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The Most Effective Migraine Medications

Migraine Medications
Key Takeaways
  • Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin) and combined medications such as Excedrin Migraine are effective for mild to moderate migraines. Triptans and dihydroergotamine are used for moderate to severe attacks.

  • Long-term relief includes beta-blockers, calcium channel blockers, and anti-seizure drugs, which help reduce the frequency and severity of migraines.

  • New treatments such as gepants (e.g., Ubrelvy) and lasmiditan (Reyvow) offer faster relief with fewer side effects, while neuromodulation therapies provide non-drug solutions by targeting nerve pathways.

Understanding Migraine Medications  

According to the National Headache Foundation and American Headache Society, there are approximately 28 million migraine sufferers in the United States. Interestingly, 21 million of them are women, and 7 million are men. There is a migraine sufferer in 1 out of every 4 households in America. The International Headache Society estimates that 17% of women and 6% of men worldwide suffer from migraines.

What Are Migraine Headaches?

Migraine headaches are headaches that cause severe head pain, typically on one side of the head. The pain is throbbing or pulsing in nature. It can occur along with other symptoms such as nausea, vomiting, visual symptoms, and light/sound sensitivity. 

Some people experience an “aura” just before a migraine headache, consisting of flashing lights, visual disturbances, tingling, or problems with speaking. Women sometimes have a menstrual migraine in association with their period. Hemiplegic migraine causes weakness on one side of the body along with the headache.

Types of Migraine Medications  

Migraine pain can last for several hours, even days, making it difficult to do daily activities. While there is no cure for migraines, effective migraine treatments are available. Abortive medications and preventive treatment can help to manage this headache disorder. 

A neurologist (a doctor who specializes in the treatment of the brain, spinal cord, peripheral nerves, and muscles) can make a migraine diagnosis based on your history, physical examination, and imaging tests, if required. Besides acute migraine treatment for immediate pain relief, preventive treatment (migraine prophylaxis) is also available. 

Learning about the different medications used for the prevention and acute treatment of migraine headaches can help you understand your treatment options. This way, you can work with your doctor to choose the best migraine medications for you.

 

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Treatment of Migraine Headaches

There are many different types of headache disorders, such as a cluster headache, chronic daily headache, sinus headache, and migraine headache. Migraines are characterized by recurrent attacks. The goal of migraine treatment is to stop current migraine attacks and prevent future episodes.

Medications used to treat migraine headaches broadly fall into two categories. First, pain-relieving medications are used for acute treatment, i.e., to stop symptoms or abort a migraine headache that has already started. Second, preventive migraine medications are taken regularly to reduce the frequency of migraine headaches (migraine prophylaxis).

Drugs for Acute Treatment and Immediate Relief from Migraine Headache

Migraine drugs used to relieve pain work best when they are taken at the first sign of a migraine attack. Here is a summary and comparison chart to quickly guide decision-making and highlight key differences among acute migraine treatments.

First Line Treatments for Mild Migraines
  • Acetaminophen (Tylenol)

  • NSAIDs like ibuprofen (Motrin, Advil)

  • Combined migraine medicines like acetaminophen, aspirin, caffeine (Excedrin Migraine)

Second Line Treatments for Moderate Migraines
  • Triptans 

  • Combined triptans and NSAIDs, for example, sumatriptan and naproxen (Treximet)

  • Dihydroergotamine (DHE 45)

  • Antiemetics

  • NSAIDs by injection (ketorolac)

Third-Line Treatments for Severe Migraines
  • Ditans (lasmiditan)

  • CGRP receptor antagonists

Treatment of Refractory Migraine (severe migraine that is difficult to treat and does not respond to standard treatments and migraine prophylaxis)
  • Intravenous steroids (dexamethasone)

  • Intravenous, intramuscular, or subcutaneous dihydroergotamine (DHE 45)

  • Intravenous magnesium sulfate for migraine with aura

  • Opioid pain relievers

  • Intravenous antiepileptic drugs like valproate

Over-The-Counter Pain Relievers

Several over-the-counter medications can be used to treat episodic migraines. The most common ones are acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen (Advil, Motrin, Naprosyn). These are usually the first line of acute treatment for mild to moderate migraine headaches. They work by blocking the production of chemicals called prostaglandins that cause pain and inflammation.

Some other over-the-counter medications for migraine relief, such as Excedrin Migraine, contain a combination of caffeine, aspirin, and acetaminophen. They can be especially helpful for mild migraine pain. 

However, prolonged use of these medications for migraine symptoms can cause rebound headaches or medication-overuse headaches. Chronic use of NSAIDs can also cause other adverse effects like stomach ulcers, gastrointestinal bleeding, and kidney injury. 

Prescription Medications for Acute Migraine

Other migraine medications like triptans, ergot alkaloids, anti-nausea medications, and combination pain medications are used for abortive treatment of moderate to severe migraines. Some of these medications are second- or third-line therapies. Meaning, they are used in select patients based on headache severity or for refractory migraine (migraine headache that does not respond to first-line migraine medications). 

Triptans

Triptan medications such as sumatriptan nasal spray (Imitrex) and rizatriptan (Maxalt) are prescription drugs available as pills, nasal sprays, and injections to treat migraine pain. They constrict blood vessels and block pain pathways in the brain to relieve migraine symptoms. Learn more about sumatriptan for acute migraine.

The 7 triptans that have been approved by the FDA include:

However, triptans may not be safe for all migraine sufferers, especially those at a high risk of heart attack or stroke.

Dihydroergotamine

This medication is available as an injection and nasal spray. It is effective when taken soon after migraine symptoms start. In particular, it is useful for migraine headaches that last more than 24 hours. This drug works by tightening blood vessels in the brain and preventing the release of certain natural substances that cause swelling and pain. Examples are Migranal and DHE 45

However, dihydroergotamine can cause worsening nausea and vomiting as a side effect. It is not suitable for people with high blood pressure, coronary artery disease, liver disease, or kidney disease

Lasmiditan 

This is a newer medication that is used to treat migraines. Clinical trials have shown it can significantly improve headache pain. It works by blocking pain pathways in the brain. 

Side effects include drowsiness and dizziness. You must refrain from driving or doing anything that requires mental focus for at least eight hours after taking lasmiditan (brand name Reyvow).

CGRP Receptor Antagonists

Ubrogepant (Ubrelvy) was the first calcitonin gene-related peptide receptor antagonist (CGRP receptor antagonist) approved to treat migraines. It works by blocking the action of a natural substance called CGRP, which is involved in headache pain. This oral medication was found during placebo-controlled trials to relieve migraine pain plus other migraine symptoms such as light, sound sensitivity, and nausea. 

Examples of CGRP receptor antagonists or gepants include ubrogepant (brand name Ubrelvy) and rimegepant (Nurtec ODT). 

Possible side effects of ubrogepant include drowsiness and dry mouth. People who are taking drugs that are CYP3A4 inhibitors should not take CGRP receptor antagonists. A few examples of CYP3A4 inhibitors are itraconazole, clarithromycin, erythromycin, diltiazem, ritonavir, verapamil, and grapefruit products. Talk to your doctor or pharmacist to see if any of your current medications will interact with CGRP receptor antagonists. 

Antiemetics

Some migraine drugs help to relieve other symptoms of migraine headaches, such as visual disturbances, nausea, and vomiting. Acute medications for nausea and vomiting (antiemetics) include: 

They are usually taken along with pain-relieving medications.

Opioid Pain Relievers

Narcotic pain medications like oxycodone (OxyContin) or hydrocodone (Vicodin) may be prescribed to people with severe pain who cannot take other medications for acute migraine. They work by blocking pain signals. However, opioid medications are habit-forming and carry a high risk of addiction. Therefore, they should be used with caution under the close supervision of the prescribing physician. 

Keep in mind that some of these OTC and prescription drugs for relieving pain are not safe for pregnant women. So if you are pregnant, could be pregnant, or plan to become pregnant, please tell your doctor before starting migraine treatment. 

Migraine Prophylaxis: Drugs for Preventive Migraine Treatment

Certain migraine drugs can be taken regularly for migraine prevention. Doctors usually prescribe these drugs to people who have severe, frequent, or long-lasting migraine headaches that do not respond well to acute migraine medications. 

Preventive migraine drugs help reduce the frequency, severity, and duration of migraine attacks, i.e., they reduce how often you get migraine headaches, how bad they are, and how long your severe headaches last. Some medications used for migraine prevention are described below in detail. But first, here is a comparison table summarizing the key medication types used for migraine prevention.

First Line Prevention
Second Line Prevention
  • Calcium channel blockers (flunarizine)

  • Antidepressants (amitriptyline)

  • Antiepileptic drugs (sodium valproate)

Third Line PreventionCGRP monoclonal antibodies

Antihypertensives

Certain blood pressure-lowering medications like beta-blockers (propranolol or Inderal, metoprolol or Lopressor) and calcium channel blockers (verapamil or Verelan) can help prevent migraines that come on with an aura. Learn more about using propranolol for migraines.

Migraines are associated with dilated (widened) blood vessels. It is believed that beta-blockers and calcium channel blockers which are used to treat high blood pressure may help prevent migraine headaches because they stabilize the brain blood vessels, thus, preventing their dilation. 

The exact mechanism of how beta-blockers work to prevent migraine headaches is not well-known. At the beginning of a migraine, the blood vessels in the brain constrict, and this phenomenon signals the brain to think that it needs more blood, but in reality, it does not. It results in the dilation of brain blood vessels, causing more blood to rush to the brain, resulting in migraine pain. 

Antidepressants

Some antidepressant medications, like tricyclic antidepressants (amitriptyline), can be used as preventive medication for migraine headaches. They work by changing the levels of neurotransmitters (natural chemicals) in the brain. However, other antidepressants, like selective serotonin reuptake inhibitors (SSRIs), are not effective in migraine prevention. 

Anti-Seizure Drugs

Medications used to treat neurological disorders like epilepsy might help people with less frequent migraine attacks. They work by increasing the activity of GABA, an inhibitory neurotransmitter in the brain, to reduce brain activity and headache pain. 

Examples of antiseizure medications used for migraine prevention include topiramate (Topamax) and valproate (Depakote). 

However, these drugs can cause side effects like nausea, dizziness, and weight gain. Also, they are not safe to take during pregnancy. 

Botox Injections

Some adults benefit from injections of onabotulinumtoxinA (Botox). This injection treatment works by blocking the transmission of nerve impulses and pain signals from the muscles of the head and face to the brain. The Botox treatment needs to be repeated every 12 weeks or so if it is effective. 

CGRP Monoclonal Antibodies

These are newer drugs approved by the FDA to prevent episodic migraine. They are given by injection every month or every 3 months and work by blocking the effects of a substance called CGRP, which plays a role in the development of headache pain. 

Examples of CGRP monoclonal antibodies used for preventing migraines include: 

Long-Term Benefits and Potential Side Effects  

This migraine information page has been written to give you an overview of the types of migraine treatment available. Taking too many migraine medicines or taking them too often can result in adverse effects like rebound headaches and other complications. 

For this reason, it is important not to self-treat migraine headaches. You should work with your healthcare provider to identify the best migraine drugs for you. Your doctor can provide medical advice and recommend migraine treatments based on the frequency, severity, and duration of your headaches, as well as your other symptoms, such as visual symptoms. They may recommend preventive medications for severe or frequent migraines. This can help to avoid rebound headaches from overuse of acute migraine medicines.

Effectiveness and Safety of Migraine Medications for Headache Treatment

What Are The Top 3 Migraine Medicines?

Studies have found that the top 3 migraine medicines reported as most useful by migraine sufferers are:

  • Triptans such as eletriptan (Relpax), zolmitriptan (Zomig), and sumatriptan (Imitrex).

  • Ergots such as dihydroergotamine (Migranal).

  • Anti-emetics such as promethazine (Phenergan).

What Is The Fastest Migraine Relief Medicine?

Triptans are some of the fastest acting migraine relief medicines. In particular, rizatriptan (Maxalt MLT) has the fastest onset of action among oral triptans and starts working within 30 minutes. Other options for fast migraine relief include subcutaneous injection of sumatriptan which also starts working in 15 to 30 minutes.

What Is The Best Pill For Migraines and Headaches?

Studies show that the best pill for migraines and headaches is eletriptan (Relpax), which is effective almost 80% of the time, as reported by migraine sufferers. Other triptans, such as zolmitriptan (Zomig) and sumatriptan (Imitrex), are also very effective.

What Is The First Choice Drug For Migraine?

Research suggests that ibuprofen (Motrin, Advil), an over-the-counter nonsteroidal anti-inflammatory drug (NSAID) pain reliever, is the first choice drug for migraine. However, while ibuprofen is the most frequently used migraine medicine and the go-to treatment for many migraine sufferers, people with migraine report that ibuprofen only works about 40% of the time, and other migraine-specific medicines like triptans are more helpful.

What Is The Best Medicine for Menstrual Migraine?

The best medicine for menstrual migraine may be preventive therapy with a nonsteroidal anti-inflammatory drug (ibuprofen, naproxen) taken twice a day for 5-7 days around the start of a period. A triptan such as eletriptan or sumatriptan taken early in the migraine attack may also help.

Common Side Effects and Safety Considerations

Migraine medicines can cause many adverse effects. These drugs may not be safe for everyone to use and can interact with your other medicines. In addition, overuse of migraine medicines for acute treatment of migraine can lead to medication overuse headaches. That’s why it’s important to seek professional medical care for migraine management. 

Emerging Trends in Migraine Treatment  

Emerging trends in migraine treatment include: 

  • New drugs like CGRP monoclonal antibodies (CGRP antagonists or blockers), gepants, and lasmiditan. 

  • New delivery systems such as nasal sprays and injections. 

  • Neuromodulation, a non-drug treatment approach that uses electric or magnetic stimulation to regulate abnormal nerve pathways in the nervous system.

Innovative Medications and Their Potential  

Some innovative medications and treatments for migraines include: 

  • Gepants are oral medications that can be used for acute migraines, such as ubrogepant (Ubrelvy). They can also be used for migraine prevention, such as atogepant (Qulipta). Another drug from this class, rimegepant (Nurtec), is used for both treatment and prevention and is less likely to cause rebound headaches. 

  • Lasmiditan (Reyvow) attaches to serotonin receptors in the central nervous system and stops migraine attacks. 

  • Calcitonin gene-related peptides (CGRP) monoclonal antibodies: These medications, including Aimovig (erenumab-aooe), Ajovy (fremanezumab-vfrm), Emgality (galcanezumab-gnlm), and Vyepti (eptinezumab-jjmr), offer the convenience of monthly or quarterly injections for migraine prophylaxis (prevention).

Managing Triggers and Lifestyle Changes  

Common Migraine Triggers  

In addition to taking migraine medicines, it’s important to avoid migraine triggers to manage your headaches. Common triggers for migraine include: 

  • Alcohol.

  • Caffeine.

  • Stress.

  • Sensory stimuli like loud noises, bright lights, strong smells, and second-hand exposure to cigarette smoke.

  • Lack of adequate sleep or oversleeping.

  • Physical strain, such as intense exercise or sexual activity.

  • Weather changes.

  • Certain foods like aged cheeses, salty snacks, and ultra-processed foods.

  • Food additives, preservatives, and sugar substitutes like MSG and aspartame.

  • Skipping meals.

  • Hormonal changes in women related to menstrual cycles, pregnancy, and menopause. 

  • Certain medications like birth control pills and vasodilators like nitroglycerine that widen blood vessels. 

Complementary and Alternative Treatments

The American Migraine Foundation recommends trying the following complementary and alternative treatments that can benefit some people with migraine headaches:

  • Acupressure and acupuncture

  • Green light therapy

  • Biofeedback and relaxation