The Secrets of Optimal Migraine Treatment

Do you use nonpharmacologic approaches to treat your patients living with migraines? Which ones do you prefer?
I always like to start with nonpharmacologic approaches (also termed bio-behavioral approaches) with my patients. I talk to patients about sleep hygiene because if they don't sleep well, they're going to have more headaches. Most of my patients have issues with sleep and rarely feel refreshed in the morning. Most of them have middle insomnia; they wake up between 2 am and 4 am and cannot get back to sleep.

I also talk to my patients about eating properly. If patients don't eat on time or miss a meal, they often get headaches.  While timing is probably more critical, what they eat is important also. Poor diet can lead to decreased energy, and patients can become obese. Obesity impacts headache—especially migraine. I am not sure if there are any particularly good or bad foods for migraine patients, but in general, they should eat fewer fatty foods, fewer carbohydrates, more chicken, and fish than red meat, and a lot of fruits, vegetables, salads, nuts, and whole grains. A good trick is to limit the volume of each meal; do not go back for seconds and limit desserts and alcohol. 

Exercise is beneficial to decrease headaches, and the converse is even more true. Patients should start with low-impact, brief exercise like short walks and slowly build up to 20 minutes of cardio as tolerated, 3 to 5 times per week. Like poor diet choices, a sedentary lifestyle can lead to obesity and then not doing well with headaches and so on. 

What are your goals for treating your patients at the start of a migraine attack?

The goals for treating a migraine attack are to reduce the intensity of the pain quickly and, if possible, make the patient pain-free in ≤2 hours. We also try to reduce their most bothersome symptom, which is usually sensitivity to light or nausea, without causing any adverse effects from the treatment. Possibly as important, we want to get the patient back to functioning at work or at home, so they need no further treatment for that attack.

Unfortunately, many of the medicines we have available do cause adverse events, which are sometimes worse than the headache itself.  A patient can't continue to take a medication that causes significant side effects.

It is also critical to stop the headache quickly, as we don't want patients to take the prescribed acute care medicine and then, if they don’t feel like it’s working, proceed to take aspirin and then acetaminophen and then an anti-inflammatory tablet. The more medicine they take, the more likely they'll get medication overuse headache (MOH).  

MOH is not a great name, but it does imply that patients are taking one or many medications per week to stop their headaches, not realizing that this can worsen and prolong their headaches rather than helping them. They can also experience adverse events from taking so much medication. 

Finally, we want the patients to get rid of a headache so that they do not need to go to an emergency room, and we want to use medication that is cost effective and gets the patient functioning. Some medicines and devices are extremely expensive and not well covered by insurance companies but imagine the patient who takes a new medicine or uses a new device and gets better rapidly. If they hadn't done that, they may have lost a day or 2 of pay from missing work, or they might have gone to work and not done a very effective job because they were feeling miserable and couldn’t think or speak well. 

Do you prescribe triptans?

Definitely. The triptans first became available 30 years ago. There are 7 different triptans, and some work better for some patients than others. They come in tablets, injections, and nasal sprays. Sometimes patients need to try 2 or 3 different triptans to see which one is the most effective for them. If a patient has no success with tablets, there's a possibility that an injection or even a nasal spray would be more effective.
There are 2 triptans available as a nasal spray. I happen to like a triptan nasal spray called zolmitriptan, which usually works faster with fewer adverse events than the tablets.

There's also an injection of sumatriptan available, which is the fastest way to get relief from a triptan. Patients usually don't prefer it because it is an injection that they give themselves via an auto injector, and it may hurt and can be a bit complex to administer. There are definitely more adverse events when sumatriptan is given by injection, but because an injection can deliver very fast results that stop the headache reliably, some patients prefer it.

Triptans have been the mainstay treatment to stop an ongoing migraine attack for 30 years. We have always known there is some constriction of blood vessels and triptan-related side effects such as dizziness, drowsiness, and tingling sensations, so not every patient can take them. The newer medications that block calcitonin gene-related peptide (CGRP) do not constrict blood vessels and have fewer adverse events but cost a lot more if not covered by insurance.

Another newer, nontriptan nasal spray is dihydroergotamine (DHE) mesylate for acute care. It is one of the best medications to use if the patient’s migraine has been going on for 24 hours, as it tends to work well for a long-lasting headache. It also works for a long period, giving the patient a rest before their next attack. A nasal spray works faster than a tablet form, as the medication is absorbed from the nasal mucosa and does not have to make its way through the GI tract, then to the liver for metabolism, and finally, up to the brain before it begins to work. There can be some side effects in the nose such as discomfort or stuffiness, but if it works well, patients usually tolerate it. 

There's also a newer class of medicine called ditans. In a recent study, lasmiditan, which comes in a 50-mg and a 100-mg tablet for acute care of migraine, showed no vasoconstrictive effects, suggesting that ditans could be a safe option for patients living with chronic cardio- and cerebrovascular disease. Lasmiditan could be an alternative to triptans when they are contraindicated in patients with blood vessel disease, obesity, high blood pressure or cholesterol levels, or in nonresponsive patients. Lasmiditan does cause some dizziness and drowsiness, so patients cannot drive for 8 hours after taking it. However, it does have good efficacy.

When do you prescribe gepants?

Gepants are small-molecule CGRP receptor blockers. They are tablets that sit on the receptor, preventing the CGRP from docking on the receptor and increasing the headache during a migraine attack. There are 2 gepants that can be used to stop a headache that is just starting or in progress: ubrogepant and rimegepant. 

Ubrogepant is a regular tablet that is available in 50-mg or 100-mg strengths. If the first dose does not make a patient pain free, a second dose is recommended about 2 hours later. Rimegepant is a meltaway tablet and only comes in a 75-mg strength. It should be taken early in the attack, and usually the patient does not need further treatment that day. If they do, they need to switch to another treatment, as rimegepant should not be repeated that day. Rimegepant may be used for both acute care and prevention. It is the only tablet that can be used for both. 

Both drugs have been shown to provide pain freedom for about 20% of patients at 2 hours, which is statistically better than the patients that received the placebo. These drugs generally don’t cause many adverse events but can cause a little nausea or drowsiness in some patients. Ubrogepant has a few contraindications; patients on certain medications such as antibiotics or antifungals cannot take it. If a patient is not doing well on a triptan or should not be given a drug that constricts blood vessels, I often switch them to one of these gepants (if covered by insurance). Both drugs have a plan to let the patient try them at a low cost. 

How are the gepants used acutely?

Gepants are used just like a triptan. As soon as the patient has a migraine headache starting, they take either ubrogepant or rimegepant as quickly as possible. Some patients say they feel the gepant begin to work within an hour or less, and some patients say it doesn't work at all, so I have them try the other gepant. 

Gepants are probably a better option than triptans if the patient is >40 years because triptans can constrict blood vessels. Older patients, and certainly those who have any kind of cardiac or cerebral blood vessel issues or even peripheral blood vessel disease, should not be given triptans.

When do you consider using preventive treatment in migraine?

If a patient has ≥4 moderate-to-severe headache days a month, or fewer with severe disability, or does not respond to acute care medications or those drugs are contraindicated, I consider giving them preventive therapy for migraine. The goal is to decrease the number of migraine days per month and to decrease the intensity, duration, and disability of the attacks.

Which gepants can you use for prevention of migraine?

I discussed rimegepant as an acute care medication, but the same 75-mg meltaway tablet given every other day works preventively to decrease the number of headaches. I like it, as it has few adverse events—<3% of patients experience nausea and abdominal pain—and it can also be used to stop a headache on days the patient did not take a tablet.

Atogepant is a newer, US Food and Drug Administration (FDA)-approved gepant taken once daily by mouth for prevention of migraine, and it works to decrease headache days per month. It has more side effects than the other gepants, including constipation, drowsiness, and nausea. If a patient does not have many adverse events while taking it, it is a good migraine preventive. 

How do you feel about monoclonal antibodies that bind to CGRP or its receptor for migraine preventive treatment?

Before the gepants became available, 4 different pharmaceutical companies were making monoclonal antibodies (mAbs) that bind to either CGRP or its receptor. This class of medication can be quite effective for most patients needing migraine prevention, as these medications last for a long time if the patient keeps taking it. 

Antibodies, when injected, continue to work for 1 to 3 months, making them perfect for migraine prevention, but they must be given either by the patient using an autoinjector with a tiny needle or by intravenous (IV) infusion in a hospital or office. They tend to be quite effective and have few adverse events.  

The first one to come out was erenumab, then frenanezumab, and galcanezumab. The newest one is eptinezumab, given by IV infusion over 30 minutes. Erenumab is the only mAb that sits on the receptor to prevent the CGRP from docking on the receptor, and it's the only one that seems to cause adverse events such as constipation and increased blood pressure in some patients. Eptinezumab is the only drug in this category given by IV infusion; patients must come to the office to receive the injection every 3 months. Even though eptinezumab is a powerful drug, I find that patients generally don't like coming in for IV treatment. I reserve it for when a patient has failed several other preventive treatments. The other 3 drugs (erenumab, fremanezumab, galcanezumab) are subcutaneous injections that the patient can self-administer at home. Fremanezumab can be taken once a month or once every 3 months, depending on the dose prescribed. 

What migraine devices do you like to prescribe?

The device that I tend to have my patients use is called Nerivio®; it has been cleared by the FDA for acute treatment of migraine in patients ≥12 years. An article was just published in the journal Headache on its use in prevention of migraine. The company expects the FDA to clear it very soon for prevention when used for 45 minutes every other day.

Nerivio® is an electrical stimulator that is placed on the upper arm like a blood pressure cuff. It is battery-powered and links to an app on a smartphone. I have my patients turn it up slowly to a higher gain, and when they feel a slight discomfort, they lower down until they do not feel it. That's where I recommend that they keep it for 45 minutes of treatment, starting at the beginning of a migraine attack. 

Nerivio® also has a behavioral medicine program incorporated into the smartphone app that lasts for 25 minutes. While the patient is receiving the 45 minutes of electrical stimulation, they are also being guided through relaxation techniques to help ease the headache. The company has done a controlled study comparing the efficacy of Nerivio® with and without the behavioral treatment and found that the 2 together are more effective than Nerivio® alone. 

The early double-blind studies of this device, as sent to the FDA for clearance, have excellent efficacy data with very few adverse events. Thus, it is used by many patients. The company has arranged a lower cost for the first month of treatment so a patient can see whether the device is effective.

There's also a device called Relivion®, which is worn like a tiara on the head to stimulate 4 nerves above the eyebrows that are part of the trigeminal system and 2 in the back of the head that affect the occipital nerves.

One of the earliest devices to launch is the gammaCore vagal nerve stimulator. It is handheld and controlled by the patient. It is placed on the front and side of the neck in the region of the vagal nerve. For acute care of migraine, the patient stimulates for 2 minutes and then waits several minutes before repeating 2 minutes of treatment. If you want to prescribe it for the prevention of migraine, a patient could do this sequence twice per day. It has been approved for acute care and prevention of migraine and, along with other medication for cluster headaches, it is easy to use and approved for almost any kind of headache. Unfortunately, it is extremely expensive for patients and is not covered well by insurance unless the patient is a veteran or goes to a Veterans Health Administration hospital for care. 

There are a few other devices that also work for migraine. Most electrical stimulation devices are costly, but we do hope that insurance companies will begin to cover them soon. Most devices cause few adverse events, have few contraindications, and will be used more as they become more affordable.

Can you summarize migraine treatment for us in one paragraph?

No, but I will try. We have many acute care treatments for migraine that are effective. Some, such as the triptans, do constrict blood vessels, and certain patients should not be taking medications that affect blood vessels. Some medications cause certain side effects or take too long to work, and we have other options for those patients. If a patient has ≥4 headache days per month or fewer associated with a lot of disability, we need to consider prevention. We have older preventives such as beta blockers and epilepsy medications, which are less expensive and can work but usually have many side effects. Now we have 4 mAbs that bind to CGRP or its receptor, which work well for a month or more with few adverse events. We also have 2 oral gepants for prevention. When you add in several devices, I have so many options for my patients today that I am a lucky neurologist, and my patients are even luckier!

Do you use nonpharmacologic approaches to treat your patients living with migraines? Which ones do you prefer?
I always like to start with nonpharmacologic approaches (also termed bio-behavioral approaches) with my patients. I talk to patients about sleep hygiene because if they don't sleep well, they're going to have more headaches. Most of my patients have issues with sleep and rarely feel refreshed in the morning. Most of them have middle insomnia; they wake up between 2 am and 4 am and cannot get back to sleep.

I also talk to my patients about eating properly. If patients don't eat on time or miss a meal, they often get headaches.  While timing is probably more critical, what they eat is important also. Poor diet can lead to decreased energy, and patients can become obese. Obesity impacts headache—especially migraine. I am not sure if there are any particularly good or bad foods for migraine patients, but in general, they should eat fewer fatty foods, fewer carbohydrates, more chicken, and fish than red meat, and a lot of fruits, vegetables, salads, nuts, and whole grains. A good trick is to limit the volume of each meal; do not go back for seconds and limit desserts and alcohol. 

Exercise is beneficial to decrease headaches, and the converse is even more true. Patients should start with low-impact, brief exercise like short walks and slowly build up to 20 minutes of cardio as tolerated, 3 to 5 times per week. Like poor diet choices, a sedentary lifestyle can lead to obesity and then not doing well with headaches and so on. 

What are your goals for treating your patients at the start of a migraine attack?

The goals for treating a migraine attack are to reduce the intensity of the pain quickly and, if possible, make the patient pain-free in ≤2 hours. We also try to reduce their most bothersome symptom, which is usually sensitivity to light or nausea, without causing any adverse effects from the treatment. Possibly as important, we want to get the patient back to functioning at work or at home, so they need no further treatment for that attack.

Unfortunately, many of the medicines we have available do cause adverse events, which are sometimes worse than the headache itself.  A patient can't continue to take a medication that causes significant side effects.

It is also critical to stop the headache quickly, as we don't want patients to take the prescribed acute care medicine and then, if they don’t feel like it’s working, proceed to take aspirin and then acetaminophen and then an anti-inflammatory tablet. The more medicine they take, the more likely they'll get medication overuse headache (MOH).  

MOH is not a great name, but it does imply that patients are taking one or many medications per week to stop their headaches, not realizing that this can worsen and prolong their headaches rather than helping them. They can also experience adverse events from taking so much medication. 

Finally, we want the patients to get rid of a headache so that they do not need to go to an emergency room, and we want to use medication that is cost effective and gets the patient functioning. Some medicines and devices are extremely expensive and not well covered by insurance companies but imagine the patient who takes a new medicine or uses a new device and gets better rapidly. If they hadn't done that, they may have lost a day or 2 of pay from missing work, or they might have gone to work and not done a very effective job because they were feeling miserable and couldn’t think or speak well. 

Do you prescribe triptans?

Definitely. The triptans first became available 30 years ago. There are 7 different triptans, and some work better for some patients than others. They come in tablets, injections, and nasal sprays. Sometimes patients need to try 2 or 3 different triptans to see which one is the most effective for them. If a patient has no success with tablets, there's a possibility that an injection or even a nasal spray would be more effective.
There are 2 triptans available as a nasal spray. I happen to like a triptan nasal spray called zolmitriptan, which usually works faster with fewer adverse events than the tablets.

There's also an injection of sumatriptan available, which is the fastest way to get relief from a triptan. Patients usually don't prefer it because it is an injection that they give themselves via an auto injector, and it may hurt and can be a bit complex to administer. There are definitely more adverse events when sumatriptan is given by injection, but because an injection can deliver very fast results that stop the headache reliably, some patients prefer it.

Triptans have been the mainstay treatment to stop an ongoing migraine attack for 30 years. We have always known there is some constriction of blood vessels and triptan-related side effects such as dizziness, drowsiness, and tingling sensations, so not every patient can take them. The newer medications that block calcitonin gene-related peptide (CGRP) do not constrict blood vessels and have fewer adverse events but cost a lot more if not covered by insurance.

Another newer, nontriptan nasal spray is dihydroergotamine (DHE) mesylate for acute care. It is one of the best medications to use if the patient’s migraine has been going on for 24 hours, as it tends to work well for a long-lasting headache. It also works for a long period, giving the patient a rest before their next attack. A nasal spray works faster than a tablet form, as the medication is absorbed from the nasal mucosa and does not have to make its way through the GI tract, then to the liver for metabolism, and finally, up to the brain before it begins to work. There can be some side effects in the nose such as discomfort or stuffiness, but if it works well, patients usually tolerate it. 

There's also a newer class of medicine called ditans. In a recent study, lasmiditan, which comes in a 50-mg and a 100-mg tablet for acute care of migraine, showed no vasoconstrictive effects, suggesting that ditans could be a safe option for patients living with chronic cardio- and cerebrovascular disease. Lasmiditan could be an alternative to triptans when they are contraindicated in patients with blood vessel disease, obesity, high blood pressure or cholesterol levels, or in nonresponsive patients. Lasmiditan does cause some dizziness and drowsiness, so patients cannot drive for 8 hours after taking it. However, it does have good efficacy.

When do you prescribe gepants?

Gepants are small-molecule CGRP receptor blockers. They are tablets that sit on the receptor, preventing the CGRP from docking on the receptor and increasing the headache during a migraine attack. There are 2 gepants that can be used to stop a headache that is just starting or in progress: ubrogepant and rimegepant. 

Ubrogepant is a regular tablet that is available in 50-mg or 100-mg strengths. If the first dose does not make a patient pain free, a second dose is recommended about 2 hours later. Rimegepant is a meltaway tablet and only comes in a 75-mg strength. It should be taken early in the attack, and usually the patient does not need further treatment that day. If they do, they need to switch to another treatment, as rimegepant should not be repeated that day. Rimegepant may be used for both acute care and prevention. It is the only tablet that can be used for both. 

Both drugs have been shown to provide pain freedom for about 20% of patients at 2 hours, which is statistically better than the patients that received the placebo. These drugs generally don’t cause many adverse events but can cause a little nausea or drowsiness in some patients. Ubrogepant has a few contraindications; patients on certain medications such as antibiotics or antifungals cannot take it. If a patient is not doing well on a triptan or should not be given a drug that constricts blood vessels, I often switch them to one of these gepants (if covered by insurance). Both drugs have a plan to let the patient try them at a low cost. 

How are the gepants used acutely?

Gepants are used just like a triptan. As soon as the patient has a migraine headache starting, they take either ubrogepant or rimegepant as quickly as possible. Some patients say they feel the gepant begin to work within an hour or less, and some patients say it doesn't work at all, so I have them try the other gepant. 

Gepants are probably a better option than triptans if the patient is >40 years because triptans can constrict blood vessels. Older patients, and certainly those who have any kind of cardiac or cerebral blood vessel issues or even peripheral blood vessel disease, should not be given triptans.

When do you consider using preventive treatment in migraine?

If a patient has ≥4 moderate-to-severe headache days a month, or fewer with severe disability, or does not respond to acute care medications or those drugs are contraindicated, I consider giving them preventive therapy for migraine. The goal is to decrease the number of migraine days per month and to decrease the intensity, duration, and disability of the attacks.

Which gepants can you use for prevention of migraine?

I discussed rimegepant as an acute care medication, but the same 75-mg meltaway tablet given every other day works preventively to decrease the number of headaches. I like it, as it has few adverse events—<3% of patients experience nausea and abdominal pain—and it can also be used to stop a headache on days the patient did not take a tablet.

Atogepant is a newer, US Food and Drug Administration (FDA)-approved gepant taken once daily by mouth for prevention of migraine, and it works to decrease headache days per month. It has more side effects than the other gepants, including constipation, drowsiness, and nausea. If a patient does not have many adverse events while taking it, it is a good migraine preventive. 

How do you feel about monoclonal antibodies that bind to CGRP or its receptor for migraine preventive treatment?

Before the gepants became available, 4 different pharmaceutical companies were making monoclonal antibodies (mAbs) that bind to either CGRP or its receptor. This class of medication can be quite effective for most patients needing migraine prevention, as these medications last for a long time if the patient keeps taking it. 

Antibodies, when injected, continue to work for 1 to 3 months, making them perfect for migraine prevention, but they must be given either by the patient using an autoinjector with a tiny needle or by intravenous (IV) infusion in a hospital or office. They tend to be quite effective and have few adverse events.  

The first one to come out was erenumab, then frenanezumab, and galcanezumab. The newest one is eptinezumab, given by IV infusion over 30 minutes. Erenumab is the only mAb that sits on the receptor to prevent the CGRP from docking on the receptor, and it's the only one that seems to cause adverse events such as constipation and increased blood pressure in some patients. Eptinezumab is the only drug in this category given by IV infusion; patients must come to the office to receive the injection every 3 months. Even though eptinezumab is a powerful drug, I find that patients generally don't like coming in for IV treatment. I reserve it for when a patient has failed several other preventive treatments. The other 3 drugs (erenumab, fremanezumab, galcanezumab) are subcutaneous injections that the patient can self-administer at home. Fremanezumab can be taken once a month or once every 3 months, depending on the dose prescribed. 

What migraine devices do you like to prescribe?

The device that I tend to have my patients use is called Nerivio®; it has been cleared by the FDA for acute treatment of migraine in patients ≥12 years. An article was just published in the journal Headache on its use in prevention of migraine. The company expects the FDA to clear it very soon for prevention when used for 45 minutes every other day.

Nerivio® is an electrical stimulator that is placed on the upper arm like a blood pressure cuff. It is battery-powered and links to an app on a smartphone. I have my patients turn it up slowly to a higher gain, and when they feel a slight discomfort, they lower down until they do not feel it. That's where I recommend that they keep it for 45 minutes of treatment, starting at the beginning of a migraine attack. 

Nerivio® also has a behavioral medicine program incorporated into the smartphone app that lasts for 25 minutes. While the patient is receiving the 45 minutes of electrical stimulation, they are also being guided through relaxation techniques to help ease the headache. The company has done a controlled study comparing the efficacy of Nerivio® with and without the behavioral treatment and found that the 2 together are more effective than Nerivio® alone. 

The early double-blind studies of this device, as sent to the FDA for clearance, have excellent efficacy data with very few adverse events. Thus, it is used by many patients. The company has arranged a lower cost for the first month of treatment so a patient can see whether the device is effective.

There's also a device called Relivion®, which is worn like a tiara on the head to stimulate 4 nerves above the eyebrows that are part of the trigeminal system and 2 in the back of the head that affect the occipital nerves.

One of the earliest devices to launch is the gammaCore vagal nerve stimulator. It is handheld and controlled by the patient. It is placed on the front and side of the neck in the region of the vagal nerve. For acute care of migraine, the patient stimulates for 2 minutes and then waits several minutes before repeating 2 minutes of treatment. If you want to prescribe it for the prevention of migraine, a patient could do this sequence twice per day. It has been approved for acute care and prevention of migraine and, along with other medication for cluster headaches, it is easy to use and approved for almost any kind of headache. Unfortunately, it is extremely expensive for patients and is not covered well by insurance unless the patient is a veteran or goes to a Veterans Health Administration hospital for care. 

There are a few other devices that also work for migraine. Most electrical stimulation devices are costly, but we do hope that insurance companies will begin to cover them soon. Most devices cause few adverse events, have few contraindications, and will be used more as they become more affordable.

Can you summarize migraine treatment for us in one paragraph?

No, but I will try. We have many acute care treatments for migraine that are effective. Some, such as the triptans, do constrict blood vessels, and certain patients should not be taking medications that affect blood vessels. Some medications cause certain side effects or take too long to work, and we have other options for those patients. If a patient has ≥4 headache days per month or fewer associated with a lot of disability, we need to consider prevention. We have older preventives such as beta blockers and epilepsy medications, which are less expensive and can work but usually have many side effects. Now we have 4 mAbs that bind to CGRP or its receptor, which work well for a month or more with few adverse events. We also have 2 oral gepants for prevention. When you add in several devices, I have so many options for my patients today that I am a lucky neurologist, and my patients are even luckier!

Do you use nonpharmacologic approaches to treat your patients living with migraines? Which ones do you prefer?
I always like to start with nonpharmacologic approaches (also termed bio-behavioral approaches) with my patients. I talk to patients about sleep hygiene because if they don't sleep well, they're going to have more headaches. Most of my patients have issues with sleep and rarely feel refreshed in the morning. Most of them have middle insomnia; they wake up between 2 am and 4 am and cannot get back to sleep.

I also talk to my patients about eating properly. If patients don't eat on time or miss a meal, they often get headaches.  While timing is probably more critical, what they eat is important also. Poor diet can lead to decreased energy, and patients can become obese. Obesity impacts headache—especially migraine. I am not sure if there are any particularly good or bad foods for migraine patients, but in general, they should eat fewer fatty foods, fewer carbohydrates, more chicken, and fish than red meat, and a lot of fruits, vegetables, salads, nuts, and whole grains. A good trick is to limit the volume of each meal; do not go back for seconds and limit desserts and alcohol. 

Exercise is beneficial to decrease headaches, and the converse is even more true. Patients should start with low-impact, brief exercise like short walks and slowly build up to 20 minutes of cardio as tolerated, 3 to 5 times per week. Like poor diet choices, a sedentary lifestyle can lead to obesity and then not doing well with headaches and so on. 

What are your goals for treating your patients at the start of a migraine attack?

The goals for treating a migraine attack are to reduce the intensity of the pain quickly and, if possible, make the patient pain-free in ≤2 hours. We also try to reduce their most bothersome symptom, which is usually sensitivity to light or nausea, without causing any adverse effects from the treatment. Possibly as important, we want to get the patient back to functioning at work or at home, so they need no further treatment for that attack.

Unfortunately, many of the medicines we have available do cause adverse events, which are sometimes worse than the headache itself.  A patient can't continue to take a medication that causes significant side effects.

It is also critical to stop the headache quickly, as we don't want patients to take the prescribed acute care medicine and then, if they don’t feel like it’s working, proceed to take aspirin and then acetaminophen and then an anti-inflammatory tablet. The more medicine they take, the more likely they'll get medication overuse headache (MOH).  

MOH is not a great name, but it does imply that patients are taking one or many medications per week to stop their headaches, not realizing that this can worsen and prolong their headaches rather than helping them. They can also experience adverse events from taking so much medication. 

Finally, we want the patients to get rid of a headache so that they do not need to go to an emergency room, and we want to use medication that is cost effective and gets the patient functioning. Some medicines and devices are extremely expensive and not well covered by insurance companies but imagine the patient who takes a new medicine or uses a new device and gets better rapidly. If they hadn't done that, they may have lost a day or 2 of pay from missing work, or they might have gone to work and not done a very effective job because they were feeling miserable and couldn’t think or speak well. 

Do you prescribe triptans?

Definitely. The triptans first became available 30 years ago. There are 7 different triptans, and some work better for some patients than others. They come in tablets, injections, and nasal sprays. Sometimes patients need to try 2 or 3 different triptans to see which one is the most effective for them. If a patient has no success with tablets, there's a possibility that an injection or even a nasal spray would be more effective.
There are 2 triptans available as a nasal spray. I happen to like a triptan nasal spray called zolmitriptan, which usually works faster with fewer adverse events than the tablets.

There's also an injection of sumatriptan available, which is the fastest way to get relief from a triptan. Patients usually don't prefer it because it is an injection that they give themselves via an auto injector, and it may hurt and can be a bit complex to administer. There are definitely more adverse events when sumatriptan is given by injection, but because an injection can deliver very fast results that stop the headache reliably, some patients prefer it.

Triptans have been the mainstay treatment to stop an ongoing migraine attack for 30 years. We have always known there is some constriction of blood vessels and triptan-related side effects such as dizziness, drowsiness, and tingling sensations, so not every patient can take them. The newer medications that block calcitonin gene-related peptide (CGRP) do not constrict blood vessels and have fewer adverse events but cost a lot more if not covered by insurance.

Another newer, nontriptan nasal spray is dihydroergotamine (DHE) mesylate for acute care. It is one of the best medications to use if the patient’s migraine has been going on for 24 hours, as it tends to work well for a long-lasting headache. It also works for a long period, giving the patient a rest before their next attack. A nasal spray works faster than a tablet form, as the medication is absorbed from the nasal mucosa and does not have to make its way through the GI tract, then to the liver for metabolism, and finally, up to the brain before it begins to work. There can be some side effects in the nose such as discomfort or stuffiness, but if it works well, patients usually tolerate it. 

There's also a newer class of medicine called ditans. In a recent study, lasmiditan, which comes in a 50-mg and a 100-mg tablet for acute care of migraine, showed no vasoconstrictive effects, suggesting that ditans could be a safe option for patients living with chronic cardio- and cerebrovascular disease. Lasmiditan could be an alternative to triptans when they are contraindicated in patients with blood vessel disease, obesity, high blood pressure or cholesterol levels, or in nonresponsive patients. Lasmiditan does cause some dizziness and drowsiness, so patients cannot drive for 8 hours after taking it. However, it does have good efficacy.

When do you prescribe gepants?

Gepants are small-molecule CGRP receptor blockers. They are tablets that sit on the receptor, preventing the CGRP from docking on the receptor and increasing the headache during a migraine attack. There are 2 gepants that can be used to stop a headache that is just starting or in progress: ubrogepant and rimegepant. 

Ubrogepant is a regular tablet that is available in 50-mg or 100-mg strengths. If the first dose does not make a patient pain free, a second dose is recommended about 2 hours later. Rimegepant is a meltaway tablet and only comes in a 75-mg strength. It should be taken early in the attack, and usually the patient does not need further treatment that day. If they do, they need to switch to another treatment, as rimegepant should not be repeated that day. Rimegepant may be used for both acute care and prevention. It is the only tablet that can be used for both. 

Both drugs have been shown to provide pain freedom for about 20% of patients at 2 hours, which is statistically better than the patients that received the placebo. These drugs generally don’t cause many adverse events but can cause a little nausea or drowsiness in some patients. Ubrogepant has a few contraindications; patients on certain medications such as antibiotics or antifungals cannot take it. If a patient is not doing well on a triptan or should not be given a drug that constricts blood vessels, I often switch them to one of these gepants (if covered by insurance). Both drugs have a plan to let the patient try them at a low cost. 

How are the gepants used acutely?

Gepants are used just like a triptan. As soon as the patient has a migraine headache starting, they take either ubrogepant or rimegepant as quickly as possible. Some patients say they feel the gepant begin to work within an hour or less, and some patients say it doesn't work at all, so I have them try the other gepant. 

Gepants are probably a better option than triptans if the patient is >40 years because triptans can constrict blood vessels. Older patients, and certainly those who have any kind of cardiac or cerebral blood vessel issues or even peripheral blood vessel disease, should not be given triptans.

When do you consider using preventive treatment in migraine?

If a patient has ≥4 moderate-to-severe headache days a month, or fewer with severe disability, or does not respond to acute care medications or those drugs are contraindicated, I consider giving them preventive therapy for migraine. The goal is to decrease the number of migraine days per month and to decrease the intensity, duration, and disability of the attacks.

Which gepants can you use for prevention of migraine?

I discussed rimegepant as an acute care medication, but the same 75-mg meltaway tablet given every other day works preventively to decrease the number of headaches. I like it, as it has few adverse events—<3% of patients experience nausea and abdominal pain—and it can also be used to stop a headache on days the patient did not take a tablet.

Atogepant is a newer, US Food and Drug Administration (FDA)-approved gepant taken once daily by mouth for prevention of migraine, and it works to decrease headache days per month. It has more side effects than the other gepants, including constipation, drowsiness, and nausea. If a patient does not have many adverse events while taking it, it is a good migraine preventive. 

How do you feel about monoclonal antibodies that bind to CGRP or its receptor for migraine preventive treatment?

Before the gepants became available, 4 different pharmaceutical companies were making monoclonal antibodies (mAbs) that bind to either CGRP or its receptor. This class of medication can be quite effective for most patients needing migraine prevention, as these medications last for a long time if the patient keeps taking it. 

Antibodies, when injected, continue to work for 1 to 3 months, making them perfect for migraine prevention, but they must be given either by the patient using an autoinjector with a tiny needle or by intravenous (IV) infusion in a hospital or office. They tend to be quite effective and have few adverse events.  

The first one to come out was erenumab, then frenanezumab, and galcanezumab. The newest one is eptinezumab, given by IV infusion over 30 minutes. Erenumab is the only mAb that sits on the receptor to prevent the CGRP from docking on the receptor, and it's the only one that seems to cause adverse events such as constipation and increased blood pressure in some patients. Eptinezumab is the only drug in this category given by IV infusion; patients must come to the office to receive the injection every 3 months. Even though eptinezumab is a powerful drug, I find that patients generally don't like coming in for IV treatment. I reserve it for when a patient has failed several other preventive treatments. The other 3 drugs (erenumab, fremanezumab, galcanezumab) are subcutaneous injections that the patient can self-administer at home. Fremanezumab can be taken once a month or once every 3 months, depending on the dose prescribed. 

What migraine devices do you like to prescribe?

The device that I tend to have my patients use is called Nerivio®; it has been cleared by the FDA for acute treatment of migraine in patients ≥12 years. An article was just published in the journal Headache on its use in prevention of migraine. The company expects the FDA to clear it very soon for prevention when used for 45 minutes every other day.

Nerivio® is an electrical stimulator that is placed on the upper arm like a blood pressure cuff. It is battery-powered and links to an app on a smartphone. I have my patients turn it up slowly to a higher gain, and when they feel a slight discomfort, they lower down until they do not feel it. That's where I recommend that they keep it for 45 minutes of treatment, starting at the beginning of a migraine attack. 

Nerivio® also has a behavioral medicine program incorporated into the smartphone app that lasts for 25 minutes. While the patient is receiving the 45 minutes of electrical stimulation, they are also being guided through relaxation techniques to help ease the headache. The company has done a controlled study comparing the efficacy of Nerivio® with and without the behavioral treatment and found that the 2 together are more effective than Nerivio® alone. 

The early double-blind studies of this device, as sent to the FDA for clearance, have excellent efficacy data with very few adverse events. Thus, it is used by many patients. The company has arranged a lower cost for the first month of treatment so a patient can see whether the device is effective.

There's also a device called Relivion®, which is worn like a tiara on the head to stimulate 4 nerves above the eyebrows that are part of the trigeminal system and 2 in the back of the head that affect the occipital nerves.

One of the earliest devices to launch is the gammaCore vagal nerve stimulator. It is handheld and controlled by the patient. It is placed on the front and side of the neck in the region of the vagal nerve. For acute care of migraine, the patient stimulates for 2 minutes and then waits several minutes before repeating 2 minutes of treatment. If you want to prescribe it for the prevention of migraine, a patient could do this sequence twice per day. It has been approved for acute care and prevention of migraine and, along with other medication for cluster headaches, it is easy to use and approved for almost any kind of headache. Unfortunately, it is extremely expensive for patients and is not covered well by insurance unless the patient is a veteran or goes to a Veterans Health Administration hospital for care. 

There are a few other devices that also work for migraine. Most electrical stimulation devices are costly, but we do hope that insurance companies will begin to cover them soon. Most devices cause few adverse events, have few contraindications, and will be used more as they become more affordable.

Can you summarize migraine treatment for us in one paragraph?

No, but I will try. We have many acute care treatments for migraine that are effective. Some, such as the triptans, do constrict blood vessels, and certain patients should not be taking medications that affect blood vessels. Some medications cause certain side effects or take too long to work, and we have other options for those patients. If a patient has ≥4 headache days per month or fewer associated with a lot of disability, we need to consider prevention. We have older preventives such as beta blockers and epilepsy medications, which are less expensive and can work but usually have many side effects. Now we have 4 mAbs that bind to CGRP or its receptor, which work well for a month or more with few adverse events. We also have 2 oral gepants for prevention. When you add in several devices, I have so many options for my patients today that I am a lucky neurologist, and my patients are even luckier!