What was the old medicine for epilepsy?

October 7, 2025 •

4 min read

The first effective medicine for epilepsy, potassium bromide, was introduced in 1857 by Sir Charles Locock, marking a pivotal shift from centuries of ineffective or spiritual remedies [1.3.4, 1.4.2]. Before this breakthrough, treatments ranged from herbal concoctions to surgical procedures like trepanation [1.8.2]. So, what was the old medicine for epilepsy before pharmacology transformed patient care?

Quick Summary

A deep dive into historical epilepsy treatments, covering early remedies like bromides and phenobarbital. It explores the evolution of antiepileptic drugs, their mechanisms, and the shift towards safer, more effective modern medications.

Key Points

Ancient Treatments: Before scientific medicine, epilepsy was treated with methods like trepanation (drilling holes in the skull), herbal remedies, and fasting [1.8.2, 1.8.3].
First Effective Drug: Potassium bromide, introduced in 1857 by Sir Charles Locock, was the first chemical compound shown to be effective against seizures, though it was highly toxic [1.3.4, 1.4.2].
The Barbiturate Era: Phenobarbital, discovered in 1912, became the next standard of care. It was as effective as bromide but less toxic, though it caused significant sedation [1.3.5, 1.4.6].
A Major Breakthrough: Phenytoin (Dilantin), discovered in 1938, was the first non-sedating anti-seizure medication, revolutionizing epilepsy treatment [1.3.1, 1.6.5].
Dietary Therapy: The ketogenic diet was developed in 1921 as a non-pharmacological treatment that mimics the anti-seizure effects of fasting [1.7.2, 1.7.5].
Modern Era Foundation: The systematic screening process that led to phenytoin's discovery laid the groundwork for the development of all subsequent anti-seizure medications [1.3.1, 1.6.1].

The Ancient World's Approach to the 'Sacred Disease'

For millennia, epilepsy was shrouded in mysticism and fear, often referred to as the “Sacred Disease” [1.4.1]. Treatments were not based on scientific understanding but on spiritual beliefs, superstitions, and empirical observations [1.4.1, 1.4.3]. One of the most dramatic and oldest known surgical interventions was trepanation—drilling or scraping a hole into the skull [1.8.2, 1.8.5]. Archaeological evidence from the Neolithic period shows skulls with trepanation holes, some even showing signs of healing, suggesting the person survived the procedure [1.8.5, 1.8.6]. The rationale was likely to release evil spirits or relieve pressure [1.8.3, 1.8.5].

Beyond surgery, ancient treatments included [1.4.3, 1.8.3]:

Herbal and botanical remedies
Strict diets and fasting
Lifestyle modifications
Prayers and exorcisms

In Ancient Rome, some even believed that consuming the blood of gladiators could cure epilepsy [1.4.7]. It wasn't until the mid-19th century that a scientific approach to treatment began to emerge, moving away from these crude and often dangerous methods [1.4.1].

The Dawn of Modern Pharmacology: Bromides

The story of modern epilepsy medication begins in 1857 with a serendipitous observation by Sir Charles Locock, an obstetrician to Queen Victoria [1.3.1]. He noted that potassium bromide, known for its sedative effects, successfully controlled seizures in 14 of his 15 female patients with "hysterical" (likely catamenial) epilepsy [1.2.1, 1.3.1]. This marked the first time a chemical compound was used effectively to treat epilepsy [1.3.4].

For over 50 years, bromides became the primary treatment for epilepsy [1.4.2]. However, their effectiveness came at a high cost. Bromides have a very narrow therapeutic index and were highly toxic [1.3.1, 1.3.5]. Chronic use often led to a condition called "bromism," characterized by severe side effects, including:

Lethargy and sedation [1.3.1]
Severe skin reactions [1.3.1]
Psychosis and delirium [1.3.1]
The concept of the "epileptic personality," which was actually a result of the medication's effects on behavior [1.3.3]

The Barbiturate Era: Phenobarbital

A significant improvement arrived in 1912 with the discovery of phenobarbital's anticonvulsant properties by German physician Alfred Hauptmann [1.2.1, 1.3.4]. Originally marketed as a sedative and hypnotic called Luminal, Hauptmann administered it to his epilepsy patients to help them sleep, and discovered it also reduced their daytime seizures [1.3.2].

Phenobarbital was as effective as bromides but was less toxic and easier to administer, quickly becoming the new standard of care [1.3.5, 1.4.6]. Despite being an improvement, phenobarbital was not without its own significant side effects. As a central nervous system depressant, its use was associated with [1.5.3, 1.5.4]:

Drowsiness, sedation, and fatigue
Cognitive issues, such as problems with memory and concentration
Behavioral changes, particularly hyperactivity in children
Physical dependence and the risk of withdrawal seizures if stopped abruptly

Even with these drawbacks, phenobarbital remains one of the most widely prescribed antiepileptic drugs in the developing world due to its low cost and effectiveness [1.3.2].

The First Non-Sedative AED: Phenytoin

The next major leap forward came from a systematic, scientific approach to drug discovery. In the 1930s, researchers Tracy Putnam and H. Houston Merritt sought an effective anticonvulsant that did not cause sedation [1.3.3]. Using a new electroshock seizure model in cats, they screened hundreds of compounds [1.3.1]. In 1938, they identified phenytoin (marketed as Dilantin), a drug synthesized in 1908 but never used medically because it lacked sedative effects [1.6.5, 1.6.6].

Phenytoin proved to be highly effective against tonic-clonic and partial seizures without the heavy sedation of phenobarbital, earning it the reputation of a "miracle" drug [1.3.5, 1.6.5]. It quickly became a first-line treatment for decades [1.3.1]. The discovery of phenytoin was a landmark moment, proving that seizure control could be separated from sedation and validating the use of animal models for screening potential new drugs [1.6.1, 1.6.5]. Its introduction truly marks the beginning of the modern era of antiepileptic therapy [1.3.2].

Comparison of Early Epilepsy Treatments


Treatment	Era of Prominence	Mechanism/Rationale	Major Drawbacks
Trepanation	Ancient Times	Release evil spirits or cranial pressure [1.8.3, 1.8.5]	Highly invasive, high risk of infection and death [1.8.1]
Potassium Bromide	1857–1912	Sedative effect on the nervous system [1.3.1]	High toxicity (bromism), severe skin and psychiatric effects [1.3.1, 1.3.5]
Phenobarbital	1912–1930s	Central nervous system depressant [1.3.6, 1.5.4]	Heavy sedation, cognitive impairment, physical dependence [1.5.3, 1.5.4]
Phenytoin	1938 onwards	Stabilizes neuronal membranes (sodium channel blocker) [1.6.4, 1.6.5]	Complex pharmacokinetics, gingival hyperplasia, various side effects [1.6.3]

Non-Pharmacological Historical Treatments: The Ketogenic Diet

Parallel to the development of early drugs, dietary therapies were also explored. The use of fasting to treat epilepsy dates back to ancient times [1.7.2]. In 1911, French physicians first documented the modern use of starvation for epilepsy treatment [1.4.4, 1.7.2]. Building on this, Dr. Russel M. Wilder at the Mayo Clinic proposed in 1921 that a high-fat, low-carbohydrate diet could mimic the metabolic state of fasting and produce ketosis, which had an anti-seizure effect [1.7.2, 1.7.5]. This became known as the ketogenic diet.

Initially used in the 1920s and 1930s, the diet's popularity waned with the discovery of effective drugs like phenytoin [1.7.4]. However, it saw a resurgence in the 1990s as a valuable option for drug-resistant epilepsy, particularly in children [1.7.4].

Conclusion: From Superstition to Science

The journey to find effective epilepsy treatments has been a long one, moving from the trepanned skulls of the Neolithic era to the targeted pharmacology of the 21st century. The old medicines for epilepsy, starting with the toxic but groundbreaking bromides, followed by the heavily sedating phenobarbital, laid the foundation for modern therapy. The discovery of phenytoin was a paradigm shift, introducing the possibility of effective seizure control without sedation and heralding a new, scientific approach to drug development [1.3.1, 1.3.3]. These early discoveries paved the way for the dozens of anti-seizure medications available today, offering patients more options with improved efficacy and fewer side effects than ever before [1.2.6].

For more information, a good resource is the Epilepsy Foundation.

Frequently Asked Questions

The first effective medicine for epilepsy was potassium bromide, introduced in 1857. It was used for its sedative properties to control seizures but had severe toxic side effects [1.2.1, 1.3.4].

Yes, after its anticonvulsant properties were discovered in 1912, phenobarbital became the main treatment for epilepsy for several decades, replacing the more toxic bromides. It was effective but caused significant drowsiness [1.2.2, 1.4.2].

The discovery of phenytoin in 1938 was a landmark event because it was the first highly effective anti-seizure medication that did not cause significant sedation. This proved that seizure control could be separated from general nervous system depression [1.3.1, 1.6.5].

Trepanation is an ancient surgical procedure involving drilling or scraping a hole in the skull. Archaeological evidence suggests it was used in prehistoric times for various ailments, including what was likely epilepsy, possibly to release evil spirits or relieve pressure [1.8.2, 1.8.3].

Bromides caused a condition known as 'bromism,' which included severe side effects like lethargy, psychosis, delirium, and serious skin reactions. This toxicity is why they are no longer used in humans [1.3.1, 1.3.5].

The ketogenic diet was developed in the 1920s, based on the ancient observation that fasting could reduce seizures. It works by changing the body's metabolism to use fat for energy, producing ketones that have an anti-seizure effect [1.7.2, 1.7.5].

Phenobarbital is still one of the most widely prescribed anti-seizure medications in developing countries due to its low cost and effectiveness [1.3.2]. Phenytoin is also still in use for certain types of seizures [1.6.2]. Bromides are now only rarely used, primarily in veterinary medicine for dogs [1.3.1, 1.3.3].