Potassium bromide is a chemical with anticonvulsant properties that was used to treat seizures in epilepsy patients in the 19th century. Although it is not currently available by prescription in North America, research suggests it may be able to reduce seizure activity in Dravet syndrome patients. Dravet syndrome is a severe form of epilepsy with seizures beginning in early infancy.
How potassium bromide works
The exact mechanism by which potassium bromide inhibits seizure activity is not known. However, it is thought to act on sodium channels of GABA receptors. GABA is a signaling molecule in the brain that inhibits nerve cell activity. It acts by binding to GABA receptors. Nerve cells communicate with each other via electric signals, and sodium channels are needed for signal transduction.
The majority of Dravet syndrome patients carry a mutation in the SCN1A gene, which provides instructions to build the NaV1.1 sub-unit of sodium channels. The mutation is thought to affect mainly GABA-releasing neurons, which leads to aberrant signaling that causes seizures. Potassium bromide seems to compensate for the defect in sodium channels.
Potassium bromide in clinical trials
Potassium bromide has not been tested in randomized clinical trials specifically for Dravet syndrome patients. Some small studies suggest, however, that it might benefit Dravet syndrome patients.
A retrospective study analyzed data from 32 Dravet syndrome patients carrying an SCN1A mutation. Six patients received potassium bromide temporarily as monotherapy, while 26 patients received the medication as add-on therapy. The mean treatment duration was 47 months with a mean maximum daily oral dose of 63.2 mg per kilogram (kg) body weight of potassium bromide.
Three months after treatment began, 31 % of the patients experienced complete seizure control. Seizures were reduced by more than 75% in 6% of the patients, and by more than 50% in 19% of them.
After 12 months, 28 patients continued to receive potassium bromide. One patient (3% of all patients) was seizure-free, while 25% had a seizure reduction by more than 75%, and 19% by more than 50%.
Another retrospective study analyzed data from 109 Dravet syndrome patients with a history of status epilepticus (prolonged seizures). A total of 48 patients received a daily mean oral dose of 59.6 mg per kg body weight of potassium bromide. The treatment was considered excellent if the medication completely prevented status epilepticus and moderate if the frequency and duration of seizures were reduced by 10-90%.
In 41.7% of the patients receiving potassium bromide, the treatment effectiveness was excellent. In another 41.7%, it was moderate, while in 16.7% the treatment had no effect. Potassium bromide had significantly higher effectiveness than valproate and zonisamide, two frequently-used anticonvulsants in Dravet syndrome.
In a third study, 22 Dravet syndrome patients received potassium bromide as an add-on therapy to other anticonvulsants. The mean daily oral dose of potassium bromide was 58 mg per kg body weight.
After three months of potassium bromide induction, the frequency and duration of seizures decreased by more than 75% in 36% and by more than 50% in 41% of patients with generalized tonic-clonic seizures. Four of seven patients with partial seizures (57%) had a seizure reduction of more than 50%.
After 12 months, five patients who initially responded to treatment no longer were responsive while 32% still had a seizure reduction of more than 75% and 11% of more than 50%. Of the patients who had partial seizures, one still had a decrease of more than 50% in seizure frequency and duration. In one out of five patients with myoclonic and absence seizures, seizures were reduced by more than 50%.
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