A Guide to Medications for Migraine Prevention

There are various types of medications used to prevent migraine attacks in people living with migraine.

These range from general medications like antidepressants and anti-seizure drugs that have been used for many years to more specific treatments such as calcitonin gene-related peptide (CGRP) inhibitors, which were developed to target migraine.

This article will discuss each type of preventive medication used for migraine.

What Is Migraine Preventive Treatment?

Preventive medicines are taken regularly. Some medications are taken daily, while the newer, injectable medicines are taken every one to three months. Some goals of preventive therapy are:

• Decrease the number of migraine attacks (some healthcare providers use 50% improvement as a goal)
• Decrease the severity of symptoms of migraine attacks
• Decrease the overall impact of a migraine attack (such as missed work or school)
• Improve response to acute medicine
• Prevent emergency room or urgent care visits
• Prevent overuse of acute medications, as this can lead to medication overuse headaches (rebound headache)
• Improve quality of life

Do You Need Migraine Preventive Treatment?

Generally, you may need preventive migraine treatment if:

• You experience disabling migraine attacks, even with treatment.
• You experience frequent migraine attacks (generally one per week or more).
• You do not respond sufficiently (or at all) to medications you take to treat a migraine attack (called rescue medications or acute treatments), or you cannot take or tolerate these treatments.
• You have a history of frequently or excessively taking medications that make headaches worse.

The following medications are ones that have been prescribed for migraine prevention.

Antidepressants

Clinical guidelines from the American Academy of Family Physicians (AAFP) note that the best antidepressants for migraine prevention include amitriptyline and venlafaxine, which are considered similarly effective. However, other antidepressants may be prescribed.

Amitriptyline

Amitriptyline is part of a group of drugs called tricyclic antidepressants. It is only available as a generic medication but is sometimes referred to by the brand name Elavil (which is no longer available).

The Food and Drug Administration (FDA) approved amitriptyline to treat depression. However, it is also used off-label to prevent migraine. It works by increasing levels of the neurotransmitters norepinephrine and serotonin in the brain.

Tricyclic antidepressants like amitriptyline are associated with many side effects, including:

• Blurry vision
• Constipation
• Sedation
• Dry mouth
• Confusion
• Problems urinating
• Fast heart rate

These side effects are especially problematic in older adults, who are more sensitive to these effects.

Venlafaxine

Venlafaxine, also known by the brand name Effexor XR (an extended-release formulation), is part of a group of drugs called serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressants.

Effexor XR is FDA-approved to treat depression and anxiety disorders. It is also prescribed off-label to prevent migraine.

Like amitriptyline, venlafaxine works by increasing norepinephrine and serotonin in the brain. Common side effects of venlafaxine include:

• Nausea
• Drowsiness
• Dry mouth
• Sweating
• Sexual problems
• Appetite loss
• Constipation

Anti-Seizure Drugs

Anti-seizure drugs (anticonvulsants), such as Depakote (divalproex sodium) or Topamax (topiramate), may be used to prevent migraine attacks. Studies show that both drugs are effective and well-tolerated.

Topamax and Depakote are both FDA-approved to prevent certain types of seizures, as well as prevent migraine. The way anti-seizure drugs work to prevent migraine is not completely understood, but they are thought to act on certain parts of the brain to decrease abnormal brain excitability and protect nerve cells.

Common side effects of these drugs include:

• Appetite and weight changes
• Problems with thinking or memory
• Altered taste
• Stomach problems such as nausea, stomach pain, and diarrhea

Clinical guidelines state that either of these drugs may be considered a first-line option for preventing migraine headaches. However, these drugs should not be used in pregnant individuals because they could cause harm to the fetus.

Beta-Blockers

Beta-blockers are medications used to treat high blood pressure and other heart-related conditions.

There are various beta-blockers available. However, propranolol, Lopressor (metoprolol), and timolol are the beta-blockers that are recommended as a first choice of therapy for migraine prevention due to their effectiveness, as shown in clinical trials.

The way beta-blockers work to prevent migraine is not completely understood, although many theories are suggested, such as affecting serotonin and excitability.

Common side effects of beta-blockers include:

• Drowsiness
• Cold hands or feet
• Weakness
• Dizziness
• Dry mouth, eyes, and skin

Botox

Botox (onabotulinumtoxinA) is a form of botulinum toxin, a neurotoxin (a poison) that affects the nervous system.

Botox is injected every three months into 31 specific points where nerves are active during migraines. These points include above the bridge of the nose, the forehead, the top of the neck, behind the head, and in the muscles that connect the neck and shoulders. Botox prevents muscle contractions, and works to prevent migraine by blocking pain signals in nerves in the head, neck, and shoulders for up to three months.

Botox is not considered effective in preventing episodic migraine, but may be effective in preventing chronic migraine. People with episodic migraine have up to 14 headache days per month, while people with chronic migraine have 15 or more headache days per month.

Common side effects of Botox include:

• Neck pain
• Stiffness
• Temporary headache (for a day or two after the procedure)
• May change facial features, such as the arch of the eyebrow, lines in the forehead, and, sometimes, the eyelid, causing it to droop

Calcium Channel Blockers

Calcium channel blockers are medications used to treat high blood pressure, chest pain, and irregular heartbeat.

While past research evidence suggested calcium channel blockers—specifically verapamil (brand name is Verelan) and nimodipine (brand is Nimotop)—were effective for migraine prevention, supporting data are weak and insufficient. One drug in this classification, Cardene (nicardipine), however, is still considered “possibly effective” for migraine prevention.

Some research concludes all calcium channel blockers have conflicting or inadequate evidence to support their use for migraine prevention.

Common side effects of nicardipine include:

• Headache
• Stomach upset
• Dizziness
• Tiredness
• Flushing
• Numbness
• Fast heartbeat
• Constipation
• Dry mouth
• Muscle cramps

CGRP Inhibitors

Calcitonin gene-related peptide inhibitors are the newest class of drugs to be FDA-approved for migraine. They are the first class of drugs specifically developed as targeted therapy for migraine.

CGRP is a protein that is released during migraine attacks. CGRP inhibitors block this protein to help prevent (and sometimes also treat) migraine.

CGRP inhibitors for migraine prevention include:

• Aimovig (erenumab-aooe)
• Ajovy (fremanezumab-vfrm)
• Emgality (galcanezumab-gnlm)
• Nurtec ODT (rimegepant)
• Qulipta (atogepant)
• Vyepti (eptinezumab-jjmr)

Aimovig

Aimovig (erenumab-aooe) is an injectable medicine used to prevent migraine in adults. It is injected once a month under the skin of the abdomen, thigh, or upper arm. Common side effects are injection site reactions (such as pain and redness) and constipation.

Ajovy

Ajovy (fremanezumab-vfrm) is an injectable medicine used to prevent migraine in adults. It is injected once monthly under the skin of the abdomen, thigh, or upper arm.

Alternatively, a higher dose may be injected every three months. Injection site reactions are the most common side effect.

Emgality

Emgality (galcanezumab-gnlm) is an injectable medicine used to prevent migraine in adults. It can also be used to treat episodic cluster headaches.

For migraine prevention, the first dose is a onetime higher dose of 240 milligrams (mg). This is called a loading dose. Then, the regular dose of 120 mg is injected every month.

Emgality is injected under the skin of the abdomen, thigh, buttocks, or upper arm. Injection site reactions are the most common side effect.

Nurtec ODT

Nurtec ODT (rimegepant) is an orally disintegrating tablet that is placed on or under the tongue to dissolve. It is FDA-approved to prevent episodic migraine in adults.

For this use, it is taken every other day. It can also be taken as needed for acute migraine treatment. However, no more than 18 doses can be taken in 30 days. Common side effects include nausea, stomach pain, and indigestion.

Qulipta

Qulipta (atogepant) is an oral tablet taken once a day to prevent migraine in adults. Common side effects include nausea, constipation, and drowsiness/tiredness.

Vyepti

Vyepti (eptinezumab-jjmr) is given by intravenous infusion (into a vein). It is administered once every three months and takes about 30 minutes to complete.

Common side effects include allergic reactions and symptoms of the common cold.

How Long Does It Take to Work?

While results vary by individual, it may take anywhere from two to six months to see the full benefits of preventive treatment.

Keeping track of your migraine attacks and staying in contact with your healthcare provider can help you narrow down which medication and dose work best for you. This may help you notice benefits faster than if you do not keep track.

Other Tips for Migraine Prevention

Some other tips for migraine prevention include:

It is also helpful to keep track of migraine attacks in a journal or with a mobile app. Doing so can also help you identify and avoid triggers. Some common triggers are:

• Missing meals
• Menstruation
• Stress
• Weather changes
• Alcohol
• Certain odors

Dietary triggers for some people include chocolate, soft cheeses, red wine, and certain food additives, such as monosodium glutamate (MSG).

Your healthcare provider can also give personalized medical advice on avoiding and managing triggers.

Summary

Although migraine attacks can be frustrating and interfere with your quality of life, there are various options available that can help reduce the frequency and severity of these attacks.

Combining medication with other methods, such as dietary supplements, therapy, and avoiding triggers, can help as well.

Consult your healthcare provider for more information and medical advice on migraine prevention.