Headache & Migraine

Intranasal (IN) ketamine may be a feasible treatment alternative for people with chronic, refractory migraine who don’t respond to other medications, new research shows.

Half of the study participants who used IN ketamine for chronic, treatment-refractory migraine in a new retrospective cohort study reported it as “very effective” and over one-third said it boosted their quality of life.

“In our study, we showed that with even a few uses per day, intranasal ketamine can still improve patients’ quality of life,” lead investigator Hsiangkuo Yuan, MD, PhD, said in an interview. Dr. Yuan is associate professor of neurology at Thomas Jefferson University, Philadelphia, and director of clinical research at the Jefferson Headache Center.

He added that “multiple medications failed these patients, and the majority of patients were having daily headaches. So, if anything works, even partially and shortly, it may still give patients some relief to get through the day.”

The findings were published online in Regional Anesthesia & Pain Medicine.  
 

Daily migraine, failed medications

Use of IN ketamine has not been studied for the treatment of chronic, treatment-refractory migraine – although it has been studied in patients with cluster headache and migraine, the investigators note.

Ketamine is not yet approved by the Food and Drug Administration to treat migraine.

To further explore ketamine’s effect in those with chronic, treatment-refractory migraine, the investigators retrospectively analyzed electronic health records of patients at the Jefferson Headache Center who had received IN ketamine for the treatment of migraine between January 2019 and February 2020.

Of 242 patients who had received IN ketamine, Dr. Yuan’s team followed up with 169 who agreed to be part of the study.

The majority (67%) had daily migraine, and 85% had tried more than three classes of preventive medications for migraine. They currently used a median of two medications, the most common of which was a CGRP monoclonal antibody.

On average, patients used six sprays per day for a median 10 days per month. Median pain relief onset was 52 minutes after dosage.

Almost three-quarters of patients reported at least one side effect from the ketamine, most commonly fatigue (22%), double/blurred vision (21%), and confusion/dissociation (21%). These effects were mostly temporary, the researchers report.

The most common reasons for initiating IN ketamine included an incomplete response to prior acute medications (59%), incomplete response to prior preventive medications (31%), and prior benefit from IV ketamine (23%).

Study investigators noted that ketamine has the potential to become addictive and indicated that “clinicians should only consider the use of a potentially addictive medication such as ketamine for significantly disabled patients with migraine.”

About half of the participants who used IN ketamine found it “very effective,” and 40% found it “somewhat effective.” Within the same group, 36% and 43% found the overall impact of IN ketamine on their quality of life was much better and somewhat better, respectively.

Among those still using ketamine during study follow-up, 82% reported that ketamine was very effective.

Compared with other acute headache medications, IN ketamine was considered much better (43%) or somewhat better (30%).

Nearly 75% of participants reported using fewer pain relievers when using IN ketamine.

Dr. Yuan said that future research might focus on finding predictors for IN ketamine response or determining the optimal effective and safe dose for the drug in those with chronic, treatment-refractory migraine.  

“We still need a prospective, randomized controlled trial to assess the efficacy and tolerability of intranasal ketamine,” he added.
 

‘Impressive result’

Commenting on the findings for this article, Richard Lipton, MD, professor of neurology, psychiatry and behavioral sciences and director of the Montefiore Headache Center at Albert Einstein College of Medicine, New York, said that “in this refractory population with multiple treatment failures, this is a very impressive, open-label result.”

“This real-world data suggests that ketamine is an effective option for people with medically intractable chronic migraine,” said Dr. Lipton, who was not part of the study. “In these very difficult to treat patients, 65% of those who started on ketamine persisted. Of those who remained on ketamine, 82% found it very effective.”

“This study makes me more confident that intranasal ketamine is a helpful treatment option, and I plan to use it more often in the future,” he added.

Like Dr. Yuan, Dr. Lipton highlighted the need for “well-designed placebo-controlled trials” and “rigorous comparative effectiveness studies.”

The study was funded by Miles for Migraine. Dr. Yuan has received institutional support for serving as an investigator from Teva and AbbVie, and royalties from Cambridge University Press and MedLink. Dr. Lipton has received compensation for consultation from Alder/Lumbeck, Axsome, Supernus, Theranica, Upsher-Smith, and Satsuma. He has participated in speaker bureaus for Eli Lilly and Amgen/Novartis and has received institutional support for serving as principal investigator from Teva, GammaCore, and Allergan/AbbVie. He has received payments for authorship or royalties from Demos Medical, Cambridge University Press, and MedLink.

A version of this article originally appeared on Medscape.com.

Intranasal (IN) ketamine may be a feasible treatment alternative for people with chronic, refractory migraine who don’t respond to other medications, new research shows.

Half of the study participants who used IN ketamine for chronic, treatment-refractory migraine in a new retrospective cohort study reported it as “very effective” and over one-third said it boosted their quality of life.

“In our study, we showed that with even a few uses per day, intranasal ketamine can still improve patients’ quality of life,” lead investigator Hsiangkuo Yuan, MD, PhD, said in an interview. Dr. Yuan is associate professor of neurology at Thomas Jefferson University, Philadelphia, and director of clinical research at the Jefferson Headache Center.

He added that “multiple medications failed these patients, and the majority of patients were having daily headaches. So, if anything works, even partially and shortly, it may still give patients some relief to get through the day.”

The findings were published online in Regional Anesthesia & Pain Medicine.  
 

Daily migraine, failed medications

Use of IN ketamine has not been studied for the treatment of chronic, treatment-refractory migraine – although it has been studied in patients with cluster headache and migraine, the investigators note.

Ketamine is not yet approved by the Food and Drug Administration to treat migraine.

To further explore ketamine’s effect in those with chronic, treatment-refractory migraine, the investigators retrospectively analyzed electronic health records of patients at the Jefferson Headache Center who had received IN ketamine for the treatment of migraine between January 2019 and February 2020.

Of 242 patients who had received IN ketamine, Dr. Yuan’s team followed up with 169 who agreed to be part of the study.

The majority (67%) had daily migraine, and 85% had tried more than three classes of preventive medications for migraine. They currently used a median of two medications, the most common of which was a CGRP monoclonal antibody.

On average, patients used six sprays per day for a median 10 days per month. Median pain relief onset was 52 minutes after dosage.

Almost three-quarters of patients reported at least one side effect from the ketamine, most commonly fatigue (22%), double/blurred vision (21%), and confusion/dissociation (21%). These effects were mostly temporary, the researchers report.

The most common reasons for initiating IN ketamine included an incomplete response to prior acute medications (59%), incomplete response to prior preventive medications (31%), and prior benefit from IV ketamine (23%).

Study investigators noted that ketamine has the potential to become addictive and indicated that “clinicians should only consider the use of a potentially addictive medication such as ketamine for significantly disabled patients with migraine.”

About half of the participants who used IN ketamine found it “very effective,” and 40% found it “somewhat effective.” Within the same group, 36% and 43% found the overall impact of IN ketamine on their quality of life was much better and somewhat better, respectively.

Among those still using ketamine during study follow-up, 82% reported that ketamine was very effective.

Compared with other acute headache medications, IN ketamine was considered much better (43%) or somewhat better (30%).

Nearly 75% of participants reported using fewer pain relievers when using IN ketamine.

Dr. Yuan said that future research might focus on finding predictors for IN ketamine response or determining the optimal effective and safe dose for the drug in those with chronic, treatment-refractory migraine.  

“We still need a prospective, randomized controlled trial to assess the efficacy and tolerability of intranasal ketamine,” he added.
 

‘Impressive result’

Commenting on the findings for this article, Richard Lipton, MD, professor of neurology, psychiatry and behavioral sciences and director of the Montefiore Headache Center at Albert Einstein College of Medicine, New York, said that “in this refractory population with multiple treatment failures, this is a very impressive, open-label result.”

“This real-world data suggests that ketamine is an effective option for people with medically intractable chronic migraine,” said Dr. Lipton, who was not part of the study. “In these very difficult to treat patients, 65% of those who started on ketamine persisted. Of those who remained on ketamine, 82% found it very effective.”

“This study makes me more confident that intranasal ketamine is a helpful treatment option, and I plan to use it more often in the future,” he added.

Like Dr. Yuan, Dr. Lipton highlighted the need for “well-designed placebo-controlled trials” and “rigorous comparative effectiveness studies.”

The study was funded by Miles for Migraine. Dr. Yuan has received institutional support for serving as an investigator from Teva and AbbVie, and royalties from Cambridge University Press and MedLink. Dr. Lipton has received compensation for consultation from Alder/Lumbeck, Axsome, Supernus, Theranica, Upsher-Smith, and Satsuma. He has participated in speaker bureaus for Eli Lilly and Amgen/Novartis and has received institutional support for serving as principal investigator from Teva, GammaCore, and Allergan/AbbVie. He has received payments for authorship or royalties from Demos Medical, Cambridge University Press, and MedLink.

A version of this article originally appeared on Medscape.com.

Intranasal (IN) ketamine may be a feasible treatment alternative for people with chronic, refractory migraine who don’t respond to other medications, new research shows.

Half of the study participants who used IN ketamine for chronic, treatment-refractory migraine in a new retrospective cohort study reported it as “very effective” and over one-third said it boosted their quality of life.

“In our study, we showed that with even a few uses per day, intranasal ketamine can still improve patients’ quality of life,” lead investigator Hsiangkuo Yuan, MD, PhD, said in an interview. Dr. Yuan is associate professor of neurology at Thomas Jefferson University, Philadelphia, and director of clinical research at the Jefferson Headache Center.

He added that “multiple medications failed these patients, and the majority of patients were having daily headaches. So, if anything works, even partially and shortly, it may still give patients some relief to get through the day.”

The findings were published online in Regional Anesthesia & Pain Medicine.  
 

Daily migraine, failed medications

Use of IN ketamine has not been studied for the treatment of chronic, treatment-refractory migraine – although it has been studied in patients with cluster headache and migraine, the investigators note.

Ketamine is not yet approved by the Food and Drug Administration to treat migraine.

To further explore ketamine’s effect in those with chronic, treatment-refractory migraine, the investigators retrospectively analyzed electronic health records of patients at the Jefferson Headache Center who had received IN ketamine for the treatment of migraine between January 2019 and February 2020.

Of 242 patients who had received IN ketamine, Dr. Yuan’s team followed up with 169 who agreed to be part of the study.

The majority (67%) had daily migraine, and 85% had tried more than three classes of preventive medications for migraine. They currently used a median of two medications, the most common of which was a CGRP monoclonal antibody.

On average, patients used six sprays per day for a median 10 days per month. Median pain relief onset was 52 minutes after dosage.

Almost three-quarters of patients reported at least one side effect from the ketamine, most commonly fatigue (22%), double/blurred vision (21%), and confusion/dissociation (21%). These effects were mostly temporary, the researchers report.

The most common reasons for initiating IN ketamine included an incomplete response to prior acute medications (59%), incomplete response to prior preventive medications (31%), and prior benefit from IV ketamine (23%).

Study investigators noted that ketamine has the potential to become addictive and indicated that “clinicians should only consider the use of a potentially addictive medication such as ketamine for significantly disabled patients with migraine.”

About half of the participants who used IN ketamine found it “very effective,” and 40% found it “somewhat effective.” Within the same group, 36% and 43% found the overall impact of IN ketamine on their quality of life was much better and somewhat better, respectively.

Among those still using ketamine during study follow-up, 82% reported that ketamine was very effective.

Compared with other acute headache medications, IN ketamine was considered much better (43%) or somewhat better (30%).

Nearly 75% of participants reported using fewer pain relievers when using IN ketamine.

Dr. Yuan said that future research might focus on finding predictors for IN ketamine response or determining the optimal effective and safe dose for the drug in those with chronic, treatment-refractory migraine.  

“We still need a prospective, randomized controlled trial to assess the efficacy and tolerability of intranasal ketamine,” he added.
 

‘Impressive result’

Commenting on the findings for this article, Richard Lipton, MD, professor of neurology, psychiatry and behavioral sciences and director of the Montefiore Headache Center at Albert Einstein College of Medicine, New York, said that “in this refractory population with multiple treatment failures, this is a very impressive, open-label result.”

“This real-world data suggests that ketamine is an effective option for people with medically intractable chronic migraine,” said Dr. Lipton, who was not part of the study. “In these very difficult to treat patients, 65% of those who started on ketamine persisted. Of those who remained on ketamine, 82% found it very effective.”

“This study makes me more confident that intranasal ketamine is a helpful treatment option, and I plan to use it more often in the future,” he added.

Like Dr. Yuan, Dr. Lipton highlighted the need for “well-designed placebo-controlled trials” and “rigorous comparative effectiveness studies.”

The study was funded by Miles for Migraine. Dr. Yuan has received institutional support for serving as an investigator from Teva and AbbVie, and royalties from Cambridge University Press and MedLink. Dr. Lipton has received compensation for consultation from Alder/Lumbeck, Axsome, Supernus, Theranica, Upsher-Smith, and Satsuma. He has participated in speaker bureaus for Eli Lilly and Amgen/Novartis and has received institutional support for serving as principal investigator from Teva, GammaCore, and Allergan/AbbVie. He has received payments for authorship or royalties from Demos Medical, Cambridge University Press, and MedLink.

A version of this article originally appeared on Medscape.com.

The field of headache medicine has changed significantly since 2018 with the advent of calcitonin gene-related peptide (CGRP)–targeted medications. Although many patients improve after their first injection, and there is even a significant portion of "super responders" who can revert to nearly zero headache days per month, the majority of patients have a moderate response. Many patients who have not had a significant decrease in the frequency and severity of migraine attacks over 12 weeks wonder whether they will eventually achieve this on a CGRP medication. Barbanti and colleagues looked specifically at the subpopulation of late responders to CGRP treatments.

This was a multicenter, prospective study lasting 24 weeks, defining the differences in responders to CGRP treatments. Participants in this study had failed three or more prior preventive medications and had high-frequency, episodic, or chronic migraine. Their response rate was determined as follows: "responder" patients had a more than 50% reduction in baseline monthly migraine days between weeks 9 and 12, and "late responder" patients achieved that reduction after 12 weeks. All three injectable CGRP monoclonal antibodies were included in this trial.

Nearly 66% of patients treated with a CGRP monoclonal antibody had a 50% or greater response at 12 weeks. Of the study participants, 34% were considered nonresponders at 12 weeks, and 55% of those nonresponders did become responders between 13 and 24 weeks. This subpopulation of late responders was noted to have higher body mass index (BMI), more frequent prior treatment failures, as well as other pain and psychiatric comorbidities. Allodynia and unilateral cranial autonomic symptoms were also noted to be significantly higher in this population.

This study helps better determine the length of a CGRP trial for prevention. Patients with more treatment failures and comorbidities should be given additional time for this class of medications to work, even beyond the initial 12 weeks.

The COVID-19 pandemic has changed the way of life for everyone, and this is especially true for people with chronic medical conditions. Hrytsenko and colleagues sought to quantify the effect that COVID-19 had on patients with a history of episodic or chronic migraine. They used a scale to determine "psycho-emotional state deterioration" in patients with migraine with and without a history of COVID-19.

The investigators included 133 participants with a prior diagnosis of migraine, either chronic or episodic. Of these, 95 had a positive polymerase chain reaction (PCR) test for COVID-19, indicating SARS-CoV-2 infection; 38 did not. The Hamilton Anxiety Rating Scale (HARS) was used to assess the severity of perceived anxiety symptoms and was used to determine psycho-emotional state. The Migraine Disability Assessment test (MIDAS) was used to determine their quality of life and degree of disability related to migraine. Patients with a history of COVID-19 had an increased usage of antimigraine medications, increased frequency of attacks, and higher HARS ratings. The average MIDAS score also increased significantly.

Many of our patients who were struggling prior to the COVID-19 pandemic unfortunately have done much worse after SARS-CoV-2 infection. A number of potential explanations exist for this, including worsening neuroinflammation in the context of COVID-19, which can specifically increase the propagation of inflammatory neurotransmitters, such as CGRP. Patients with a history of migraine respond to this with heightened frequency and severity of migraine.

There is a notable growing connection between certain neurologic conditions and vasomotor symptoms. Specifically, there appears to be an increased incidence of migraine and certain hypertensive or tachycardic conditions. Migraine is well known to be a vascular risk factor and migraine with aura even more so. Faubion and colleagues sought to quantify this in a specific menopausal population.

This was a large cross-sectional study, with an older median age compared with average migraine studies: 52.8 years. Nearly 60% of participants were postmenopausal and were recruited from a Mayo Clinic menopause registry. Participants were evaluated for a history of migraine based on The International Classification of Headache Disorders, third edition (ICHD3), criteria. They also had their symptoms measured on a menopause rating scale (the symptoms measured included hot flashes, sleep problems, physical and mental exhaustion, joint and muscular discomfort, and mood). Additional information was cross-referenced, including BMI, race, ethnicity, education, marital status, hypertension, and menopause status.

A diagnosis of migraine was associated with hypertension. There was no association between hypertension and hot flash severity, and there was a suggestion that hot flash severity and migraine history were not associated. The presence of other pain disorders also did not correlate with any other vasomotor symptoms.

This study does again link vasomotor issues with migraines. This connection remains well-founded and relevant. Antihypertensive medications have been some of the first preventive options ever offered to people with migraine. CGRP medications may actually lead to an increase in the risk for hypertension. Disconnection remains relevant and is something to discuss with patients with migraine, especially if they are at a higher risk.

The field of headache medicine has changed significantly since 2018 with the advent of calcitonin gene-related peptide (CGRP)–targeted medications. Although many patients improve after their first injection, and there is even a significant portion of "super responders" who can revert to nearly zero headache days per month, the majority of patients have a moderate response. Many patients who have not had a significant decrease in the frequency and severity of migraine attacks over 12 weeks wonder whether they will eventually achieve this on a CGRP medication. Barbanti and colleagues looked specifically at the subpopulation of late responders to CGRP treatments.

This was a multicenter, prospective study lasting 24 weeks, defining the differences in responders to CGRP treatments. Participants in this study had failed three or more prior preventive medications and had high-frequency, episodic, or chronic migraine. Their response rate was determined as follows: "responder" patients had a more than 50% reduction in baseline monthly migraine days between weeks 9 and 12, and "late responder" patients achieved that reduction after 12 weeks. All three injectable CGRP monoclonal antibodies were included in this trial.

Nearly 66% of patients treated with a CGRP monoclonal antibody had a 50% or greater response at 12 weeks. Of the study participants, 34% were considered nonresponders at 12 weeks, and 55% of those nonresponders did become responders between 13 and 24 weeks. This subpopulation of late responders was noted to have higher body mass index (BMI), more frequent prior treatment failures, as well as other pain and psychiatric comorbidities. Allodynia and unilateral cranial autonomic symptoms were also noted to be significantly higher in this population.

This study helps better determine the length of a CGRP trial for prevention. Patients with more treatment failures and comorbidities should be given additional time for this class of medications to work, even beyond the initial 12 weeks.

The COVID-19 pandemic has changed the way of life for everyone, and this is especially true for people with chronic medical conditions. Hrytsenko and colleagues sought to quantify the effect that COVID-19 had on patients with a history of episodic or chronic migraine. They used a scale to determine "psycho-emotional state deterioration" in patients with migraine with and without a history of COVID-19.

The investigators included 133 participants with a prior diagnosis of migraine, either chronic or episodic. Of these, 95 had a positive polymerase chain reaction (PCR) test for COVID-19, indicating SARS-CoV-2 infection; 38 did not. The Hamilton Anxiety Rating Scale (HARS) was used to assess the severity of perceived anxiety symptoms and was used to determine psycho-emotional state. The Migraine Disability Assessment test (MIDAS) was used to determine their quality of life and degree of disability related to migraine. Patients with a history of COVID-19 had an increased usage of antimigraine medications, increased frequency of attacks, and higher HARS ratings. The average MIDAS score also increased significantly.

Many of our patients who were struggling prior to the COVID-19 pandemic unfortunately have done much worse after SARS-CoV-2 infection. A number of potential explanations exist for this, including worsening neuroinflammation in the context of COVID-19, which can specifically increase the propagation of inflammatory neurotransmitters, such as CGRP. Patients with a history of migraine respond to this with heightened frequency and severity of migraine.

There is a notable growing connection between certain neurologic conditions and vasomotor symptoms. Specifically, there appears to be an increased incidence of migraine and certain hypertensive or tachycardic conditions. Migraine is well known to be a vascular risk factor and migraine with aura even more so. Faubion and colleagues sought to quantify this in a specific menopausal population.

This was a large cross-sectional study, with an older median age compared with average migraine studies: 52.8 years. Nearly 60% of participants were postmenopausal and were recruited from a Mayo Clinic menopause registry. Participants were evaluated for a history of migraine based on The International Classification of Headache Disorders, third edition (ICHD3), criteria. They also had their symptoms measured on a menopause rating scale (the symptoms measured included hot flashes, sleep problems, physical and mental exhaustion, joint and muscular discomfort, and mood). Additional information was cross-referenced, including BMI, race, ethnicity, education, marital status, hypertension, and menopause status.

A diagnosis of migraine was associated with hypertension. There was no association between hypertension and hot flash severity, and there was a suggestion that hot flash severity and migraine history were not associated. The presence of other pain disorders also did not correlate with any other vasomotor symptoms.

This study does again link vasomotor issues with migraines. This connection remains well-founded and relevant. Antihypertensive medications have been some of the first preventive options ever offered to people with migraine. CGRP medications may actually lead to an increase in the risk for hypertension. Disconnection remains relevant and is something to discuss with patients with migraine, especially if they are at a higher risk.

The field of headache medicine has changed significantly since 2018 with the advent of calcitonin gene-related peptide (CGRP)–targeted medications. Although many patients improve after their first injection, and there is even a significant portion of "super responders" who can revert to nearly zero headache days per month, the majority of patients have a moderate response. Many patients who have not had a significant decrease in the frequency and severity of migraine attacks over 12 weeks wonder whether they will eventually achieve this on a CGRP medication. Barbanti and colleagues looked specifically at the subpopulation of late responders to CGRP treatments.

This was a multicenter, prospective study lasting 24 weeks, defining the differences in responders to CGRP treatments. Participants in this study had failed three or more prior preventive medications and had high-frequency, episodic, or chronic migraine. Their response rate was determined as follows: "responder" patients had a more than 50% reduction in baseline monthly migraine days between weeks 9 and 12, and "late responder" patients achieved that reduction after 12 weeks. All three injectable CGRP monoclonal antibodies were included in this trial.

Nearly 66% of patients treated with a CGRP monoclonal antibody had a 50% or greater response at 12 weeks. Of the study participants, 34% were considered nonresponders at 12 weeks, and 55% of those nonresponders did become responders between 13 and 24 weeks. This subpopulation of late responders was noted to have higher body mass index (BMI), more frequent prior treatment failures, as well as other pain and psychiatric comorbidities. Allodynia and unilateral cranial autonomic symptoms were also noted to be significantly higher in this population.

This study helps better determine the length of a CGRP trial for prevention. Patients with more treatment failures and comorbidities should be given additional time for this class of medications to work, even beyond the initial 12 weeks.

The COVID-19 pandemic has changed the way of life for everyone, and this is especially true for people with chronic medical conditions. Hrytsenko and colleagues sought to quantify the effect that COVID-19 had on patients with a history of episodic or chronic migraine. They used a scale to determine "psycho-emotional state deterioration" in patients with migraine with and without a history of COVID-19.

The investigators included 133 participants with a prior diagnosis of migraine, either chronic or episodic. Of these, 95 had a positive polymerase chain reaction (PCR) test for COVID-19, indicating SARS-CoV-2 infection; 38 did not. The Hamilton Anxiety Rating Scale (HARS) was used to assess the severity of perceived anxiety symptoms and was used to determine psycho-emotional state. The Migraine Disability Assessment test (MIDAS) was used to determine their quality of life and degree of disability related to migraine. Patients with a history of COVID-19 had an increased usage of antimigraine medications, increased frequency of attacks, and higher HARS ratings. The average MIDAS score also increased significantly.

Many of our patients who were struggling prior to the COVID-19 pandemic unfortunately have done much worse after SARS-CoV-2 infection. A number of potential explanations exist for this, including worsening neuroinflammation in the context of COVID-19, which can specifically increase the propagation of inflammatory neurotransmitters, such as CGRP. Patients with a history of migraine respond to this with heightened frequency and severity of migraine.

There is a notable growing connection between certain neurologic conditions and vasomotor symptoms. Specifically, there appears to be an increased incidence of migraine and certain hypertensive or tachycardic conditions. Migraine is well known to be a vascular risk factor and migraine with aura even more so. Faubion and colleagues sought to quantify this in a specific menopausal population.

This was a large cross-sectional study, with an older median age compared with average migraine studies: 52.8 years. Nearly 60% of participants were postmenopausal and were recruited from a Mayo Clinic menopause registry. Participants were evaluated for a history of migraine based on The International Classification of Headache Disorders, third edition (ICHD3), criteria. They also had their symptoms measured on a menopause rating scale (the symptoms measured included hot flashes, sleep problems, physical and mental exhaustion, joint and muscular discomfort, and mood). Additional information was cross-referenced, including BMI, race, ethnicity, education, marital status, hypertension, and menopause status.

A diagnosis of migraine was associated with hypertension. There was no association between hypertension and hot flash severity, and there was a suggestion that hot flash severity and migraine history were not associated. The presence of other pain disorders also did not correlate with any other vasomotor symptoms.

This study does again link vasomotor issues with migraines. This connection remains well-founded and relevant. Antihypertensive medications have been some of the first preventive options ever offered to people with migraine. CGRP medications may actually lead to an increase in the risk for hypertension. Disconnection remains relevant and is something to discuss with patients with migraine, especially if they are at a higher risk.

What is your experience with prescribing preventive medication for your patients with migraine?

Roughly 40% of patients living with migraine should be on preventive medication or other treatment, but probably fewer than 15% of patients with migraine are currently receiving therapy. There are several reasons for this: General physicians rarely put patients on preventive medication unless they are interested in or knowledgeable about headache, and the older preventive medicines that neurologists and headache specialists have used for many years have a lot of potential side effects and do not begin to work quickly.

It takes approximately 2 to 3 months for preventive medication to become effective, and many patients need to be slowly titrated up to an effective dose. By the time patients reach a steady state over a few weeks, if it is still not working well, they must slowly taper it and try something else. This is  what often occurs with older preventive migraine medications—especially one of the most commonly used preventives, topiramate (Topamax). This drug was first indicated for epilepsy and then later for mood stabilization. Though it has good efficacy in reducing migraine attacks, it has many possible side effects, some of them troublesome. I often had multiple calls from patients in their first month of taking it complain of memory or word-finding issues and tingling in the extremities. More serious adverse events can be increased pressure in the eyes, such as glaucoma, and kidney stones. I often get referrals from other neurologists and headache specialists regarding patients who have failed multiple preventive medicines; 90% percent of these referrals need to be switched to the newer, more costly calcitonin gene-related peptide (CGRP)-blocking preventative medications, if insurance companies will cover them. 

What categories of migraine preventive drugs do you generally prescribe your patients?

Of the older medications, most are epilepsy medicines, beta blockers, antidepressants, or cardiac medications such as angiotensin receptor blockers (candesartan). Of the newer medications, I use 1 of the 4 injectable monoclonal antibodies (mAbs), or 1 of the 2 gepants.

Older migraine preventive medication

Anticonvulsants (epilepsy medications)

Anticonvulsants are used for the treatment of several conditions, including epilepsy and pain control, but some can help reduce migraine attacks. These medicines, like all drugs, have the potential to cause side effects, especially topiramate; this medicine often causes paresthesia or tingling in the extremities as well as trouble with speech and memory, kidney stones, pancreatitis, and weight loss. The weight loss side effect of this drug has made it more appealing for some patients who had previously gained 10 to 15 pounds taking antidepressant medication to treat their migraine. I personally thought it was the most effective of all the preventive migraine medications if the patient could tolerate it.

Beta Blockers

Beta blockers cause the heart rate to decrease and also lower blood pressure. Most of my migraine patients are healthy females in their 20s and 30s and, when taking a beta blocker, can get short of breath when they exercise. These medications can also cause some depression and gastrointestinal issues and raise cholesterol levels.

Antidepressants

The type of antidepressants that I normally prescribe for migraine prevention are the tricyclic antidepressants. The one that has the best data in the literature and is often prescribed is amitriptyline (Elavil); I prefer a cousin to this medicine, nortriptyline. I prescribe tricyclics because many of my migraine patients have 2 other comorbid problems: depression and trouble staying asleep at night. Amitriptyline tends to cause drowsiness and can help patients sleep. It can also cause dry mouth, trouble urinating (especially in men), constipation, weight gain, and can slow patients down mentally, so it should not be prescribed to elderly patients. These antidepressants should be prescribed in very low doses and taken an hour before bedtime. The dose should be increased gradually over several weeks to help reduce adverse events. The best dose for migraine is often lower than the antidepressant dose, so sometimes a depressed patient needs 2 types of antidepressants. The typical dose for migraine prevention is about 50 to 75 mg. For depression, it is about 150 mg.

The patient would then need to increase their dose gradually for a month and remain on the target dose for at least another month. At the end of 2 months, they would have some idea whether it was working for them. If it was not, I might increase the dose even further. It is important to set expectations with patients at the beginning of treatment and tell them it is going to take 2 to 3 months to see if it works.  If it does not work, I tell them, we will have to try another one, and that is going to take 2 or 3 months as well, until we can switch to the newer medications, which start to work in the first month, often in the first few days. 

Why wouldn’t we just start with the newer preventives? Insurance companies require patients to fail, on average, 2 categories of the older medications before they will pay for the newer ones. Medicare usually only covers the older generic medications.

New migraine preventive medications

Monoclonal Antibodies

mAbs that block CGRP for the prevention of migraine, such as erenumab, fremanezumab, galcanezumab, and eptinezumab, target either the CGRP ligand itself or block the receptor to CGRP. This class of medication became available about 5 years ago. The first one approved was erenumab (Aimovig). It was tried by a lot of headache specialists, many neurologists, and then some general physicians once it came to market. It is the only one in its class that grabs the ligand CGRP and prevents it from docking on its receptor. Recently, 5-year safety data indicated it is extremely safe with only a few side effects, (it has been shown to cause some constipation and hypertension). It does, however, tend to lower the number of migraine days per month by about 40% to 50%. At the beginning of erenumab’s availability, researchers took patients that had 8 to 22 days of migraine per month and put them in double-blind, placebo-controlled, randomized trials. They found that some patients' migraine days went down gradually to 10 to 12 days from 20 migraine days per month. Erenumab works quickly, and most patients improve within 2 weeks.

Fremanezumab (AJOVY™) was the second mAb approved, followed pretty quickly by the third, galcanezumab (Emgality™). All 3 of these mAbs are administered once a month by a subcutaneous injection from an autoinjector. If a patient takes 3 fremanezumab injections in 1 day, they do not have to repeat that dose for 3 months. The upside of these 3 treatments is that the patient can self-administer the medication at home with few, if any, adverse events; the downside is they are expensive medications, costing about $600 per month. 

Shortly thereafter, a fourth mAb, eptinezumab (VYEPTI™), was brought to market. Unlike the other 3 mAbs, it is administered as an intravenous infusion. The patient must come to an office or infusion center for a 30-minute intravenous infusion, which is not as convenient as treating themselves with an autoinjector at home. Eptinezumab is a strong medication that is often prescribed when other treatments are not effective. Each of the 4 mAbs has its own possible adverse events, but these are few and usually mild. The mAbs have a half-life of about 28 to 32 days; it takes 5 to 6 months after an injection for these mAbs to be metabolized by the reticuloendothelial system. 

Gepants

The gepants are small molecule CGRP receptor blockers with much shorter half-lives than mAbs. They work by blocking the CGRP receptor so the CGRP ligand cannot dock there and cause vasodilation and increased pain transmission. Gepants have half-lives of 6 to 12 hours and can be used to treat a migraine acutely. Several drug companies studied the effects of taking a gepant every day or every other day, showing it can also be used as a migraine preventive medication. Ubrogepant (Ubrelvy®) was the first gepant to receive approval from the US Food and Drug Administration (FDA), but it was authorized only for acute care. Rimegepant (Nurtec®) was the second gepant approved, initially for acute treatment and later becoming the first gepant approved for migraine prevention. The same tablet can be used for acute care or for prevention. Preventive treatment consists of one 75 mg oral disintegrating tablet taken every second day. It works quite well as a preventive and has very few side effects. Nausea and abdominal discomfort occur in < 3% of patients. Some patients prefer to take a pill every other day over having an injection once per month or once every 3 months. It makes more sense for a woman of childbearing potential to take a drug with very short half-life vs one that lasts for 5 to 6 months in case she decides to become pregnant (or unexpectedly becomes pregnant).

A third gepant, atogepant (Qulipta™), was later approved, but only for prevention. It is available in 3 different strengths: 10 mg, 30 mg, and 60 mg. I tend to prescribe the 60-mg strength, and the dose is 1 pill every day. 

If you compare rimegepant, which is taken once every other day, and atogepant, taken once daily, the latter tends to have slightly more side effects of nausea, drowsiness, and constipation, whereas rimegepant has been shown to have fewer side effects in double-blind, randomized studies. Like all gepants, it is quite effective and fast acting. 

The goal of preventive medications is to decrease the frequency, severity, and duration of migraine attacks. Effective treatment can increase responsiveness to acute migraine therapy and improve the quality of life in patients suffering from migraine. Every patient is different and thus the side effects they experience vary. With time and patience, most patients find the relief from migraine they have been desperately seeking through the preventive medicines discussed above. This is a good time to have migraine, if you can get in to see a knowledgeable doctor and your insurance company cooperates. When I started my neurology practice 51 years ago, we had few preventives, and none approved by the FDA. Now we have several older, approved preventives—4 newer mAbs, and 2 newer gepants—as well as several devices, which we will discuss in the future.

What is your experience with prescribing preventive medication for your patients with migraine?

Roughly 40% of patients living with migraine should be on preventive medication or other treatment, but probably fewer than 15% of patients with migraine are currently receiving therapy. There are several reasons for this: General physicians rarely put patients on preventive medication unless they are interested in or knowledgeable about headache, and the older preventive medicines that neurologists and headache specialists have used for many years have a lot of potential side effects and do not begin to work quickly.

It takes approximately 2 to 3 months for preventive medication to become effective, and many patients need to be slowly titrated up to an effective dose. By the time patients reach a steady state over a few weeks, if it is still not working well, they must slowly taper it and try something else. This is  what often occurs with older preventive migraine medications—especially one of the most commonly used preventives, topiramate (Topamax). This drug was first indicated for epilepsy and then later for mood stabilization. Though it has good efficacy in reducing migraine attacks, it has many possible side effects, some of them troublesome. I often had multiple calls from patients in their first month of taking it complain of memory or word-finding issues and tingling in the extremities. More serious adverse events can be increased pressure in the eyes, such as glaucoma, and kidney stones. I often get referrals from other neurologists and headache specialists regarding patients who have failed multiple preventive medicines; 90% percent of these referrals need to be switched to the newer, more costly calcitonin gene-related peptide (CGRP)-blocking preventative medications, if insurance companies will cover them. 

What categories of migraine preventive drugs do you generally prescribe your patients?

Of the older medications, most are epilepsy medicines, beta blockers, antidepressants, or cardiac medications such as angiotensin receptor blockers (candesartan). Of the newer medications, I use 1 of the 4 injectable monoclonal antibodies (mAbs), or 1 of the 2 gepants.

Older migraine preventive medication

Anticonvulsants (epilepsy medications)

Anticonvulsants are used for the treatment of several conditions, including epilepsy and pain control, but some can help reduce migraine attacks. These medicines, like all drugs, have the potential to cause side effects, especially topiramate; this medicine often causes paresthesia or tingling in the extremities as well as trouble with speech and memory, kidney stones, pancreatitis, and weight loss. The weight loss side effect of this drug has made it more appealing for some patients who had previously gained 10 to 15 pounds taking antidepressant medication to treat their migraine. I personally thought it was the most effective of all the preventive migraine medications if the patient could tolerate it.

Beta Blockers

Beta blockers cause the heart rate to decrease and also lower blood pressure. Most of my migraine patients are healthy females in their 20s and 30s and, when taking a beta blocker, can get short of breath when they exercise. These medications can also cause some depression and gastrointestinal issues and raise cholesterol levels.

Antidepressants

The type of antidepressants that I normally prescribe for migraine prevention are the tricyclic antidepressants. The one that has the best data in the literature and is often prescribed is amitriptyline (Elavil); I prefer a cousin to this medicine, nortriptyline. I prescribe tricyclics because many of my migraine patients have 2 other comorbid problems: depression and trouble staying asleep at night. Amitriptyline tends to cause drowsiness and can help patients sleep. It can also cause dry mouth, trouble urinating (especially in men), constipation, weight gain, and can slow patients down mentally, so it should not be prescribed to elderly patients. These antidepressants should be prescribed in very low doses and taken an hour before bedtime. The dose should be increased gradually over several weeks to help reduce adverse events. The best dose for migraine is often lower than the antidepressant dose, so sometimes a depressed patient needs 2 types of antidepressants. The typical dose for migraine prevention is about 50 to 75 mg. For depression, it is about 150 mg.

The patient would then need to increase their dose gradually for a month and remain on the target dose for at least another month. At the end of 2 months, they would have some idea whether it was working for them. If it was not, I might increase the dose even further. It is important to set expectations with patients at the beginning of treatment and tell them it is going to take 2 to 3 months to see if it works.  If it does not work, I tell them, we will have to try another one, and that is going to take 2 or 3 months as well, until we can switch to the newer medications, which start to work in the first month, often in the first few days. 

Why wouldn’t we just start with the newer preventives? Insurance companies require patients to fail, on average, 2 categories of the older medications before they will pay for the newer ones. Medicare usually only covers the older generic medications.

New migraine preventive medications

Monoclonal Antibodies

mAbs that block CGRP for the prevention of migraine, such as erenumab, fremanezumab, galcanezumab, and eptinezumab, target either the CGRP ligand itself or block the receptor to CGRP. This class of medication became available about 5 years ago. The first one approved was erenumab (Aimovig). It was tried by a lot of headache specialists, many neurologists, and then some general physicians once it came to market. It is the only one in its class that grabs the ligand CGRP and prevents it from docking on its receptor. Recently, 5-year safety data indicated it is extremely safe with only a few side effects, (it has been shown to cause some constipation and hypertension). It does, however, tend to lower the number of migraine days per month by about 40% to 50%. At the beginning of erenumab’s availability, researchers took patients that had 8 to 22 days of migraine per month and put them in double-blind, placebo-controlled, randomized trials. They found that some patients' migraine days went down gradually to 10 to 12 days from 20 migraine days per month. Erenumab works quickly, and most patients improve within 2 weeks.

Fremanezumab (AJOVY™) was the second mAb approved, followed pretty quickly by the third, galcanezumab (Emgality™). All 3 of these mAbs are administered once a month by a subcutaneous injection from an autoinjector. If a patient takes 3 fremanezumab injections in 1 day, they do not have to repeat that dose for 3 months. The upside of these 3 treatments is that the patient can self-administer the medication at home with few, if any, adverse events; the downside is they are expensive medications, costing about $600 per month. 

Shortly thereafter, a fourth mAb, eptinezumab (VYEPTI™), was brought to market. Unlike the other 3 mAbs, it is administered as an intravenous infusion. The patient must come to an office or infusion center for a 30-minute intravenous infusion, which is not as convenient as treating themselves with an autoinjector at home. Eptinezumab is a strong medication that is often prescribed when other treatments are not effective. Each of the 4 mAbs has its own possible adverse events, but these are few and usually mild. The mAbs have a half-life of about 28 to 32 days; it takes 5 to 6 months after an injection for these mAbs to be metabolized by the reticuloendothelial system. 

Gepants

The gepants are small molecule CGRP receptor blockers with much shorter half-lives than mAbs. They work by blocking the CGRP receptor so the CGRP ligand cannot dock there and cause vasodilation and increased pain transmission. Gepants have half-lives of 6 to 12 hours and can be used to treat a migraine acutely. Several drug companies studied the effects of taking a gepant every day or every other day, showing it can also be used as a migraine preventive medication. Ubrogepant (Ubrelvy®) was the first gepant to receive approval from the US Food and Drug Administration (FDA), but it was authorized only for acute care. Rimegepant (Nurtec®) was the second gepant approved, initially for acute treatment and later becoming the first gepant approved for migraine prevention. The same tablet can be used for acute care or for prevention. Preventive treatment consists of one 75 mg oral disintegrating tablet taken every second day. It works quite well as a preventive and has very few side effects. Nausea and abdominal discomfort occur in < 3% of patients. Some patients prefer to take a pill every other day over having an injection once per month or once every 3 months. It makes more sense for a woman of childbearing potential to take a drug with very short half-life vs one that lasts for 5 to 6 months in case she decides to become pregnant (or unexpectedly becomes pregnant).

A third gepant, atogepant (Qulipta™), was later approved, but only for prevention. It is available in 3 different strengths: 10 mg, 30 mg, and 60 mg. I tend to prescribe the 60-mg strength, and the dose is 1 pill every day. 

If you compare rimegepant, which is taken once every other day, and atogepant, taken once daily, the latter tends to have slightly more side effects of nausea, drowsiness, and constipation, whereas rimegepant has been shown to have fewer side effects in double-blind, randomized studies. Like all gepants, it is quite effective and fast acting. 

The goal of preventive medications is to decrease the frequency, severity, and duration of migraine attacks. Effective treatment can increase responsiveness to acute migraine therapy and improve the quality of life in patients suffering from migraine. Every patient is different and thus the side effects they experience vary. With time and patience, most patients find the relief from migraine they have been desperately seeking through the preventive medicines discussed above. This is a good time to have migraine, if you can get in to see a knowledgeable doctor and your insurance company cooperates. When I started my neurology practice 51 years ago, we had few preventives, and none approved by the FDA. Now we have several older, approved preventives—4 newer mAbs, and 2 newer gepants—as well as several devices, which we will discuss in the future.

What is your experience with prescribing preventive medication for your patients with migraine?

Roughly 40% of patients living with migraine should be on preventive medication or other treatment, but probably fewer than 15% of patients with migraine are currently receiving therapy. There are several reasons for this: General physicians rarely put patients on preventive medication unless they are interested in or knowledgeable about headache, and the older preventive medicines that neurologists and headache specialists have used for many years have a lot of potential side effects and do not begin to work quickly.

It takes approximately 2 to 3 months for preventive medication to become effective, and many patients need to be slowly titrated up to an effective dose. By the time patients reach a steady state over a few weeks, if it is still not working well, they must slowly taper it and try something else. This is  what often occurs with older preventive migraine medications—especially one of the most commonly used preventives, topiramate (Topamax). This drug was first indicated for epilepsy and then later for mood stabilization. Though it has good efficacy in reducing migraine attacks, it has many possible side effects, some of them troublesome. I often had multiple calls from patients in their first month of taking it complain of memory or word-finding issues and tingling in the extremities. More serious adverse events can be increased pressure in the eyes, such as glaucoma, and kidney stones. I often get referrals from other neurologists and headache specialists regarding patients who have failed multiple preventive medicines; 90% percent of these referrals need to be switched to the newer, more costly calcitonin gene-related peptide (CGRP)-blocking preventative medications, if insurance companies will cover them. 

What categories of migraine preventive drugs do you generally prescribe your patients?

Of the older medications, most are epilepsy medicines, beta blockers, antidepressants, or cardiac medications such as angiotensin receptor blockers (candesartan). Of the newer medications, I use 1 of the 4 injectable monoclonal antibodies (mAbs), or 1 of the 2 gepants.

Older migraine preventive medication

Anticonvulsants (epilepsy medications)

Anticonvulsants are used for the treatment of several conditions, including epilepsy and pain control, but some can help reduce migraine attacks. These medicines, like all drugs, have the potential to cause side effects, especially topiramate; this medicine often causes paresthesia or tingling in the extremities as well as trouble with speech and memory, kidney stones, pancreatitis, and weight loss. The weight loss side effect of this drug has made it more appealing for some patients who had previously gained 10 to 15 pounds taking antidepressant medication to treat their migraine. I personally thought it was the most effective of all the preventive migraine medications if the patient could tolerate it.

Beta Blockers

Beta blockers cause the heart rate to decrease and also lower blood pressure. Most of my migraine patients are healthy females in their 20s and 30s and, when taking a beta blocker, can get short of breath when they exercise. These medications can also cause some depression and gastrointestinal issues and raise cholesterol levels.

Antidepressants

The type of antidepressants that I normally prescribe for migraine prevention are the tricyclic antidepressants. The one that has the best data in the literature and is often prescribed is amitriptyline (Elavil); I prefer a cousin to this medicine, nortriptyline. I prescribe tricyclics because many of my migraine patients have 2 other comorbid problems: depression and trouble staying asleep at night. Amitriptyline tends to cause drowsiness and can help patients sleep. It can also cause dry mouth, trouble urinating (especially in men), constipation, weight gain, and can slow patients down mentally, so it should not be prescribed to elderly patients. These antidepressants should be prescribed in very low doses and taken an hour before bedtime. The dose should be increased gradually over several weeks to help reduce adverse events. The best dose for migraine is often lower than the antidepressant dose, so sometimes a depressed patient needs 2 types of antidepressants. The typical dose for migraine prevention is about 50 to 75 mg. For depression, it is about 150 mg.

The patient would then need to increase their dose gradually for a month and remain on the target dose for at least another month. At the end of 2 months, they would have some idea whether it was working for them. If it was not, I might increase the dose even further. It is important to set expectations with patients at the beginning of treatment and tell them it is going to take 2 to 3 months to see if it works.  If it does not work, I tell them, we will have to try another one, and that is going to take 2 or 3 months as well, until we can switch to the newer medications, which start to work in the first month, often in the first few days. 

Why wouldn’t we just start with the newer preventives? Insurance companies require patients to fail, on average, 2 categories of the older medications before they will pay for the newer ones. Medicare usually only covers the older generic medications.

New migraine preventive medications

Monoclonal Antibodies

mAbs that block CGRP for the prevention of migraine, such as erenumab, fremanezumab, galcanezumab, and eptinezumab, target either the CGRP ligand itself or block the receptor to CGRP. This class of medication became available about 5 years ago. The first one approved was erenumab (Aimovig). It was tried by a lot of headache specialists, many neurologists, and then some general physicians once it came to market. It is the only one in its class that grabs the ligand CGRP and prevents it from docking on its receptor. Recently, 5-year safety data indicated it is extremely safe with only a few side effects, (it has been shown to cause some constipation and hypertension). It does, however, tend to lower the number of migraine days per month by about 40% to 50%. At the beginning of erenumab’s availability, researchers took patients that had 8 to 22 days of migraine per month and put them in double-blind, placebo-controlled, randomized trials. They found that some patients' migraine days went down gradually to 10 to 12 days from 20 migraine days per month. Erenumab works quickly, and most patients improve within 2 weeks.

Fremanezumab (AJOVY™) was the second mAb approved, followed pretty quickly by the third, galcanezumab (Emgality™). All 3 of these mAbs are administered once a month by a subcutaneous injection from an autoinjector. If a patient takes 3 fremanezumab injections in 1 day, they do not have to repeat that dose for 3 months. The upside of these 3 treatments is that the patient can self-administer the medication at home with few, if any, adverse events; the downside is they are expensive medications, costing about $600 per month. 

Shortly thereafter, a fourth mAb, eptinezumab (VYEPTI™), was brought to market. Unlike the other 3 mAbs, it is administered as an intravenous infusion. The patient must come to an office or infusion center for a 30-minute intravenous infusion, which is not as convenient as treating themselves with an autoinjector at home. Eptinezumab is a strong medication that is often prescribed when other treatments are not effective. Each of the 4 mAbs has its own possible adverse events, but these are few and usually mild. The mAbs have a half-life of about 28 to 32 days; it takes 5 to 6 months after an injection for these mAbs to be metabolized by the reticuloendothelial system. 

Gepants

The gepants are small molecule CGRP receptor blockers with much shorter half-lives than mAbs. They work by blocking the CGRP receptor so the CGRP ligand cannot dock there and cause vasodilation and increased pain transmission. Gepants have half-lives of 6 to 12 hours and can be used to treat a migraine acutely. Several drug companies studied the effects of taking a gepant every day or every other day, showing it can also be used as a migraine preventive medication. Ubrogepant (Ubrelvy®) was the first gepant to receive approval from the US Food and Drug Administration (FDA), but it was authorized only for acute care. Rimegepant (Nurtec®) was the second gepant approved, initially for acute treatment and later becoming the first gepant approved for migraine prevention. The same tablet can be used for acute care or for prevention. Preventive treatment consists of one 75 mg oral disintegrating tablet taken every second day. It works quite well as a preventive and has very few side effects. Nausea and abdominal discomfort occur in < 3% of patients. Some patients prefer to take a pill every other day over having an injection once per month or once every 3 months. It makes more sense for a woman of childbearing potential to take a drug with very short half-life vs one that lasts for 5 to 6 months in case she decides to become pregnant (or unexpectedly becomes pregnant).

A third gepant, atogepant (Qulipta™), was later approved, but only for prevention. It is available in 3 different strengths: 10 mg, 30 mg, and 60 mg. I tend to prescribe the 60-mg strength, and the dose is 1 pill every day. 

If you compare rimegepant, which is taken once every other day, and atogepant, taken once daily, the latter tends to have slightly more side effects of nausea, drowsiness, and constipation, whereas rimegepant has been shown to have fewer side effects in double-blind, randomized studies. Like all gepants, it is quite effective and fast acting. 

The goal of preventive medications is to decrease the frequency, severity, and duration of migraine attacks. Effective treatment can increase responsiveness to acute migraine therapy and improve the quality of life in patients suffering from migraine. Every patient is different and thus the side effects they experience vary. With time and patience, most patients find the relief from migraine they have been desperately seeking through the preventive medicines discussed above. This is a good time to have migraine, if you can get in to see a knowledgeable doctor and your insurance company cooperates. When I started my neurology practice 51 years ago, we had few preventives, and none approved by the FDA. Now we have several older, approved preventives—4 newer mAbs, and 2 newer gepants—as well as several devices, which we will discuss in the future.

Key clinical point: Two months of supplementation with omega-3 fatty acids had favorable effects on inflammatory and anti-inflammatory markers in patients with episodic migraine.

Major finding: After 2 months of treatment, the serum concentration of anti-inflammatory interleukin-4 (IL-4) was significantly increased (P = .010) whereas that of proinflammatory interferon gamma was significantly decreased (P = .001) in the omega-3 supplementation vs placebo group. The serum concentration of transforming growth factor beta or IL-17 was not significantly different between the groups.

Study details: The data come from a randomized controlled trial including 40 patients with episodic migraine who were randomly assigned to receive omega-3 supplementation (2 capsules/day; each capsule containing 600 mg eicosapentaenoic acid and 300 mg docosahexaenoic acid; n = 20) or placebo (paraffin oil capsules; n = 20) for 2 months.

Disclosures: This study did not receive any funding. The authors declared no potential conflicts of interest.

Source: Djalali M et al. The effect of omega-3 fatty acids supplementation on inflammatory biomarkers in subjects with migraine: A randomized, double-blind, placebo-controlled trial. Immunopharmacol Immunotoxicol. 2023 (Apr 26). doi: 10.1080/08923973.2023.2196600

Key clinical point: Two months of supplementation with omega-3 fatty acids had favorable effects on inflammatory and anti-inflammatory markers in patients with episodic migraine.

Major finding: After 2 months of treatment, the serum concentration of anti-inflammatory interleukin-4 (IL-4) was significantly increased (P = .010) whereas that of proinflammatory interferon gamma was significantly decreased (P = .001) in the omega-3 supplementation vs placebo group. The serum concentration of transforming growth factor beta or IL-17 was not significantly different between the groups.

Study details: The data come from a randomized controlled trial including 40 patients with episodic migraine who were randomly assigned to receive omega-3 supplementation (2 capsules/day; each capsule containing 600 mg eicosapentaenoic acid and 300 mg docosahexaenoic acid; n = 20) or placebo (paraffin oil capsules; n = 20) for 2 months.

Disclosures: This study did not receive any funding. The authors declared no potential conflicts of interest.

Source: Djalali M et al. The effect of omega-3 fatty acids supplementation on inflammatory biomarkers in subjects with migraine: A randomized, double-blind, placebo-controlled trial. Immunopharmacol Immunotoxicol. 2023 (Apr 26). doi: 10.1080/08923973.2023.2196600

Key clinical point: Two months of supplementation with omega-3 fatty acids had favorable effects on inflammatory and anti-inflammatory markers in patients with episodic migraine.

Major finding: After 2 months of treatment, the serum concentration of anti-inflammatory interleukin-4 (IL-4) was significantly increased (P = .010) whereas that of proinflammatory interferon gamma was significantly decreased (P = .001) in the omega-3 supplementation vs placebo group. The serum concentration of transforming growth factor beta or IL-17 was not significantly different between the groups.

Study details: The data come from a randomized controlled trial including 40 patients with episodic migraine who were randomly assigned to receive omega-3 supplementation (2 capsules/day; each capsule containing 600 mg eicosapentaenoic acid and 300 mg docosahexaenoic acid; n = 20) or placebo (paraffin oil capsules; n = 20) for 2 months.

Disclosures: This study did not receive any funding. The authors declared no potential conflicts of interest.

Source: Djalali M et al. The effect of omega-3 fatty acids supplementation on inflammatory biomarkers in subjects with migraine: A randomized, double-blind, placebo-controlled trial. Immunopharmacol Immunotoxicol. 2023 (Apr 26). doi: 10.1080/08923973.2023.2196600

Key clinical point: Maternal migraine diagnosis is associated with a higher risk for several childhood cancers in offspring.

Major finding: A significant positive association was observed between maternal migraine and the risk for non-Hodgkin lymphoma (odds ratio [OR] 1.70; 95% CI 1.01-2.86), central nervous system tumors (OR 1.31; 95% CI 1.02-1.68; particularly glioma: OR 1.64; 95% CI 1.12-2.40), neuroblastoma (OR 1.75; 95% CI 1.00-3.08), and osteosarcoma (OR 2.60; 95% CI 1.18-5.76).

Study details: This study included children age < 20 years with cancers (cases) and birth year- and sex-matched (25:1) children without cancers (control individuals).

Disclosures: This study was supported by the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Orimoloye HT et al. Maternal migraine and risk of pediatric cancers. Pediatr Blood Cancer. 2023 (Apr 26). doi: 10.1002/pbc.30385

Key clinical point: Maternal migraine diagnosis is associated with a higher risk for several childhood cancers in offspring.

Major finding: A significant positive association was observed between maternal migraine and the risk for non-Hodgkin lymphoma (odds ratio [OR] 1.70; 95% CI 1.01-2.86), central nervous system tumors (OR 1.31; 95% CI 1.02-1.68; particularly glioma: OR 1.64; 95% CI 1.12-2.40), neuroblastoma (OR 1.75; 95% CI 1.00-3.08), and osteosarcoma (OR 2.60; 95% CI 1.18-5.76).

Study details: This study included children age < 20 years with cancers (cases) and birth year- and sex-matched (25:1) children without cancers (control individuals).

Disclosures: This study was supported by the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Orimoloye HT et al. Maternal migraine and risk of pediatric cancers. Pediatr Blood Cancer. 2023 (Apr 26). doi: 10.1002/pbc.30385

Key clinical point: Maternal migraine diagnosis is associated with a higher risk for several childhood cancers in offspring.

Major finding: A significant positive association was observed between maternal migraine and the risk for non-Hodgkin lymphoma (odds ratio [OR] 1.70; 95% CI 1.01-2.86), central nervous system tumors (OR 1.31; 95% CI 1.02-1.68; particularly glioma: OR 1.64; 95% CI 1.12-2.40), neuroblastoma (OR 1.75; 95% CI 1.00-3.08), and osteosarcoma (OR 2.60; 95% CI 1.18-5.76).

Study details: This study included children age < 20 years with cancers (cases) and birth year- and sex-matched (25:1) children without cancers (control individuals).

Disclosures: This study was supported by the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Orimoloye HT et al. Maternal migraine and risk of pediatric cancers. Pediatr Blood Cancer. 2023 (Apr 26). doi: 10.1002/pbc.30385

Key clinical point: This meta-analysis demonstrated a significant bidirectional association between psoriasis and migraine, with greater severity of psoriasis being associated with an increasingly higher risk of developing migraine.

Major finding: Presence vs absence of psoriasis was associated with 1.69-fold higher odds of prevalent migraine (pooled odds ratio [OR] 1.69; 95% CI 1.26-2.28), with the risk for incident migraine being significantly higher in patients with mild (incidence rate ratio [IRR] 1.37; 95% CI 1.30-1.44) and severe (IRR 1.55; 95% CI 1.29-1.86) psoriasis and psoriatic arthritis (IRR 1.92; 95% CI 1.65-2.23). Moreover, presence vs absence of migraine was associated with 1.88-fold higher odds of prevalent psoriasis (OR 1.88; 95% CI 1.32-3.67).

Study details: Findings are from a systematic review and meta-analysis of 10 studies including 6,745,968 participants.

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

Source: Huang IH et al. Bidirectional associations between psoriasis and migraine: A systematic review and meta-analysis. J Dtsch Dermatol Ges. 2023;21(5):493-502 (Apr 17). doi: 10.1111/ddg.14994

Key clinical point: This meta-analysis demonstrated a significant bidirectional association between psoriasis and migraine, with greater severity of psoriasis being associated with an increasingly higher risk of developing migraine.

Major finding: Presence vs absence of psoriasis was associated with 1.69-fold higher odds of prevalent migraine (pooled odds ratio [OR] 1.69; 95% CI 1.26-2.28), with the risk for incident migraine being significantly higher in patients with mild (incidence rate ratio [IRR] 1.37; 95% CI 1.30-1.44) and severe (IRR 1.55; 95% CI 1.29-1.86) psoriasis and psoriatic arthritis (IRR 1.92; 95% CI 1.65-2.23). Moreover, presence vs absence of migraine was associated with 1.88-fold higher odds of prevalent psoriasis (OR 1.88; 95% CI 1.32-3.67).

Study details: Findings are from a systematic review and meta-analysis of 10 studies including 6,745,968 participants.

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

Source: Huang IH et al. Bidirectional associations between psoriasis and migraine: A systematic review and meta-analysis. J Dtsch Dermatol Ges. 2023;21(5):493-502 (Apr 17). doi: 10.1111/ddg.14994

Key clinical point: This meta-analysis demonstrated a significant bidirectional association between psoriasis and migraine, with greater severity of psoriasis being associated with an increasingly higher risk of developing migraine.

Major finding: Presence vs absence of psoriasis was associated with 1.69-fold higher odds of prevalent migraine (pooled odds ratio [OR] 1.69; 95% CI 1.26-2.28), with the risk for incident migraine being significantly higher in patients with mild (incidence rate ratio [IRR] 1.37; 95% CI 1.30-1.44) and severe (IRR 1.55; 95% CI 1.29-1.86) psoriasis and psoriatic arthritis (IRR 1.92; 95% CI 1.65-2.23). Moreover, presence vs absence of migraine was associated with 1.88-fold higher odds of prevalent psoriasis (OR 1.88; 95% CI 1.32-3.67).

Study details: Findings are from a systematic review and meta-analysis of 10 studies including 6,745,968 participants.

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

Source: Huang IH et al. Bidirectional associations between psoriasis and migraine: A systematic review and meta-analysis. J Dtsch Dermatol Ges. 2023;21(5):493-502 (Apr 17). doi: 10.1111/ddg.14994

Key clinical point: Cross-sectional study confirms a significant association of migraine history with the severity of vasomotor symptoms (VMS) and hypertension in midlife women, potentially helping to identify those at risk for severe menopause symptoms.

Major finding: The likelihood of severe or very severe vs no hot flashes (adjusted odds ratio [aOR] 1.34; P = .007) and risk for hypertension (aOR 1.31; P = .002) were significantly higher among women with vs without a history of migraine.

Study details: Findings are from a cross-sectional study including 5708 women aged between 45 and 60 years, of whom 23.7% had a history of migraine.

Disclosures: This study was partially supported by a grant from the National Institute on Aging. Dr. Kling and Dr. Kapoor declared serving as consultants for various sources.

Source: Faubion SS et al. Association of migraine and vasomotor symptoms. Mayo Clin Proc. 2023;98(5):701-712 (May 1). doi: 10.1016/j.mayocp.2023.01.010.

Key clinical point: Cross-sectional study confirms a significant association of migraine history with the severity of vasomotor symptoms (VMS) and hypertension in midlife women, potentially helping to identify those at risk for severe menopause symptoms.

Major finding: The likelihood of severe or very severe vs no hot flashes (adjusted odds ratio [aOR] 1.34; P = .007) and risk for hypertension (aOR 1.31; P = .002) were significantly higher among women with vs without a history of migraine.

Study details: Findings are from a cross-sectional study including 5708 women aged between 45 and 60 years, of whom 23.7% had a history of migraine.

Disclosures: This study was partially supported by a grant from the National Institute on Aging. Dr. Kling and Dr. Kapoor declared serving as consultants for various sources.

Source: Faubion SS et al. Association of migraine and vasomotor symptoms. Mayo Clin Proc. 2023;98(5):701-712 (May 1). doi: 10.1016/j.mayocp.2023.01.010.

Key clinical point: Cross-sectional study confirms a significant association of migraine history with the severity of vasomotor symptoms (VMS) and hypertension in midlife women, potentially helping to identify those at risk for severe menopause symptoms.

Major finding: The likelihood of severe or very severe vs no hot flashes (adjusted odds ratio [aOR] 1.34; P = .007) and risk for hypertension (aOR 1.31; P = .002) were significantly higher among women with vs without a history of migraine.

Study details: Findings are from a cross-sectional study including 5708 women aged between 45 and 60 years, of whom 23.7% had a history of migraine.

Disclosures: This study was partially supported by a grant from the National Institute on Aging. Dr. Kling and Dr. Kapoor declared serving as consultants for various sources.

Source: Faubion SS et al. Association of migraine and vasomotor symptoms. Mayo Clin Proc. 2023;98(5):701-712 (May 1). doi: 10.1016/j.mayocp.2023.01.010.

Key clinical point: Patients with migraine who recovered from COVID-19 showed an increase in the frequency of headache attacks, level of anxiety, and use of antimigraine drugs.

Major finding: Among patients with migraine, those with vs without a history of COVID-19 showed a significant increase in the frequency of headache attacks (P = .01), level of anxiety (P = .002), and use of antimigraine drugs (P = .04) after recovering from COVID-19, with no significant difference being observed in the headache intensity (P = .51) and the dynamics of the Beck Depression scale score (P = .09).

Study details: Findings are from a retrospective study including 133 patients aged 18-55 years with chronic and episodic migraine and with (n = 95) or without (n = 38) a history of COVID-19.

Disclosures: This study did not receive any funding. The authors declared no potential conflicts of interest.

Source: Hrytsenko O et al. The impact of the COVID-19 pandemic on patients with migraine. SAGE Open Med. 2023 (Apr 28). doi: 10.1177/20503121231170726

Key clinical point: Patients with migraine who recovered from COVID-19 showed an increase in the frequency of headache attacks, level of anxiety, and use of antimigraine drugs.

Major finding: Among patients with migraine, those with vs without a history of COVID-19 showed a significant increase in the frequency of headache attacks (P = .01), level of anxiety (P = .002), and use of antimigraine drugs (P = .04) after recovering from COVID-19, with no significant difference being observed in the headache intensity (P = .51) and the dynamics of the Beck Depression scale score (P = .09).

Study details: Findings are from a retrospective study including 133 patients aged 18-55 years with chronic and episodic migraine and with (n = 95) or without (n = 38) a history of COVID-19.

Disclosures: This study did not receive any funding. The authors declared no potential conflicts of interest.

Source: Hrytsenko O et al. The impact of the COVID-19 pandemic on patients with migraine. SAGE Open Med. 2023 (Apr 28). doi: 10.1177/20503121231170726

Key clinical point: Patients with migraine who recovered from COVID-19 showed an increase in the frequency of headache attacks, level of anxiety, and use of antimigraine drugs.

Major finding: Among patients with migraine, those with vs without a history of COVID-19 showed a significant increase in the frequency of headache attacks (P = .01), level of anxiety (P = .002), and use of antimigraine drugs (P = .04) after recovering from COVID-19, with no significant difference being observed in the headache intensity (P = .51) and the dynamics of the Beck Depression scale score (P = .09).

Study details: Findings are from a retrospective study including 133 patients aged 18-55 years with chronic and episodic migraine and with (n = 95) or without (n = 38) a history of COVID-19.

Disclosures: This study did not receive any funding. The authors declared no potential conflicts of interest.

Source: Hrytsenko O et al. The impact of the COVID-19 pandemic on patients with migraine. SAGE Open Med. 2023 (Apr 28). doi: 10.1177/20503121231170726

Key clinical point: The alpha-calcitonin gene-related peptide (CGRP) level was significantly elevated in patients with chronic migraine (CM) vs control individuals, which eventually normalized after treatment with CGRP monoclonal antibodies (mAb) and correlated with clinical response.

Major finding: The significantly higher alpha-CGRP levels in patients with CM vs control individuals (P = .004) normalized at 2 weeks (median 40.4 pg/mL; 95% CI 35.6-48.1 pg/mL) and 3 months (median 40.9 pg/mL; 95% CI 36.3-45.9 pg/mL) post-treatment with a CGRP mAb. A significant correlation was observed between decrease in monthly migraine days at the third month and absolute decrease in alpha-CGRP content at the same time-point (P = .02).

Study details: The data come from an observational study including 103 patients with CM who initiated treatment with CGRP mAb and 78 matched control individuals.

Disclosures: This study was supported by the Instituto de Salud Carlos III, IDIVAL Spain, and Lilly grant. J Pascual and V González-Quintanilla declared receiving advisory or speaker honoraria from various sources, including Lilly. Other authors declared no conflicts of interest.

Source: Gárate G et al. Serum alpha and beta-CGRP levels in chronic migraine patients before and after monoclonal antibodies against CGRP or its receptor. Ann Neurol. 2023 (Apr 11). doi: 10.1002/ana.26658

Key clinical point: The alpha-calcitonin gene-related peptide (CGRP) level was significantly elevated in patients with chronic migraine (CM) vs control individuals, which eventually normalized after treatment with CGRP monoclonal antibodies (mAb) and correlated with clinical response.

Major finding: The significantly higher alpha-CGRP levels in patients with CM vs control individuals (P = .004) normalized at 2 weeks (median 40.4 pg/mL; 95% CI 35.6-48.1 pg/mL) and 3 months (median 40.9 pg/mL; 95% CI 36.3-45.9 pg/mL) post-treatment with a CGRP mAb. A significant correlation was observed between decrease in monthly migraine days at the third month and absolute decrease in alpha-CGRP content at the same time-point (P = .02).

Study details: The data come from an observational study including 103 patients with CM who initiated treatment with CGRP mAb and 78 matched control individuals.

Disclosures: This study was supported by the Instituto de Salud Carlos III, IDIVAL Spain, and Lilly grant. J Pascual and V González-Quintanilla declared receiving advisory or speaker honoraria from various sources, including Lilly. Other authors declared no conflicts of interest.

Source: Gárate G et al. Serum alpha and beta-CGRP levels in chronic migraine patients before and after monoclonal antibodies against CGRP or its receptor. Ann Neurol. 2023 (Apr 11). doi: 10.1002/ana.26658

Key clinical point: The alpha-calcitonin gene-related peptide (CGRP) level was significantly elevated in patients with chronic migraine (CM) vs control individuals, which eventually normalized after treatment with CGRP monoclonal antibodies (mAb) and correlated with clinical response.

Major finding: The significantly higher alpha-CGRP levels in patients with CM vs control individuals (P = .004) normalized at 2 weeks (median 40.4 pg/mL; 95% CI 35.6-48.1 pg/mL) and 3 months (median 40.9 pg/mL; 95% CI 36.3-45.9 pg/mL) post-treatment with a CGRP mAb. A significant correlation was observed between decrease in monthly migraine days at the third month and absolute decrease in alpha-CGRP content at the same time-point (P = .02).

Study details: The data come from an observational study including 103 patients with CM who initiated treatment with CGRP mAb and 78 matched control individuals.

Disclosures: This study was supported by the Instituto de Salud Carlos III, IDIVAL Spain, and Lilly grant. J Pascual and V González-Quintanilla declared receiving advisory or speaker honoraria from various sources, including Lilly. Other authors declared no conflicts of interest.

Source: Gárate G et al. Serum alpha and beta-CGRP levels in chronic migraine patients before and after monoclonal antibodies against CGRP or its receptor. Ann Neurol. 2023 (Apr 11). doi: 10.1002/ana.26658

Key clinical point: Switching calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) may benefit patients with episodic migraine (EM) or chronic migraine (CM) who had failed to respond to the first CGRP-mAb or experienced a loss of efficacy over time.

Major finding: Overall, 71.9% of patients responded to the first CGRP-mAb, 42.3% of those who did not respond or experienced a loss of efficacy over time to the first CGRP-mAb responded to the second CGRP-mAb, and 28.6% of patients who received the third CGRP-mAb showed a response.

Study details: Findings are from a retrospective, real-world case series including 171 patients with EM or CM who received one (n = 137), two (n = 27), or all three(n = 7) CGRP-mAb as migraine preventive therapy.

Disclosures: This study received no specific funding from any source. Some authors declared receiving personal fees, unrestricted grants, honoraria, or travel grants from various sources.

Source: Kaltseis K et al. Monoclonal antibodies against CGRP (R): Non-responders and switchers: Real world data from an Austrian case series. BMC Neurol. 2023;23(1):174 (Apr 28). doi: 10.1186/s12883-023-03203-9

Key clinical point: Switching calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) may benefit patients with episodic migraine (EM) or chronic migraine (CM) who had failed to respond to the first CGRP-mAb or experienced a loss of efficacy over time.

Major finding: Overall, 71.9% of patients responded to the first CGRP-mAb, 42.3% of those who did not respond or experienced a loss of efficacy over time to the first CGRP-mAb responded to the second CGRP-mAb, and 28.6% of patients who received the third CGRP-mAb showed a response.

Study details: Findings are from a retrospective, real-world case series including 171 patients with EM or CM who received one (n = 137), two (n = 27), or all three(n = 7) CGRP-mAb as migraine preventive therapy.

Disclosures: This study received no specific funding from any source. Some authors declared receiving personal fees, unrestricted grants, honoraria, or travel grants from various sources.

Source: Kaltseis K et al. Monoclonal antibodies against CGRP (R): Non-responders and switchers: Real world data from an Austrian case series. BMC Neurol. 2023;23(1):174 (Apr 28). doi: 10.1186/s12883-023-03203-9

Key clinical point: Switching calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) may benefit patients with episodic migraine (EM) or chronic migraine (CM) who had failed to respond to the first CGRP-mAb or experienced a loss of efficacy over time.

Major finding: Overall, 71.9% of patients responded to the first CGRP-mAb, 42.3% of those who did not respond or experienced a loss of efficacy over time to the first CGRP-mAb responded to the second CGRP-mAb, and 28.6% of patients who received the third CGRP-mAb showed a response.

Study details: Findings are from a retrospective, real-world case series including 171 patients with EM or CM who received one (n = 137), two (n = 27), or all three(n = 7) CGRP-mAb as migraine preventive therapy.

Disclosures: This study received no specific funding from any source. Some authors declared receiving personal fees, unrestricted grants, honoraria, or travel grants from various sources.

Source: Kaltseis K et al. Monoclonal antibodies against CGRP (R): Non-responders and switchers: Real world data from an Austrian case series. BMC Neurol. 2023;23(1):174 (Apr 28). doi: 10.1186/s12883-023-03203-9