Clinical Edge Journal Scan Commentary: Migraine May 2022

Cefaly is a commonly used nonprescription device that uses external trigeminal nerve stimulation (e-TNS) to either abort or prevent migraine attacks. The pivotal Cefaly study was published about 10 years ago, and Cefaly was the first US Food and Drug Administration–cleared neurostimulation device for headache. The initial acute data were gathered primarily in the hospital setting, and the investigators in the study by Kuruvilla and colleagues intended to replicate a more real-world scenario for the acute use of Cefaly.

This was a prospective, multicenter, sham-controlled study. Patients were enrolled if they developed migraine prior to age 50 years and experienced two to eight attacks per month of moderate to severe intensity. Patients were randomized to either Cefaly or a sham device. The Cefaly device itself has two setting: acute and preventive. For this study, the acute setting was used for 2 hours at a time during an acute attack (within the first 4 hours). The supraorbital and supratrochlear branches of trigeminal nerves bilaterally are stimulated with a continuous stimulation via a self-adhesive electrode. This has previously been shown to be safe and effective with the most common side effect noted to be skin irritation at the electrode site.

Patients collected data about their headaches in an e-diary and continued to treat for 2 months. The co-primary outcomes were headache freedom and resolution of most bothersome syndrome at 2 hours. Secondary outcomes were pain relief at 2 hours, resolution of any migraine-associated symptom at 2 hours after beginning e-TNS treatment, sustained pain freedom (defined as pain freedom at 2 hours and pain freedom at 24 hours without the use of antimigraine medication during those 24 hours), and use of a rescue medication between 2 and 24 hours after beginning an e-TNS session.

A total of 538 patients were enrolled. The percentage of patients with both freedom from pain and resolution of the most bothersome symptoms were statistically different in the intervention and sham groups. The secondary outcomes were also statistically improved in the device group, with the exception of use of rescue medications between 2 and 24 hours. The most common adverse events were forehead discomfort and paresthesia.

This study does show the effectiveness of Cefaly, especially when used for longer periods of time than had been previously recommended. The outcomes were all met with the exception of rescue medication use, and there is no contraindication to using any rescue medication while using the Cefaly device. Cefaly can be an excellent add-on for acute treatment, especially in patients that may need to use more than one intervention acutely for their migraine attacks.

Providers often discuss when to start medications but do not as often discuss when to stop medications. This is especially true for preventive medications for migraine. The best-case scenario is that a preventive medication is so effective that it is no longer necessary; but in other circumstances, preventive medications have to be stopped, for instance, during pregnancy planning. One concern especially when starting and stopping a monoclonal antibody (mAb) medication is the development of neutralizing antibodies to negate the effect of restarting the medication. This study was designed to determine whether restarting calcitonin gene-related peptide (CGRP)–mAb medications was still effective after having been previously stopped.

Raffaelli and colleagues managed a small (39 patients) open-label prospective study. Patients either had a diagnosis of episodic or chronic migraine and were initially given CGRP-mAbs for at least 8 months. They then stopped the therapy for at least 3 months and were restarted on the same mAb that they had initially used. They tracked their headache symptoms for 3 months after restarting therapy. If another treatment had been started in between, those patients were excluded.

The primary outcome was change in mean monthly migraine days between the last 4 weeks of treatment discontinuation and weeks 9-12 after restarting therapy. Secondary endpoints were the changes in mean monthly headache days across the other observation points and Headache Impact Test-6 (HIT-6) sum scores. Of the 39 patients enrolled, 16 were given erenumab, 15 galcanezumab, and 8 fremanezumab.

Mean migraine days and mean headache days were shown to have a statistically significant decrease after resumption of therapy. Restarting CGRP medications was not associated with other adverse events associated with these medications. This gives us evidence in favor of restarting the same CGRP medication when a patient's symptoms start to worsen after they have discontinued because of improvement or after pregnancy and breastfeeding.

The use of implanted devices for migraine treatment is considered somewhat controversial. Surgical interventions and implantations for migraine have not been well studied; however small case series have been published, and non-neurologists report anecdotally that these interventions can be helpful for refractory headache disorders. The study by Evans and colleagues reviewed via meta-analysis much of the prior data for nerve stimulation in migraine.

Studies included in this meta-analysis were English-language, peer-reviewed articles of prospective studies with patients over age 18 years for migraine diagnosed according to International Classification of Headache Disorders (ICHD) criteria. The devices were transcutaneous nerve stimulator devices in a single region of the head (occipital, supraorbital/supratrochlear areas) and enrolled a minimum of 10 patients in the treatment groups. A total of 14 studies were identified; 13 of the studies did report significant adverse events related to treatment.

Regarding migraine frequency, only four of the studies were considered comparable, investigating episodic migraine with 2-3 months of transcutaneous stimulation, and two were comparable in investigating chronic migraine. The episodic migraine studies had a pooled reduction by 2.8 days of migraine per month; chronic migraine was noted to be 2.97 days fewer per month. Three comparable studies for episodic migraine showed a pooled reduction in severity by 2.23 points after 3 months.

Occipital and other trigeminal branch stimulation implants are invasive and associated with risk, most prominently leading to migration and worsening headache and neck pain. This meta-analysis did reveal important pooled data, but it becomes less impressive when considering the published data for standard oral or injection therapies. The fact that there can be long-term worsening and adverse events with surgical implantation makes this choice a higher risk. Of note, there are now neurostimulation devices, such as Cefaly, that allow similar transcutaneous stimulation without the risk of surgery.

Cefaly is a commonly used nonprescription device that uses external trigeminal nerve stimulation (e-TNS) to either abort or prevent migraine attacks. The pivotal Cefaly study was published about 10 years ago, and Cefaly was the first US Food and Drug Administration–cleared neurostimulation device for headache. The initial acute data were gathered primarily in the hospital setting, and the investigators in the study by Kuruvilla and colleagues intended to replicate a more real-world scenario for the acute use of Cefaly.

This was a prospective, multicenter, sham-controlled study. Patients were enrolled if they developed migraine prior to age 50 years and experienced two to eight attacks per month of moderate to severe intensity. Patients were randomized to either Cefaly or a sham device. The Cefaly device itself has two setting: acute and preventive. For this study, the acute setting was used for 2 hours at a time during an acute attack (within the first 4 hours). The supraorbital and supratrochlear branches of trigeminal nerves bilaterally are stimulated with a continuous stimulation via a self-adhesive electrode. This has previously been shown to be safe and effective with the most common side effect noted to be skin irritation at the electrode site.

Patients collected data about their headaches in an e-diary and continued to treat for 2 months. The co-primary outcomes were headache freedom and resolution of most bothersome syndrome at 2 hours. Secondary outcomes were pain relief at 2 hours, resolution of any migraine-associated symptom at 2 hours after beginning e-TNS treatment, sustained pain freedom (defined as pain freedom at 2 hours and pain freedom at 24 hours without the use of antimigraine medication during those 24 hours), and use of a rescue medication between 2 and 24 hours after beginning an e-TNS session.

A total of 538 patients were enrolled. The percentage of patients with both freedom from pain and resolution of the most bothersome symptoms were statistically different in the intervention and sham groups. The secondary outcomes were also statistically improved in the device group, with the exception of use of rescue medications between 2 and 24 hours. The most common adverse events were forehead discomfort and paresthesia.

This study does show the effectiveness of Cefaly, especially when used for longer periods of time than had been previously recommended. The outcomes were all met with the exception of rescue medication use, and there is no contraindication to using any rescue medication while using the Cefaly device. Cefaly can be an excellent add-on for acute treatment, especially in patients that may need to use more than one intervention acutely for their migraine attacks.

Providers often discuss when to start medications but do not as often discuss when to stop medications. This is especially true for preventive medications for migraine. The best-case scenario is that a preventive medication is so effective that it is no longer necessary; but in other circumstances, preventive medications have to be stopped, for instance, during pregnancy planning. One concern especially when starting and stopping a monoclonal antibody (mAb) medication is the development of neutralizing antibodies to negate the effect of restarting the medication. This study was designed to determine whether restarting calcitonin gene-related peptide (CGRP)–mAb medications was still effective after having been previously stopped.

Raffaelli and colleagues managed a small (39 patients) open-label prospective study. Patients either had a diagnosis of episodic or chronic migraine and were initially given CGRP-mAbs for at least 8 months. They then stopped the therapy for at least 3 months and were restarted on the same mAb that they had initially used. They tracked their headache symptoms for 3 months after restarting therapy. If another treatment had been started in between, those patients were excluded.

The primary outcome was change in mean monthly migraine days between the last 4 weeks of treatment discontinuation and weeks 9-12 after restarting therapy. Secondary endpoints were the changes in mean monthly headache days across the other observation points and Headache Impact Test-6 (HIT-6) sum scores. Of the 39 patients enrolled, 16 were given erenumab, 15 galcanezumab, and 8 fremanezumab.

Mean migraine days and mean headache days were shown to have a statistically significant decrease after resumption of therapy. Restarting CGRP medications was not associated with other adverse events associated with these medications. This gives us evidence in favor of restarting the same CGRP medication when a patient's symptoms start to worsen after they have discontinued because of improvement or after pregnancy and breastfeeding.

The use of implanted devices for migraine treatment is considered somewhat controversial. Surgical interventions and implantations for migraine have not been well studied; however small case series have been published, and non-neurologists report anecdotally that these interventions can be helpful for refractory headache disorders. The study by Evans and colleagues reviewed via meta-analysis much of the prior data for nerve stimulation in migraine.

Studies included in this meta-analysis were English-language, peer-reviewed articles of prospective studies with patients over age 18 years for migraine diagnosed according to International Classification of Headache Disorders (ICHD) criteria. The devices were transcutaneous nerve stimulator devices in a single region of the head (occipital, supraorbital/supratrochlear areas) and enrolled a minimum of 10 patients in the treatment groups. A total of 14 studies were identified; 13 of the studies did report significant adverse events related to treatment.

Regarding migraine frequency, only four of the studies were considered comparable, investigating episodic migraine with 2-3 months of transcutaneous stimulation, and two were comparable in investigating chronic migraine. The episodic migraine studies had a pooled reduction by 2.8 days of migraine per month; chronic migraine was noted to be 2.97 days fewer per month. Three comparable studies for episodic migraine showed a pooled reduction in severity by 2.23 points after 3 months.

Occipital and other trigeminal branch stimulation implants are invasive and associated with risk, most prominently leading to migration and worsening headache and neck pain. This meta-analysis did reveal important pooled data, but it becomes less impressive when considering the published data for standard oral or injection therapies. The fact that there can be long-term worsening and adverse events with surgical implantation makes this choice a higher risk. Of note, there are now neurostimulation devices, such as Cefaly, that allow similar transcutaneous stimulation without the risk of surgery.

Cefaly is a commonly used nonprescription device that uses external trigeminal nerve stimulation (e-TNS) to either abort or prevent migraine attacks. The pivotal Cefaly study was published about 10 years ago, and Cefaly was the first US Food and Drug Administration–cleared neurostimulation device for headache. The initial acute data were gathered primarily in the hospital setting, and the investigators in the study by Kuruvilla and colleagues intended to replicate a more real-world scenario for the acute use of Cefaly.

This was a prospective, multicenter, sham-controlled study. Patients were enrolled if they developed migraine prior to age 50 years and experienced two to eight attacks per month of moderate to severe intensity. Patients were randomized to either Cefaly or a sham device. The Cefaly device itself has two setting: acute and preventive. For this study, the acute setting was used for 2 hours at a time during an acute attack (within the first 4 hours). The supraorbital and supratrochlear branches of trigeminal nerves bilaterally are stimulated with a continuous stimulation via a self-adhesive electrode. This has previously been shown to be safe and effective with the most common side effect noted to be skin irritation at the electrode site.

Patients collected data about their headaches in an e-diary and continued to treat for 2 months. The co-primary outcomes were headache freedom and resolution of most bothersome syndrome at 2 hours. Secondary outcomes were pain relief at 2 hours, resolution of any migraine-associated symptom at 2 hours after beginning e-TNS treatment, sustained pain freedom (defined as pain freedom at 2 hours and pain freedom at 24 hours without the use of antimigraine medication during those 24 hours), and use of a rescue medication between 2 and 24 hours after beginning an e-TNS session.

A total of 538 patients were enrolled. The percentage of patients with both freedom from pain and resolution of the most bothersome symptoms were statistically different in the intervention and sham groups. The secondary outcomes were also statistically improved in the device group, with the exception of use of rescue medications between 2 and 24 hours. The most common adverse events were forehead discomfort and paresthesia.

This study does show the effectiveness of Cefaly, especially when used for longer periods of time than had been previously recommended. The outcomes were all met with the exception of rescue medication use, and there is no contraindication to using any rescue medication while using the Cefaly device. Cefaly can be an excellent add-on for acute treatment, especially in patients that may need to use more than one intervention acutely for their migraine attacks.

Providers often discuss when to start medications but do not as often discuss when to stop medications. This is especially true for preventive medications for migraine. The best-case scenario is that a preventive medication is so effective that it is no longer necessary; but in other circumstances, preventive medications have to be stopped, for instance, during pregnancy planning. One concern especially when starting and stopping a monoclonal antibody (mAb) medication is the development of neutralizing antibodies to negate the effect of restarting the medication. This study was designed to determine whether restarting calcitonin gene-related peptide (CGRP)–mAb medications was still effective after having been previously stopped.

Raffaelli and colleagues managed a small (39 patients) open-label prospective study. Patients either had a diagnosis of episodic or chronic migraine and were initially given CGRP-mAbs for at least 8 months. They then stopped the therapy for at least 3 months and were restarted on the same mAb that they had initially used. They tracked their headache symptoms for 3 months after restarting therapy. If another treatment had been started in between, those patients were excluded.

The primary outcome was change in mean monthly migraine days between the last 4 weeks of treatment discontinuation and weeks 9-12 after restarting therapy. Secondary endpoints were the changes in mean monthly headache days across the other observation points and Headache Impact Test-6 (HIT-6) sum scores. Of the 39 patients enrolled, 16 were given erenumab, 15 galcanezumab, and 8 fremanezumab.

Mean migraine days and mean headache days were shown to have a statistically significant decrease after resumption of therapy. Restarting CGRP medications was not associated with other adverse events associated with these medications. This gives us evidence in favor of restarting the same CGRP medication when a patient's symptoms start to worsen after they have discontinued because of improvement or after pregnancy and breastfeeding.

The use of implanted devices for migraine treatment is considered somewhat controversial. Surgical interventions and implantations for migraine have not been well studied; however small case series have been published, and non-neurologists report anecdotally that these interventions can be helpful for refractory headache disorders. The study by Evans and colleagues reviewed via meta-analysis much of the prior data for nerve stimulation in migraine.

Studies included in this meta-analysis were English-language, peer-reviewed articles of prospective studies with patients over age 18 years for migraine diagnosed according to International Classification of Headache Disorders (ICHD) criteria. The devices were transcutaneous nerve stimulator devices in a single region of the head (occipital, supraorbital/supratrochlear areas) and enrolled a minimum of 10 patients in the treatment groups. A total of 14 studies were identified; 13 of the studies did report significant adverse events related to treatment.

Regarding migraine frequency, only four of the studies were considered comparable, investigating episodic migraine with 2-3 months of transcutaneous stimulation, and two were comparable in investigating chronic migraine. The episodic migraine studies had a pooled reduction by 2.8 days of migraine per month; chronic migraine was noted to be 2.97 days fewer per month. Three comparable studies for episodic migraine showed a pooled reduction in severity by 2.23 points after 3 months.

Occipital and other trigeminal branch stimulation implants are invasive and associated with risk, most prominently leading to migration and worsening headache and neck pain. This meta-analysis did reveal important pooled data, but it becomes less impressive when considering the published data for standard oral or injection therapies. The fact that there can be long-term worsening and adverse events with surgical implantation makes this choice a higher risk. Of note, there are now neurostimulation devices, such as Cefaly, that allow similar transcutaneous stimulation without the risk of surgery.