Migraine Treatments

What Can We Do About Migraine?

If you live with migraine, there can be relief.

There are two different approaches;

  1. treating the symptoms when they occur (acute intervention)
  2. taking medication routinely to reduce the intensity and frequency of migraine attacks (preventive or prophylactic medications)

If you are currently using medication to manage your migraine disease, you may want to use a Migraine Medication Diary to track its effectiveness.

Download the Migraine Diary

Track date, time, symptoms, intensity, what you were doing and what you did to help treat your migraine attack

Guides for the Latest Migraine Treatments

CGRP Monoclonal Antibodies

BRAND NAMEAIMOVIG®AJOVY®EMGALITY®VYEPTI®
GENERIC NAMEerenumab-aooefremanezumab-vfrmgalcanezumab-gnlmeptinezumab-jjmr
MANUFACTURERAmgen/NovartisTeva PharmaceuitcalsEli Lilly & CompanyLundbeck
INDICATIONPreventive treatment of migraine in adultsPreventive treatment of migraine in adultsPreventive treatment of migraine in adults
*Also approved for episodic cluster
Preventive treatment of migraine in adults
PRICE & SAVINGS PROGRAMSList price: $638.77/month
Insured patients pay from $0-$128 per month. Savings program: aimovigaccesscard.com
As low as $5 for eligible commerically insured patients with savings program:
ajovy.com/savings
List price: $627.60/month
Insured patients pay from $0-$354 per month. Savings program: emgality.com/savings
List Price: $1,532.38 for recommended dose every 3 months. Most people do not pay the list price.
Savings program: vyepti.com/savings-and-support
DOSAGE70 mg once monthly or 140 mg once monthly225 mg monthly or 675 mg every 3 months240 mg loading dose then monthly 120 mg doses*100 mg infusion every 3 months
*Some may benefit from a 300 mg dose.
EFFICACY
*See individual websites for complete study results
~40% of chronic patients and ~50% of episodic patients had their monthly migraine days reduced by at least 50%.39.2% of chronic patients and 46% of episodic patients had their monthly migraine days reduced by at least 50%.~61% patients had ≥ 50% reduction in headache days*
~37% patients had ≥ 75% reduction in headache days*
~14% patients had 100% headache day reduction*
Episodic ~45% reduction in average monthly migraine days
Chronic: ~48% reduction in average monthly migraine days
*100 mg dose, months 1-3
DELIVERY ADMINISTRATIONmonthly subcutaneous injectionmonthly or quarterly subcutaneous injectionmonthly subcutaneous injectionquarterly intravenous infusion
HALF LIFE28 days31 days27 days27 days
PRIMARY SIDE EFFECTSInjection site reaction, constipation, allergic reactionsInjection site reaction, allergic reactionsInjection site reaction, allergic reactionsStuffy nose, scratchy throat, allergic reactions

Gepants

BRAND NAMEUbrelvy®Nurtec® ODTQulipta™
GENERIC NAMEubrogepantrimegepantatogepant
MANUFACTURERAbbVieBiohaven PharmaceuticalsAbbVie
INDICATIONAcute treatment of migraineAcute treatment of migraine & preventive treatment of episodic migrainePreventive treatment of episodic migraine
PRICE & SAVINGS PLANAs low as $0 for eligible commerically insured patients using savings program: ubrelvy.com/savings
As low as $0 for eligible commerically insured patients using savings program: nurtec.com/savingsAs low as $0 for eligible commerically insured patients using savings program: qulipta.com/savings
DOSAGE50 or 100 mg, as needed
Max dose: 200 mg in 24 hours
Acute: 75 mg, as needed
Max dose: 75 mg in 24 hours
Preventive: 75 mg every other day
Max dose: 75 mg in 24 hours
10 mg, 30 mg, or 60 mg, orally once daily
Max dose: 60 mg in 24 hours
EFFICACY
*See individual websites for complete study results

Measured at 2 hours post-dose
Pain Relief:

60.7% at 50 mg

61.4% at 100 mg

Pain Free:

19.2% at 50 mg

21.2% at 100 mg

Measured at 2 hours post-dose
Pain Free: 21.2% at 75 mg
Pain Relief: 59.3% at 75 mg Prevention: 30% reduction in weekly migraine days at Week 1

53% migraine day reduction in week 1
54% migraine reduction across 12 weeks

HALF LIFE5-7 hours11 hours11 hours
PRIMARY SIDE EFFECTSnausea and sleepinessnausea, stomach pain, indigestionnausea, constipation, decreased appetite and fatigue

Devices

BRAND NAMECEFALY®Nerivio®gammaCore Sapphire™Relivion® MG
MANUFACTURERCEFALY TechnologyTheranicaelectroCore Neurolief
INDICATION
*unless otherwise explained, indications are
for patients 18+ years old
Acute and Preventive Treatment of Episodic Migraine*Acute Treatment of Episodic and Chronic Migraine
Approved for 12 years and older
Acute & Preventive Treatment of Migraine & Cluster
Migraine approval for 12 years and older. Also approved for other headache types
Acute Treatment of Episodic Migraine
PRICE$379 for a device
$25 - $33 for additional electrodes for more uses
(Available w/o prescription)
With the Nerivio Express Saving Program, eligible patients will receive their first Nerivio device for $10. The specialty pharmacy will review an individual’s coverage for refills following a benefit investigation. Contact Customer Service at 1.888.903.2673 as pricing varies. Patients may complete a telehealth consult for a prescription & purchase at www.gammaCore.com.Visit relivion.com for details
EFFICACY
*See individual websites for complete study results. Stats given for migraine only.
Acute: 79% of patients reported pain relief at 1 hr*
Preventive: Patients experienced a reduction in migraine days, pain severity & acute drug intake
67% of patients 18+ achieved pain relief & 71.8% of those aged 12 to 17 achieved pain reliefAcute: 41% pain relief at 2 hrs
Preventive: 4.6 fewer headache days/month & 5.5 fewer for those with migraine with aura
76% of patients achieved headache relief at 2 hours.
46% of the patients reached complete pain freedom.
DELIVERY ADMINISTRATION

On Forehead

Acute: 60 minutes at onset or during migraine
Preventive: 20 minutes daily
Start within 1 hour of migraine onset, on outer upper arm. Set intensity to a strong but not painful level and keep it at that setting for 45 minutes. Can be used more than once a dayAcute: A 2-minute stimulation as directed on neck, up to 24 stimulations per day.
Preventive: Two, 2-minute stimulations 3 times a day (morning, mid-day & night)
Visit relivion.com for details
SIDE EFFECTSSleepiness, temporary allergic rash or redness on forehead, low-grade headache following preventive treatmentWarmth, itching, tingling or mild pain in the arm, shoulders, or neck, muscle spasm, or temporary numbness in arm or handApplication site discomfort, irritation, muscle twitching of face/head/neck resolving after treatment finishesScalp numbness, persistent tingling, pain, skin reaction, fatigue, sleep disruptions, dizziness, headache

Preventive Treatments

A study found that 38% of those with episodic migraine would benefit from preventive therapy. Based on the American Headache Society’s 2021 Consensus Statement, preventive therapy is indicated for those who experience attacks that interfere with daily life despite acute treatment, prefer to be on a preventive treatment regimen or need to take acute treatments too frequently. 

Preventive therapy should be considered when someone has 4 or more headache days per month or has 2 headache days with significant disability. Finding a preventive medication that is effective and has tolerable side effects involves trial and error. It is best to try one medication at a time to determine if there is a positive or negative response. Some treatment options do work best as combination therapies so adding another therapy may be beneficial after trialing a new medication. Always consult with your doctor if you plan to use multiple therapies, even if they are over-the-counter.

Preventive Medication Options for Migraine

Many of the medications commonly FDA-approved for migraine prevention were actually originally intended for other medical conditions such as high blood pressure, depression, epilepsy or cosmetic changes (ex. wrinkles). Typically the medications used for these conditions are prescribed in lower doses for migraine. Therefore, you may or may not see benefits for both conditions. 

More recently, CGRP monoclonal antibodies and gepants have been approved for the prevention of migraine. Many neuromodulation devices are also cleared by the FDA. 

There are also many medications used “off-label” for migraine treatments that are not FDA-approved for migraine such as certain antidepressants, vitamins, supplements and more. 

Preventive Medications Need to be Taken Daily

“Start low and go slow”

Preventive medications should be started at a low dose to minimize side effects. You and your doctor should discuss a plan to slowly increase your dose until the desired dose is reached.

  • Many medications should be trialed for 8-12 weeks to determine if they work or not.
  • CGRP monoclonal antibodies that are given monthly should be continued for 3 months to determine if they are effective.
  • CGRP monoclonal antibodies that are given quarterly should be assessed at 6 months to determine if they are working properly.

If you are experiencing side effects or would like to discontinue your medication, please consult with your clinician. Some medications need to be tapered or weaned off slowly to avoid unpleasant side effects. Sometimes lowering the dose minimizes side effects but still offers some improvement for migraine.

Preventives Aim to Reduce Severity and Frequency

Migraine preventive treatments do not prevent all migraine attacks, but can work to reduce the frequency, severity and disability of attacks. 

Inform Your HCP On Upcoming Life Events

It is important to let your provider know if you are pregnant, plan to become pregnant or use hormonal contraception (i.e. birth control, IUD) because of medication interactions.

Preventive Medications Are NOT Forever

If a preventive treatment works well, then it is typically continued for several months (usually 6-12 months). Once a person has better symptom control, a clinician may wean down the dose, until the person is tapered off. Sadly, there is a risk of the headaches returning. 

*This information is NOT intended to endorse treatments or recommend therapy. While these reviews might be helpful, they are not a substitute for the expertise, knowledge and judgment of healthcare practitioners in patient care. Only your provider can decide which medications are right for you. Never stop, start or change the way you use a prescription medicine without first consulting your provider.

CGRP Monoclonal Antibodies

What is CGRP?

Calcitonin gene-related peptide, or CGRP, is a protein found in the peripheral and central nervous systems. Studies have proven that CGRP levels are higher during a migraine attack and lower between attacks. CGRP causes inflammation, blood vessel swelling and dilation. CGRP also sends pain messages to the brain during a migraine attack. 

Gepants and CGRP monoclonal antibodies are two new medication classes that are designed to target CGRP or its receptors. 

What Are Anti-CGRP Monoclonal Antibodies?

Antibodies are naturally produced by the immune system in response to a harmful substance known as an antigen. Scientists have been able to create antibodies that are similar to the ones your body makes. These are known as monoclonal antibodies. Anti-CGRP monoclonal antibodies help prevent migraine by targeting the CGRP signaling pathway. These new medications block either the CGRP protein or its receptor. 

What CGRP Monoclonal Antibodies Are There?

There are currently four different FDA-approved CGRP-blocking monoclonal antibodies for treating migraine: erenumab, galcanezumab, fremanezumab and eptinezumab. 

Erenumab is the only monoclonal antibody that targets the CGRP receptor. It is given as a monthly subcutaneous injection. The dose is either 70 mg or 140 mg.

The other three monoclonal antibodies attach to the CGRP protein and block it from binding to the receptor.

Fremanezumab is a monthly or quarterly subcutaneous injection (225 mg or 675 mg). 

Galcanezumab is a monthly subcutaneous injection (initial dose 240 mg, then 120 mg). 

After an initial administration under supervision and in the safety of a medical facility, patients can use the autoinjector at home. The antibodies can be injected subcutaneously in an arm, leg or the abdomen.

Eptinezumab is the only monoclonal antibody that is administered intravenously. A single intravenous dose of eptinezumab (100 mg or 300 mg) is given every 3 months. For more information on this monoclonal antibody click here

Who Should Use These Medications?

They have all been studied in people with episodic or chronic migraine. They have been shown to be effective for all migraine types as well as medication adaptation headache. They are all FDA-approved for people 18 years or older. Insurance coverage varies and may require failure of two other preventive medications prior to authorization.

What Are The Risks of These Medications?

  • Monoclonal antibodies are not currently associated with any drug interactions. Patients who use monoclonal antibodies do not have to stop taking any of their current preventive or abortive medications or other treatments. 
  • These medications are also not associated with carcinogenesis or genetic interference. 
  • The injection of monoclonal antibodies is relatively painless but there can be a burning sensation for some people. Constipation is one of the most common side effects. A stool softener may be helpful. Hair loss has also been anecdotally reported after the use of some CGRP-blocking monoclonal antibodies. High blood pressure is another possible side effect.
  • Monoclonal antibodies do cross the placenta and appear in breast milk.
  • The long-term effects of blocking CGRP in a developing fetus or child is not clear. If a woman is planning a pregnancy, she should stop monoclonal injections 6 months prior to contraception. 
  • The FDA has a pregnancy registry for each of these medications. If a woman has a baby while on this medication, this database will collect information about the medication risks. 

Patients who use monoclonal antibodies do not have to stop taking any of their current medications. This includes migraine abortive and preventive medications or other treatments.

High Blood Pressure Medications

High Blood Pressure Medications for Migraine

Beta blockers, Angiotensin II Receptor blockers (ARB’s) and Ace Inhibitors are used to treat high blood pressure but have also been found to be effective for migraine prevention. Propranolol is FDA approved for migraine prevention. Other blood pressure medications are also used “off-label” for migraine. Recent studies have found that calcium channel blockers such as verapamil showed no benefit compared to placebo.

How Do Beta Blockers Help Migraine?

Beta Blockers are first line treatments to help prevent migraine attacks because they affect the blood vessels in the brain, make the nervous system less excitable and increase activity in the hypothalamus.  

  • Propranolol (60-240 mg/day)*, Metoprolol (25-200 mg/day), Atenolol 100 mg/day (50-200 mg), Timolol (10-15 mg/day), Nadolol (40-80 mg/day, up to 240 mg/day)
  • Timolol also has an eye drop solution that can be used as an abortive option. See abortive treatments for more information. 
  • Side effects: low heart rate, low blood pressure, activity intolerance, fatigue, erectile dysfunction, vivid dreams, airway bronchospasm, depression and more.
  • Caution in those who are pregnant and/or have asthma, diabetes, circulation issues, COPD, low blood pressure, heart block and more.

How Do Angiotensin II Receptor Blockers (ARB's) Help Migraine?

Angiotensin II receptor blockers (ARB’s) are thought to help prevent migraine attacks because they constrict the blood vessels in the brain and decrease the number of inflammatory proteins. 

  • Candesartan 16 mg/day
  • Side effects: high potassium, headache, dizziness, abnormal kidney levels, cold symptoms and more.

How Do Ace Inhibitors Help Migraine?

Ace Inhibitors are thought to help prevent migraine attacks by constricting the blood vessels in the brain and decreasing the number of inflammatory proteins. 

  • Lisinopril 20 mg/day
  • Side effects: low blood pressure, cough, fatigue, dizziness, headache, decreased or cloudy urine, blurred vision and more.

Anti-Seizure Medications

Anti-Seizure Medications for Migraine

It is unknown exactly how anti-seizure medications help prevent migraine attacks. It is thought that these medications calm hyper-excitable nerve cells, or neurons, in the brain. 

Topiramate for Migraine Prevention

Topiramate (Topamax) is FDA approved for migraine and is commonly used as a first-line medication for prevention

  • Recommended dose: 25 mg/day administered nightly for the first week. The dosage is typically increased weekly by increments of 25 mg per the provider's recommendations. 100 mg/day administered in two divided doses is the recommended dose.
  • Side effects: tingling in the hands and feet, nausea, vomiting, diarrhea, stomach pain and cramps, fatigue, sleepiness, brain fog, hair loss, change in the way foods taste, weight loss, dizziness, loss of appetite
  • Consult your doctor if you have lower back pain or pain with urination or other signs of kidney stones or if you report a new onset of blurred vision and eye pain. Do not take this medication if you have a history of glaucoma.

Divalproex Sodium for Migraine Prevention

Divalproex sodium (Depakote) is FDA approved for migraine prevention and is commonly used as a first line medication for migraine prevention

  • The recommended starting dose is 250 mg twice daily, thereafter increasing to a maximum of 1000 mg/day as needed. 
  • Side effects: drowsiness, nausea, abdominal pain, diarrhea, vomiting, low platelet count, tremors, dizziness, double vision, weight gain, tiredness, problems with walking or coordination, headache, weakness, tremor, increased appetite or loss of appetite and hair loss. 
  • Divalproex can cause serious side effects of inflammation of the pancreas (pancreatitis) and damage to the liver. Monitor liver function and blood counts. 

Valproic Acid for Migraine Prevention

Valproic acid (Stavzor) is FDA-approved for migraine prevention

  • Recommended dose: 250 mg twice daily 
  • Side effects: nausea, diarrhea, vomiting, abdominal pain, increased appetite, indigestion, dizziness, tremor, weight gain, back pain, weakness, hair loss and sleepiness.
  • Valproic acid can cause serious side effects of inflammation of the pancreas (pancreatitis) and damage to the liver. Monitor liver function and blood counts.

Warning

Alcohol should be avoided with all anti-seizure medications and any thoughts of suicide should be reported to a healthcare provider or notify the National Suicide Prevention Lifeline at: 800-273-8255. Anti-seizure medications may reduce the effectiveness of oral contraception, harm a baby during pregnancy and pass through breast milk. Be sure to consult with your healthcare provider. These medications should never be stopped abruptly, they should be weaned off with guidance from a clinician.

Supplements and Vitamins

Vitamins and Supplements

Although supplements and vitamins are available over the counter, it is very important to consult with a doctor before starting a new supplement or vitamin.

The FDA is not required to check the quality of vitamins and supplements. It is important to ensure that these products are purchased from a reputable company that makes quality supplements. Remember, cheaper does not mean better.

To listen to a podcast on vitamins and supplements for migraine, click here.

Magnesium

Magnesium is one of the most well studied supplements that is used for prevention of migraine. A study found that there is a correlation between low magnesium levels and migraine, leading to the belief that magnesium deficiency may be a risk factor for migraine. Deficiency of magnesium is thought to play a role in cortical spreading depression which could be responsible for the aura phenomenon associated with migraine. 

Some types of magnesium that are recommended for oral consumption include: 

  • magnesium glycinate
  • magnesium pidolate
  • magnesium gluconate
  • magnesium L- threonate  

Recommended Dosage: 200-1200 mg daily (common: 400- 500 mg) 

Side Effects: nausea, abdominal cramping, diarrhea  

Topical administration of magnesium chloride is another option, especially for those who experience gastrointestinal symptoms from oral medication or live with a gastrointestinal disorder. 

Interactions: Can lower blood pressure and interact with some heart medications, diuretics, antibiotics (aminoglycosides) and muscle relaxants. 

Riboflavin

Riboflavin, also known as B2, is a vitamin that is found in foods such as organ meats, fortified breakfast cereals, oats, dairy and more. It is unclear how this B vitamin helps with migraine but it may be due to the fact that riboflavin helps with energy metabolism of the cells and decreases certain neuro-inflammatory substances. People living with migraine have been found to have lower levels of riboflavin compared to those without migraine. A study found that supplementing with 400 mg of riboflavin decreased the number of headache days compared to placebo but more studies are needed.

Recommended dosage:  500 mg daily

Side Effects: Bright yellow urine and nausea. 

Interactions: Can interact with anticholinergics, phenobarbital and probenecid. 

Coenzyme Q10

Coenzyme Q10, also known as CoQ10, is a compound that is present in almost every cell in the body and is largely responsible for energy production of the cells. Coenzyme Q10 may help those with migraine by decreasing inflammation, improving cell energy in the brain and reducing CGRP. A study found Coenzyme Q10 levels to be lower in those with migraine than in those without. A recent review of 6 studies found that Coenzyme Q10 was effective in reducing the duration and frequency of migraine attacks.  

Recommended Dosage: 100 mg three times daily, consume with fatty foods for best absorption

Side effects: Upset stomach, rash, poor sleep, headache, dizziness and light sensitivity

Interactions: May interact with blood pressure medicines (especially timolol), blood thinners, cholesterol medicines, insulin, some cancer drugs and tricyclic antidepressants. 

Omega 3

Omega 3 is a fatty acid that you must get from your diet as the body does not make it naturally. Omega 3s are thought to be beneficial for migraine because they regulate serotonin levels in the brain, reduce inflammation and decrease the amount of inflammatory proteins. Common sources of omega 3 include: fatty fish, flaxseed, chia seeds, walnuts and soybeans. 

A study found that diets high in omega 3s were able to reduce the frequency and intensity of migraine attacks. The study also found greater results when the diet had high levels of omega 3s and low levels of omega 6s. 

Recommended Dosage: It is recommended to consume 250–500 mg of DHA and EPA daily, which are two types of omega 3s. 

Feverfew

Feverfew as a migraine preventive is controversial because there is a lack of evidence to support it as a treatment. Feverfew is thought to decrease inflammation, relax smooth muscles in the blood vessels and prevent widening of the blood vessels during a migraine attack. Abrupt discontinuation of feverfew can result in “post feverfew syndrome” and should be tapered with consultation of a provider. Feverfew should not be used during pregnancy. 

Recommended dosage: 6.25 mg three times daily

Side effects: Abdominal pain, diarrhea, mouth ulcers, nausea, vomiting.

Interactions/Precautions: Avoid during pregnancy (risk of miscarriage), combining with aspirin (increases bleeding). Watch for ragweed, chamomile or yarrow cross-sensitivity. 

Melatonin

Melatonin is a hormone produced by the brain that controls our sleep and wake cycle. The brain increases the amount of melatonin at night and when it gets dark, and decreases it when it is light out. Melatonin may help migraine by improving sleep, decreasing anxiety, regulating neurotransmitters, decreasing the release of CGRP and by acting as a pain reliever. A study found melatonin to be more effective than placebo and as effective as amitriptyline 25 mg in preventing migraine. 

Recommended dose: Varies by person, typically 3mg prior to bedtime is recommended

Side effects: Drowsiness, fogginess in the morning, dizziness, nausea

Interactions: Can reduce the effectiveness or increase the risk of side effects when used with  certain medications (blood pressure drugs, seizure-prevention drugs, antidepressants, anticoagulants, immunosuppressants and birth control medications) and increase blood sugar levels. Certain individuals may have an increased sensitivity to melatonin such as children, shift workers, those with depression, etc.

Vitamin D

Vitamin D is not actually a vitamin. It is a hormone. Vitamin D can help migraine by decreasing inflammation and the amount of nitric oxide (a molecule that widens the blood vessels). Vitamin D also influences the release of dopamine and serotonin in the body. Magnesium may not be absorbed as well if there are low levels of Vitamin D. A review did find a link between low Vitamin D levels and migraine. There was not enough evidence to recommend supplementation in all migraine patients, unless there is a Vitamin D deficiency. 

Recommended dose: The optimal dose for migraine prevention is to be determined. 

Side effects: Constipation, nausea, vomiting, weight loss, kidney stones, irregular heart beat, confusion, chest pain

*If you have heart disease, an irregular heartbeat or kidney problems, please consult your doctor before starting Vitamin D. 

Botulinum Toxins

What is Botulinum Toxin?

Botulinum toxin is a neurotoxin that is produced by bacteria known as Clostridium botulinum. There are currently four different botulinum toxins available for chronic migraine: onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA and rimabotulinumtoxinB.

Who Can Use Botulinum Toxins?

OnabotulinumtoxinA was the first to be FDA-approved for the prevention of chronic migraine in adults. It is also currently the most commonly used botulinum toxin for migraine. Chronic migraine is defined as head pain on 15 or more days per month with at least eight of those headaches accompanied by migraine symptoms.

What Does a Treatment Look Like?

A treatment consists of 31-39 injections (totaling 155-195 units) delivered into 7 key muscle areas of the head and neck. The toxin relaxes the muscles and is thought to be absorbed by the nerves in the head and neck which may block pain signaling chemicals known as neurotransmitters. Injections should be administered every 12 weeks. The procedure takes roughly 15 minutes.

Side Effects

Side effects may include: eyelid drooping, neck pain, headache and pain at the injection site. A headache may develop within 24 hours of injection. It can take up to 2 weeks to reach full efficacy. It is recommended to try at least 3 sessions of botulinum toxins for best results.

 

Antidepressants

Are Antidepressants Used for Migraine Prevention?

Antidepressants are commonly used to prevent migraine attacks. Although none of these are approved by the FDA for treatment of migraine, they have shown positive results in clinical trials. They help stabilize the levels of neurotransmitters in the brain which fluctuate during a migraine attack and in-between attacks.

What are Tricyclic Antidepressants?

Tricyclic antidepressants increase the amount of serotonin and norepinephrine in the brain. 

Amitriptyline - Has the best evidence in migraine clinical trials in comparison to the other antidepressants

  • Recommended dose: Starting dose is 10 mg daily but may be increased up to 25 mg per day. It is recommended to take it at bedtime. 
  • Side effects: dry mouth, weight gain, sleepiness, brain fog, retention of urine, lightheadedness when standing up, irregular heart beat, dizziness, constipation, headaches and more.

Nortriptyline - Often prescribed for those who have side effects with amitriptyline and cannot tolerate the medication.

  • Recommended dose: 25 mg at bedtime. It is usually increased by 25 mg every week until the desired dose is reached. Max dose 150 mg. 
  • Side effects: Dry mouth, weight gain, drowsiness, dizziness, constipation, changes in sex drive, breast enlargement, nausea, vomiting, diarrhea, increased heart rate, skin rash and more.

*These medications should be avoided in those with glaucoma, heart disease, urinary issues and an enlarged prostate. Caution in those who are pregnant or have diabetes. 

What Are Serotonin Norepinephrine Reuptake Inhibitors?

Serotonin Norepinephrine Reuptake Inhibitors (SNRI’s) increase the amount of serotonin and norepinephrine in the brain. 

Venlafaxine 

  • Recommended dose: Starting dose 37.5 mg then may increase to 150 mg daily. Can be taken in the morning.
  • Side effects: dry mouth, sexual dysfunction, nervousness, nausea, headache, increased sweating, dizziness, drowsiness and more.

What are Selective Serotonin Reuptake Inhibitors (SSRI's) and Are They Helpful for Migraine Prevention?

Selective Serotonin Reuptake Inhibitors (SSRIs) increase the amount of serotonin in the brain. At this time SSRIs such as fluoxetine and sertraline have not shown effectiveness for migraine prevention but may work well for common migraine comorbidities such as depression and anxiety.

Suicidal Warning

Any thoughts of suicide while on any of the antidepressant medications should be reported immediately to a provider or call the National Suicide Prevention Lifeline at: 800-273-8255. These medications should never be stopped abruptly. They should be weaned off with guidance from a clinician.

Memantine

What Is Memantine and Is It Effective For Migraine Prevention?

Memantine is a NMDA receptor antagonist which means it helps reduce abnormal activity and excitation in the brain. Although it is used to help treat the symptoms of Alzheimer’s Disease, this medication has been classified as “probably effective” for the prevention of migraine. 

  1. Recommended dose: 10 mg - 20 mg daily.
  2. Side effects: dizziness, headache, constipation and confusion

Download the Patient Brochure

Diagnostic questions, treatment options, dosages and preventative measures.

Interventional Treatments

When managing your triggers is not enough to control your symptoms, you may want to consider a medicine that will “calm down” your nervous system. They are designed to make subtle changes in how the nervous system transfers information and this can reduce the intensity, duration and frequency of pain and other unpleasant symptoms.

These recommendations are based on the strength of clinical trials studies and therefore you must understand that there are other medicines that may work but have not been studied thoroughly enough to be in the top two tiers of these guidelines.

In other words, these guidelines list those medications that have been best evaluated and showed the greatest promise that they might work.

Caution: This information is NOT intended to endorse drugs or recommend therapy. Only your doctor can decide which medications are right for you. Never stop, start or change the way you use a prescription medicine without first consulting your doctor. Not all side effects are described. Call your doctor or consult your pharmacist for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Acetaminophen, Aspirin and Caffeine

Ex. Excedrin Migraine

Many migraineurs find this OTC medication effective for their occasional headaches and other migraine-related symptoms.

Possible side effects

  • GI bleed
  • Migraine is not relieved or worsens after first dose
  • Tinnitus
  • Loss of hearing
  • New or unexpected symptoms develop

Acetaminophen, Butalbital and Caffeine

Ex. Fioricet

How it works

Acetaminophen is a pain reliever and fever reducer. Butalbital is in a group of drugs called barbiturates. It relaxes muscle contractions involved in a tension headache. Caffeine is a central nervous system stimulant. It relaxes muscle contractions in blood vessels to improve blood flow.

Possible side effects

Get emergency medical help if you have any of these signs of an allergic reaction:

  • hives
  • difficulty breathing
  • swelling of your face, lips, tongue, or throat

In rare cases, Acetaminophen may cause a severe skin reaction that can be fatal. This could occur even if you have taken acetaminophen in the past and had no reaction. Stop taking this medicine and call your doctor right away if you have skin redness or a rash that spreads and causes blistering and peeling. If you have this type of reaction, you should never again take any medicine that contains acetaminophen.

Stop using Fioricet and call your doctor at once if you have:

  • Confusion or seizure (convulsions)
  • Shortness of breath
  • A light-headed feeling or feeling like you might pass out
  • Nausea
  • Upper stomach pain
  • Itching
  • Loss of appetite
  • Dark urine
  • Clay-colored stools
  • Jaundice (yellowing of the skin or eyes)

Common Fioricet side effects include:

  • Drowsiness or dizziness
  • Feeling anxious or restless
  • Drunk feeling
  • Sleep problems (insomnia)

Triptans

Ex. Imitrex, Maxalt, Zomig, Amerge, Frova, Relpax, Axert

There are seven triptans—almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan— that target specific serotonin receptors on the brain’s blood vessels and nerve endings. Triptans block the neurotransmitter CGRP and narrow blood vessels, which decreases the pain and inflammation of a migraine attack. Triptans should be taken early in the attack for best results. Certain triptans may be taken again in 2-4 hours if needed. The seven triptans vary in the onset of action. They may be taken orally, intranasally or subcutaneously which also affects how quickly they work. Triptans are rated as level A evidence for the acute treatment of migraine. In addition, Naproxen in combination with sumatriptan is rated as level A evidence for the acute treatment of migraine.

Side Effects

  • Side effects may vary based on the triptan but may include: chest pain, nausea, dizziness, flushing, tingling and neck pain. 

Caution

  • Tell your doctor if you have a history of heart disease, high blood pressure, impaired liver function, diabetes, peripheral vascular disease or Raynaud’s syndrome as triptans are then typically avoided.
  • Do not take more than 2 doses in 24 hours
  • Use of triptans more than 9 times per month can contribute to medication adaptation headache
  • A person taking triptans may develop serotonin syndrome which is a dangerous but rare condition caused by excessive release of the neurotransmitter serotonin. Tell your doctor if you are taking other medications that increase serotonin levels such as antidepressants, ditans or opioids. Signs and symptoms of serotonin syndrome include: nausea, vomiting, agitation, restlessness, confusion, fever, high blood pressure and a rapid heart rate.
  • Do not take with other type of triptan or ergot alkaloid 
  • Avoid in people living with hemiplegic migraine

NSAIDS

NSAIDs, such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Anaprox) can effectively control migraine pain in many conditions.

How they work

They suppress the pain and inflammatory phase of a migraine attack. Normally during migraine attacks, prostaglandins are released and they sensitize pain sensors. NSAIDs block the synthesis of prostaglandins.

NSAIDs block the enzyme cyclooxygenase (COX) from synthesizing prostaglandins, which cause pain and inflammation. NSAIDs may not only reduce pain transmissions through these nerves, but reduce the generation of further cortical spreading depressions.

Ditans

Lasmiditan

Ex. Reyvow

Lasmiditan is an FDA approved medication for the acute treatment of migraine with or without aura. It belongs to the new class of medications known as ditans. It activates a specific serotonin receptor known as 5-HT1F that is found on the nerves. This serotonin receptor is involved in pain pathways. When the receptor is activated, it is able to stop the release of neurotransmitters and block pain. Because lasmiditan acts on the serotonin receptor on the nerve and not in the blood vessels (like triptans), this acute medication can be used in those who have cardiovascular disease, high blood pressure, diabetes and stroke. 

Side effects

  • Dizziness and lightheadedness (increases with higher doses), fatigue, paresthesia (“pins and needles”), sedation, nausea, vomiting and muscle weakness. 

Dosage

  • 50 mg, 100 mg or 200 mg. 

Caution

  • Lasmiditan is a controlled substance and must be prescribed by a doctor. There is a driving restriction and people should not drive or operate heavy machinery for eight hours after taking the dose. 
  • This medication should not be used more than 9 times per month because it can contribute to medication adaptation headache. 
  • Do not take this medication more than one time in a 24 hour period.
  • A person taking ditans may develop serotonin syndrome which is a dangerous but rare condition caused by excessive release of the neurotransmitter serotonin. Tell your doctor if you are taking other medications that increase serotonin levels such as antidepressants, triptans or opioids. Signs and symptoms of serotonin syndrome include: nausea, vomiting, agitation, restlessness, confusion, fever, high blood pressure and a rapid heart rate
  • Inform your provider if you are on medications that lower your heart rate such as beta blockers.

Acute and Preventive Therapies

Gepants

What is CGRP?

Calcitonin gene-related peptide, or CGRP, is a protein found in the peripheral and central nervous systems. Studies have proven that CGRP levels are higher during a migraine attack and lower between attacks. CGRP causes inflammation, blood vessel swelling and dilation. CGRP also sends pain messages to the brain during a migraine attack.

Gepants and CGRP monoclonal antibodies are two new medication classes that are designed to target CGRP or its receptors.

What are Gepants?

Gepants are a medication class that are known as CGRP antagonists. This means gepants block the CGRP protein from attaching to its receptor. There are three gepants currently available:

  • Rimegepant (orally dissolving tablet) - approved for acute and preventive treatment of migraine
  • Ubrogepant (oral tablet) - approved for the acute treatment of migraine
  • Atogepant (oral tablet) - approved for the preventive treatment of migraine

Zavegepant is currently being studied as an abortive nasal spray.

Benefits of Gepants:

  • They don’t have the same risk of medication adaptation headache as some other migraine and pain relievers.
  • They are longer and faster acting than some other common migraine medications.
  • They do not cause blood vessels to constrict, so unlike triptans, they should be safe in those with vascular disease.
  • They appear to work for patients who did not gain relief from triptans.
  • While they are best used early in a migraine attack, many still find relief even if it is taken late during an attack.

Who Should Use These Medications?

All FDA-approved gepants have been studied and show efficacy for adults with episodic or chronic migraine. It is safe for all migraine types as well as medication adaptation headache.

Side Effects

  • Fatigue and nausea are the most commonly reported symptoms.
  • The long-term effects of blocking CGRP in a developing fetus or child are not clear.
  • If a woman is planning a pregnancy, she should stop gepants 6 months prior to contraception.

Can I Take Gepants With My Other Medications?

There are no known drug interactions with gepants. Patients who use gepants do not have to stop taking any of their current medications, including other acute and preventive migraine medications. Always consult with your doctor before taking a new medication.

Neuromodulation

External Trigeminal Nerve Stimulation (e-TNS)

Ex. Cefaly®

The trigeminal nerve is the largest nerve in the brain and plays a big role in migraine attacks. The external trigeminal nerve stimulation device is worn on the forehead where it stimulates the top branches (supraorbital and supratrochlear nerves) of the trigeminal nerve. It is thought that migraine pain can be interrupted by stimulating the trigeminal nerve.

This is an FDA cleared device for the acute and preventive treatment of episodic migraine in those over 18 years old. As a preventive agent, it is used once a day for 20 minutes. It can be used for break-through acute migraine attacks up to 60 minutes per day.

Side effects: Sleepiness, temporary allergic rash or redness on forehead, low-grade headache following preventive treatment

For the user manual/safety information on cefaly, click here.

*This is currently the only neuromodulation device that does not require a prescription.

Non-Invasive Vagus Nerve Stimulation

Ex. Gammacore™

Non-invasive vagus nerve stimulation stimulates the vagus nerve through the skin. The vagus nerve runs from the brain through the face to the abdomen. It is thought that stimulation of this nerve helps block pain signals that cause migraine.

It is FDA cleared for:

  • acute and preventive treatment of migraine (12 years and older)
  • acute and adjunctive preventive treatment of cluster headache
  • acute treatment of hemicrania continua and paroxysmal hemicrania.

The device is placed at the neck where a pulse can be felt. Intensity should be Increased until muscle contractions or lip pulling can be felt. You can schedule a 1:1 video call with a company representative prior to use.

For migraine prevention the device should be used for 2 stimulations, 3 times a day for a total of 6 stimulations, all on the same side of the neck. Each stimulation should be 2-minutes long. The device will automatically stop after 1 two-minute stimulation is completed so be sure to use it for one more stimulation. The first use should be within 1 hour of waking up in the morning, the second use should be 4-6 hours after the first treatment and then the third use should be at night. Be sure to apply the conductive gel that was supplied with the device prior to stimulation.

For acute treatment of migraine, the device should be used for two 2-minute stimulations at the onset of pain. Wait 10 seconds after each stimulation. If the pain does not resolve within 20 minutes, try again with two more 2-minute stimulations. After 2 hours, if you still have pain, try another two 2-minute stimulations.

Side effects: dizziness, redness, application site discomfort, irritation, muscle twitching of face/head/neck or tingling resolving after treatment finishes.

Gammacore safety information is located here.

Remote Electrical Neuromodulation

Ex. Nerivio™

Remote electrical neuromodulation is FDA cleared for the acute treatment of episodic and chronic migraine in those 12 years and older. It is applied to the upper arm where it stimulates the nerve fibers. These signals travel from the upper arm into the brainstem. This process helps to stop pain messages that occur in the brain during a migraine attack.

This device is worn on the upper arm and secured with the strap provided. It is controlled by an app on a cell phone. The device should be started at the onset of an attack and worn for 45 minutes. Set intensity to a strong but not painful level for the entire session.

Side effects: warmth, itching, tingling or mild pain in the arm, shoulders, or neck, muscle spasm, or temporary numbness in arm or hand

*Safety information from Nerivio can be found here.

Non-Invasive Combined Occipital and Trigeminal Nerve Stimulation

Ex. Relivion® MG

The non-invasive combined occipital and trigeminal nerve stimulation was cleared by the FDA for the acute treatment of episodic migraine in those 18 or older.

This device is an electronic headset that wraps around the forehead to the back of the head. It has 4 electrodes that stimulate the trigeminal nerve and 2 electrodes on the back of the headset that stimulate the occipital nerves. During use, the device sends signals to both of these nerve pathways. These signals are relayed to the brainstem to provide relief from a migraine attack.

The headset is connected to a cell phone app that stores all the treatment data and can be shared with a health care provider. Treatment times vary for each patient. Proper fitting is critical in receiving an effective treatment. Guided device fittings are offered by the manufacturer and should be scheduled prior to using the device.

Side effects: Scalp numbness, persistent tingling, pain, skin reaction, fatigue, sleep disruptions, dizziness, headache

*Safety information for Relivion can be found here.

Single-Pulse Transcranial Magnetic Stimulation

Ex. sTMS mini®

The company that offers the single-pulse transcranial magnetic stimulator is no longer in business. Therefore, these devices are no longer available. If you still have a device, please refer to the company’s website for more information.

Other Therapies

Cold Therapy (Cyrotherapy)

How it works

Lower temperature applied to the skin reduces pain by temporarily inactivating pain sensors in the skin and muscles. It may also reduce muscle tension.

Possible side effects

  • Freezing the skin
  • Reduced blood flow to the heart and rest of the body

Nerve Blocks

Trigger Point Injections

Trigger points are focal areas of muscle spasm, often located in the upper back and shoulder areas. A trigger point injection involves the injection of medication (steroids, saline and/or anesthetic medicine) directly into the trigger point. With the injection, the trigger point is made inactive and the pain is alleviated. Usually, a brief course of treatment will result in sustained relief. Injections are given in a doctor’s office and usually take just a few minutes. Several sites may be injected in one visit.

Trigger point injections can be used to treat a number of conditions including fibromyalgia, tension headache, and myofascial pain syndrome.

Greater Occipital Nerve (GON) block

Neurologists working in the headache field used GON local anesthetic (lidocaine, bupivacaine, clonidine, and fentanyl) or steroid injections into region of the sensory nerves at the back of the neck (the greater occipital nerve and lesser occipital nerves). The exact composition of the nerve block can vary between physicians.

The goal is to provide pain relief for up to 2 months in chronic migraine sufferers. In a recent study the GON block did not reduce the frequency of moderate to severe migraine days in patients with episodic or chronic migraine compared to placebo*.

The efficacy and use of GON blockade in primary headache other than migraine, for example, cluster headache and cervicogenic headaches (unilateral neck pain and stiffness), is already better established.

* Dilli E, Halker R, Vargas B, Hentz J, Radam T, Rogers R, Dodick D. Occipital nerve block for the short-term preventive treatment of migraine: A randomized, double-blinded, placebo-controlled study. Cephalalgia. 2015 Oct;35(11):959-68.

Cognitive-behavioral therapy (CBT)

Cognitive-behavioral therapy (CBT) is a psychological approach to managing headaches and migraine. The reason that people with headaches and migraine see a psychologist is not because those conditions are lacking a physical basis and it is all in their imaginations. Psychologists are involved in the treatment of pain for 2 reasons: 1) There are effective treatments for migraine and headache (e.g., relaxation strategies, stress management and coping strategies, assertive communication) that psychologists have been trained to administer, and 2) Patients suffering from chronic headaches and migraine may also be in a vicious cycle which is often helpful to discuss with someone familiar with them, i.e. pain causes stress, tension, anxiety, and/or depression which also causes more pain.

CBT assists in the reduction of the vicious cycle by facilitating the development of skills that increase your ability to cope with pain and reduce headache-related psychological distress. CBT is an intervention based on scientific evidence that uses various cognitive and behavioral strategies. A study of outpatient combined group and individual cognitive-behavioral treatment for adult patients with migraine and tension-type headache found a significant reduction in average headache intensity, headache frequency, and unhelpful thoughts about headache as well as an increase in the use of adaptive coping strategies. A review of the existing research showed that cognitive-behavioral therapy and relaxation techniques lead to a significant reduction in headache activity ranging from 30% to 60%.

Cognitive-based interventions are based on the assumption that much of what we feel is determined by what we think. Cognitive strategies focus on identifying and challenging unhelpful thoughts and responses to stressful events. They aim to enhance headache sufferers’ ability to engage in behaviors that enhance their self-management of headaches. Reductions in negative thoughts about headache pain and the use of a greater number of positive coping strategies were associated with reductions in the disabling effects of headache in a research study comparing behavioral migraine management training, use of beta blocker medications, and a placebo.

Increasing and/or fine-tuning your coping skills can also positively impact your headache experiences. CBT also includes learning how to recognize and cope with headache triggers. Treatment also typically includes:

Improving Wellness Activities

  • These include strategies to improve: Sleep, Physical Activity, Hydration, and Eating Habits.
  • Inconsistent and/or poor habits in these areas contribute to headaches and often involve small changes that reap large benefits.

Relaxation Strategies

  • These reduce the arousal of the central nervous system and reduce muscle tension which both are implicated in headaches.   In addition, you are absorbed in a pleasant state which is incompatible with pain.
  • Effective relaxation strategies include: Progressive Muscle Relaxation, Visual Imagery, Autogenic Relaxation, and Meditation.

Stress Management Techniques

  • Stress can precipitate individual headache episodes, exacerbate the progression of headaches, worsen the headache sufferer’s quality of life, and be a result of frequent headaches.
  • Stress management techniques include the altering or adapting to stress triggers, getting support for undertaking tasks, problem-solving skills, and assertive communication as well as the previously mentioned relaxation strategies.

Managing Headache Triggers

  • Light/glare, weather, smells/odors, dust, and alcohol can be headache triggers.
  • While many individuals have developed some strategies to manage these triggers, often fine-tuning strategies can be valuable.

Pacing of Activities

  • Headache sufferers get concerned about how headaches impede their productivity or functioning at work, home, or in social situations. In an effort to make up for lost time, when pain is tolerable they overexert themselves and usually increase their pain.
  • Pacing is based on observing what activities increase pain after what period of time and an awareness of one’s limits. The objective is for the patient to be able to alternate active times with sedentary times and thereby get more accomplished without increasing pain and fatigue.

The chief goal of CBT is to exchange sick time for wellness time. You can spend the exchanged time enjoying yourself, staying healthy, managing triggers and stress thereby minimizing headaches

Cannabis

What is Cannabis?

Cannabis is a plant that contains over 500 cannabinoids and 104 compounds. Two types of cannabis are hemp and marijuana. Hemp contains less than 0.3% THC and contains higher concentrations of CBD, while marijuana contains greater than 0.3% THC and has smaller concentrations of CBD. 

THC vs. CBD

THC is known for its psychoactive properties but can be used for nausea, pain relief, insomnia and as an appetite stimulant. CBD can decrease pain, inflammation and anxiety without a psychoactive effect. It is believed that CBD and THC are more effective when consumed together. 

How to Consume Cannabis?

The quickest onset of consumption is inhalation by smoking or vaping. According to the CDC, vaporized THC has been linked to EVALI (E-cigarette or vaping associated lung injury) due to additives in the product. Cannabis can also be consumed as an edible, a topical application, sublingually (under the tongue), or as a transdermal patch. It is recommended to start CBD at a low dose around 5 mg per day and slowly increase to 20-50 mg per day. For THC, it is common to begin around 2.5 mg-5 mg. Currently, this therapy is not covered by insurance and may be costly for quality products. Always consult with a health care provider prior to starting a new treatment or changing dosages. 

Precautions/Side Effects

CBD must be used in caution with drugs that induce the liver enzymes CYP3A4 or 2C19 such as anticoagulants, antiepileptics, antiarrhythmics and thyroid medications. Cannabinoids should be avoided in children and during pregnancy because of concerns about brain development and lowering a child’s potential IQ. For a small number of users there are serious risks of hyperemesis syndrome, chronic psychosis, unveiling underlying schizophrenia and an estimated 9% risk of addiction. Typical cannabinoid side effects include: drowsiness, increased appetite, diarrhea, dry mouth and elevations in transaminase. Any user of THC should avoid driving and use of heavy mechanized equipment because of potential impaired attention and heightened anxiety. 

Please note this description is for medical cannabis. Cannabis is still considered federally illegal and laws vary from state to state. For more information on cannabis and migraine visit Migraine Buds.