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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
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
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
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.