Anticonvulsants can cause life-threatening reactions

Molecular tests and other screening tools may reduce the risk of potentially fatal reactions to the anticonvulsant drugs that millions of Americans take to treat epilepsy and other conditions, but skin rashes still require prompt medical attention, according to a Rutgers Health study.

Rashes are a common side effect of antiseizure medications, occurring in 2% to 16% of patients depending on which of the 26 FDA-approved drugs they use.

While most rashes do not indicate serious problems, about 5% signal life-threatening reactions. The FDA recently issued a warning about serious reactions to two antiseizure drugs: levetiracetam and clobazam.

“Dangerous reactions are rare, but patients and their caregivers need to understand the risk and know how to respond if something happens,” said Ram Mani, chief of adult epilepsy at Rutgers Robert Wood Johnson Medical School and lead author of the study published in Current Treatment Options in Neurology.

“Patients should seek medical attention if they develop a rash rather than wait for it to go away,” Mani said. "If the symptoms are mild, they can contact their neurologist or GP, but severe symptoms such as a high temperature require a trip to the emergency department or an ambulance."

The right anticonvulsant drug can eliminate epilepsy symptoms in 70% of patients and relieve them in most others. Such drugs also help many patients with bipolar disorder, anxiety, migraines and neuropathic pain.

The new study summarises the published data on each individual anticonvulsant drug, distinguishes between the different types of rashes these drugs can cause and explains how to treat each.

Factors that increase the risk of severe reactions include the use of aromatic anticonvulsants, rapid dose escalation, a genetic predisposition to a reaction and the concomitant use of other drugs that affect drug metabolism. Women under 50 and boys under 10 are also more likely to experience reactions, as are people with conditions like HIV or lupus, or those undergoing treatments that increase or decrease the activity of the immune system, such as radiation therapy.

“Patients who respond to one drug are more likely to respond to others, especially drugs in the same class, but with 26 FDA-approved options, we can find an effective treatment for every patient with minimal side effects,” Money said.

Anticonvulsant drugs can cause at least 10 different types of rashes. Reactions like fixed drug eruption, which is characterized by a small number of rashes, can begin within hours of the first injection, while other rashes, like lichenoid drug reactions, can occur after years of drug use.

The most common reaction is called morbilliform exanthematous eruption. These rashes usually appear in the first two weeks of treatment and cover the torso (and often the limbs) in small rashes. Symptoms usually go away without treatment within a few weeks of stopping the drug, but may get worse for several days before they begin to improve.

Serious conditions, on the other hand, often require urgent treatment. A reaction known asStevens-Johnson syndromeor toxic epidermal necrolysis, which causes fever, eye pain and sloughing skin, usually requires hospitalization in a burn department.

Money estimated that several thousand patients suffer from severe reactions to anticonvulsants each year, but added that these numbers could be reduced significantly if neurologists consistently prescribed low-risk drugs to high-risk patients.

“I gave a presentation on this topic at the American Epilepsy Society conference last year and asked the 200 or so doctors in the room how often they perform the recommended [genetic] tests on patients of South Asian descent [the only group most likely to do so]. Genes], and only a few people raised their hands,” Rami said. “So there is certainly room for improvement in patient safety.”