PHILADELPHIA - Fully optimized antiepilepsy therapy that tries at least a couple of well-chosen and properly dosed antiseizure drugs as well as follow-up with nondrug options for patients who are unresponsive to pharmaceuticals seems able to render about 80%-90% of epilepsy patients seizure free, Dr. Cynthia L. Harden said while summing up a session on epilepsy therapy at the annual meeting of the American Epilepsy Society.
Finding an appropriate and effective treatment for each epilepsy patient can be “labor intensive and expensive”; it depends in part on a patient’s mood, psychosocial profile, and willingness to comply with treatment; and it often needs the multidisciplinary expertise found at epilepsy centers. But the optimistic message from contemporary seizure-management is that by using a drug or two and in selected patients surgery, diet, or an implanted device, the vast majority of epilepsy patients can become seizure free, noted Dr. Harden, system director of clinical epilepsy services at the Mount Sinai Health System in New York and cochair of the session.
“How many of your uncontrolled patients can become seizure free with more vigilance and tender loving care?” she asked the large audience as she concluded the session. A significant fraction of uncontrolled patients become seizure free when their drug dosage is increased, another drug is substituted or added, their compliance improves, their depression diminishes, or a patient’s understanding of their epilepsy and treatment increases through education, Dr. Harden said.
Drugs remain the cornerstone of seizure control for epilepsy patients, with at least 22 agents now available for epilepsy treatment, including 13 with U.S. or European (or both) approval for initial monotherapy of epilepsy. In addition, study results have shown several agents – carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenytoin, and zonisamide – to be more or less equally effective for treating newly diagnosed focal epilepsy, which means that clinicians must also consider factors beyond just efficacy, such as adverse effects, impact on a specific patient’s comorbidities, interactions with other drugs a patient takes, and ease of use and cost, said Dr. Emilio Perucca, a neurologist and professor of pharmacology at the University of Pavia (Italy). In general, newer antiepilepsy drugs have not been more effective than older drugs, he noted.
Another feature of drug treatment is that more is usually not better. “Most patients do not need the highest tolerated dosage,” he said, and minimizing dosages to the lowest effective level helps minimize adverse effects. On the other hand, an antiepilepsy drug needs to be administered at an adequate dosage before concluding that it is ineffective for a patient.
Although a majority of patients respond to the first or second antiepilepsy agent they receive, drugs can’t render all patients seizure free. Results from several reported cohorts show that about 45% of patients with newly diagnosed epilepsy respond well to the first drug they receive and about 13% become seizure free on a second drug. After that, the response rates fall off sharply, with roughly 5% of patients responding to a third drug or drug combinations, said Dr. Patrick Kwan, professor and chairman of neurology at the University of Melbourne and head of epilepsy at Royal Melbourne Hospital. “Once a patient has failed two drugs, even if they become seizure free on a subsequent drug, there is a higher rate of relapse,” Dr. Kwan noted.
In general, 60%-65% of newly diagnosed epilepsy patients become seizure free with drug monotherapy, Dr. Kwan summarized. Epilepsy patients who fail to fully respond to the first two antiepilepsy drugs they receive need “prompt” referral to an epilepsy center. A “substantial proportion” of patients like this can become seizure free by further optimization of the dosage they receive or by addressing compliance issues, Dr. Kwan said. In addition, some patients achieve full or partial seizure freedom through multidrug treatment or with other treatments.
Two-drug combinations have generally been more effective than combinations with three or more drugs, said Dr. Josiane LaJoie, a pediatric neurologist at New York University. “Using three or more drugs probably won’t lead to better control, just more adverse events,” she cautioned. Many published study results have documented successful two-drug combinations, such as lamotrigine and valproate, and valproate and clobazam, to name just two combinations. In addition to looking at combinations with successful track records in published studies, she highlighted the importance of combining drugs with distinct mechanisms of action and avoiding combing drugs with similar adverse-event profiles. Combinations also need to be tailored to each patient’s clinical characteristics, taking possible drug-drug interactions into account, Dr. LaJoie said.