Epilepsy is a surprisingly common disorder characterized by seizures. These seizures can range from brief spells to complex, full-body convulsions which can last for hours.
Complicating this condition is that there are 25 or more epileptic syndromes, often differing by their location in the brain. These syndromes can vary by stage in life. For instance, epileptic seizures served in neonates can be quite different from those observed in adulthood.
In this series of posts, we’ll be taking a closer look at epilepsy: its many forms, diagnosis, and treatment. A special emphasis will be placed on the many unmet needs seen in this spectrum of conditions.
Seizures can be generally (and somewhat simplistically) classified as being either partial of generalized. Partial simply means that the seizure occurs in one part of the brain, whereas generalized seizures can occur simultaneously in different parts of the brain.
A third category, Unclassified seizures, and associated with conditions such as febrile seizures.
Partial seizures are typically caused by some sort of injury to the brain, such as a stroke, trauma, infection, or neoplasm. Sometimes, but not always, a resolution of the underlying condition will resolve the epilepsy. But the risk of seizure activity still remains higher than average for these patients.
For two thirds of patients, seizures can be well controlled with treatment. In some cases, neurologists feel comfortable enough to recommend cessation of all anti-epileptics. However, for patients with a family history of epilepsy, or for those on complex anti-epileptic regimens, the long-term absence of epileptic seizure activity does not necessarily mean the patient is in complete remission.
Given that there are 25+ kinds of epileptic syndromes, it stands to reason that epileptologists / neurologists can spend their entire practicing career treating a wide swath of patients, from neonates to the elderly. The choice of treatment depends not only on patient age, but a slew of other factors, such as the type, frequency, and severity of seizure activity, comorbidities, drug interactions, and treatment costs.
While many anti-epileptic drugs are now available as low-cost generics, the complex nature of treatment plans means that many patients are faced with multiple monthly copays, resulting in a surprisingly high monthly cost of therapy.
Paradoxically, some anti-epileptic therapies which are effective in one form of epilepsy may worsen seizures in another form. For example, carbamazepine is considered fist line therapy for generalized tonic-clonic seizures, yet it can worsen seizures in patients with tonic or atonic seizures.
For the ~20% of patients who cannot control seizure activity with medication, then surgery is a potential option. Surgery can be effective if the lesion is known and readily located, and if the area of the brain can be removed without disrupting the remaining brain functions and behaviors.
Historically, valproic acid, carbamazepine, and phenytoin were the most commonly prescribed anti-epileptic agents. Over the years, these drugs have lost their primary position in the treatment paradigm to levetiracetam and lamotrigine. But again, the decision to prescribe one over another is based on many factors, including the type of seizure under management, side effect profile, concurrent medications, costs, etc.
Interestingly, some of the brands in the anti-epileptic market have retained some of their share over concerns that a switch from brand to generic will result in an increased susceptibility to seizure activity. This is especially true for older agents, such as Dilantin (phenytoin) and Tegretol (carbamazepine). But this issue may continue to fade away as generics become more reliable and physicians gain confidence in them.
For some patients, much older drugs like phenobarbital and primidone are still key components of their therapy, usually when first and second-line agents are ineffective or fraught with side effects.
In our next article, we will take a closer look at the pipeline of drug candidates in development for the treatment of epilepsy. We will couple that with the unmet needs seen in epilepsy, and ask questions about the current pipeline’s ability to meet these unmet medical needs in epilepsy.