What was the first treatment for epilepsy?: Tracing the Origin of Seizure Medication

October 11, 2025 •

4 min read

The history of effective epilepsy treatment began in 1857 with the introduction of potassium bromide by English doctor Sir Charles Locock. While ancient civilizations used ineffective remedies based on superstition, bromide marked the pivotal entry into the modern, pharmacological era of treating seizures. This was a revolutionary shift that would pave the way for all subsequent antiepileptic drugs.

Quick Summary

This article explores the history of epilepsy treatments, detailing the pre-scientific era of superstition and ineffective remedies. It focuses on the introduction of potassium bromide in 1857, the first effective medication, and its replacement by phenobarbital in 1912. The journey to modern pharmaceuticals, including the development of phenytoin, is also discussed, highlighting the monumental progress in managing seizures.

Key Points

Potassium bromide was the first effective drug: Introduced in 1857 by Sir Charles Locock, potassium bromide was the first medication shown to effectively control epileptic seizures.
Early treatments were ineffective: Prior to bromide, treatments were based on superstition and included practices like trepanation and herbal remedies.
Bromism was a major side effect: Long-term use of potassium bromide caused severe side effects, such as mental dullness and skin rashes, a condition known as bromism.
Phenobarbital offered a better alternative: Discovered serendipitously in 1912, phenobarbital provided a more effective and less toxic option than bromides, becoming the standard treatment for decades.
Scientific screening led to new drugs: The development of phenytoin in 1938 and the launch of programs like the Anticonvulsant Screening Program in 1975 ushered in an era of systematic, targeted drug development.
Modern AEDs are more targeted and safer: Today's antiepileptic drugs are the result of decades of research, offering improved efficacy, fewer side effects, and wider therapeutic windows compared to early treatments.

From Superstition to Science: The Dawn of Modern Epilepsy Treatment

For millennia, epilepsy was shrouded in superstition and misunderstanding, with ancient civilizations often attributing seizures to supernatural or divine forces. Treatments during this era were, at best, empirical and, at worst, harmful. Prehistoric evidence of trepanation—the practice of drilling a hole into the skull—suggests that early societies believed this procedure would release evil spirits causing the seizures. Remedies consisted of mystical concoctions, herbal remedies, and even cannibalistic practices, such as the Roman belief that drinking gladiator's blood could cure the disease.

It wasn't until the mid-19th century that medical practice began to shift towards a more scientific approach. The crucial breakthrough came in 1857, marking the beginning of the pharmacological age of epilepsy treatment. The first scientifically recognized and effective treatment for epilepsy was the inorganic salt, potassium bromide.

The First Medical Breakthrough: Potassium Bromide

In 1857, Sir Charles Locock, a prominent English obstetrician, presented his findings on the use of potassium bromide to the Royal Medical and Chirurgical Society. Locock originally theorized that the drug could treat “hysterical” epilepsy in women linked to their menstrual cycles, a misconception based on a misunderstanding of the condition now known as catamenial epilepsy. He had observed the sedative effects of bromide salts and, mistakenly, linked sexual excitement to seizures. However, his work demonstrated that the drug was effective in controlling seizures, regardless of the patient's gender or etiology.

Bromide quickly gained traction and became the primary treatment for epilepsy for over 50 years. Despite its groundbreaking efficacy, the medication was far from a perfect solution. Chronic, high-dose use led to a constellation of severe side effects known as 'bromism', which could include:

Cognitive and psychiatric effects: Lethargy, diminished mental function, and confusion.
Neurological symptoms: A staggering gait and central nervous system effects.
Dermatological reactions: Severe skin rashes, known as bromoderma.

These undesirable outcomes led to the development of the misleading concept of an 'epileptic personality', which was, in fact, a result of the medication's toxicity rather than the condition itself.

A Better Alternative: The Arrival of Phenobarbital

Potassium bromide remained the standard until a serendipitous discovery in 1912. German physician Alfred Hauptmann, seeking a hypnotic to sedate his patients, began using phenobarbital, a new compound marketed as 'Luminal' by the company Bayer. Hauptmann noticed that not only were his patients more sedated, but their seizure frequency also dramatically decreased. He published his findings, heralding the birth of a new and improved antiepileptic drug (AED).

Phenobarbital offered significant advantages over bromide. While still a sedative, it was less toxic and easier to administer. Its widespread use in the developed world continued for decades, and even today, it remains a common and affordable treatment option in many developing countries. However, it also came with its own set of side effects, including persistent sleepiness and behavioral changes, especially in children.

The Era of Systematic Drug Development

Recognizing the limitations of serendipitous drug discoveries, the scientific community began a more systematic search for new AEDs in the 1930s. The breakthrough came with the work of Tracy Putnam and H. Houston Merritt, who developed animal models to screen compounds for anticonvulsant properties. This led to the 1938 discovery and introduction of phenytoin (Dilantin), a drug that was effective in controlling seizures with notably less sedation than phenobarbital. Phenytoin quickly became one of the most widely used AEDs and solidified the shift toward rational drug design based on scientific screening.

Following phenytoin, other first-generation AEDs emerged, such as primidone (1950s), ethosuximide (1950s), and carbamazepine (1960s). These early drugs, while valuable, often had considerable side effects and a narrow therapeutic index, complicating treatment. The next wave of progress was spurred by the establishment of the U.S. National Institute of Neurological Disorders and Stroke's Anticonvulsant Screening Program in 1975, which led to the development of many of the more specific and better-tolerated drugs used today.

Comparison of Early and Modern Epilepsy Treatments


Feature	Potassium Bromide (1857)	Phenobarbital (1912)	Modern AEDs (e.g., Levetiracetam, Lamotrigine)
Mechanism	General CNS depression, enhances GABA-ergic inhibition.	Potentiates GABA-A receptor-mediated inhibition, inhibits glutamate excitability.	More specific mechanisms, targeting various channels, receptors, or vesicle proteins to modulate brain excitability.
Efficacy	Effective, but inconsistent; only arrests seizures in a portion of patients.	Broad-spectrum efficacy against many seizure types; still widely used.	Generally highly effective and often better targeted for specific seizure types.
Side Effects	Severe bromism, including lethargy, mental dullness, skin rashes.	Sedation, behavioral changes, cognitive issues, particularly at higher doses.	Generally fewer and milder side effects; some have fewer cognitive impacts.
Therapeutic Index	Narrow; high risk of toxicity with overdose.	Narrow; risk of dependence and overdose.	Often wider therapeutic windows, increasing safety and ease of use.
Role Today	Primarily historical in human medicine; still used in veterinary care.	Widely used in developing nations due to low cost; also for status epilepticus and neonates.	First-line treatment for many forms of epilepsy; superior tolerability and safety profile.

Conclusion: A Long Road of Progress

From archaic rituals and superstitious beliefs, the treatment of epilepsy has undergone a transformative journey. The introduction of potassium bromide in 1857 marked the first true step towards effective medical intervention, despite its significant side effects. The subsequent discovery of phenobarbital in 1912 offered a superior, though still sedating, alternative. The development of systematic screening methods in the 20th century accelerated progress, leading to the creation of more targeted and tolerable medications. Today, individuals with epilepsy benefit from a wide array of modern AEDs that are more specific, safer, and better understood than their predecessors, a testament to the ongoing advancements in pharmacology and neurology. The progress made from the earliest empirical remedies to today's targeted therapies demonstrates the crucial role of scientific inquiry in improving the lives of those affected by seizures.

For more information on the history of epilepsy and its treatment, consult resources like the Epilepsy Foundation.

Frequently Asked Questions

Yes, but treatments were largely ineffective and based on superstition. Ancient remedies included trepanation (drilling a hole in the skull), herbal medicines, and rituals aimed at driving out evil spirits believed to be the cause of seizures.

Potassium bromide was replaced due to its significant and dose-related side effects, collectively known as 'bromism'. These side effects included severe lethargy, mental dullness, skin rashes, and psychiatric symptoms, which made long-term use difficult and risky.

Phenobarbital was discovered serendipitously in 1912. German physician Alfred Hauptmann observed that his epilepsy patients, who he was treating with the sedative Luminal (phenobarbital) for agitation, experienced a dramatic reduction in their seizures.

Early epilepsy drugs like bromide and phenobarbital were discovered by chance and had widespread, non-specific effects on the brain, leading to significant side effects. Modern antiepileptic drugs are more targeted, with specific mechanisms of action that improve efficacy and reduce adverse effects.

In human medicine, the use of potassium bromide is extremely rare and primarily of historical interest due to its toxicity. However, it is still widely used in veterinary medicine, particularly to treat epilepsy in dogs.

Systematic drug development began in the 1930s. The work of Tracy Putnam and H. Houston Merritt, who used animal models to screen compounds, led to the discovery of phenytoin in 1938.

Advances in diagnostic tools like EEG and high-resolution imaging have enabled clinicians to differentiate specific seizure types and epilepsy syndromes. This has informed the development of more targeted treatments, allowing for better outcomes and fewer side effects compared to the earlier one-size-fits-all approach.