People have been documenting the pain of migraine and the quest for relief since ancient times. Recounted in medical historian Katherine Foxhall’s Migraine: A History, what emerges is a fascinating timeline of theories and well-meaning migraine treatments — including binding the head, purgatives, earthworm plasters, bloodletting, and cannabis — with mixed results. Attitudes around migraine changed, too: Around the time of the Industrial Revolution, we see a new theory of migraine emerge, pivoting from being a disease of the body to a “nervous disorder” afflicting the minds of the privileged class, a stigma that persists to this day.
However, the late 20th century was blessed with scientific breakthroughs allowing science to replace fiction. This has paved the way for new, safe and effective migraine treatments to become available: preventive, acute, alternative, and holistic. Never has the field of headache medicine held more promise for patients than right now.
Timeline of Notable Migraine Treatments and Developments
13th Century B.C.
- Ancient Egyptians documented some of the earliest cases of excruciating headaches around 1200 B.C. One treatment involved relieving pain by binding a clay crocodile to the head of the patient.
5th Century B.C.
- Greek physician Hippocrates (c.460-c.370 B.C.) described the symptoms of migraine, including aura, in great detail in his writings. For symptom relief, he favored migraine treatments using plants as laxatives.
4th Century B.C.
- Ayurvedic medicine, practiced in the Indian subcontinent, prescribed cannabis for diseases of the head.
2nd Century CE (AD)
- Greek physician Aretaeus of Cappadocia (AD 81-?) describes migraine in great detail and generally gets credit for being the first to “discover” migraine, calling it as “heterocrania.”
- Roman physician and philosopher Galen of Pergman (AD 130-210), coined the term “hemicrania” to describe the pain occurring in half the head. He made note of the connections between gut disturbances and migraine. Though that observation turned out to be accurate, he was also a proponent of the debunked ancient theory that illness stemmed from imbalances in the body’s “humors,” or liquids (blood, phlegm, black bile, and yellow bile). This theory led to leaching and bloodletting.
- In China, acupuncture was being used to treat migraine as early as the second century.
- Bald’s Leechbook (c. 950), an Old English medical text, included six herbal remedies for “half headache.” Ingredients included laurel, rue, and nettles.
- Bloodlettings to release evil humors and vapors in the body were recommended migraine treatments.
- Islamic Persian physician-philosopher Avicenna, aka Abu Ali al-Husayn ibn Sina (c. 980-1037), detailed the symptoms and behaviors of people during a migraine attack in his seminal textbook The Canon of Medicine.
- Hildegard of Bingen (1098-1179), 12th century abbess of the German convent St. Rupertsberg, likely experienced migraine aura, described in detail as religious visions in illuminated manuscripts of the time.
- Household recipe books frequently contained migraine treatments, including herbal preparations, spices oils (lavender), and plasters made with earthworms.
- English physician Thomas Willis (1621-1675) is considered a founder of modern neurology and a pioneer of anatomy of the brain, nervous system, and muscles. He believed migraine was caused by vasodilation. He accurately categorized different headache types and greatly furthered the understanding of headache mechanisms and triggers for migraine attack including heredity, seasonal and atmospheric changes.
- Samuel Tissot, a Swiss physician (1728-1797), studied and wrote on migraine extensively and gained the reputation as the authority on migraine. His writings, particularly his Treatise on the nerves and nervous disorders, are considered to be the foundation for the modern understanding of migraine.
- In the late 18th century, migraine became seen more as a “nervous complaint” that could be triggered by an emotional event such as grief.
- The cultural perspective on migraine took on a negative cast. Migraine went from being seen as a legitimate disease into a stigmatized condition of the privileged. The stigma that began during this period persists today.
- In 1807, Scottish physician Thomas Trotter wrote A View of the Nervous Temperament, in which he argued that lifestyle habits, drinking tea in particular, were responsible for causing “nervous disorders” such as migraine, especially in young women.
- English physician Edward Liveing’s On Megrim, Sick-Headache, and Some Allied Disorders (1873) proposed that the cause of migraine was not vascular, but rather due to a gradual accumulation of tension within the nervous system, which would explosively discharge in a “nerve storm.” His theories contrasted with the idea of a vascular cause for migraine.
- English physician Peter Latham proposed the vasomotor theory of migraine in On Nervous or Sick-Headache (1873). He suggested that visual aura was the result of contraction of the blood vessels in the brain, and the resulting headache was due to dialation of those blood vessels. This idea is close to our modern theory of cortical spreading depression.
- By the late 19th century, migraine was considered to be part of a range of “nervous disorders” brought on by nerve weakness or exhaustion.
- More theories arise about migraine being caused by toxins, allergies, hormones, and personality type.
- In 1938, American doctors Harold Wolff and John Graham published a landmark study showing that ergotamine, a chemical compound from the ergot (fungi) family of naturally occurring organic compounds, could treat migraine pain. They theorized that ergotamine constricts the dilated cranial blood vessels, and assumed that blood vessel dilation caused the pain of migraine. This turned out to be false.
- In the 1950s, research began on serotonin, a chemical nerve cell that was found to have many effects in the body including blood vessel constriction.
- In 1956, Migril sugar-coated tablets of ergotamine, caffeine, and cyclizine (an antiemetic) came on the market to treat migraine. It was a huge success, though there were problems with ergotamine. Patient response was highly variable. Overuse sometimes led to prolonged nausea and worsened migraine attacks. Possible side effects included heart attack, miscarriage, and gangrene. Despite issues, ergotamine remained the only drug available to treat migraine attacks until the 1980s.
- In 1959, a preventive treatment, methysergide, was first used by Italian neurologist Federigo Sicuteri. It simulated the effects of serotonin, a neurotransmitter, on blood vessel receptors. Though it had many side effects, the success of a preventive began to shift the established opinion that migraine was a psychological problem. If migraine could be prevented with a medication, perhaps its origins were physiological in nature.
- New preventive drugs were tried, including some still in use, like tricyclic antidepressants, antiepileptics, beta blockers, and calcium channel blockers.
- Migraine origin theories changed with the release of studies showing that migraine without aura was not associated with any change in cerebral flow, but that migraine with aura correlated with a wave of decreased blood flow spreading across the brain. These findings undermined the formerly working theory that migraine was a singular disorder and that it was vascular-related.
- South African scientist Sir Patrick Humphrey began developing a new migraine drug based on his research on cerebrovascular pharmacology. It led to the discovery of sumatriptan to target serotonin receptors on the cranial nerves and blood vessels. Patented in 1982, sumatriptan became the first drug to be specifically designed to treat migraine attacks.
- In 1988, the International Headache Society published the first edition of International Classification of Headache Disorders, still used by headache specialists. This publication points to headache medicine becoming a more fully-formed medical speciality.
- In 1989, Botox was approved by the FDA to treat strabismus and blepharospasm, which patients noted also smoothed lines in the injection proximity. In 2002, the FDA approved Botox for cosmetic use to treat wrinkles. Patients noticed that Botox injections in the forehead also seemed to help prevent migraine. In 2010, the FDA approved Botox’s use to treat chronic migraine.
- Sumatriptan first became available in Europe in 1991, and was approved for American markets in 1992. By the end of the ‘90s, seven triptans were widely available throughout the world. This is considered a major therapeutic development for the treatment of migraine and remains the leading first-line prescription medicine for migraine.
- In 1996, the FDA approved Depakote for migraine prevention.
- In 2004, the FDA approved Topamax, an anticonvulsant, for migraine prevention.
- In the 2010s, the migraine advocacy movement gained steam, focusing on awareness, research, and reducing stigma.
- In 2017, four different pharmaceutical companies announced positive results from drug trials of monoclonal antibodies targeting the body’s calcitonin gene-related peptide (CGRP). CGRP causes activation of nerves in the brain coverings, which causes pain during a migraine attack. These CGRP receptor blockers are the first preventive treatment designed specifically for migraine disease. The FDA approved three CGRP antagonists in 2018: Aimovig, Ajovy, and Emgality. In 2020 it approved the first intravenous anti-CGRP monoclonal antibody, Vyepti.
- In 2020, the FDA approved the first small molecule (oral) drugs (gepants) that block CGRP to treat migraine acutely: Ubrelvy and Nurtec.
- In 2020, the FDA approved Reyvow, the first in the “ditan” class of drugs as a new abortive for migraine attacks. Ditans work on one of the same receptors as triptans but not on the receptor that constricts blood vessels, and thus do not constrict blood vessels around the heart (the way triptans can do for some people). Because ditans work differently than triptans, they’re now a good alternative for those who can’t tolerate triptans due to cardiovascular issues.