How migraine treatments have changed over time

1920s

In the 1920s, the first medication for migraine became available.

Ergots

Ergots were among the first drugs that doctors used to treat acute migraine. Even though its release was back in 1926, ergotamine remains popular because it is a low cost drug that remains effective for a long time. Ergots come in different formulations, including ergotamine and dihydroergotamine.

People use ergotamine to treat long-lasting migraine attacks that typically involve headache recurrence.

The drug comes in different formulations, including:

• oral pill
• inhaler
• suppository, usually containing caffeine
• intravenous (IV) infusion through the veins

Ergots work by increasing serotonin levels and reducing inflammation. However, it also constricts blood vessels, so it is unsuitable for people with certain conditions, such as uncontrolled hypertension. It also frequently causes significant side effects and carries a high risk of dependence.

1960s to 1970s

This period saw the introduction of beta-blockers to migraine treatment.

Beta-blockers

In 1966, Dr. Robert Rabkin was researching the effects of a beta-blocker known as propranolol on heart pain. During his research, he noticed that one of his study participants experienced a significant reduction in the frequency of migraine attacks.

A decade later, two other doctors presented their findings on using daily propranolol for the treatment of migraine to the Food and Drug Administration (FDA). The FDA then approved it as the first medication to prevent migraine attacks.

Propranolol is now among a group of beta-blockers, including timolol and metoprolol, that people can use to prevent migraine attacks. It is one of the preventive migraine medications that doctors around the world most commonly prescribe.

Beta-blockers slow the heart rate, relax blood vessels, and improve blood flow throughout the body. However, experts are not entirely sure how their effects help treat migraine.

The medical community regards beta-blockers as one of the most significant medical discoveries of the 20th century. This is because they play a role in migraine care and can also help treat:

• high blood pressure
• anxiety
• certain types of tremors
• chest pain
• an irregular heartbeat

1990s to 2000s

During this period, more effective medications became available to people with migraine.

Triptans

Doctors considered the development of triptans to be revolutionary in the field of migraine treatment.

The first triptan, known as sumatriptan, became available in 1991 in Europe. Until that time, no other drug had proven to be as effective in treating migraine.

In 2008, the American Headache Society declared that triptans were the most important breakthrough in headache medication in 50 years.

Drugs in this class prevent pain signals from reaching the brain. They also block the release of substances that cause pain and other symptoms of migraine, such as nausea.

Anti-calcitonin gene-related peptide (anti-CGRP) therapy

For decades, experts believed that migraine attacks were the result of a problem with blood vessels in the brain.

However, from the late 80s to the early 2000s, researchers worked to prove that dysfunctional nerve signals also played a role.

According to a 2019 research article, researchers thought that the nerves that transmit pain sensations between the face and brain — the trigeminal nerves — and a signaling molecule called CGRP played a crucial role in migraine.

CGRP is a type of protein present in the nervous system and brain. It plays a role in pain transmission in the body. The release of CGRP in the body can lead to pain from inflammation in the meninges, the protective membrane layers that surround the brain.

Researchers published the first proof-of-concept study of IV anti-CGRP therapy in 2004. This work paved the way for the development of different types of migraine drugs, including CGRP antibodies and CGRP gepants, in later decades.

2010s to 2020s

A range of new treatment options became available during this time.

Botox

The FDA approved Botox injections to prevent chronic migraine in 2010. The botulinum neurotoxins in Botox reduce the activity of certain neurotransmitters in the brain.

The approval came from research that found Botox to be effective in reducing the severity and frequency of headaches in those with chronic migraine. The treatment was also well-tolerable.

Cerena Transcranial Magnetic Stimulator (TMS) device

In 2013, the FDA approved the first device for the treatment of migraine symptoms. The manufacturers designed the device for home use.

The device, which was called the Cerena TMS, worked by delivering short pulses of magnetic energy to the back of the head. This, in turn, caused an electrical current in a certain part of the brain called the occipital cortex. This current helps reduce or eliminate the effects of migraine with aura.

The manufacturer eventually took the Cerena TMS off the market and replaced it with the Spring TMS, which the company also took off the market. Since then, the FDA has approved the SAVI Dual TMS and several other therapeutic devices, which are generally smaller and less expensive. The approved models are:

• Cefaly
• Nerivio
• gammaCore
• Relivion

CGRP antibodies

CGRP monoclonal antibodies work by blocking the action of CGRP molecules. By blocking the action of this naturally occurring substance in the body, the treatment reduces or stops migraine attacks.

The first of these drugs, erenumab-aooe (Aimovig), received FDA approval in 2018. People administer the drug by self-injection once a month.

It was the first approved preventive migraine treatment that blocks the activity of the CGRP molecule. Today, doctors may also prescribe other CGRP antibody medications, such as galcanezumab (Emgality) and fremanezumab (Ajovy).

Ditans

Ditans are also called selective serotonin receptor agonists.

In 2019, the FDA approved the first of these drugs: lasmiditan (Reyvow). It was the first new class of acute migraine treatment to receive approval in more than 20 years.

Reyvow works by stopping the inflammation of nerves and preventing pain signals from traveling to the brain.

People need to take this medication at the first sign of a migraine attack.

CGRP gepants

CGRP gepants are a type of CGRP receptor antagonist. This means that they stop the CGPR molecule from properly binding to receptor sites in the body. In doing so, they can stop the chain of events that results in a migraine attack.

Unlike triptan medications, gepants do not cause blood vessels to constrict, so healthcare professioals consider them safer for people with heart or vascular disease and those who have had a stroke.

The FDA approved the first of these drugs, ubrogepant (Ubrelvy), in 2019. In 2020, rimegepant (Nurtec) gained FDA approval. The agency also approved Atogepant (Qulipta) in 2021 and zavegepant (Zavzpret) in 2023.

CGRP antibody IV infusion

The first preventive IV migraine treatment, eptinezumab-jjmr (Vyepti), received FDA approval in 2020.

The drug blocks CGRP in the brain, which stops pain signals.

Healthcare professionals deliver it via an IV infusion over a 30-minute period, typically once every 3 months. In two phase 3 clinical trials — PROMISE-1 for episodic migraine and PROMISE-2 for chronic migraine — it significantly reduced the number of headache days per month.

Summary

Over time, migraine treatments evolved from the use of beta-blockers in the 1960s to the development of triptans in the early 90s. The medical community considered the development of triptans as a medical breakthrough in the field of migraine care.

Since then, researchers have developed other treatments, including Botox and therapeutic stimulation devices.

Once calcitonin gene-related peptide (CGRP) became a proven target for migraine treatment and prevention in the early 2000s, CGRP therapies revolutionized the field of migraine care.