From Trepanning to Tonics: Early Attempts at Relief
Before the dawn of modern pharmacology, migraine sufferers relied on a mix of superstitious beliefs, folk remedies, and rudimentary—and often dangerous—procedures. In ancient times, headaches were frequently attributed to evil spirits or demonic possession. The most extreme remedy was trepanation, a practice dating back 7,000 years, which involved drilling a hole in the skull to release the malevolent spirits causing the pain.
Other ancient and medieval practices were less invasive but equally ineffective. Ancient Egyptians would bind a clay crocodile to the patient's head, while Greek and Roman physicians, like Hippocrates and Galen, experimented with dietary changes and herbal laxatives, believing migraines were caused by digestive disturbances. In the Middle Ages, remedies included applying poultices soaked in opium and vinegar to the head.
Lists of folk remedies are a testament to the desperation felt by migraineurs, with treatments that included:
- Placing leeches on the forehead
- Rubbing temples with foul-smelling concoctions, such as cow dung and molasses
- Plaiting a handful of hair tightly on the top of the head
- Soaking feet in hot water to draw blood away from the head
The Dawn of Modern Medicine: The Role of Herbs
As medical understanding advanced, a focus on botanical solutions emerged. Some herbal remedies, such as willow bark, feverfew, and butterbur, provided some level of symptomatic relief, though the scientific reasons were poorly understood at the time. For instance, willow bark, used since the time of Hippocrates, contains salicin, the active ingredient later used to develop aspirin. Feverfew also has a long history, dating back to ancient Greece, for treating fever and inflammation. While often ineffective for severe attacks, some of these plants offered mild pain-relieving properties, forming the basis for later pharmacological development.
Ergotamine: The First Targeted Migraine Medicine
In the early 20th century, a major breakthrough occurred with the isolation of ergotamine in 1918 from the ergot fungus (Claviceps purpurea), a parasite that grows on rye. Swiss pharmaceutical company Sandoz marketed ergotamine as Gynergen, and by 1925, it was used specifically for migraine treatment. Ergotamine's mechanism of action, discovered later, involves activating serotonin receptors, which causes vasoconstriction (narrowing) of cranial blood vessels and reduces inflammation of the trigeminal nerves. This was a significant step forward, moving from treating symptoms to targeting a hypothesized cause.
The Rise and Fall of Ergotamine
For nearly half a century, ergotamine and its derivative, dihydroergotamine (DHE), were the only specific pharmacological treatments available for acute migraine attacks. However, their use came with significant drawbacks:
- Low and variable oral bioavailability, meaning the drug was poorly absorbed when taken by mouth, often requiring injections for reliable results.
- Side effects, including severe nausea and vomiting, which are already common migraine symptoms.
- Ergotism, a severe and rare condition caused by overuse, resulting in painful and potentially gangrenous vasoconstriction.
- Medication overuse headache, a risk that frequent use of ergots could lead to more frequent and severe headaches.
Comparison of Old vs. New Migraine Treatments
| Feature | Old Treatments (e.g., Ergotamine, Herbs) | Modern Treatments (e.g., Triptans, CGRP Inhibitors) |
|---|---|---|
| Efficacy | Highly variable; effective for some, but often unreliable, especially oral forms. | More consistently effective; triptans offer high response rates. |
| Mechanism | Non-selective vasoconstrictors, affecting multiple systems; poorly understood for herbs. | Highly specific action targeting serotonin or CGRP pathways implicated in migraine. |
| Side Effects | Common side effects include nausea, vomiting, dizziness, and risk of severe vasoconstriction. | Generally fewer and milder side effects; some triptans may cause chest tightness. |
| Risk of Overuse | High risk of medication overuse headache and potential for severe toxic effects. | Risk of medication overuse headache still present, but often lower for targeted drugs. |
| Bioavailability | Poor and inconsistent with oral formulations. | Significantly improved with various formulations (oral, nasal, injectable). |
Conclusion: The Evolution of Targeted Therapy
The history of migraine medicine is a journey from superstition to science. What was the old time migraine medicine reveals the limitations of earlier eras, where treatments were often hit-or-miss and sometimes harmful. The development of ergotamine in the 1920s marked a critical turning point, offering the first truly specific drug for the condition. However, it was not until the emergence of triptans in the 1990s and, more recently, CGRP inhibitors, that physicians could offer patients highly effective, targeted therapies with a better side-effect profile. This evolution underscores the importance of scientific research in transforming the lives of those living with migraine.
Learn more about modern headache management from the American Headache Society.
