, though, the advantage is that there are literally no adverse effects, as opposed to drug treatment.”
An alternative during pregnancy
Adolescents aren’t the only population where there is reluctance to use medication. Physicians have been prescribing the device for pregnant women, who are reluctant to take medication due to concerns effects on the fetus. However, pregnant women were not included in the pivotal studies. “They expect it to be safe. This study was done in order to validate that assumption. We reached out to women who either used the device during pregnancy or women from the same database who started it using afterwards, but did not use it during the pregnancy,” said Dr. Stark-Inbar, vice president of medical information at Theranica.
The study included 140 women, 59 in the remote electrical neuromodulation device group and 81 controls. The primary endpoint was gestational age, which was 38 weeks and 5 days in the remote electrical neuromodulation device group and 39 weeks among controls (P = .150). There were no significant between-group differences with respect to newborn birth weight, miscarriage rate, preterm birth rate, birth defect rate, developmental milestone rate, or emergency department visit rate.
Dr. Monteith and Dr. Ashkenazi have no relevant financial disclosures. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. Dr. Rapoport is the editor-in-chief of Neurology Reviews and on the editorial board of CNS Drugs.
AT AHS 2023
Cannabis RCT shows efficacy, AEs in migraine
AUSTIN, TEX. – Self-treatment of migraines using cannabis can be effective but comes at risk of significant side effects, according to results from a randomized, controlled trial of cannabis products in migraine. The study also suggests that typical recreational doses may be higher than needed, and that products with a mixture of THC and CBD might limit adverse effects, according to lead author Nathaniel Schuster, MD.
“Patients are using cannabis on their own, treating themselves without us having known whether this is effective in a placebo-controlled study. Knowing that there’s a lot of interest in THC and CBD, [it would be useful to know] whether one or both might be effective, as well as a mix,” said Dr. Schuster in an interview. He presented the results at the annual meeting of the American Headache Society.
Dr. Schuster and colleagues tested a cannabis product with 6% THC based on prior studies showing efficacy of that concentration for other pain conditions, according to Dr. Schuster, who is an associate professor and associate clinical director at the University of California, San Diego, center for pain medicine. He added that the study is the first randomized, controlled trial of cannabis in migraine patients that he is aware of. “It’s just hard to do this research. It’s very regulated. We had to go through a lot of government approvals to do this,” he said.
The study produced a key message. “I think one of the really important things for patients to take from this is that recreational doses are probably not necessary. The doses that we studied are lower than people use recreationally. Patients who are self-treating on their own right now are probably using higher doses than they need for the purpose of treating migraine,” said Dr. Schuster.
He also pointed out that the results offer potential insight into reducing side effects. “If [patients] are using THC only, they can hopefully have less of the side effects and tolerate it better by using a THC-CBD mix,” said Dr. Schuster.
Four therapies tested
Participants in the study could self-treat up to four migraine attacks. They were instructed to treat each migraine with one of four therapies, which were provided in a randomized, double-blind order: These included a 6% THC formulation; a mix of THC (6%) and CBD (11%); a CBD 11% formulation; and placebo cannabis with THC and CBD removed by alcohol extraction. Participants filled out a questionnaire 2 hours after treatment, and were then allowed to use rescue treatments if needed, but not additional cannabis. The age range was from 21 to 65, and inclusion criteria included 2-23 migraine days per month. Exclusion criteria included a positive urine test for THC, barbiturates, opioids, oxycodone, or methadone prior to enrollment.
The study included 73 patients who treated a migraine during the study period. There were 247 migraine attacks treated. Among participants, the median age was 41, 82.6% were female and 17.4% were male, and the median body mass index was 26.0 kg/m2. Participants experienced a median of 15 headache days per month and 6 migraine days per month, and 27.2% had chronic migraine.
At 2 hours, pain relief occurred in 48.3% of placebo treatments, 54.4% of the CBD treatments, 70.5% of the THC treatments (P = .007 versus placebo), and 69.0% of the THC/CBD treatments (P = .014 versus placebo). At 2 hours, pain freedom occurred in 15.5% of the placebo treatments, 24.6% of the CBD treatments, 29.5% of the THC treatments, and 36.2% of the THC/CBD treatments (P = .010 versus placebo). At 2 hours, freedom from most bothersome symptoms (MBS) occurred in 36.2% of the placebo treatments, 43.9% of the CBD treatments, 49.2% of the THC treatments, and 62.1% of the THC/CBD treatments (P = .004 versus placebo).
To achieve at least a 20% improvement in pain relief, compared with placebo, the number needed to treat (NNT) with THC/CBD was five. For at least a 20% improvement in pain freedom, the NNT was five, and for a 20% improvement in freedom from most bothersome symptoms, the NNT was four.
Treatment with THC was associated with the highest frequency of any adverse event (31.0%), followed by CBD and THC/CBD (19.6% each), and placebo (5.0%). At 2 hours, 18.0% of the THC treatments had an adverse event, compared with 7.0% of the CBD treatments, 6.9% of the THC/CBD treatments, and 5.2% of placebo treatments.
The number needed to treat of five for pain relief was encouraging, according to Dr. Schuster. “It’s better than some other things, but at the expense of side effects. The side effects that we see are certainly higher with cannabis than it is with other migraine treatments that patients certainly should be using beforehand. There’s also a risk of addiction, which is a concern,” said Dr. Schuster.
Useful data but questions remain
Having a clinical trial will be useful for physicians, said Ali Ezzati, MD, who attended the session. “I think it was an impressive study. Obviously, there are some challenges with cannabis studies in the medical world because of the stigma that comes with it and also the possibility of inducing addiction [and] promoting that to patients. But at the end of the day, it’s very, very common for our patients to ask us about cannabinoid use, and we really don’t have data on it. I’m glad that there are people who are running these studies so we will be able at least to answer our patients,” said Dr. Ezzati, who is an associate professor of neurology at University of California, Irvine.
Dr. Ezzati also noted that clinical trials have investigated cannabinoid use for other types of pain, such as arthritic or generalized pain. Although he said that there are some clinical similarities between other types of pain and migraine, the pathophysiology appears to be unique, which means that more work needs to be done. “It will probably take 5 or 10 years to have sufficient data to give patients a direct path for using (cannabinoids),” said Dr. Ezzati.
The study was funded by the Migraine Research Foundation. Dr. Schuster has consulted with Schedule 1 Therapeutics and Vectura Fertin. Dr. Ezzati has no relevant financial disclosures.
AUSTIN, TEX. – Self-treatment of migraines using cannabis can be effective but comes at risk of significant side effects, according to results from a randomized, controlled trial of cannabis products in migraine. The study also suggests that typical recreational doses may be higher than needed, and that products with a mixture of THC and CBD might limit adverse effects, according to lead author Nathaniel Schuster, MD.
“Patients are using cannabis on their own, treating themselves without us having known whether this is effective in a placebo-controlled study. Knowing that there’s a lot of interest in THC and CBD, [it would be useful to know] whether one or both might be effective, as well as a mix,” said Dr. Schuster in an interview. He presented the results at the annual meeting of the American Headache Society.
Dr. Schuster and colleagues tested a cannabis product with 6% THC based on prior studies showing efficacy of that concentration for other pain conditions, according to Dr. Schuster, who is an associate professor and associate clinical director at the University of California, San Diego, center for pain medicine. He added that the study is the first randomized, controlled trial of cannabis in migraine patients that he is aware of. “It’s just hard to do this research. It’s very regulated. We had to go through a lot of government approvals to do this,” he said.
The study produced a key message. “I think one of the really important things for patients to take from this is that recreational doses are probably not necessary. The doses that we studied are lower than people use recreationally. Patients who are self-treating on their own right now are probably using higher doses than they need for the purpose of treating migraine,” said Dr. Schuster.
He also pointed out that the results offer potential insight into reducing side effects. “If [patients] are using THC only, they can hopefully have less of the side effects and tolerate it better by using a THC-CBD mix,” said Dr. Schuster.
Four therapies tested
Participants in the study could self-treat up to four migraine attacks. They were instructed to treat each migraine with one of four therapies, which were provided in a randomized, double-blind order: These included a 6% THC formulation; a mix of THC (6%) and CBD (11%); a CBD 11% formulation; and placebo cannabis with THC and CBD removed by alcohol extraction. Participants filled out a questionnaire 2 hours after treatment, and were then allowed to use rescue treatments if needed, but not additional cannabis. The age range was from 21 to 65, and inclusion criteria included 2-23 migraine days per month. Exclusion criteria included a positive urine test for THC, barbiturates, opioids, oxycodone, or methadone prior to enrollment.
The study included 73 patients who treated a migraine during the study period. There were 247 migraine attacks treated. Among participants, the median age was 41, 82.6% were female and 17.4% were male, and the median body mass index was 26.0 kg/m2. Participants experienced a median of 15 headache days per month and 6 migraine days per month, and 27.2% had chronic migraine.
At 2 hours, pain relief occurred in 48.3% of placebo treatments, 54.4% of the CBD treatments, 70.5% of the THC treatments (P = .007 versus placebo), and 69.0% of the THC/CBD treatments (P = .014 versus placebo). At 2 hours, pain freedom occurred in 15.5% of the placebo treatments, 24.6% of the CBD treatments, 29.5% of the THC treatments, and 36.2% of the THC/CBD treatments (P = .010 versus placebo). At 2 hours, freedom from most bothersome symptoms (MBS) occurred in 36.2% of the placebo treatments, 43.9% of the CBD treatments, 49.2% of the THC treatments, and 62.1% of the THC/CBD treatments (P = .004 versus placebo).
To achieve at least a 20% improvement in pain relief, compared with placebo, the number needed to treat (NNT) with THC/CBD was five. For at least a 20% improvement in pain freedom, the NNT was five, and for a 20% improvement in freedom from most bothersome symptoms, the NNT was four.
Treatment with THC was associated with the highest frequency of any adverse event (31.0%), followed by CBD and THC/CBD (19.6% each), and placebo (5.0%). At 2 hours, 18.0% of the THC treatments had an adverse event, compared with 7.0% of the CBD treatments, 6.9% of the THC/CBD treatments, and 5.2% of placebo treatments.
The number needed to treat of five for pain relief was encouraging, according to Dr. Schuster. “It’s better than some other things, but at the expense of side effects. The side effects that we see are certainly higher with cannabis than it is with other migraine treatments that patients certainly should be using beforehand. There’s also a risk of addiction, which is a concern,” said Dr. Schuster.
Useful data but questions remain
Having a clinical trial will be useful for physicians, said Ali Ezzati, MD, who attended the session. “I think it was an impressive study. Obviously, there are some challenges with cannabis studies in the medical world because of the stigma that comes with it and also the possibility of inducing addiction [and] promoting that to patients. But at the end of the day, it’s very, very common for our patients to ask us about cannabinoid use, and we really don’t have data on it. I’m glad that there are people who are running these studies so we will be able at least to answer our patients,” said Dr. Ezzati, who is an associate professor of neurology at University of California, Irvine.
Dr. Ezzati also noted that clinical trials have investigated cannabinoid use for other types of pain, such as arthritic or generalized pain. Although he said that there are some clinical similarities between other types of pain and migraine, the pathophysiology appears to be unique, which means that more work needs to be done. “It will probably take 5 or 10 years to have sufficient data to give patients a direct path for using (cannabinoids),” said Dr. Ezzati.
The study was funded by the Migraine Research Foundation. Dr. Schuster has consulted with Schedule 1 Therapeutics and Vectura Fertin. Dr. Ezzati has no relevant financial disclosures.
AUSTIN, TEX. – Self-treatment of migraines using cannabis can be effective but comes at risk of significant side effects, according to results from a randomized, controlled trial of cannabis products in migraine. The study also suggests that typical recreational doses may be higher than needed, and that products with a mixture of THC and CBD might limit adverse effects, according to lead author Nathaniel Schuster, MD.
“Patients are using cannabis on their own, treating themselves without us having known whether this is effective in a placebo-controlled study. Knowing that there’s a lot of interest in THC and CBD, [it would be useful to know] whether one or both might be effective, as well as a mix,” said Dr. Schuster in an interview. He presented the results at the annual meeting of the American Headache Society.
Dr. Schuster and colleagues tested a cannabis product with 6% THC based on prior studies showing efficacy of that concentration for other pain conditions, according to Dr. Schuster, who is an associate professor and associate clinical director at the University of California, San Diego, center for pain medicine. He added that the study is the first randomized, controlled trial of cannabis in migraine patients that he is aware of. “It’s just hard to do this research. It’s very regulated. We had to go through a lot of government approvals to do this,” he said.
The study produced a key message. “I think one of the really important things for patients to take from this is that recreational doses are probably not necessary. The doses that we studied are lower than people use recreationally. Patients who are self-treating on their own right now are probably using higher doses than they need for the purpose of treating migraine,” said Dr. Schuster.
He also pointed out that the results offer potential insight into reducing side effects. “If [patients] are using THC only, they can hopefully have less of the side effects and tolerate it better by using a THC-CBD mix,” said Dr. Schuster.
Four therapies tested
Participants in the study could self-treat up to four migraine attacks. They were instructed to treat each migraine with one of four therapies, which were provided in a randomized, double-blind order: These included a 6% THC formulation; a mix of THC (6%) and CBD (11%); a CBD 11% formulation; and placebo cannabis with THC and CBD removed by alcohol extraction. Participants filled out a questionnaire 2 hours after treatment, and were then allowed to use rescue treatments if needed, but not additional cannabis. The age range was from 21 to 65, and inclusion criteria included 2-23 migraine days per month. Exclusion criteria included a positive urine test for THC, barbiturates, opioids, oxycodone, or methadone prior to enrollment.
The study included 73 patients who treated a migraine during the study period. There were 247 migraine attacks treated. Among participants, the median age was 41, 82.6% were female and 17.4% were male, and the median body mass index was 26.0 kg/m2. Participants experienced a median of 15 headache days per month and 6 migraine days per month, and 27.2% had chronic migraine.
At 2 hours, pain relief occurred in 48.3% of placebo treatments, 54.4% of the CBD treatments, 70.5% of the THC treatments (P = .007 versus placebo), and 69.0% of the THC/CBD treatments (P = .014 versus placebo). At 2 hours, pain freedom occurred in 15.5% of the placebo treatments, 24.6% of the CBD treatments, 29.5% of the THC treatments, and 36.2% of the THC/CBD treatments (P = .010 versus placebo). At 2 hours, freedom from most bothersome symptoms (MBS) occurred in 36.2% of the placebo treatments, 43.9% of the CBD treatments, 49.2% of the THC treatments, and 62.1% of the THC/CBD treatments (P = .004 versus placebo).
To achieve at least a 20% improvement in pain relief, compared with placebo, the number needed to treat (NNT) with THC/CBD was five. For at least a 20% improvement in pain freedom, the NNT was five, and for a 20% improvement in freedom from most bothersome symptoms, the NNT was four.
Treatment with THC was associated with the highest frequency of any adverse event (31.0%), followed by CBD and THC/CBD (19.6% each), and placebo (5.0%). At 2 hours, 18.0% of the THC treatments had an adverse event, compared with 7.0% of the CBD treatments, 6.9% of the THC/CBD treatments, and 5.2% of placebo treatments.
The number needed to treat of five for pain relief was encouraging, according to Dr. Schuster. “It’s better than some other things, but at the expense of side effects. The side effects that we see are certainly higher with cannabis than it is with other migraine treatments that patients certainly should be using beforehand. There’s also a risk of addiction, which is a concern,” said Dr. Schuster.
Useful data but questions remain
Having a clinical trial will be useful for physicians, said Ali Ezzati, MD, who attended the session. “I think it was an impressive study. Obviously, there are some challenges with cannabis studies in the medical world because of the stigma that comes with it and also the possibility of inducing addiction [and] promoting that to patients. But at the end of the day, it’s very, very common for our patients to ask us about cannabinoid use, and we really don’t have data on it. I’m glad that there are people who are running these studies so we will be able at least to answer our patients,” said Dr. Ezzati, who is an associate professor of neurology at University of California, Irvine.
Dr. Ezzati also noted that clinical trials have investigated cannabinoid use for other types of pain, such as arthritic or generalized pain. Although he said that there are some clinical similarities between other types of pain and migraine, the pathophysiology appears to be unique, which means that more work needs to be done. “It will probably take 5 or 10 years to have sufficient data to give patients a direct path for using (cannabinoids),” said Dr. Ezzati.
The study was funded by the Migraine Research Foundation. Dr. Schuster has consulted with Schedule 1 Therapeutics and Vectura Fertin. Dr. Ezzati has no relevant financial disclosures.
FROM AHS 2023
Migraine clusters emerge from machine-learning analysis
AUSTIN, TEX. – The findings could point to new therapeutic strategies, according to study author Ali Ezzati, MD.
“A lot of diagnostic criteria that we have in the migraine world come from consensus groups of experts, and based on their experience and available data. They classify different types of headache and then on top of that different types of migraine. Unfortunately, this type of classification does not necessarily lead to having very homogeneous groups,” said Dr. Ezzati, who presented the study at the annual meeting of the American Headache Society.
Migraines are generally categorized as episodic (0-14 headache days per month) or chronic (15 or more per month), or as with or without aura. But these broad categories fail to capture the true diversity of migraine, according to Dr. Ezzati, and this may contribute to the fact that response to migraine therapy hovers around 60%. “We feel that the key to improving therapeutic efficacy is to identify individuals who are more homogeneous, more similar to each other, so that when we give a treatment, it is specifically targeting the underlying pathophysiology that those people have,” said Dr. Ezzati, who is an associate professor of neurology and director of the neuroinformatics program at University of California, Irvine.
The analysis revealed some clinically interesting results, said Dr. Ezzati. “For example, allodynia is a symptom that is not particularly used for classification of different types of migraine. There was a specific group that was very high in allodynia, and they were not very responsive to treatments, so that might be a [group] that people have to focus on. Also, we talk a lot about comorbidities in migraine, but we don’t talk about how these comorbidities affect the therapeutic strategies and treatment response to specific medications. We showed that people who have depression are actually less responsive than other groups to treatments, especially prescription medications,” he said.
Machine learning reveals clusters
The researchers analyzed data from 4,423 patients drawn from the American Migraine Prevalence and Prevention Study, which was conducted every year between 2005 and 2009. They included adult patients who filled out surveys in both 2006 and 2007. The study population was 83.7% female and had a mean age of 46.8 years, and 6.4% had chronic migraine. The researchers then used a machine-learning based self-organizing map to group patients into similar clusters.
The algorithm produced five such groups: Cluster 1 had the lowest symptom severity, and 0.6% had chronic migraine. Cluster 2 had mild symptom severity with no chronic migraine. Cluster 3 had moderate symptom severity and a high prevalence of allodynia (88.5%, vs. 63.4% overall, P < .001) and no chronic migraine. Cluster 4 had a high frequency of depressive symptoms (63.1% vs. 19.8% overall, P < .001) and 5.2% had chronic migraine. Cluster 5 had frequent and severe migraines, and most (83.0%) had chronic migraine (P < .001).
There were some other broader trends. Triptans were more commonly used in clusters 2 (25.6%), 3 (27.9%), and 5 (28.0%), but less so in cluster 4 (17.1%; P < .001). Pain freedom at 2 hours was most common in cluster 1 (53.1%), followed by cluster 2 (46.4%), but was significantly less frequent in clusters 3 (32.2%), 4 (32.2%), and 5 (34.7%; P < .001).
Therapeutic implications
Dr. Ezzati believes that machine learning and data analysis could point the way to a future of more tailored migraine therapies. “I think we have to in general go down the path of using more evidence and more data to inform us about individualized planning for patients. For that we need larger clinical studies and larger epidemiological studies to help us identify more homogeneous subtypes of patients that we can eventually target in clinical trials,” he said.
Catherine Chong, MD, who chaired the session where the research was presented, praised the study in an interview. “Episodic migraine and chronic migraine have been developed [as categories] by headache frequency per month, and it was basically based on consensus in committee. They made basically a determination that 15 and under migraine days would be episodic migraine and over would be chronic migraine. So they dichotomized migraine, in a way, based on what people thought in the field. Looking at the data freely, and letting the algorithm determine the different subtypes, and putting everybody with migraine in it, and having these groups naturally appear from the data, I think is fascinating,” Dr. Chong said.
She echoed Dr. Ezzati’s call for further research that could create even more subgroups. “Is it really truly the case that somebody with less than 15 migraine days [per month], that 14 migraines days would be so different than somebody with 15 or over, or 8? I think we need to look at it further to see whether there are additional subgroups within that data. I think there are probably more [groups identifiable] from different data that we have out there,” said Dr. Chong.
Dr. Ezzati has consulted for or been a reviewer or advisory board member for Corium, Eisai, GlaxoSmithKline, Mint Research, and Health Care Horizon Scanning System. He has received research funding from Amgen. Dr. Chong has no relevant financial disclosures.
AUSTIN, TEX. – The findings could point to new therapeutic strategies, according to study author Ali Ezzati, MD.
“A lot of diagnostic criteria that we have in the migraine world come from consensus groups of experts, and based on their experience and available data. They classify different types of headache and then on top of that different types of migraine. Unfortunately, this type of classification does not necessarily lead to having very homogeneous groups,” said Dr. Ezzati, who presented the study at the annual meeting of the American Headache Society.
Migraines are generally categorized as episodic (0-14 headache days per month) or chronic (15 or more per month), or as with or without aura. But these broad categories fail to capture the true diversity of migraine, according to Dr. Ezzati, and this may contribute to the fact that response to migraine therapy hovers around 60%. “We feel that the key to improving therapeutic efficacy is to identify individuals who are more homogeneous, more similar to each other, so that when we give a treatment, it is specifically targeting the underlying pathophysiology that those people have,” said Dr. Ezzati, who is an associate professor of neurology and director of the neuroinformatics program at University of California, Irvine.
The analysis revealed some clinically interesting results, said Dr. Ezzati. “For example, allodynia is a symptom that is not particularly used for classification of different types of migraine. There was a specific group that was very high in allodynia, and they were not very responsive to treatments, so that might be a [group] that people have to focus on. Also, we talk a lot about comorbidities in migraine, but we don’t talk about how these comorbidities affect the therapeutic strategies and treatment response to specific medications. We showed that people who have depression are actually less responsive than other groups to treatments, especially prescription medications,” he said.
Machine learning reveals clusters
The researchers analyzed data from 4,423 patients drawn from the American Migraine Prevalence and Prevention Study, which was conducted every year between 2005 and 2009. They included adult patients who filled out surveys in both 2006 and 2007. The study population was 83.7% female and had a mean age of 46.8 years, and 6.4% had chronic migraine. The researchers then used a machine-learning based self-organizing map to group patients into similar clusters.
The algorithm produced five such groups: Cluster 1 had the lowest symptom severity, and 0.6% had chronic migraine. Cluster 2 had mild symptom severity with no chronic migraine. Cluster 3 had moderate symptom severity and a high prevalence of allodynia (88.5%, vs. 63.4% overall, P < .001) and no chronic migraine. Cluster 4 had a high frequency of depressive symptoms (63.1% vs. 19.8% overall, P < .001) and 5.2% had chronic migraine. Cluster 5 had frequent and severe migraines, and most (83.0%) had chronic migraine (P < .001).
There were some other broader trends. Triptans were more commonly used in clusters 2 (25.6%), 3 (27.9%), and 5 (28.0%), but less so in cluster 4 (17.1%; P < .001). Pain freedom at 2 hours was most common in cluster 1 (53.1%), followed by cluster 2 (46.4%), but was significantly less frequent in clusters 3 (32.2%), 4 (32.2%), and 5 (34.7%; P < .001).
Therapeutic implications
Dr. Ezzati believes that machine learning and data analysis could point the way to a future of more tailored migraine therapies. “I think we have to in general go down the path of using more evidence and more data to inform us about individualized planning for patients. For that we need larger clinical studies and larger epidemiological studies to help us identify more homogeneous subtypes of patients that we can eventually target in clinical trials,” he said.
Catherine Chong, MD, who chaired the session where the research was presented, praised the study in an interview. “Episodic migraine and chronic migraine have been developed [as categories] by headache frequency per month, and it was basically based on consensus in committee. They made basically a determination that 15 and under migraine days would be episodic migraine and over would be chronic migraine. So they dichotomized migraine, in a way, based on what people thought in the field. Looking at the data freely, and letting the algorithm determine the different subtypes, and putting everybody with migraine in it, and having these groups naturally appear from the data, I think is fascinating,” Dr. Chong said.
She echoed Dr. Ezzati’s call for further research that could create even more subgroups. “Is it really truly the case that somebody with less than 15 migraine days [per month], that 14 migraines days would be so different than somebody with 15 or over, or 8? I think we need to look at it further to see whether there are additional subgroups within that data. I think there are probably more [groups identifiable] from different data that we have out there,” said Dr. Chong.
Dr. Ezzati has consulted for or been a reviewer or advisory board member for Corium, Eisai, GlaxoSmithKline, Mint Research, and Health Care Horizon Scanning System. He has received research funding from Amgen. Dr. Chong has no relevant financial disclosures.
AUSTIN, TEX. – The findings could point to new therapeutic strategies, according to study author Ali Ezzati, MD.
“A lot of diagnostic criteria that we have in the migraine world come from consensus groups of experts, and based on their experience and available data. They classify different types of headache and then on top of that different types of migraine. Unfortunately, this type of classification does not necessarily lead to having very homogeneous groups,” said Dr. Ezzati, who presented the study at the annual meeting of the American Headache Society.
Migraines are generally categorized as episodic (0-14 headache days per month) or chronic (15 or more per month), or as with or without aura. But these broad categories fail to capture the true diversity of migraine, according to Dr. Ezzati, and this may contribute to the fact that response to migraine therapy hovers around 60%. “We feel that the key to improving therapeutic efficacy is to identify individuals who are more homogeneous, more similar to each other, so that when we give a treatment, it is specifically targeting the underlying pathophysiology that those people have,” said Dr. Ezzati, who is an associate professor of neurology and director of the neuroinformatics program at University of California, Irvine.
The analysis revealed some clinically interesting results, said Dr. Ezzati. “For example, allodynia is a symptom that is not particularly used for classification of different types of migraine. There was a specific group that was very high in allodynia, and they were not very responsive to treatments, so that might be a [group] that people have to focus on. Also, we talk a lot about comorbidities in migraine, but we don’t talk about how these comorbidities affect the therapeutic strategies and treatment response to specific medications. We showed that people who have depression are actually less responsive than other groups to treatments, especially prescription medications,” he said.
Machine learning reveals clusters
The researchers analyzed data from 4,423 patients drawn from the American Migraine Prevalence and Prevention Study, which was conducted every year between 2005 and 2009. They included adult patients who filled out surveys in both 2006 and 2007. The study population was 83.7% female and had a mean age of 46.8 years, and 6.4% had chronic migraine. The researchers then used a machine-learning based self-organizing map to group patients into similar clusters.
The algorithm produced five such groups: Cluster 1 had the lowest symptom severity, and 0.6% had chronic migraine. Cluster 2 had mild symptom severity with no chronic migraine. Cluster 3 had moderate symptom severity and a high prevalence of allodynia (88.5%, vs. 63.4% overall, P < .001) and no chronic migraine. Cluster 4 had a high frequency of depressive symptoms (63.1% vs. 19.8% overall, P < .001) and 5.2% had chronic migraine. Cluster 5 had frequent and severe migraines, and most (83.0%) had chronic migraine (P < .001).
There were some other broader trends. Triptans were more commonly used in clusters 2 (25.6%), 3 (27.9%), and 5 (28.0%), but less so in cluster 4 (17.1%; P < .001). Pain freedom at 2 hours was most common in cluster 1 (53.1%), followed by cluster 2 (46.4%), but was significantly less frequent in clusters 3 (32.2%), 4 (32.2%), and 5 (34.7%; P < .001).
Therapeutic implications
Dr. Ezzati believes that machine learning and data analysis could point the way to a future of more tailored migraine therapies. “I think we have to in general go down the path of using more evidence and more data to inform us about individualized planning for patients. For that we need larger clinical studies and larger epidemiological studies to help us identify more homogeneous subtypes of patients that we can eventually target in clinical trials,” he said.
Catherine Chong, MD, who chaired the session where the research was presented, praised the study in an interview. “Episodic migraine and chronic migraine have been developed [as categories] by headache frequency per month, and it was basically based on consensus in committee. They made basically a determination that 15 and under migraine days would be episodic migraine and over would be chronic migraine. So they dichotomized migraine, in a way, based on what people thought in the field. Looking at the data freely, and letting the algorithm determine the different subtypes, and putting everybody with migraine in it, and having these groups naturally appear from the data, I think is fascinating,” Dr. Chong said.
She echoed Dr. Ezzati’s call for further research that could create even more subgroups. “Is it really truly the case that somebody with less than 15 migraine days [per month], that 14 migraines days would be so different than somebody with 15 or over, or 8? I think we need to look at it further to see whether there are additional subgroups within that data. I think there are probably more [groups identifiable] from different data that we have out there,” said Dr. Chong.
Dr. Ezzati has consulted for or been a reviewer or advisory board member for Corium, Eisai, GlaxoSmithKline, Mint Research, and Health Care Horizon Scanning System. He has received research funding from Amgen. Dr. Chong has no relevant financial disclosures.
FROM AHS 2023