Headache & Migraine

Since the mid-2010s, the US Food and Drug Administration (FDA) has approved or cleared no fewer than 10 migraine treatments in the form of orals, injectables, nasal sprays, and devices. The medical achievements of the last decade in the field of migraine have been nothing less than stunning for physicians and their patients, whether they relied on off-label medications or those sanctioned by the FDA to treat patients living with migraine.

That said, the newer orals and injectables cannot help everyone living with migraine. The small molecule calcitonin gene-related peptide (CGRP) receptor antagonists (gepants) and the monoclonal antibodies that target the CGRP ligand or receptor, while well received by patients and physicians alike, have drawbacks for some patients, including lack of efficacy, slow response rate, and adverse events that prevent some patients from taking them. The gepants, which are oral medications—as opposed to the CGRP monoclonal antibody injectables—can occasionally cause enough nausea, drowsiness, and constipation for patients to choose to discontinue their use.

Certain patients have other reasons to shun orals and injectables. Some cannot swallow pills while others fear or do not tolerate injections. Insurance companies limit the quantity of acute care medications, so some patients cannot treat every migraine attack. Then there are those who have failed so many therapies in the past that they will not try the latest one. Consequently, some lie in bed, vomiting until the pain is gone, and some take too many over-the-counter or migraine-specific products, which make migraine symptoms worse if they develop medication overuse headache. And lastly, there are patients who have never walked through a physician’s door to secure a migraine diagnosis and get appropriate treatment.

Non interventional medical devices cleared by the FDA now allow physicians to offer relief to patients with migraine. They work either through various types of electrical neuromodulation to nerves outside the brain or they apply magnetic stimulation to the back of the brain itself to reach pain-associated pathways. A 2019 report on pain management from the US Department of Health and Human Services noted that some randomized control trials (RCTs) and other studies “have demonstrated that noninvasive vagal nerve stimulation can be effective in ameliorating pain in various types of cluster headaches and migraines.”

At least 3 devices, 1 designed to stimulate both the occipital and trigeminal nerves (eCOT-NS, Relivion, Neurolief Ltd), 1 that stimulates the vagus nerve noninvasively (nVNS, gammaCORE, electroCore), and 1 that stimulates peripheral nerves in the upper arm (remote electrical neuromodulation [REN], Nerivio, Theranica Bio-Electronics Ltd), are FDA cleared to treat episodic and chronic migraine. nVNS is also cleared to treat migraine, episodic cluster headache acutely, and chronic cluster acutely in connection with medication.

Real-world studies on all migraine treatments, especially the devices, are flooding PubMed. As for a physician’s observation, we will get to that shortly.

The Devices

Nerivio

Theranica Bio-Electronics Ltd makes a REN called Nerivio, which was FDA cleared in January 2021 to treat episodic migraine acutely in adults and adolescents. Studies have shown its effectiveness for chronic migraine patients who are treated acutely, and it has also helped patients with menstrual migraine. The patient wears the device on the upper arm. Sensory fibers, once stimulated in the arm, send an impulse to the brainstem to affect the serotonin- and norepinephrine-modulated descending inhibitory pathway to disrupt incoming pain messaging. Theranica has applied to the FDA for clearance to treat patients with chronic migraine, as well as for prevention.

Relivion

Neurolief Ltd created the external combined occipital and trigeminal nerve stimulation device (eCOT-NS), which stimulates both the occipital and trigeminal nerves. It has multiple output electrodes, which are placed on the forehead to stimulate the trigeminal supraorbital and supratrochlear nerve branches bilaterally, and over the occipital nerves in the back of the head. It is worn like a tiara as it must be in good contact with the forehead and the back of the head simultaneously. It is FDA cleared to treat acute migraine.

gammaCORE

gammaCORE is a nVNS device that is FDA cleared for acute and preventive treatment of migraine in adolescents and adults, and acute and preventive treatment of episodic cluster headache in adults. It is also cleared to treat chronic cluster headache acutely along with medication. The patient applies gel to the device’s 2 electrical contacts and then locates the vagus nerve on the side of the neck and applies the electrodes to the area that will be treated. Patients can adjust the stimulation’s intensity so that they can barely feel the stimulation; it has not been reported to be painful. nVNS is also an FDA cleared treatment for paroxysmal hemicrania and hemicrania continua. 

SAVI Dual

The s-TMS (SAVI Dual, formerly called the Spring TMS and the sTMS mini), made by eNeura, is a single-pulse, transcranial magnetic stimulation applied to the back of the head to stimulate the occipital lobes in the brain. It was FDA cleared for acute and preventive care of migraine in adolescents over 12 years and for adults in February 2019. The patient holds a handheld magnetic device against their occiput, and when the tool is discharged, a brief magnetic pulse interrupts the pattern of neuronal firing (probably cortical spreading depression) that can trigger migraine and the visual aura associated with migraine in one-third of patients.

Cefaly

The e-TNS (Cefaly) works by external trigeminal nerve stimulation of the supraorbital and trochlear nerves bilaterally in the forehead. It gradually and automatically increases in intensity and can be controlled by the patient. It is FDA cleared for acute and preventive treatment of migraine, and, unlike the other devices, it is sold over the counter without a prescription. According to the company website, there are 3 devices: 1 is for acute treatment, 1 is for preventive treatment, and 1 device has 2 settings for both acute and preventive treatment.

The Studies

While most of the published studies on devices are company-sponsored, these device makers have underwritten numerous, sometimes very well-designed, studies on their products. A review by VanderPluym et al described those studies and their various risks of bias. 

There are at least 10 studies on REN published so far. These include 2 randomized, sham-controlled trials looking at pain freedom and pain relief at 2 hours after stimulation begins. Another study detailed treatment reports from many patients in which 66.5% experienced pain relief at 2 hours post treatment initiation in half of their treatments. A subgroup of 16% of those patients were prescribed REN by their primary care physicians. Of that group, 77.8% experienced pain relief in half their treatments. That figure was very close to another study that found that 23 of 31 (74.2%) of the study patients treated virtually by non headache providers found relief in 50% of their headaches. REN comes with an education and behavioral medicine app that is used during treatment. A study done by the company shows that when a patient uses the relaxation app along with the standard stimulation, they do considerably better than with stimulation alone.

The eCOT-NS has also been tested in an RCT. At 2 hours, the responder rate was twice as high as in the sham group (66.7% vs 32%). Overall headache relief at 2 hours was higher in the responder group (76% vs 31.6%). In a study collecting real-world data on the efficacy of eCOT-NS in the preventive treatment of migraine (abstract data were presented at the American Headache Society meeting in June 2022), there was a 65.3% reduction in monthly migraine days (MMD) from baseline through 6 months. Treatment reduced MMD by 10.0 (from 15.3 to 5.3—a 76.8% reduction), and reduced acute medication use days (12.5 at baseline to 2.9) at 6 months.

Users of nVNS discussed their experiences with the device, which is the size of a large bar of soap, in a patient registry. They reported 192 attacks, with a mean pain score starting at 2.7 and dropping to 1.3 after 30 minutes. The pain levels of 70% of the attacks dropped to either mild or nonexistent. In a multicenter study on nNVS, 48 patients and 44 sham patients with episodic and chronic cluster headache showed no significant difference in the primary endpoint of pain freedom at 15 minutes between the nVNS and sham. There was also no difference in the chronic cluster headache group. But the episodic cluster subgroup showed a difference; nVNS was superior to sham, 48% to 6% (P ≤ 0.01). Those in the chronic cluster headache group reported a lower percentage of pain-free status than the sham group (5% vs 13%). In another study of 477 patients, those patients who adhered to treatment more than 67% of the time per month showed a reduction in migraine days (2.27 vs 1.53). Patients with aura also fared better than those without aura.

The e-TNS device is cleared for treating adults with migraine, acutely and preventively. It received initial clearance in 2017; in 2020, Cefaly Technology received clearance from the FDA to sell its products over the counter. The device, which resembles a large diamond that affixes to the forehead, has received differing reviews between various patient reports (found online at major retailer sites) and study results. In a blinded, intent-to-treat study involving 538 patients, 25.5% of the verum group reported they were pain-free at 2 hours; 18.3% in the sham group reported the same. Additionally, 56.4% of the subjects in the verum group reported they were free of the most bothersome migraine symptoms, as opposed to 42.3% of the sham group.

Adverse Events

The adverse events observed with these devices were, overall, relatively mild, and disappeared once the device was shut off. A few nVNS users said they experienced discomfort at the application site. With REN, 59 of 12,368 patients reported device-related issues; the vast majority were considered mild and consisted mostly of a sensation of warmth under the device. Of the 259 e-TNS  users, 8.5% reported minor and reversible occurrences, such as treatment-related discomfort, paresthesia, and burning.

Patients in the Clinic

A few observations from the clinic regarding these devices:

Some devices are easier to use than others. I know this, because at a recent demonstration session in a course for physicians on headache treatment, I agreed to be the person on whom the device was demonstrated. The physician applying the device had difficulty aligning the device’s sensors with the appropriate nerves. Making sure your patients use these devices correctly is essential, and you or your staff should demonstrate their use to the patient. No doubt, this could be time-consuming in some cases, and patients who are reading the device’s instructions while in pain will likely get frustrated if they cannot get the device to work. 

Some patients who have failed every medication class can occasionally find partial relief with these devices. One longtime patient of mine came to me severely disabled from chronic migraine and medication overuse headache but was somewhat better with 2 preventive medications. Triptans worked acutely, but she developed nearly every side effect imaginable. I was able to reverse her medication overuse headache, but the gepants, although they worked somewhat, took too long to take effect. We agreed the next step would be to use REN for each migraine attack, combined with acute care medication if necessary. (She uses REN alone for a milder headache and adds a gepant with naproxen if necessary.) She has found using the relaxation module on the REN app increases her chances of eliminating the migraine. She is not pain free all the time, but she appreciates the pain-free intervals.

One chronic cluster patient has relied on subcutaneous sumatriptan and breathing 100% oxygen at 12 liters per minute through a mask over his nose and mouth for acute relief from his headaches. His headache pain can climb from a 3 to a 10 in a matter of minutes. It starts behind and a bit above the right eye where he feels a tremendous pressure building up. He says that at times it feels like a screwdriver has been thrust into his eye and is being turned. Along with the pain, the eye becomes red, the pupil constricts, and the eyelid droops. He also has dripping from the right nostril, which stuffs up when the pain abates. The pain lasts for 1 to 2 hours, then returns 3 to 5 times a day for 5 days a week, on average. The pain never goes away for more than 3 weeks in a year’s time, hence the reason for his chronic cluster headache diagnosis.  He is now using nVNS as soon as he feels the pain coming on. If the device does not provide sufficient relief, he uses oxygen or takes the sumatriptan injection.

Some patients who get cluster headaches think of suicide if the pain cannot be stopped; but in my experience, most can become pain free, or at least realize some partial relief from a variety of treatments (sometimes given at the same time).

Doctors often do not think of devices as options, and some doctors think devices do not work even though they have no experience with using them. Devices can give good relief on their own, and when a severe headache needs stronger treatment, medications added to a device usually work better than either treatment alone.

Since the mid-2010s, the US Food and Drug Administration (FDA) has approved or cleared no fewer than 10 migraine treatments in the form of orals, injectables, nasal sprays, and devices. The medical achievements of the last decade in the field of migraine have been nothing less than stunning for physicians and their patients, whether they relied on off-label medications or those sanctioned by the FDA to treat patients living with migraine.

That said, the newer orals and injectables cannot help everyone living with migraine. The small molecule calcitonin gene-related peptide (CGRP) receptor antagonists (gepants) and the monoclonal antibodies that target the CGRP ligand or receptor, while well received by patients and physicians alike, have drawbacks for some patients, including lack of efficacy, slow response rate, and adverse events that prevent some patients from taking them. The gepants, which are oral medications—as opposed to the CGRP monoclonal antibody injectables—can occasionally cause enough nausea, drowsiness, and constipation for patients to choose to discontinue their use.

Certain patients have other reasons to shun orals and injectables. Some cannot swallow pills while others fear or do not tolerate injections. Insurance companies limit the quantity of acute care medications, so some patients cannot treat every migraine attack. Then there are those who have failed so many therapies in the past that they will not try the latest one. Consequently, some lie in bed, vomiting until the pain is gone, and some take too many over-the-counter or migraine-specific products, which make migraine symptoms worse if they develop medication overuse headache. And lastly, there are patients who have never walked through a physician’s door to secure a migraine diagnosis and get appropriate treatment.

Non interventional medical devices cleared by the FDA now allow physicians to offer relief to patients with migraine. They work either through various types of electrical neuromodulation to nerves outside the brain or they apply magnetic stimulation to the back of the brain itself to reach pain-associated pathways. A 2019 report on pain management from the US Department of Health and Human Services noted that some randomized control trials (RCTs) and other studies “have demonstrated that noninvasive vagal nerve stimulation can be effective in ameliorating pain in various types of cluster headaches and migraines.”

At least 3 devices, 1 designed to stimulate both the occipital and trigeminal nerves (eCOT-NS, Relivion, Neurolief Ltd), 1 that stimulates the vagus nerve noninvasively (nVNS, gammaCORE, electroCore), and 1 that stimulates peripheral nerves in the upper arm (remote electrical neuromodulation [REN], Nerivio, Theranica Bio-Electronics Ltd), are FDA cleared to treat episodic and chronic migraine. nVNS is also cleared to treat migraine, episodic cluster headache acutely, and chronic cluster acutely in connection with medication.

Real-world studies on all migraine treatments, especially the devices, are flooding PubMed. As for a physician’s observation, we will get to that shortly.

The Devices

Nerivio

Theranica Bio-Electronics Ltd makes a REN called Nerivio, which was FDA cleared in January 2021 to treat episodic migraine acutely in adults and adolescents. Studies have shown its effectiveness for chronic migraine patients who are treated acutely, and it has also helped patients with menstrual migraine. The patient wears the device on the upper arm. Sensory fibers, once stimulated in the arm, send an impulse to the brainstem to affect the serotonin- and norepinephrine-modulated descending inhibitory pathway to disrupt incoming pain messaging. Theranica has applied to the FDA for clearance to treat patients with chronic migraine, as well as for prevention.

Relivion

Neurolief Ltd created the external combined occipital and trigeminal nerve stimulation device (eCOT-NS), which stimulates both the occipital and trigeminal nerves. It has multiple output electrodes, which are placed on the forehead to stimulate the trigeminal supraorbital and supratrochlear nerve branches bilaterally, and over the occipital nerves in the back of the head. It is worn like a tiara as it must be in good contact with the forehead and the back of the head simultaneously. It is FDA cleared to treat acute migraine.

gammaCORE

gammaCORE is a nVNS device that is FDA cleared for acute and preventive treatment of migraine in adolescents and adults, and acute and preventive treatment of episodic cluster headache in adults. It is also cleared to treat chronic cluster headache acutely along with medication. The patient applies gel to the device’s 2 electrical contacts and then locates the vagus nerve on the side of the neck and applies the electrodes to the area that will be treated. Patients can adjust the stimulation’s intensity so that they can barely feel the stimulation; it has not been reported to be painful. nVNS is also an FDA cleared treatment for paroxysmal hemicrania and hemicrania continua. 

SAVI Dual

The s-TMS (SAVI Dual, formerly called the Spring TMS and the sTMS mini), made by eNeura, is a single-pulse, transcranial magnetic stimulation applied to the back of the head to stimulate the occipital lobes in the brain. It was FDA cleared for acute and preventive care of migraine in adolescents over 12 years and for adults in February 2019. The patient holds a handheld magnetic device against their occiput, and when the tool is discharged, a brief magnetic pulse interrupts the pattern of neuronal firing (probably cortical spreading depression) that can trigger migraine and the visual aura associated with migraine in one-third of patients.

Cefaly

The e-TNS (Cefaly) works by external trigeminal nerve stimulation of the supraorbital and trochlear nerves bilaterally in the forehead. It gradually and automatically increases in intensity and can be controlled by the patient. It is FDA cleared for acute and preventive treatment of migraine, and, unlike the other devices, it is sold over the counter without a prescription. According to the company website, there are 3 devices: 1 is for acute treatment, 1 is for preventive treatment, and 1 device has 2 settings for both acute and preventive treatment.

The Studies

While most of the published studies on devices are company-sponsored, these device makers have underwritten numerous, sometimes very well-designed, studies on their products. A review by VanderPluym et al described those studies and their various risks of bias. 

There are at least 10 studies on REN published so far. These include 2 randomized, sham-controlled trials looking at pain freedom and pain relief at 2 hours after stimulation begins. Another study detailed treatment reports from many patients in which 66.5% experienced pain relief at 2 hours post treatment initiation in half of their treatments. A subgroup of 16% of those patients were prescribed REN by their primary care physicians. Of that group, 77.8% experienced pain relief in half their treatments. That figure was very close to another study that found that 23 of 31 (74.2%) of the study patients treated virtually by non headache providers found relief in 50% of their headaches. REN comes with an education and behavioral medicine app that is used during treatment. A study done by the company shows that when a patient uses the relaxation app along with the standard stimulation, they do considerably better than with stimulation alone.

The eCOT-NS has also been tested in an RCT. At 2 hours, the responder rate was twice as high as in the sham group (66.7% vs 32%). Overall headache relief at 2 hours was higher in the responder group (76% vs 31.6%). In a study collecting real-world data on the efficacy of eCOT-NS in the preventive treatment of migraine (abstract data were presented at the American Headache Society meeting in June 2022), there was a 65.3% reduction in monthly migraine days (MMD) from baseline through 6 months. Treatment reduced MMD by 10.0 (from 15.3 to 5.3—a 76.8% reduction), and reduced acute medication use days (12.5 at baseline to 2.9) at 6 months.

Users of nVNS discussed their experiences with the device, which is the size of a large bar of soap, in a patient registry. They reported 192 attacks, with a mean pain score starting at 2.7 and dropping to 1.3 after 30 minutes. The pain levels of 70% of the attacks dropped to either mild or nonexistent. In a multicenter study on nNVS, 48 patients and 44 sham patients with episodic and chronic cluster headache showed no significant difference in the primary endpoint of pain freedom at 15 minutes between the nVNS and sham. There was also no difference in the chronic cluster headache group. But the episodic cluster subgroup showed a difference; nVNS was superior to sham, 48% to 6% (P ≤ 0.01). Those in the chronic cluster headache group reported a lower percentage of pain-free status than the sham group (5% vs 13%). In another study of 477 patients, those patients who adhered to treatment more than 67% of the time per month showed a reduction in migraine days (2.27 vs 1.53). Patients with aura also fared better than those without aura.

The e-TNS device is cleared for treating adults with migraine, acutely and preventively. It received initial clearance in 2017; in 2020, Cefaly Technology received clearance from the FDA to sell its products over the counter. The device, which resembles a large diamond that affixes to the forehead, has received differing reviews between various patient reports (found online at major retailer sites) and study results. In a blinded, intent-to-treat study involving 538 patients, 25.5% of the verum group reported they were pain-free at 2 hours; 18.3% in the sham group reported the same. Additionally, 56.4% of the subjects in the verum group reported they were free of the most bothersome migraine symptoms, as opposed to 42.3% of the sham group.

Adverse Events

The adverse events observed with these devices were, overall, relatively mild, and disappeared once the device was shut off. A few nVNS users said they experienced discomfort at the application site. With REN, 59 of 12,368 patients reported device-related issues; the vast majority were considered mild and consisted mostly of a sensation of warmth under the device. Of the 259 e-TNS  users, 8.5% reported minor and reversible occurrences, such as treatment-related discomfort, paresthesia, and burning.

Patients in the Clinic

A few observations from the clinic regarding these devices:

Some devices are easier to use than others. I know this, because at a recent demonstration session in a course for physicians on headache treatment, I agreed to be the person on whom the device was demonstrated. The physician applying the device had difficulty aligning the device’s sensors with the appropriate nerves. Making sure your patients use these devices correctly is essential, and you or your staff should demonstrate their use to the patient. No doubt, this could be time-consuming in some cases, and patients who are reading the device’s instructions while in pain will likely get frustrated if they cannot get the device to work. 

Some patients who have failed every medication class can occasionally find partial relief with these devices. One longtime patient of mine came to me severely disabled from chronic migraine and medication overuse headache but was somewhat better with 2 preventive medications. Triptans worked acutely, but she developed nearly every side effect imaginable. I was able to reverse her medication overuse headache, but the gepants, although they worked somewhat, took too long to take effect. We agreed the next step would be to use REN for each migraine attack, combined with acute care medication if necessary. (She uses REN alone for a milder headache and adds a gepant with naproxen if necessary.) She has found using the relaxation module on the REN app increases her chances of eliminating the migraine. She is not pain free all the time, but she appreciates the pain-free intervals.

One chronic cluster patient has relied on subcutaneous sumatriptan and breathing 100% oxygen at 12 liters per minute through a mask over his nose and mouth for acute relief from his headaches. His headache pain can climb from a 3 to a 10 in a matter of minutes. It starts behind and a bit above the right eye where he feels a tremendous pressure building up. He says that at times it feels like a screwdriver has been thrust into his eye and is being turned. Along with the pain, the eye becomes red, the pupil constricts, and the eyelid droops. He also has dripping from the right nostril, which stuffs up when the pain abates. The pain lasts for 1 to 2 hours, then returns 3 to 5 times a day for 5 days a week, on average. The pain never goes away for more than 3 weeks in a year’s time, hence the reason for his chronic cluster headache diagnosis.  He is now using nVNS as soon as he feels the pain coming on. If the device does not provide sufficient relief, he uses oxygen or takes the sumatriptan injection.

Some patients who get cluster headaches think of suicide if the pain cannot be stopped; but in my experience, most can become pain free, or at least realize some partial relief from a variety of treatments (sometimes given at the same time).

Doctors often do not think of devices as options, and some doctors think devices do not work even though they have no experience with using them. Devices can give good relief on their own, and when a severe headache needs stronger treatment, medications added to a device usually work better than either treatment alone.

Since the mid-2010s, the US Food and Drug Administration (FDA) has approved or cleared no fewer than 10 migraine treatments in the form of orals, injectables, nasal sprays, and devices. The medical achievements of the last decade in the field of migraine have been nothing less than stunning for physicians and their patients, whether they relied on off-label medications or those sanctioned by the FDA to treat patients living with migraine.

That said, the newer orals and injectables cannot help everyone living with migraine. The small molecule calcitonin gene-related peptide (CGRP) receptor antagonists (gepants) and the monoclonal antibodies that target the CGRP ligand or receptor, while well received by patients and physicians alike, have drawbacks for some patients, including lack of efficacy, slow response rate, and adverse events that prevent some patients from taking them. The gepants, which are oral medications—as opposed to the CGRP monoclonal antibody injectables—can occasionally cause enough nausea, drowsiness, and constipation for patients to choose to discontinue their use.

Certain patients have other reasons to shun orals and injectables. Some cannot swallow pills while others fear or do not tolerate injections. Insurance companies limit the quantity of acute care medications, so some patients cannot treat every migraine attack. Then there are those who have failed so many therapies in the past that they will not try the latest one. Consequently, some lie in bed, vomiting until the pain is gone, and some take too many over-the-counter or migraine-specific products, which make migraine symptoms worse if they develop medication overuse headache. And lastly, there are patients who have never walked through a physician’s door to secure a migraine diagnosis and get appropriate treatment.

Non interventional medical devices cleared by the FDA now allow physicians to offer relief to patients with migraine. They work either through various types of electrical neuromodulation to nerves outside the brain or they apply magnetic stimulation to the back of the brain itself to reach pain-associated pathways. A 2019 report on pain management from the US Department of Health and Human Services noted that some randomized control trials (RCTs) and other studies “have demonstrated that noninvasive vagal nerve stimulation can be effective in ameliorating pain in various types of cluster headaches and migraines.”

At least 3 devices, 1 designed to stimulate both the occipital and trigeminal nerves (eCOT-NS, Relivion, Neurolief Ltd), 1 that stimulates the vagus nerve noninvasively (nVNS, gammaCORE, electroCore), and 1 that stimulates peripheral nerves in the upper arm (remote electrical neuromodulation [REN], Nerivio, Theranica Bio-Electronics Ltd), are FDA cleared to treat episodic and chronic migraine. nVNS is also cleared to treat migraine, episodic cluster headache acutely, and chronic cluster acutely in connection with medication.

Real-world studies on all migraine treatments, especially the devices, are flooding PubMed. As for a physician’s observation, we will get to that shortly.

The Devices

Nerivio

Theranica Bio-Electronics Ltd makes a REN called Nerivio, which was FDA cleared in January 2021 to treat episodic migraine acutely in adults and adolescents. Studies have shown its effectiveness for chronic migraine patients who are treated acutely, and it has also helped patients with menstrual migraine. The patient wears the device on the upper arm. Sensory fibers, once stimulated in the arm, send an impulse to the brainstem to affect the serotonin- and norepinephrine-modulated descending inhibitory pathway to disrupt incoming pain messaging. Theranica has applied to the FDA for clearance to treat patients with chronic migraine, as well as for prevention.

Relivion

Neurolief Ltd created the external combined occipital and trigeminal nerve stimulation device (eCOT-NS), which stimulates both the occipital and trigeminal nerves. It has multiple output electrodes, which are placed on the forehead to stimulate the trigeminal supraorbital and supratrochlear nerve branches bilaterally, and over the occipital nerves in the back of the head. It is worn like a tiara as it must be in good contact with the forehead and the back of the head simultaneously. It is FDA cleared to treat acute migraine.

gammaCORE

gammaCORE is a nVNS device that is FDA cleared for acute and preventive treatment of migraine in adolescents and adults, and acute and preventive treatment of episodic cluster headache in adults. It is also cleared to treat chronic cluster headache acutely along with medication. The patient applies gel to the device’s 2 electrical contacts and then locates the vagus nerve on the side of the neck and applies the electrodes to the area that will be treated. Patients can adjust the stimulation’s intensity so that they can barely feel the stimulation; it has not been reported to be painful. nVNS is also an FDA cleared treatment for paroxysmal hemicrania and hemicrania continua. 

SAVI Dual

The s-TMS (SAVI Dual, formerly called the Spring TMS and the sTMS mini), made by eNeura, is a single-pulse, transcranial magnetic stimulation applied to the back of the head to stimulate the occipital lobes in the brain. It was FDA cleared for acute and preventive care of migraine in adolescents over 12 years and for adults in February 2019. The patient holds a handheld magnetic device against their occiput, and when the tool is discharged, a brief magnetic pulse interrupts the pattern of neuronal firing (probably cortical spreading depression) that can trigger migraine and the visual aura associated with migraine in one-third of patients.

Cefaly

The e-TNS (Cefaly) works by external trigeminal nerve stimulation of the supraorbital and trochlear nerves bilaterally in the forehead. It gradually and automatically increases in intensity and can be controlled by the patient. It is FDA cleared for acute and preventive treatment of migraine, and, unlike the other devices, it is sold over the counter without a prescription. According to the company website, there are 3 devices: 1 is for acute treatment, 1 is for preventive treatment, and 1 device has 2 settings for both acute and preventive treatment.

The Studies

While most of the published studies on devices are company-sponsored, these device makers have underwritten numerous, sometimes very well-designed, studies on their products. A review by VanderPluym et al described those studies and their various risks of bias. 

There are at least 10 studies on REN published so far. These include 2 randomized, sham-controlled trials looking at pain freedom and pain relief at 2 hours after stimulation begins. Another study detailed treatment reports from many patients in which 66.5% experienced pain relief at 2 hours post treatment initiation in half of their treatments. A subgroup of 16% of those patients were prescribed REN by their primary care physicians. Of that group, 77.8% experienced pain relief in half their treatments. That figure was very close to another study that found that 23 of 31 (74.2%) of the study patients treated virtually by non headache providers found relief in 50% of their headaches. REN comes with an education and behavioral medicine app that is used during treatment. A study done by the company shows that when a patient uses the relaxation app along with the standard stimulation, they do considerably better than with stimulation alone.

The eCOT-NS has also been tested in an RCT. At 2 hours, the responder rate was twice as high as in the sham group (66.7% vs 32%). Overall headache relief at 2 hours was higher in the responder group (76% vs 31.6%). In a study collecting real-world data on the efficacy of eCOT-NS in the preventive treatment of migraine (abstract data were presented at the American Headache Society meeting in June 2022), there was a 65.3% reduction in monthly migraine days (MMD) from baseline through 6 months. Treatment reduced MMD by 10.0 (from 15.3 to 5.3—a 76.8% reduction), and reduced acute medication use days (12.5 at baseline to 2.9) at 6 months.

Users of nVNS discussed their experiences with the device, which is the size of a large bar of soap, in a patient registry. They reported 192 attacks, with a mean pain score starting at 2.7 and dropping to 1.3 after 30 minutes. The pain levels of 70% of the attacks dropped to either mild or nonexistent. In a multicenter study on nNVS, 48 patients and 44 sham patients with episodic and chronic cluster headache showed no significant difference in the primary endpoint of pain freedom at 15 minutes between the nVNS and sham. There was also no difference in the chronic cluster headache group. But the episodic cluster subgroup showed a difference; nVNS was superior to sham, 48% to 6% (P ≤ 0.01). Those in the chronic cluster headache group reported a lower percentage of pain-free status than the sham group (5% vs 13%). In another study of 477 patients, those patients who adhered to treatment more than 67% of the time per month showed a reduction in migraine days (2.27 vs 1.53). Patients with aura also fared better than those without aura.

The e-TNS device is cleared for treating adults with migraine, acutely and preventively. It received initial clearance in 2017; in 2020, Cefaly Technology received clearance from the FDA to sell its products over the counter. The device, which resembles a large diamond that affixes to the forehead, has received differing reviews between various patient reports (found online at major retailer sites) and study results. In a blinded, intent-to-treat study involving 538 patients, 25.5% of the verum group reported they were pain-free at 2 hours; 18.3% in the sham group reported the same. Additionally, 56.4% of the subjects in the verum group reported they were free of the most bothersome migraine symptoms, as opposed to 42.3% of the sham group.

Adverse Events

The adverse events observed with these devices were, overall, relatively mild, and disappeared once the device was shut off. A few nVNS users said they experienced discomfort at the application site. With REN, 59 of 12,368 patients reported device-related issues; the vast majority were considered mild and consisted mostly of a sensation of warmth under the device. Of the 259 e-TNS  users, 8.5% reported minor and reversible occurrences, such as treatment-related discomfort, paresthesia, and burning.

Patients in the Clinic

A few observations from the clinic regarding these devices:

Some devices are easier to use than others. I know this, because at a recent demonstration session in a course for physicians on headache treatment, I agreed to be the person on whom the device was demonstrated. The physician applying the device had difficulty aligning the device’s sensors with the appropriate nerves. Making sure your patients use these devices correctly is essential, and you or your staff should demonstrate their use to the patient. No doubt, this could be time-consuming in some cases, and patients who are reading the device’s instructions while in pain will likely get frustrated if they cannot get the device to work. 

Some patients who have failed every medication class can occasionally find partial relief with these devices. One longtime patient of mine came to me severely disabled from chronic migraine and medication overuse headache but was somewhat better with 2 preventive medications. Triptans worked acutely, but she developed nearly every side effect imaginable. I was able to reverse her medication overuse headache, but the gepants, although they worked somewhat, took too long to take effect. We agreed the next step would be to use REN for each migraine attack, combined with acute care medication if necessary. (She uses REN alone for a milder headache and adds a gepant with naproxen if necessary.) She has found using the relaxation module on the REN app increases her chances of eliminating the migraine. She is not pain free all the time, but she appreciates the pain-free intervals.

One chronic cluster patient has relied on subcutaneous sumatriptan and breathing 100% oxygen at 12 liters per minute through a mask over his nose and mouth for acute relief from his headaches. His headache pain can climb from a 3 to a 10 in a matter of minutes. It starts behind and a bit above the right eye where he feels a tremendous pressure building up. He says that at times it feels like a screwdriver has been thrust into his eye and is being turned. Along with the pain, the eye becomes red, the pupil constricts, and the eyelid droops. He also has dripping from the right nostril, which stuffs up when the pain abates. The pain lasts for 1 to 2 hours, then returns 3 to 5 times a day for 5 days a week, on average. The pain never goes away for more than 3 weeks in a year’s time, hence the reason for his chronic cluster headache diagnosis.  He is now using nVNS as soon as he feels the pain coming on. If the device does not provide sufficient relief, he uses oxygen or takes the sumatriptan injection.

Some patients who get cluster headaches think of suicide if the pain cannot be stopped; but in my experience, most can become pain free, or at least realize some partial relief from a variety of treatments (sometimes given at the same time).

Doctors often do not think of devices as options, and some doctors think devices do not work even though they have no experience with using them. Devices can give good relief on their own, and when a severe headache needs stronger treatment, medications added to a device usually work better than either treatment alone.

Calcitonin gene-related peptide (CGRP) antagonist medications are becoming more and more of a mainstay of both migraine prevention and acute treatment. Four CGRP monoclonal antibody medications and three oral CGRP antagonists are now available for prevention and acute treatment of migraine. When this class of medications was developed, many patients and providers were initially concerned regarding any potentially unanticipated long-term adverse events. The first CGRP antagonist medication, erenumab, was associated with constipation, and, although this has not been formally reported with other CGRP medications, there is some anecdotal evidence of gastrointestinal (GI) discomfort with both oral and other monoclonal antibody medications in this class. In 2021, erenumab was also reported to be associated with hypertension and a formal warning was issued for this.

Before CGRP was used for migraine prevention, it had been known to be a potent vasodilator. Although the randomized controlled trials (RCT) for all CGRP medications included a longitudinal review of blood pressure (BP) measures, none of those initial trials revealed an increased risk for hypertension or other cardiovascular events or concerns. Some of the initial trials even included patients at higher cardiovascular risk. Migraine itself is associated with an increased vascular risk; it is therefore extremely important to determine whether a potential treatment may be increasing this risk further.

In the study by de Vries and colleagues, all patients were started on either erenumab or fremanezumab and were included if they had a follow-up blood pressure measurement within 6 months. All patients had at least8 migraine days per month and had used four or more preventive medications. Patients taking erenumab were first started at 70 mg monthly and were optionally increased to 140 mg after 3 months. Fremanezumab was always given at a dose of 225 mg monthly (as opposed to 675 mg every 3 months). BP data were collected at baseline and followed up at every visit, with a maximum of 12 months of review. Patients were excluded if their baseline BP was measured while they were undergoing tapering an antihypertensive medication at the same time that they were starting the CGRP antagonist. Patients already treated for hypertension were included only if there were no changes to their hypertensive regimen.

Patients were also compared with a control group with a similar distribution in sex, age, and diagnosis, and who were not taking any migraine preventive medication that would affect their BP. Control group BP was also measured at least two different time points 1-3 months from baseline.

A total of 211 patients were enrolled: 109 in the erenumab group and 87 in the fremanezumab group. The erenumab group was also associated with an increase in both systolic BP (SBP) and diastolic BP (DBP) (SBP ≤ 9 mm Hg; DBP ≤ 6.3 mm Hg). The fremanezumab group had a lower increase in SBP (1 mm Hg) and no increase in DBP. Nine patients were started on antihypertensive medications, five of them after the baseline BP recording only. There was no change over time in the control group.

As noted, CGRP has a potent vasodilatory effect. Although not proven, a theory has been posited that CGRP receptor antagonist medications are somewhat more likely to lead to systemic adverse effects than are ligand-blocking medications. This may, at least in part, explain why erenumab appears to have more associated GI discomfort and constipation as well as a vascular effect with hypertension. In light of these findings, it is absolutely necessary for the additional CGRP medications to also be studied for these potential risk factors.

With the advent of novel acute treatments for migraine, many providers ask themselves what the potential risks and benefits are for each new class of drugs developed and approved over the past few years. Johnston and colleagues reviewed five recently published RCT to compare risk-benefit profiles for lasmiditan, rimegepant, and ubrogepant. Lasmiditan is the only medication in the ditan class, a serotonin (5HT-1F) receptor agonist medication approved for the acute treatment of migraine. Rimegepant and ubrogepant are oral CGRP antagonists.

Lasmiditan does have a potential risk for impairment while driving due to excessive sedation and dizziness; it is also more likely than the CGRP medications to lead to the development of medication overuse headache. The CGRP medications, however, are associated with a smaller responder rate for headache freedom at 2 hours. The investigators reviewed the data published in five RCT to develop a statistically based decision-making process that correlates with the number needed to treat vs the number needed to harm for all three of these medications. The number needed to treat is a statistically defined parameter that characterizes the number of patients that need to be treated with an intervention to achieve a positive event. The number needed to harm refers to an additional negative event relative to the reference treatment (placebo in the case of an RCT).

The reviewed studies compared multiple dosages of these medications. Efficacy outcomes were pain relief and pain freedom at 2 hours, sustained pain relief from 2 to 24 hours, and freedom from the most bothersome symptom at 2 hours. Safety outcomes were dizziness and nausea.

The number needed to treat was the lowest for 200 mg lasmiditan (twice the highest recommended acute dose), followed by 75 mg rimegepant. The number needed to harm was highest for 25 mg ubrogepant (half of the lowest recommended acute dose). Nausea was lowest for 75 mg rimegepant.

An individualized approach is always recommended when considering both preventive and acute treatments for migraine. It is definitely worth keeping these results in mind when discussing potential acute treatment options with patients. This is especially true when considering patients who may be more likely to experience either dizziness or nausea with other acute treatments. It is also worth individualizing a potential acute treatment when a patient experiences rapid-onset migraine symptoms. Further investigations into both acute and preventive treatments would enlighten and further individualize our clinical approaches.

Erenumab currently carries a prescriber warning for constipation. Although there has been some anecdotal evidence for constipation with other CGRP antagonists, this has never fully been investigated. Currently, the other CGRP medication options have fewer side effects and not all  are associated with constipation. Kudrow and colleagues sought to review the incidence of constipation, and GI motility in general, with both erenumab and galcanezumab. Their hypothesis was that a single dose of erenumab would be associated with delayed GI motility and a single dose of galcanezumab would not be.

This study was conducted as a multicenter trial with single-blinding. A total of 65 patients were enrolled and given either 140 mg erenumab or 240 mg galcanezumab (the loading dose). GI motility was measured via a wireless motility capsule at baseline before treatment and repeated at 2 weeks. This test is approved by the US Food and Drug Administration for evaluation of gastric transit time in patients with suspected gastroparesis and for evaluation of colonic transit time in patients with chronic idiopathic constipation. Patients with prior GI symptoms were excluded, as were patients taking a tricyclic antidepressant or a calcium-channel blocker, owing to known constipation with these agents.

The primary endpoint in this study was change from a baseline colonic transit time 2 weeks after injection with the CGRP monoclonal antibody. Secondary endpoints included change from baseline in whole-gut transit time, gastric emptying time, small-bowel transfer time, and combined small- and large-bowel transfer time. The Gastrointestinal Symptom Rating Scale (GSRS) was also used, evaluating abdominal pain, reflux, indigestion, constipation, and diarrhea based on a 7-point response, ranging from no discomfort to very severe discomfort.

The primary endpoint of baseline change in colonic transit time was not statistically significant between the groups: A mean change of 5.8 hours was noted for erenumab and 5.4 hours for galcanezumab. Most secondary endpoints were also not statistically significantly different between the two groups. Small-bowel transit time was  decreased in the galcanezumab group. When the patient-reported scales were reviewed, spontaneous bowel movements decreased significantly in the erenumab group, a finding that was not seen in the galcanezumab group and was statistically significant. The GSRS also showed a small but statistically significant change in the erenumab group.

This study does appear to show a significant difference in the two CGRP antagonist medications. The full side-effect profiles of the four CGRP monoclonal antibodies and three oral CGRP blocking medications available remain unknown. Further head-to-head comparisons will allow better differentiation of these options and better individualization of patient care.

Calcitonin gene-related peptide (CGRP) antagonist medications are becoming more and more of a mainstay of both migraine prevention and acute treatment. Four CGRP monoclonal antibody medications and three oral CGRP antagonists are now available for prevention and acute treatment of migraine. When this class of medications was developed, many patients and providers were initially concerned regarding any potentially unanticipated long-term adverse events. The first CGRP antagonist medication, erenumab, was associated with constipation, and, although this has not been formally reported with other CGRP medications, there is some anecdotal evidence of gastrointestinal (GI) discomfort with both oral and other monoclonal antibody medications in this class. In 2021, erenumab was also reported to be associated with hypertension and a formal warning was issued for this.

Before CGRP was used for migraine prevention, it had been known to be a potent vasodilator. Although the randomized controlled trials (RCT) for all CGRP medications included a longitudinal review of blood pressure (BP) measures, none of those initial trials revealed an increased risk for hypertension or other cardiovascular events or concerns. Some of the initial trials even included patients at higher cardiovascular risk. Migraine itself is associated with an increased vascular risk; it is therefore extremely important to determine whether a potential treatment may be increasing this risk further.

In the study by de Vries and colleagues, all patients were started on either erenumab or fremanezumab and were included if they had a follow-up blood pressure measurement within 6 months. All patients had at least8 migraine days per month and had used four or more preventive medications. Patients taking erenumab were first started at 70 mg monthly and were optionally increased to 140 mg after 3 months. Fremanezumab was always given at a dose of 225 mg monthly (as opposed to 675 mg every 3 months). BP data were collected at baseline and followed up at every visit, with a maximum of 12 months of review. Patients were excluded if their baseline BP was measured while they were undergoing tapering an antihypertensive medication at the same time that they were starting the CGRP antagonist. Patients already treated for hypertension were included only if there were no changes to their hypertensive regimen.

Patients were also compared with a control group with a similar distribution in sex, age, and diagnosis, and who were not taking any migraine preventive medication that would affect their BP. Control group BP was also measured at least two different time points 1-3 months from baseline.

A total of 211 patients were enrolled: 109 in the erenumab group and 87 in the fremanezumab group. The erenumab group was also associated with an increase in both systolic BP (SBP) and diastolic BP (DBP) (SBP ≤ 9 mm Hg; DBP ≤ 6.3 mm Hg). The fremanezumab group had a lower increase in SBP (1 mm Hg) and no increase in DBP. Nine patients were started on antihypertensive medications, five of them after the baseline BP recording only. There was no change over time in the control group.

As noted, CGRP has a potent vasodilatory effect. Although not proven, a theory has been posited that CGRP receptor antagonist medications are somewhat more likely to lead to systemic adverse effects than are ligand-blocking medications. This may, at least in part, explain why erenumab appears to have more associated GI discomfort and constipation as well as a vascular effect with hypertension. In light of these findings, it is absolutely necessary for the additional CGRP medications to also be studied for these potential risk factors.

With the advent of novel acute treatments for migraine, many providers ask themselves what the potential risks and benefits are for each new class of drugs developed and approved over the past few years. Johnston and colleagues reviewed five recently published RCT to compare risk-benefit profiles for lasmiditan, rimegepant, and ubrogepant. Lasmiditan is the only medication in the ditan class, a serotonin (5HT-1F) receptor agonist medication approved for the acute treatment of migraine. Rimegepant and ubrogepant are oral CGRP antagonists.

Lasmiditan does have a potential risk for impairment while driving due to excessive sedation and dizziness; it is also more likely than the CGRP medications to lead to the development of medication overuse headache. The CGRP medications, however, are associated with a smaller responder rate for headache freedom at 2 hours. The investigators reviewed the data published in five RCT to develop a statistically based decision-making process that correlates with the number needed to treat vs the number needed to harm for all three of these medications. The number needed to treat is a statistically defined parameter that characterizes the number of patients that need to be treated with an intervention to achieve a positive event. The number needed to harm refers to an additional negative event relative to the reference treatment (placebo in the case of an RCT).

The reviewed studies compared multiple dosages of these medications. Efficacy outcomes were pain relief and pain freedom at 2 hours, sustained pain relief from 2 to 24 hours, and freedom from the most bothersome symptom at 2 hours. Safety outcomes were dizziness and nausea.

The number needed to treat was the lowest for 200 mg lasmiditan (twice the highest recommended acute dose), followed by 75 mg rimegepant. The number needed to harm was highest for 25 mg ubrogepant (half of the lowest recommended acute dose). Nausea was lowest for 75 mg rimegepant.

An individualized approach is always recommended when considering both preventive and acute treatments for migraine. It is definitely worth keeping these results in mind when discussing potential acute treatment options with patients. This is especially true when considering patients who may be more likely to experience either dizziness or nausea with other acute treatments. It is also worth individualizing a potential acute treatment when a patient experiences rapid-onset migraine symptoms. Further investigations into both acute and preventive treatments would enlighten and further individualize our clinical approaches.

Erenumab currently carries a prescriber warning for constipation. Although there has been some anecdotal evidence for constipation with other CGRP antagonists, this has never fully been investigated. Currently, the other CGRP medication options have fewer side effects and not all  are associated with constipation. Kudrow and colleagues sought to review the incidence of constipation, and GI motility in general, with both erenumab and galcanezumab. Their hypothesis was that a single dose of erenumab would be associated with delayed GI motility and a single dose of galcanezumab would not be.

This study was conducted as a multicenter trial with single-blinding. A total of 65 patients were enrolled and given either 140 mg erenumab or 240 mg galcanezumab (the loading dose). GI motility was measured via a wireless motility capsule at baseline before treatment and repeated at 2 weeks. This test is approved by the US Food and Drug Administration for evaluation of gastric transit time in patients with suspected gastroparesis and for evaluation of colonic transit time in patients with chronic idiopathic constipation. Patients with prior GI symptoms were excluded, as were patients taking a tricyclic antidepressant or a calcium-channel blocker, owing to known constipation with these agents.

The primary endpoint in this study was change from a baseline colonic transit time 2 weeks after injection with the CGRP monoclonal antibody. Secondary endpoints included change from baseline in whole-gut transit time, gastric emptying time, small-bowel transfer time, and combined small- and large-bowel transfer time. The Gastrointestinal Symptom Rating Scale (GSRS) was also used, evaluating abdominal pain, reflux, indigestion, constipation, and diarrhea based on a 7-point response, ranging from no discomfort to very severe discomfort.

The primary endpoint of baseline change in colonic transit time was not statistically significant between the groups: A mean change of 5.8 hours was noted for erenumab and 5.4 hours for galcanezumab. Most secondary endpoints were also not statistically significantly different between the two groups. Small-bowel transit time was  decreased in the galcanezumab group. When the patient-reported scales were reviewed, spontaneous bowel movements decreased significantly in the erenumab group, a finding that was not seen in the galcanezumab group and was statistically significant. The GSRS also showed a small but statistically significant change in the erenumab group.

This study does appear to show a significant difference in the two CGRP antagonist medications. The full side-effect profiles of the four CGRP monoclonal antibodies and three oral CGRP blocking medications available remain unknown. Further head-to-head comparisons will allow better differentiation of these options and better individualization of patient care.

Calcitonin gene-related peptide (CGRP) antagonist medications are becoming more and more of a mainstay of both migraine prevention and acute treatment. Four CGRP monoclonal antibody medications and three oral CGRP antagonists are now available for prevention and acute treatment of migraine. When this class of medications was developed, many patients and providers were initially concerned regarding any potentially unanticipated long-term adverse events. The first CGRP antagonist medication, erenumab, was associated with constipation, and, although this has not been formally reported with other CGRP medications, there is some anecdotal evidence of gastrointestinal (GI) discomfort with both oral and other monoclonal antibody medications in this class. In 2021, erenumab was also reported to be associated with hypertension and a formal warning was issued for this.

Before CGRP was used for migraine prevention, it had been known to be a potent vasodilator. Although the randomized controlled trials (RCT) for all CGRP medications included a longitudinal review of blood pressure (BP) measures, none of those initial trials revealed an increased risk for hypertension or other cardiovascular events or concerns. Some of the initial trials even included patients at higher cardiovascular risk. Migraine itself is associated with an increased vascular risk; it is therefore extremely important to determine whether a potential treatment may be increasing this risk further.

In the study by de Vries and colleagues, all patients were started on either erenumab or fremanezumab and were included if they had a follow-up blood pressure measurement within 6 months. All patients had at least8 migraine days per month and had used four or more preventive medications. Patients taking erenumab were first started at 70 mg monthly and were optionally increased to 140 mg after 3 months. Fremanezumab was always given at a dose of 225 mg monthly (as opposed to 675 mg every 3 months). BP data were collected at baseline and followed up at every visit, with a maximum of 12 months of review. Patients were excluded if their baseline BP was measured while they were undergoing tapering an antihypertensive medication at the same time that they were starting the CGRP antagonist. Patients already treated for hypertension were included only if there were no changes to their hypertensive regimen.

Patients were also compared with a control group with a similar distribution in sex, age, and diagnosis, and who were not taking any migraine preventive medication that would affect their BP. Control group BP was also measured at least two different time points 1-3 months from baseline.

A total of 211 patients were enrolled: 109 in the erenumab group and 87 in the fremanezumab group. The erenumab group was also associated with an increase in both systolic BP (SBP) and diastolic BP (DBP) (SBP ≤ 9 mm Hg; DBP ≤ 6.3 mm Hg). The fremanezumab group had a lower increase in SBP (1 mm Hg) and no increase in DBP. Nine patients were started on antihypertensive medications, five of them after the baseline BP recording only. There was no change over time in the control group.

As noted, CGRP has a potent vasodilatory effect. Although not proven, a theory has been posited that CGRP receptor antagonist medications are somewhat more likely to lead to systemic adverse effects than are ligand-blocking medications. This may, at least in part, explain why erenumab appears to have more associated GI discomfort and constipation as well as a vascular effect with hypertension. In light of these findings, it is absolutely necessary for the additional CGRP medications to also be studied for these potential risk factors.

With the advent of novel acute treatments for migraine, many providers ask themselves what the potential risks and benefits are for each new class of drugs developed and approved over the past few years. Johnston and colleagues reviewed five recently published RCT to compare risk-benefit profiles for lasmiditan, rimegepant, and ubrogepant. Lasmiditan is the only medication in the ditan class, a serotonin (5HT-1F) receptor agonist medication approved for the acute treatment of migraine. Rimegepant and ubrogepant are oral CGRP antagonists.

Lasmiditan does have a potential risk for impairment while driving due to excessive sedation and dizziness; it is also more likely than the CGRP medications to lead to the development of medication overuse headache. The CGRP medications, however, are associated with a smaller responder rate for headache freedom at 2 hours. The investigators reviewed the data published in five RCT to develop a statistically based decision-making process that correlates with the number needed to treat vs the number needed to harm for all three of these medications. The number needed to treat is a statistically defined parameter that characterizes the number of patients that need to be treated with an intervention to achieve a positive event. The number needed to harm refers to an additional negative event relative to the reference treatment (placebo in the case of an RCT).

The reviewed studies compared multiple dosages of these medications. Efficacy outcomes were pain relief and pain freedom at 2 hours, sustained pain relief from 2 to 24 hours, and freedom from the most bothersome symptom at 2 hours. Safety outcomes were dizziness and nausea.

The number needed to treat was the lowest for 200 mg lasmiditan (twice the highest recommended acute dose), followed by 75 mg rimegepant. The number needed to harm was highest for 25 mg ubrogepant (half of the lowest recommended acute dose). Nausea was lowest for 75 mg rimegepant.

An individualized approach is always recommended when considering both preventive and acute treatments for migraine. It is definitely worth keeping these results in mind when discussing potential acute treatment options with patients. This is especially true when considering patients who may be more likely to experience either dizziness or nausea with other acute treatments. It is also worth individualizing a potential acute treatment when a patient experiences rapid-onset migraine symptoms. Further investigations into both acute and preventive treatments would enlighten and further individualize our clinical approaches.

Erenumab currently carries a prescriber warning for constipation. Although there has been some anecdotal evidence for constipation with other CGRP antagonists, this has never fully been investigated. Currently, the other CGRP medication options have fewer side effects and not all  are associated with constipation. Kudrow and colleagues sought to review the incidence of constipation, and GI motility in general, with both erenumab and galcanezumab. Their hypothesis was that a single dose of erenumab would be associated with delayed GI motility and a single dose of galcanezumab would not be.

This study was conducted as a multicenter trial with single-blinding. A total of 65 patients were enrolled and given either 140 mg erenumab or 240 mg galcanezumab (the loading dose). GI motility was measured via a wireless motility capsule at baseline before treatment and repeated at 2 weeks. This test is approved by the US Food and Drug Administration for evaluation of gastric transit time in patients with suspected gastroparesis and for evaluation of colonic transit time in patients with chronic idiopathic constipation. Patients with prior GI symptoms were excluded, as were patients taking a tricyclic antidepressant or a calcium-channel blocker, owing to known constipation with these agents.

The primary endpoint in this study was change from a baseline colonic transit time 2 weeks after injection with the CGRP monoclonal antibody. Secondary endpoints included change from baseline in whole-gut transit time, gastric emptying time, small-bowel transfer time, and combined small- and large-bowel transfer time. The Gastrointestinal Symptom Rating Scale (GSRS) was also used, evaluating abdominal pain, reflux, indigestion, constipation, and diarrhea based on a 7-point response, ranging from no discomfort to very severe discomfort.

The primary endpoint of baseline change in colonic transit time was not statistically significant between the groups: A mean change of 5.8 hours was noted for erenumab and 5.4 hours for galcanezumab. Most secondary endpoints were also not statistically significantly different between the two groups. Small-bowel transit time was  decreased in the galcanezumab group. When the patient-reported scales were reviewed, spontaneous bowel movements decreased significantly in the erenumab group, a finding that was not seen in the galcanezumab group and was statistically significant. The GSRS also showed a small but statistically significant change in the erenumab group.

This study does appear to show a significant difference in the two CGRP antagonist medications. The full side-effect profiles of the four CGRP monoclonal antibodies and three oral CGRP blocking medications available remain unknown. Further head-to-head comparisons will allow better differentiation of these options and better individualization of patient care.

Key clinical point: Cinnarizine appeared safe and effective in migraine prophylaxis, with cinnarizine-treated patients reporting significant improvements in migraine frequency and severity.

Major finding: Over 12 weeks, cinnarizine vs placebo significantly improved the frequency (overall mean difference [OMD] −3.10; P < .001) and intensity (OMD −1.54; P < .001) of migraine attacks per month; additionally, patients receiving cinnarizine showed better improvements in migraine intensity compared with those receiving topiramate (P < .05), but showed similar improvements when compared with those receiving propranolol or sodium valproate. The most common adverse events following cinnarizine intake were somnolence and fatigue.

Study details: Findings are from a systematic review and meta-analysis of 7 randomized controlled trials and 3 quasi-experimental studies including patients with migraine with or without aura who received cinnarizine, placebo, propranolol, sodium valproate, or topiramate.

Disclosures: This study did not report the funding source. No conflicts of interest were declared.

Source: Shafie'ei M et al. Application of cinnarizine in migraine prevention: A systematic review and meta-analysis. Pain Pract. 2022 (Sep 23). Doi: 10.1111/papr.13164

Key clinical point: Cinnarizine appeared safe and effective in migraine prophylaxis, with cinnarizine-treated patients reporting significant improvements in migraine frequency and severity.

Major finding: Over 12 weeks, cinnarizine vs placebo significantly improved the frequency (overall mean difference [OMD] −3.10; P < .001) and intensity (OMD −1.54; P < .001) of migraine attacks per month; additionally, patients receiving cinnarizine showed better improvements in migraine intensity compared with those receiving topiramate (P < .05), but showed similar improvements when compared with those receiving propranolol or sodium valproate. The most common adverse events following cinnarizine intake were somnolence and fatigue.

Study details: Findings are from a systematic review and meta-analysis of 7 randomized controlled trials and 3 quasi-experimental studies including patients with migraine with or without aura who received cinnarizine, placebo, propranolol, sodium valproate, or topiramate.

Disclosures: This study did not report the funding source. No conflicts of interest were declared.

Source: Shafie'ei M et al. Application of cinnarizine in migraine prevention: A systematic review and meta-analysis. Pain Pract. 2022 (Sep 23). Doi: 10.1111/papr.13164

Key clinical point: Cinnarizine appeared safe and effective in migraine prophylaxis, with cinnarizine-treated patients reporting significant improvements in migraine frequency and severity.

Major finding: Over 12 weeks, cinnarizine vs placebo significantly improved the frequency (overall mean difference [OMD] −3.10; P < .001) and intensity (OMD −1.54; P < .001) of migraine attacks per month; additionally, patients receiving cinnarizine showed better improvements in migraine intensity compared with those receiving topiramate (P < .05), but showed similar improvements when compared with those receiving propranolol or sodium valproate. The most common adverse events following cinnarizine intake were somnolence and fatigue.

Study details: Findings are from a systematic review and meta-analysis of 7 randomized controlled trials and 3 quasi-experimental studies including patients with migraine with or without aura who received cinnarizine, placebo, propranolol, sodium valproate, or topiramate.

Disclosures: This study did not report the funding source. No conflicts of interest were declared.

Source: Shafie'ei M et al. Application of cinnarizine in migraine prevention: A systematic review and meta-analysis. Pain Pract. 2022 (Sep 23). Doi: 10.1111/papr.13164

Key clinical point: The risk for inpatient constipation within 90 days of treatment initiation was similar in patients with migraine initiating erenumab vs other anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibodies (mAb), but was lower in those initiating erenumab vs standard of care antiepileptic drugs (AED).

Major finding: The risk for inpatient constipation within 90 days of treatment initiation was similar with erenumab vs other CGRP mAb (odds ratio [OR] 1.06; 95% CI 0.72-1.55), whereas the risk was lower with erenumab vs AED (OR 0.69; 95% CI0.51-0.94).

Study details: This retrospective cohort study included 80,803 patients with migraine who initiated erenumab (n = 17,902), other CGRP mAb (n = 13,404), or AED (n = 49,497), with erenumab initiators propensity-score matched with initiators of other CGRP mAb or AED.

Disclosures: This study was funded by Amgen Inc., USA. Nine authors reported being current or former employees of or owning stocks in UnitedHealth Group, Amgen, and other sources. P McAllister reported receiving personal fees and research support from various sources.

Source: Chomistek AK et al. Inpatient constipation among migraine patients prescribed anti-calcitonin gene-related peptide monoclonal antibodies and standard of care antiepileptic drugs: A retrospective cohort study in a United States electronic health record database. Pain Ther. 2022 (Oct 7). Doi: 10.1007/s40122-022-00440-7

Key clinical point: The risk for inpatient constipation within 90 days of treatment initiation was similar in patients with migraine initiating erenumab vs other anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibodies (mAb), but was lower in those initiating erenumab vs standard of care antiepileptic drugs (AED).

Major finding: The risk for inpatient constipation within 90 days of treatment initiation was similar with erenumab vs other CGRP mAb (odds ratio [OR] 1.06; 95% CI 0.72-1.55), whereas the risk was lower with erenumab vs AED (OR 0.69; 95% CI0.51-0.94).

Study details: This retrospective cohort study included 80,803 patients with migraine who initiated erenumab (n = 17,902), other CGRP mAb (n = 13,404), or AED (n = 49,497), with erenumab initiators propensity-score matched with initiators of other CGRP mAb or AED.

Disclosures: This study was funded by Amgen Inc., USA. Nine authors reported being current or former employees of or owning stocks in UnitedHealth Group, Amgen, and other sources. P McAllister reported receiving personal fees and research support from various sources.

Source: Chomistek AK et al. Inpatient constipation among migraine patients prescribed anti-calcitonin gene-related peptide monoclonal antibodies and standard of care antiepileptic drugs: A retrospective cohort study in a United States electronic health record database. Pain Ther. 2022 (Oct 7). Doi: 10.1007/s40122-022-00440-7

Key clinical point: The risk for inpatient constipation within 90 days of treatment initiation was similar in patients with migraine initiating erenumab vs other anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibodies (mAb), but was lower in those initiating erenumab vs standard of care antiepileptic drugs (AED).

Major finding: The risk for inpatient constipation within 90 days of treatment initiation was similar with erenumab vs other CGRP mAb (odds ratio [OR] 1.06; 95% CI 0.72-1.55), whereas the risk was lower with erenumab vs AED (OR 0.69; 95% CI0.51-0.94).

Study details: This retrospective cohort study included 80,803 patients with migraine who initiated erenumab (n = 17,902), other CGRP mAb (n = 13,404), or AED (n = 49,497), with erenumab initiators propensity-score matched with initiators of other CGRP mAb or AED.

Disclosures: This study was funded by Amgen Inc., USA. Nine authors reported being current or former employees of or owning stocks in UnitedHealth Group, Amgen, and other sources. P McAllister reported receiving personal fees and research support from various sources.

Source: Chomistek AK et al. Inpatient constipation among migraine patients prescribed anti-calcitonin gene-related peptide monoclonal antibodies and standard of care antiepileptic drugs: A retrospective cohort study in a United States electronic health record database. Pain Ther. 2022 (Oct 7). Doi: 10.1007/s40122-022-00440-7

Key clinical point: Patients with chronic migraine vs healthy controls had highly impaired cognition and worsened quality of life (QoL), which improved after 3 months of treatment with botulinum toxin or oral drugs.

Major finding: Patients with chronic migraine had worse scores than healthy controls for cognition, QoL, and emotional status at baseline (P < .0001), but showed significant improvements in Rey-Osterrieth Complex Figure test memory task (P < .0001), Trail Making Test A attention test (P  =  .007), and 36-item Short Form Health Survey based QoL measures for bodily pain (P  =  .040) and general health (P  =  .003) after 3 months of preventive treatment.

Study details: This observational study analyzed 46 patients with chronic migraine and 50 age- and sex-matched healthy controls for mood, cognition, and QoL before and 3 months after receiving preventive treatment with botulinum toxin or oral drugs.

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

Source: González-Mingot C et al. Preventive treatment can reverse cognitive impairment in chronic migraine. J Headache Pain. 2022;23:121 (Sep 15). Doi: 10.1186/s10194-022-01486-w

Key clinical point: Patients with chronic migraine vs healthy controls had highly impaired cognition and worsened quality of life (QoL), which improved after 3 months of treatment with botulinum toxin or oral drugs.

Major finding: Patients with chronic migraine had worse scores than healthy controls for cognition, QoL, and emotional status at baseline (P < .0001), but showed significant improvements in Rey-Osterrieth Complex Figure test memory task (P < .0001), Trail Making Test A attention test (P  =  .007), and 36-item Short Form Health Survey based QoL measures for bodily pain (P  =  .040) and general health (P  =  .003) after 3 months of preventive treatment.

Study details: This observational study analyzed 46 patients with chronic migraine and 50 age- and sex-matched healthy controls for mood, cognition, and QoL before and 3 months after receiving preventive treatment with botulinum toxin or oral drugs.

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

Source: González-Mingot C et al. Preventive treatment can reverse cognitive impairment in chronic migraine. J Headache Pain. 2022;23:121 (Sep 15). Doi: 10.1186/s10194-022-01486-w

Key clinical point: Patients with chronic migraine vs healthy controls had highly impaired cognition and worsened quality of life (QoL), which improved after 3 months of treatment with botulinum toxin or oral drugs.

Major finding: Patients with chronic migraine had worse scores than healthy controls for cognition, QoL, and emotional status at baseline (P < .0001), but showed significant improvements in Rey-Osterrieth Complex Figure test memory task (P < .0001), Trail Making Test A attention test (P  =  .007), and 36-item Short Form Health Survey based QoL measures for bodily pain (P  =  .040) and general health (P  =  .003) after 3 months of preventive treatment.

Study details: This observational study analyzed 46 patients with chronic migraine and 50 age- and sex-matched healthy controls for mood, cognition, and QoL before and 3 months after receiving preventive treatment with botulinum toxin or oral drugs.

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

Source: González-Mingot C et al. Preventive treatment can reverse cognitive impairment in chronic migraine. J Headache Pain. 2022;23:121 (Sep 15). Doi: 10.1186/s10194-022-01486-w

Key clinical point: Treatments with galcanezumab and erenumab increase constipation-related gastrointestinal discomfort, while erenumab also worsens stool form and bowel habits in patients with episodic migraine.

Major finding: An increase in the gastrointestinal symptom rating scale-constipation domain score was observed with both galcanezumab (least squares mean change [LSMC] 0.4; P  =  .002) and erenumab (LSMC 0.3; P  =  .016); additionally, erenumab significantly reduced Bristol Stool Form Scale (LSMC −0.5; P  =  .004) and spontaneous bowel movement (LSMC −1.2; P  =  .012) scores. No severe treatment-emergent adverse events were reported.

Study details: This phase 4 clinical trial included 65 patients with episodic migraine with or without aura and without significant gastrointestinal symptoms who were randomized to receive galcanezumab or erenumab.

Disclosures: This study was funded by Eli Lilly and Company. Six authors declared being full-time employees or minor shareholders or statistical contractors at Eli Lilly. Some authors reported receiving grants, contracts, consulting fees, or payment for speaker’s bureaus from various sources, including Eli Lilly.

Source: Kudrow D et al. A phase IV clinical trial of gastrointestinal motility in adult patients with migraine before and after initiation of a calcitonin gene-related peptide ligand (galcanezumab) or receptor (erenumab) antagonist. Headache. 2022 (Sep 16). Doi: 10.1111/head.14390

Key clinical point: Treatments with galcanezumab and erenumab increase constipation-related gastrointestinal discomfort, while erenumab also worsens stool form and bowel habits in patients with episodic migraine.

Major finding: An increase in the gastrointestinal symptom rating scale-constipation domain score was observed with both galcanezumab (least squares mean change [LSMC] 0.4; P  =  .002) and erenumab (LSMC 0.3; P  =  .016); additionally, erenumab significantly reduced Bristol Stool Form Scale (LSMC −0.5; P  =  .004) and spontaneous bowel movement (LSMC −1.2; P  =  .012) scores. No severe treatment-emergent adverse events were reported.

Study details: This phase 4 clinical trial included 65 patients with episodic migraine with or without aura and without significant gastrointestinal symptoms who were randomized to receive galcanezumab or erenumab.

Disclosures: This study was funded by Eli Lilly and Company. Six authors declared being full-time employees or minor shareholders or statistical contractors at Eli Lilly. Some authors reported receiving grants, contracts, consulting fees, or payment for speaker’s bureaus from various sources, including Eli Lilly.

Source: Kudrow D et al. A phase IV clinical trial of gastrointestinal motility in adult patients with migraine before and after initiation of a calcitonin gene-related peptide ligand (galcanezumab) or receptor (erenumab) antagonist. Headache. 2022 (Sep 16). Doi: 10.1111/head.14390

Key clinical point: Treatments with galcanezumab and erenumab increase constipation-related gastrointestinal discomfort, while erenumab also worsens stool form and bowel habits in patients with episodic migraine.

Major finding: An increase in the gastrointestinal symptom rating scale-constipation domain score was observed with both galcanezumab (least squares mean change [LSMC] 0.4; P  =  .002) and erenumab (LSMC 0.3; P  =  .016); additionally, erenumab significantly reduced Bristol Stool Form Scale (LSMC −0.5; P  =  .004) and spontaneous bowel movement (LSMC −1.2; P  =  .012) scores. No severe treatment-emergent adverse events were reported.

Study details: This phase 4 clinical trial included 65 patients with episodic migraine with or without aura and without significant gastrointestinal symptoms who were randomized to receive galcanezumab or erenumab.

Disclosures: This study was funded by Eli Lilly and Company. Six authors declared being full-time employees or minor shareholders or statistical contractors at Eli Lilly. Some authors reported receiving grants, contracts, consulting fees, or payment for speaker’s bureaus from various sources, including Eli Lilly.

Source: Kudrow D et al. A phase IV clinical trial of gastrointestinal motility in adult patients with migraine before and after initiation of a calcitonin gene-related peptide ligand (galcanezumab) or receptor (erenumab) antagonist. Headache. 2022 (Sep 16). Doi: 10.1111/head.14390

Key clinical point: Patients with migraine and low serum levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) at 2-4 weeks after initiating erenumab experienced a greater reduction in monthly migraine days (MMD) at 3 months after treatment initiation; however, CGRP-LI levels at treatment initiation showed no effect on clinical response.

Major finding: Absolute reduction in MMD after 3 months of initiating erenumab was significantly associated with serum CGRP-LI levels after 2-4 weeks of erenumab treatment (β −2.13; P  =  .003) but not with those before starting erenumab treatment (β −0.80; P  =  .24).

Study details: Findings are from a study including 94 patients with episodic or chronic migraine with/without aura who previously failed ≥4 migraine prophylactics and were treated with erenumab (70 mg) once every 4 weeks.

Disclosures: This study was supported by Vici grant from the Dutch Research Council. Two authors declared receiving consultancy or industry grant support or independent support from various sources, including Dutch Research Council.

Source: de Vries Lentsch S et al. Serum CGRP in migraine patients using erenumab as preventive treatment. J Headache Pain. 2022;23:120 (Sep 12). Doi: 10.1186/s10194-022-01483-z

Key clinical point: Patients with migraine and low serum levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) at 2-4 weeks after initiating erenumab experienced a greater reduction in monthly migraine days (MMD) at 3 months after treatment initiation; however, CGRP-LI levels at treatment initiation showed no effect on clinical response.

Major finding: Absolute reduction in MMD after 3 months of initiating erenumab was significantly associated with serum CGRP-LI levels after 2-4 weeks of erenumab treatment (β −2.13; P  =  .003) but not with those before starting erenumab treatment (β −0.80; P  =  .24).

Study details: Findings are from a study including 94 patients with episodic or chronic migraine with/without aura who previously failed ≥4 migraine prophylactics and were treated with erenumab (70 mg) once every 4 weeks.

Disclosures: This study was supported by Vici grant from the Dutch Research Council. Two authors declared receiving consultancy or industry grant support or independent support from various sources, including Dutch Research Council.

Source: de Vries Lentsch S et al. Serum CGRP in migraine patients using erenumab as preventive treatment. J Headache Pain. 2022;23:120 (Sep 12). Doi: 10.1186/s10194-022-01483-z

Key clinical point: Patients with migraine and low serum levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) at 2-4 weeks after initiating erenumab experienced a greater reduction in monthly migraine days (MMD) at 3 months after treatment initiation; however, CGRP-LI levels at treatment initiation showed no effect on clinical response.

Major finding: Absolute reduction in MMD after 3 months of initiating erenumab was significantly associated with serum CGRP-LI levels after 2-4 weeks of erenumab treatment (β −2.13; P  =  .003) but not with those before starting erenumab treatment (β −0.80; P  =  .24).

Study details: Findings are from a study including 94 patients with episodic or chronic migraine with/without aura who previously failed ≥4 migraine prophylactics and were treated with erenumab (70 mg) once every 4 weeks.

Disclosures: This study was supported by Vici grant from the Dutch Research Council. Two authors declared receiving consultancy or industry grant support or independent support from various sources, including Dutch Research Council.

Source: de Vries Lentsch S et al. Serum CGRP in migraine patients using erenumab as preventive treatment. J Headache Pain. 2022;23:120 (Sep 12). Doi: 10.1186/s10194-022-01483-z

Key clinical point: Doses of 200 mg lasmiditan and 75 mg rimegepant had the lowest numbers needed to treat (NNT) to achieve immediate and sustained pain freedom, respectively, whereas 25 mg ubrogepant had higher numbers needed to harm (NNH) for nausea and dizziness in acute treatment for migraine.

Major finding: Compared with placebo, 200 mg lasmiditan had the lowest NNT for immediate pain freedom at 2 hours (NNT 7; 95% credible interval [CrI] 5-9) and 75 mg rimegepant had the lowest NNT for sustained pain freedom at 2-24 hours (NNT 7; 95% CrI 5-12); although statistically insignificant, 25 mg ubrogepant had a high NNH for dizziness and nausea.

Study details: Findings are from a fixed-effects Bayesian network meta-analysis of five phase 3 randomized controlled trials including 10,060 patients with migraine who received lasmiditan, rimegepant, ubrogepant, or placebo for acute treatment.

Disclosures: This study was supported by Biohaven Pharmaceuticals. Seven authors declared being employees of and owning stock or stock options in Biohaven or a company funded by Biohaven.

Source: Johnston K et al. Rimegepant, ubrogepant, and lasmiditan in the acute treatment of migraine examining the benefit-risk profile using number needed to treat/harm. Clin J Pain. 2022;38(11):680-685  (Sep 26). Doi: 10.1097/AJP.0000000000001072

Key clinical point: Doses of 200 mg lasmiditan and 75 mg rimegepant had the lowest numbers needed to treat (NNT) to achieve immediate and sustained pain freedom, respectively, whereas 25 mg ubrogepant had higher numbers needed to harm (NNH) for nausea and dizziness in acute treatment for migraine.

Major finding: Compared with placebo, 200 mg lasmiditan had the lowest NNT for immediate pain freedom at 2 hours (NNT 7; 95% credible interval [CrI] 5-9) and 75 mg rimegepant had the lowest NNT for sustained pain freedom at 2-24 hours (NNT 7; 95% CrI 5-12); although statistically insignificant, 25 mg ubrogepant had a high NNH for dizziness and nausea.

Study details: Findings are from a fixed-effects Bayesian network meta-analysis of five phase 3 randomized controlled trials including 10,060 patients with migraine who received lasmiditan, rimegepant, ubrogepant, or placebo for acute treatment.

Disclosures: This study was supported by Biohaven Pharmaceuticals. Seven authors declared being employees of and owning stock or stock options in Biohaven or a company funded by Biohaven.

Source: Johnston K et al. Rimegepant, ubrogepant, and lasmiditan in the acute treatment of migraine examining the benefit-risk profile using number needed to treat/harm. Clin J Pain. 2022;38(11):680-685  (Sep 26). Doi: 10.1097/AJP.0000000000001072

Key clinical point: Doses of 200 mg lasmiditan and 75 mg rimegepant had the lowest numbers needed to treat (NNT) to achieve immediate and sustained pain freedom, respectively, whereas 25 mg ubrogepant had higher numbers needed to harm (NNH) for nausea and dizziness in acute treatment for migraine.

Major finding: Compared with placebo, 200 mg lasmiditan had the lowest NNT for immediate pain freedom at 2 hours (NNT 7; 95% credible interval [CrI] 5-9) and 75 mg rimegepant had the lowest NNT for sustained pain freedom at 2-24 hours (NNT 7; 95% CrI 5-12); although statistically insignificant, 25 mg ubrogepant had a high NNH for dizziness and nausea.

Study details: Findings are from a fixed-effects Bayesian network meta-analysis of five phase 3 randomized controlled trials including 10,060 patients with migraine who received lasmiditan, rimegepant, ubrogepant, or placebo for acute treatment.

Disclosures: This study was supported by Biohaven Pharmaceuticals. Seven authors declared being employees of and owning stock or stock options in Biohaven or a company funded by Biohaven.

Source: Johnston K et al. Rimegepant, ubrogepant, and lasmiditan in the acute treatment of migraine examining the benefit-risk profile using number needed to treat/harm. Clin J Pain. 2022;38(11):680-685  (Sep 26). Doi: 10.1097/AJP.0000000000001072

Key clinical point: At the onset of attack, many patients with migraine with aura (MwA) experience stroke-like symptoms, whereas many patients with acute ischemic stroke (AIS) experience migraine-like symptoms, highlighting the need for additional clinical investigation for careful differential diagnosis.

Major finding: Migraine-like irritative sensations were experienced by 32.1% and 35.2% of patients with stroke who experienced visual disturbances and sensory disturbances, respectively, whereas stroke-like symptoms were reported by 12.0% and 31.4% of patients with MwA who experienced visual disturbances and sensory disturbances, respectively.

Study details: Findings are from a questionnaire-based observational study including 343 patients with MwA and 350 patients with AIS.

Disclosures: This study was supported by Swiss Heart Foundation. Several authors reported receiving research support, grants, personal fees, speaker fees, consulting or advisory support from Swiss Heart Foundation or other sources.

Source: Scutelnic A et al. Migraine aura-like symptoms at onset of stroke and stroke-like symptoms in migraine with aura. Front Neurol. 2022;13:1004058 (Sep 14). Doi: 10.3389/fneur.2022.1004058

Key clinical point: At the onset of attack, many patients with migraine with aura (MwA) experience stroke-like symptoms, whereas many patients with acute ischemic stroke (AIS) experience migraine-like symptoms, highlighting the need for additional clinical investigation for careful differential diagnosis.

Major finding: Migraine-like irritative sensations were experienced by 32.1% and 35.2% of patients with stroke who experienced visual disturbances and sensory disturbances, respectively, whereas stroke-like symptoms were reported by 12.0% and 31.4% of patients with MwA who experienced visual disturbances and sensory disturbances, respectively.

Study details: Findings are from a questionnaire-based observational study including 343 patients with MwA and 350 patients with AIS.

Disclosures: This study was supported by Swiss Heart Foundation. Several authors reported receiving research support, grants, personal fees, speaker fees, consulting or advisory support from Swiss Heart Foundation or other sources.

Source: Scutelnic A et al. Migraine aura-like symptoms at onset of stroke and stroke-like symptoms in migraine with aura. Front Neurol. 2022;13:1004058 (Sep 14). Doi: 10.3389/fneur.2022.1004058

Key clinical point: At the onset of attack, many patients with migraine with aura (MwA) experience stroke-like symptoms, whereas many patients with acute ischemic stroke (AIS) experience migraine-like symptoms, highlighting the need for additional clinical investigation for careful differential diagnosis.

Major finding: Migraine-like irritative sensations were experienced by 32.1% and 35.2% of patients with stroke who experienced visual disturbances and sensory disturbances, respectively, whereas stroke-like symptoms were reported by 12.0% and 31.4% of patients with MwA who experienced visual disturbances and sensory disturbances, respectively.

Study details: Findings are from a questionnaire-based observational study including 343 patients with MwA and 350 patients with AIS.

Disclosures: This study was supported by Swiss Heart Foundation. Several authors reported receiving research support, grants, personal fees, speaker fees, consulting or advisory support from Swiss Heart Foundation or other sources.

Source: Scutelnic A et al. Migraine aura-like symptoms at onset of stroke and stroke-like symptoms in migraine with aura. Front Neurol. 2022;13:1004058 (Sep 14). Doi: 10.3389/fneur.2022.1004058

Key clinical point: Galcanezumab demonstrated persistent efficacy in improving migraine features and disability scores and was well tolerated over 1 year in real-life patients with high frequency episodic migraine (HFEM) or chronic migraine (CM).

Major finding: The monthly migraine days (MMD) significantly reduced in patients with HFEM (from 11.5 ± 3.5 to 5.5 ± 5.5) and CM (from 19.3 ± 5.8 to 7.4 ± 5.9; both P < .00001) over 12 months along with a significant decrease in pain intensity, monthly acute medication intake, Headache Impact Test-6, and Migraine Disability Assessment questionnaire scores (all P < .00001). Overall, 56.5% of patients presented with a response rate of ≥50% reduction in MMD for 9 cumulative months. No serious adverse events were reported.

Study details: Findings are from a prospective ongoing study including 191 patients with HFEM or CM who received galcanezumab and completed the 12 months of observation since galcanezumab initiation.

Disclosures: This study was supported by Campus Bio-Medico University. Several authors reported receiving grants or honoraria from various sources.

Source: Vernieri F et al for the GARLIT Study Group. Maintenance of response and predictive factors of 1-year GalcanezumAb treatment in real-life migraine patients in Italy: The multicenter prospective cohort GARLIT study. Eur J Neurol. 2022 (Sep 13). Doi: 10.1111/ene.15563

Key clinical point: Galcanezumab demonstrated persistent efficacy in improving migraine features and disability scores and was well tolerated over 1 year in real-life patients with high frequency episodic migraine (HFEM) or chronic migraine (CM).

Major finding: The monthly migraine days (MMD) significantly reduced in patients with HFEM (from 11.5 ± 3.5 to 5.5 ± 5.5) and CM (from 19.3 ± 5.8 to 7.4 ± 5.9; both P < .00001) over 12 months along with a significant decrease in pain intensity, monthly acute medication intake, Headache Impact Test-6, and Migraine Disability Assessment questionnaire scores (all P < .00001). Overall, 56.5% of patients presented with a response rate of ≥50% reduction in MMD for 9 cumulative months. No serious adverse events were reported.

Study details: Findings are from a prospective ongoing study including 191 patients with HFEM or CM who received galcanezumab and completed the 12 months of observation since galcanezumab initiation.

Disclosures: This study was supported by Campus Bio-Medico University. Several authors reported receiving grants or honoraria from various sources.

Source: Vernieri F et al for the GARLIT Study Group. Maintenance of response and predictive factors of 1-year GalcanezumAb treatment in real-life migraine patients in Italy: The multicenter prospective cohort GARLIT study. Eur J Neurol. 2022 (Sep 13). Doi: 10.1111/ene.15563

Key clinical point: Galcanezumab demonstrated persistent efficacy in improving migraine features and disability scores and was well tolerated over 1 year in real-life patients with high frequency episodic migraine (HFEM) or chronic migraine (CM).

Major finding: The monthly migraine days (MMD) significantly reduced in patients with HFEM (from 11.5 ± 3.5 to 5.5 ± 5.5) and CM (from 19.3 ± 5.8 to 7.4 ± 5.9; both P < .00001) over 12 months along with a significant decrease in pain intensity, monthly acute medication intake, Headache Impact Test-6, and Migraine Disability Assessment questionnaire scores (all P < .00001). Overall, 56.5% of patients presented with a response rate of ≥50% reduction in MMD for 9 cumulative months. No serious adverse events were reported.

Study details: Findings are from a prospective ongoing study including 191 patients with HFEM or CM who received galcanezumab and completed the 12 months of observation since galcanezumab initiation.

Disclosures: This study was supported by Campus Bio-Medico University. Several authors reported receiving grants or honoraria from various sources.

Source: Vernieri F et al for the GARLIT Study Group. Maintenance of response and predictive factors of 1-year GalcanezumAb treatment in real-life migraine patients in Italy: The multicenter prospective cohort GARLIT study. Eur J Neurol. 2022 (Sep 13). Doi: 10.1111/ene.15563