User login
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
Galcanezumab safe and effective for chronic migraine and medication overuse headache
Key clinical point: Galcanezumab was safe and effective in a patient population severely impaired by chronic migraine (CM) and medication overuse headache (MOH).
Major finding: Galcanezumab led to a significant reduction in migraine days per month, painkillers per month, number of days on medication, numeric rating scale scores, 6-item Headache Impact Test scores, and Migraine Disability Assessment questionnaire scores (all P < .001), with improvements being the greatest during the first 3 months of treatment. Adverse events were mostly mild, with only one case of treatment discontinuation because of severe low back pain.
Study details: The data come from a single-center, prospective study including 78 patients with CM and MOH who received galcanezumab.
Disclosures: This study did not report the funding source. S Guerzoni and C Baraldi declared receiving honoraria from various sources. L Pani declared serving as the Chief Scientific Officer of EDRA-LSWR Publishing Company and Inpeco SA Total Lab Automation Company and had ties to other sources. Other authors declared no conflicts of interest.
Source: Guerzoni S et al. Galcanezumab for the treatment of chronic migraine and medication overuse headache: Real-world clinical evidence in a severely impaired patient population. Brain Behav. 2023;13:e2799 (May 19). doi: 10.1002/brb3.2799
Key clinical point: Galcanezumab was safe and effective in a patient population severely impaired by chronic migraine (CM) and medication overuse headache (MOH).
Major finding: Galcanezumab led to a significant reduction in migraine days per month, painkillers per month, number of days on medication, numeric rating scale scores, 6-item Headache Impact Test scores, and Migraine Disability Assessment questionnaire scores (all P < .001), with improvements being the greatest during the first 3 months of treatment. Adverse events were mostly mild, with only one case of treatment discontinuation because of severe low back pain.
Study details: The data come from a single-center, prospective study including 78 patients with CM and MOH who received galcanezumab.
Disclosures: This study did not report the funding source. S Guerzoni and C Baraldi declared receiving honoraria from various sources. L Pani declared serving as the Chief Scientific Officer of EDRA-LSWR Publishing Company and Inpeco SA Total Lab Automation Company and had ties to other sources. Other authors declared no conflicts of interest.
Source: Guerzoni S et al. Galcanezumab for the treatment of chronic migraine and medication overuse headache: Real-world clinical evidence in a severely impaired patient population. Brain Behav. 2023;13:e2799 (May 19). doi: 10.1002/brb3.2799
Key clinical point: Galcanezumab was safe and effective in a patient population severely impaired by chronic migraine (CM) and medication overuse headache (MOH).
Major finding: Galcanezumab led to a significant reduction in migraine days per month, painkillers per month, number of days on medication, numeric rating scale scores, 6-item Headache Impact Test scores, and Migraine Disability Assessment questionnaire scores (all P < .001), with improvements being the greatest during the first 3 months of treatment. Adverse events were mostly mild, with only one case of treatment discontinuation because of severe low back pain.
Study details: The data come from a single-center, prospective study including 78 patients with CM and MOH who received galcanezumab.
Disclosures: This study did not report the funding source. S Guerzoni and C Baraldi declared receiving honoraria from various sources. L Pani declared serving as the Chief Scientific Officer of EDRA-LSWR Publishing Company and Inpeco SA Total Lab Automation Company and had ties to other sources. Other authors declared no conflicts of interest.
Source: Guerzoni S et al. Galcanezumab for the treatment of chronic migraine and medication overuse headache: Real-world clinical evidence in a severely impaired patient population. Brain Behav. 2023;13:e2799 (May 19). doi: 10.1002/brb3.2799
Ketogenic diet may improve sleep complaints in patients with migraine
Key clinical point: Ketogenic diet (KD) significantly improved sleep complaints in patients with migraine, irrespective of migraine improvements and anthropometric modifications.
Major finding: Migraine intensity, headache frequency, and the severity of headache-related disability improved significantly after 3 months of KD therapy (all P < .001) along with a significant decrease in the rate of insomnia (before vs after treatment: 60% vs 40%; P < .001) and number of patients experiencing poor sleep (reduced to half at follow-up; P < .001). The modifications in sleep features showed no correlation with migraine improvements and anthropometric changes.
Study details: This study included 70 patients with migraine who received KD as a preventive therapy for migraine.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Merlino G et al. Sleep of migraine patients is ameliorated by ketogenic diet, independently of pain control. Sleep Med. 2023;107:196-201 (May 9). doi: 10.1016/j.sleep.2023.05.006
Key clinical point: Ketogenic diet (KD) significantly improved sleep complaints in patients with migraine, irrespective of migraine improvements and anthropometric modifications.
Major finding: Migraine intensity, headache frequency, and the severity of headache-related disability improved significantly after 3 months of KD therapy (all P < .001) along with a significant decrease in the rate of insomnia (before vs after treatment: 60% vs 40%; P < .001) and number of patients experiencing poor sleep (reduced to half at follow-up; P < .001). The modifications in sleep features showed no correlation with migraine improvements and anthropometric changes.
Study details: This study included 70 patients with migraine who received KD as a preventive therapy for migraine.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Merlino G et al. Sleep of migraine patients is ameliorated by ketogenic diet, independently of pain control. Sleep Med. 2023;107:196-201 (May 9). doi: 10.1016/j.sleep.2023.05.006
Key clinical point: Ketogenic diet (KD) significantly improved sleep complaints in patients with migraine, irrespective of migraine improvements and anthropometric modifications.
Major finding: Migraine intensity, headache frequency, and the severity of headache-related disability improved significantly after 3 months of KD therapy (all P < .001) along with a significant decrease in the rate of insomnia (before vs after treatment: 60% vs 40%; P < .001) and number of patients experiencing poor sleep (reduced to half at follow-up; P < .001). The modifications in sleep features showed no correlation with migraine improvements and anthropometric changes.
Study details: This study included 70 patients with migraine who received KD as a preventive therapy for migraine.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Merlino G et al. Sleep of migraine patients is ameliorated by ketogenic diet, independently of pain control. Sleep Med. 2023;107:196-201 (May 9). doi: 10.1016/j.sleep.2023.05.006
Migraine history raises susceptibility to Alzheimer’s disease
Key clinical point: The risk of developing Alzheimer’s disease (AD) dementia is significantly higher in individuals with vs without migraine, with younger age, obesity, and chronic migraine being significant risk factors for AD dementia among individuals with migraine.
Major finding: A prior history of migraine is a significant risk factor for AD dementia (hazard ratio [HR] 1.32; 95% CI 1.30-1.35). The risk was prominently higher among individuals with vs without migraine who were younger (HR 1.58; 95% CI 1.52-1.64) and had obesity (HR 1.39; 95% CI 1.35-1.43) and among those with chronic vs episodic migraine (CM HR 1.48, 95% CI 1.44-1.52; vs EM HR 1.26, 95% CI 1.27-1.29).
Study details: This retrospective, nationwide cohort study included individuals without (n = 5,863,348) and with (n = 212,836) migraine.
Disclosures: This study was supported by grants from the National Research Foundation funded by the Ministry of Education, the Technology Development Program funded by the Ministry of SMEs and Startups (Korea), and others. The authors declared no conflicts of interest.
Source: Kim J et al. Association between migraine and Alzheimer’s disease: A nationwide cohort study. Front Aging Neurosci. 2023;15:1196185 (May 25). doi: 10.3389/fnagi.2023.1196185
Key clinical point: The risk of developing Alzheimer’s disease (AD) dementia is significantly higher in individuals with vs without migraine, with younger age, obesity, and chronic migraine being significant risk factors for AD dementia among individuals with migraine.
Major finding: A prior history of migraine is a significant risk factor for AD dementia (hazard ratio [HR] 1.32; 95% CI 1.30-1.35). The risk was prominently higher among individuals with vs without migraine who were younger (HR 1.58; 95% CI 1.52-1.64) and had obesity (HR 1.39; 95% CI 1.35-1.43) and among those with chronic vs episodic migraine (CM HR 1.48, 95% CI 1.44-1.52; vs EM HR 1.26, 95% CI 1.27-1.29).
Study details: This retrospective, nationwide cohort study included individuals without (n = 5,863,348) and with (n = 212,836) migraine.
Disclosures: This study was supported by grants from the National Research Foundation funded by the Ministry of Education, the Technology Development Program funded by the Ministry of SMEs and Startups (Korea), and others. The authors declared no conflicts of interest.
Source: Kim J et al. Association between migraine and Alzheimer’s disease: A nationwide cohort study. Front Aging Neurosci. 2023;15:1196185 (May 25). doi: 10.3389/fnagi.2023.1196185
Key clinical point: The risk of developing Alzheimer’s disease (AD) dementia is significantly higher in individuals with vs without migraine, with younger age, obesity, and chronic migraine being significant risk factors for AD dementia among individuals with migraine.
Major finding: A prior history of migraine is a significant risk factor for AD dementia (hazard ratio [HR] 1.32; 95% CI 1.30-1.35). The risk was prominently higher among individuals with vs without migraine who were younger (HR 1.58; 95% CI 1.52-1.64) and had obesity (HR 1.39; 95% CI 1.35-1.43) and among those with chronic vs episodic migraine (CM HR 1.48, 95% CI 1.44-1.52; vs EM HR 1.26, 95% CI 1.27-1.29).
Study details: This retrospective, nationwide cohort study included individuals without (n = 5,863,348) and with (n = 212,836) migraine.
Disclosures: This study was supported by grants from the National Research Foundation funded by the Ministry of Education, the Technology Development Program funded by the Ministry of SMEs and Startups (Korea), and others. The authors declared no conflicts of interest.
Source: Kim J et al. Association between migraine and Alzheimer’s disease: A nationwide cohort study. Front Aging Neurosci. 2023;15:1196185 (May 25). doi: 10.3389/fnagi.2023.1196185
Opioid use more frequent in patients with chronic migraine
Key clinical point: Use of opioids is still prevalent among patients with migraine, thus indicating non-adherence to evidence-based international guidelines; moreover, the opioid use is more frequent and prolonged among patients with chronic migraine (CM) than among those with episodic migraine (EM).
Major finding: Overall, 13.4% of patients reported ever using an opioid for headache, with 46.3% using opioids occasionally, whereas 27.0% and 11.3% reported using them for >1 month and >1 year, respectively. Additionally, 2.4% of participants used opioids without a prescription. Patients with CM vs EM reported more frequent (21.6% vs 11.7%; P < .001) and prolonged (>1 month: 33.6% vs 24.4%; P < .003; >1 year: 17.7% vs 8.7%; P < .001) opioid use.
Study details: Findings are from a cross-sectional questionnaire-based study including 3712 patients with migraine (CM n = 629; EM n = 3,083).
Disclosures: This study did not receive any funding. GM Terwindt declared receiving consultancy support and independent support from various sources. No other conflicts of interest were declared.
Source: van Welie RF, van Welie FC, et al. Characterizing opioid use in a Dutch cohort with migraine. Cephalalgia. 2023;43(5) (May 11). doi: 10.1177/03331024231174160
Key clinical point: Use of opioids is still prevalent among patients with migraine, thus indicating non-adherence to evidence-based international guidelines; moreover, the opioid use is more frequent and prolonged among patients with chronic migraine (CM) than among those with episodic migraine (EM).
Major finding: Overall, 13.4% of patients reported ever using an opioid for headache, with 46.3% using opioids occasionally, whereas 27.0% and 11.3% reported using them for >1 month and >1 year, respectively. Additionally, 2.4% of participants used opioids without a prescription. Patients with CM vs EM reported more frequent (21.6% vs 11.7%; P < .001) and prolonged (>1 month: 33.6% vs 24.4%; P < .003; >1 year: 17.7% vs 8.7%; P < .001) opioid use.
Study details: Findings are from a cross-sectional questionnaire-based study including 3712 patients with migraine (CM n = 629; EM n = 3,083).
Disclosures: This study did not receive any funding. GM Terwindt declared receiving consultancy support and independent support from various sources. No other conflicts of interest were declared.
Source: van Welie RF, van Welie FC, et al. Characterizing opioid use in a Dutch cohort with migraine. Cephalalgia. 2023;43(5) (May 11). doi: 10.1177/03331024231174160
Key clinical point: Use of opioids is still prevalent among patients with migraine, thus indicating non-adherence to evidence-based international guidelines; moreover, the opioid use is more frequent and prolonged among patients with chronic migraine (CM) than among those with episodic migraine (EM).
Major finding: Overall, 13.4% of patients reported ever using an opioid for headache, with 46.3% using opioids occasionally, whereas 27.0% and 11.3% reported using them for >1 month and >1 year, respectively. Additionally, 2.4% of participants used opioids without a prescription. Patients with CM vs EM reported more frequent (21.6% vs 11.7%; P < .001) and prolonged (>1 month: 33.6% vs 24.4%; P < .003; >1 year: 17.7% vs 8.7%; P < .001) opioid use.
Study details: Findings are from a cross-sectional questionnaire-based study including 3712 patients with migraine (CM n = 629; EM n = 3,083).
Disclosures: This study did not receive any funding. GM Terwindt declared receiving consultancy support and independent support from various sources. No other conflicts of interest were declared.
Source: van Welie RF, van Welie FC, et al. Characterizing opioid use in a Dutch cohort with migraine. Cephalalgia. 2023;43(5) (May 11). doi: 10.1177/03331024231174160
Fremanezumab switch may benefit migraine patients who are not responding to anti-CGRP mAb
Key clinical point: Switching to fremanezumab may provide clinical benefits in patients with difficult-to-treat episodic or chronic migraine who have not responded to prior monoclonal antibody (mAb) therapy targeting the calcitonin gene-related peptide (anti-CGRP) pathway.
Major finding: Overall, 42.8% of patients achieved a 50% reduction in the monthly migraine days (MMD) after switching to fremanezumab. The MMD decreased from 13.6 to 7.2 (P < .0001), Migraine Disability Assessment scores were reduced from 73.3 to 50.3 (P = .0014), and acute migraine medication use decreased from 9.7 to 4.9 days/month (P < .0001) after 3 months of fremanezumab therapy.
Study details: This subgroup analysis of the real-world, non-interventional Finesse study included 153 patients with episodic or chronic migraine who switched to fremanezumab from other anti-CGRP mAb treatments.
Disclosures: This study was funded by TEVA GmbH. Two authors declared being employees of TEVA GmbH. Several authors, including the lead author, declared serving as consultants or on advisory or speaker boards or receiving research grants from various sources, including TEVA GmbH.
Source: Straube A et al. Real-world effectiveness of fremanezumab in patients with migraine switching from another mAb targeting the CGRP pathway: A subgroup analysis of the Finesse Study. J Headache Pain. 2023;24:59 (May 23). doi: 10.1186/s10194-023-01593-2
Key clinical point: Switching to fremanezumab may provide clinical benefits in patients with difficult-to-treat episodic or chronic migraine who have not responded to prior monoclonal antibody (mAb) therapy targeting the calcitonin gene-related peptide (anti-CGRP) pathway.
Major finding: Overall, 42.8% of patients achieved a 50% reduction in the monthly migraine days (MMD) after switching to fremanezumab. The MMD decreased from 13.6 to 7.2 (P < .0001), Migraine Disability Assessment scores were reduced from 73.3 to 50.3 (P = .0014), and acute migraine medication use decreased from 9.7 to 4.9 days/month (P < .0001) after 3 months of fremanezumab therapy.
Study details: This subgroup analysis of the real-world, non-interventional Finesse study included 153 patients with episodic or chronic migraine who switched to fremanezumab from other anti-CGRP mAb treatments.
Disclosures: This study was funded by TEVA GmbH. Two authors declared being employees of TEVA GmbH. Several authors, including the lead author, declared serving as consultants or on advisory or speaker boards or receiving research grants from various sources, including TEVA GmbH.
Source: Straube A et al. Real-world effectiveness of fremanezumab in patients with migraine switching from another mAb targeting the CGRP pathway: A subgroup analysis of the Finesse Study. J Headache Pain. 2023;24:59 (May 23). doi: 10.1186/s10194-023-01593-2
Key clinical point: Switching to fremanezumab may provide clinical benefits in patients with difficult-to-treat episodic or chronic migraine who have not responded to prior monoclonal antibody (mAb) therapy targeting the calcitonin gene-related peptide (anti-CGRP) pathway.
Major finding: Overall, 42.8% of patients achieved a 50% reduction in the monthly migraine days (MMD) after switching to fremanezumab. The MMD decreased from 13.6 to 7.2 (P < .0001), Migraine Disability Assessment scores were reduced from 73.3 to 50.3 (P = .0014), and acute migraine medication use decreased from 9.7 to 4.9 days/month (P < .0001) after 3 months of fremanezumab therapy.
Study details: This subgroup analysis of the real-world, non-interventional Finesse study included 153 patients with episodic or chronic migraine who switched to fremanezumab from other anti-CGRP mAb treatments.
Disclosures: This study was funded by TEVA GmbH. Two authors declared being employees of TEVA GmbH. Several authors, including the lead author, declared serving as consultants or on advisory or speaker boards or receiving research grants from various sources, including TEVA GmbH.
Source: Straube A et al. Real-world effectiveness of fremanezumab in patients with migraine switching from another mAb targeting the CGRP pathway: A subgroup analysis of the Finesse Study. J Headache Pain. 2023;24:59 (May 23). doi: 10.1186/s10194-023-01593-2
Real-world data show benefits of anti-CGRP mAb in migraine patients age ≥ 65 years
Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) are a safe and effective treatment option for patients age > 65 years with migraine and who did not respond to ≥3 prior migraine preventive medications.
Major finding: At 6 months, monthly migraine days, monthly headache days, and monthly acute medication intake days reduced by 10.1 days (P = .0001), 10.5 days (P < .001), and 9.4 days (P < .001), respectively. Nearly 25.3% of the patients experienced adverse effects at some point during follow-up, which were mostly mild in severity.
Study details: The data come from an observational retrospective study including 162 patients age > 65 years with migraine who did not respond to ≥3 migraine preventive medications and were treated with any one of the three anti-CGRP mAb (erenumab, galcanezumab, or fremanezumab).
Disclosures: This study did not receive any specific grant. Several authors, including the lead author, reported receiving honoraria for consulting, speaking, or advisory board participation; research funding; or travel funding from various sources.
Source: Muñoz-Vendrell A et al. Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: A real-life multicentre analysis of 162 patients. J Headache Pain. 2023;24:63 (Jun 2). doi: 10.1186/s10194-023-01585-2
Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) are a safe and effective treatment option for patients age > 65 years with migraine and who did not respond to ≥3 prior migraine preventive medications.
Major finding: At 6 months, monthly migraine days, monthly headache days, and monthly acute medication intake days reduced by 10.1 days (P = .0001), 10.5 days (P < .001), and 9.4 days (P < .001), respectively. Nearly 25.3% of the patients experienced adverse effects at some point during follow-up, which were mostly mild in severity.
Study details: The data come from an observational retrospective study including 162 patients age > 65 years with migraine who did not respond to ≥3 migraine preventive medications and were treated with any one of the three anti-CGRP mAb (erenumab, galcanezumab, or fremanezumab).
Disclosures: This study did not receive any specific grant. Several authors, including the lead author, reported receiving honoraria for consulting, speaking, or advisory board participation; research funding; or travel funding from various sources.
Source: Muñoz-Vendrell A et al. Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: A real-life multicentre analysis of 162 patients. J Headache Pain. 2023;24:63 (Jun 2). doi: 10.1186/s10194-023-01585-2
Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) are a safe and effective treatment option for patients age > 65 years with migraine and who did not respond to ≥3 prior migraine preventive medications.
Major finding: At 6 months, monthly migraine days, monthly headache days, and monthly acute medication intake days reduced by 10.1 days (P = .0001), 10.5 days (P < .001), and 9.4 days (P < .001), respectively. Nearly 25.3% of the patients experienced adverse effects at some point during follow-up, which were mostly mild in severity.
Study details: The data come from an observational retrospective study including 162 patients age > 65 years with migraine who did not respond to ≥3 migraine preventive medications and were treated with any one of the three anti-CGRP mAb (erenumab, galcanezumab, or fremanezumab).
Disclosures: This study did not receive any specific grant. Several authors, including the lead author, reported receiving honoraria for consulting, speaking, or advisory board participation; research funding; or travel funding from various sources.
Source: Muñoz-Vendrell A et al. Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: A real-life multicentre analysis of 162 patients. J Headache Pain. 2023;24:63 (Jun 2). doi: 10.1186/s10194-023-01585-2
Perimenstrual migraine attacks are exclusively migraine attacks without aura, recommends study
Key clinical point: The perimenstrual period was associated with an increased susceptibility to migraine without aura exclusively in both women who experienced migraine with and without aura; hence, the study recommended that only attacks without aura should be considered for a perimenstrual migraine diagnosis.
Major finding: A significant interaction was observed between the perimenstrual window and migraine subtype for migraine attack occurrence (P = .022), with the effect of the perimenstrual window being greater among women with migraine without aura (odds ratio [OR] 1.57; 95% CI 1.45-1.69) vs with aura (OR 1.36; 95% CI 1.24-1.49). Women with migraine with vs without aura showed similar increase in migraine attacks without aura during the perimenstrual window (P = .224).
Study details: This longitudinal electronic diary study included 526 premenopausal women diagnosed with migraine with or without aura.
Disclosures: This study was supported by ZonMw and the Dutch Brain Foundation. Five authors, including the lead author, declared receiving independent support from the study funders. Some authors declared receiving consultancy and independent support from various sources.
Source: Verhagen IE et al. Migraine with and without aura in relation to the menstrual cycle and other hormonal milestones: A prospective cohort study. Cephalalgia. 2023;43(6) (May 31). doi: 10.1177/03331024231164322
Key clinical point: The perimenstrual period was associated with an increased susceptibility to migraine without aura exclusively in both women who experienced migraine with and without aura; hence, the study recommended that only attacks without aura should be considered for a perimenstrual migraine diagnosis.
Major finding: A significant interaction was observed between the perimenstrual window and migraine subtype for migraine attack occurrence (P = .022), with the effect of the perimenstrual window being greater among women with migraine without aura (odds ratio [OR] 1.57; 95% CI 1.45-1.69) vs with aura (OR 1.36; 95% CI 1.24-1.49). Women with migraine with vs without aura showed similar increase in migraine attacks without aura during the perimenstrual window (P = .224).
Study details: This longitudinal electronic diary study included 526 premenopausal women diagnosed with migraine with or without aura.
Disclosures: This study was supported by ZonMw and the Dutch Brain Foundation. Five authors, including the lead author, declared receiving independent support from the study funders. Some authors declared receiving consultancy and independent support from various sources.
Source: Verhagen IE et al. Migraine with and without aura in relation to the menstrual cycle and other hormonal milestones: A prospective cohort study. Cephalalgia. 2023;43(6) (May 31). doi: 10.1177/03331024231164322
Key clinical point: The perimenstrual period was associated with an increased susceptibility to migraine without aura exclusively in both women who experienced migraine with and without aura; hence, the study recommended that only attacks without aura should be considered for a perimenstrual migraine diagnosis.
Major finding: A significant interaction was observed between the perimenstrual window and migraine subtype for migraine attack occurrence (P = .022), with the effect of the perimenstrual window being greater among women with migraine without aura (odds ratio [OR] 1.57; 95% CI 1.45-1.69) vs with aura (OR 1.36; 95% CI 1.24-1.49). Women with migraine with vs without aura showed similar increase in migraine attacks without aura during the perimenstrual window (P = .224).
Study details: This longitudinal electronic diary study included 526 premenopausal women diagnosed with migraine with or without aura.
Disclosures: This study was supported by ZonMw and the Dutch Brain Foundation. Five authors, including the lead author, declared receiving independent support from the study funders. Some authors declared receiving consultancy and independent support from various sources.
Source: Verhagen IE et al. Migraine with and without aura in relation to the menstrual cycle and other hormonal milestones: A prospective cohort study. Cephalalgia. 2023;43(6) (May 31). doi: 10.1177/03331024231164322