Antiseizure medications help the majority of people with focal epilepsy, a common form of the neurological disorder. Yet most will still have episodes for at least a year after their treatment begins, until their doctors can find the right drug and dosage for them, a new study shows.
Accounting for about 60% of people with epilepsy, focal epilepsy occurs when nerve cells in a certain brain region send out a sudden, excessive burst of electrical signals. This uncontrolled activity, which is called a focal seizure, can cause problems such as abnormal emotions or feelings and unusual behaviors. Much attention has been paid to the minority of patients who do not respond well to available treatments, but the current study looks at another group: those who may not respond to the first medication or regimen prescribed, but perhaps to another tried later.
Led by researchers at NYU Langone Health as part of the international Human Epilepsy Project, the study is among the first in a decade to focus on those whose seizures ultimately can be prevented or controlled with drugs. Results for nearly 450 men, women, and teens newly diagnosed with the disorder revealed that while more than half would eventually receive a medication or regimen that worked for them, major improvements were not achieved until an average of 12 months. Many needed even longer to find relief.
"Our findings suggest that those with focal epilepsy should expect a long adjustment period as their health care provider determines the best treatment regimen for them," said study senior author and neurologist Jacqueline French, MD.
A possible explanation for this delay is that physicians are not selecting the ideal antiseizure therapy on their first try, adds French, a professor in the Department of Neurology at the NYU Grossman School of Medicine and co-principal investigator of the Human Epilepsy Project.
Neurologists commonly start patients on levetiracetam, a drug that can target many types of seizures and has few interactions with other medications. Based on the new results, however, they may want to rethink this approach, says French, noting that while 57% of the study participants were initially prescribed levetiracetam, only a quarter became seizure free on their first try.
A report on the findings is publishing online Aug. 25 in the journal JAMA Neurology.
Thirty-four epilepsy centers in the United States, Europe, and Australia were involved in the study, which took place from 2012 to 2019. The team collected data about the patients' medical histories, demographic factors such as sex and race, and the details of their epilepsy diagnoses, including seizure frequency, the age of onset, and MRI readings. All were provided annual follow-ups for either three or six years.
During this time, participants tracked their seizure frequency in an electronic diary, describing each day as either "seizure free" or "had a seizure." The time, duration, and type of episode, along with other notes, were also recorded. The study volunteers also reported information about their antiseizure medications, noting the type, dose, and reasons for discontinuing a regimen.
Patients were considered seizure free if they did not have an episode for at least a year (or longer if their seizures were infrequent).
The study further showed that together, 63% of all participants experienced ongoing or even worsening seizures during the first year of therapy, whether or not they would eventually find relief.
Notably, those who had seizures only a few times per year prior to treatment were more likely to respond to medication than those who had them weekly. In addition, participants with a history of psychological disorders such as anxiety and depression were almost twice as likely to resist the drugs than those without such a history.
"Our results show that the best way to a new treatment plan is sometimes through making better use of the tools we already have instead of always searching for the next breakthrough drug," said French, who is also a member of NYU Langone's Comprehensive Epilepsy Center.
The researchers next plan to more closely examine those who did not become seizure free during the study period, says French.
French cautions that the investigation did not directly assess the role of regimen choice, dose, or side effects on the way patients responded to treatment, and it did not exclude participants who failed to adhere to their prescribed regimen.
The Human Epilepsy Project is a collaboration of hundreds of researchers, physicians, and other health care workers seeking new insight into how patients with the disorder respond to therapies and become seizure free.
Funding for the study was provided by the Epilepsy Study Consortium, which receives support from pharmaceutical companies UCB, Eisai Co., Pfizer, Lundbeck., and Sunovion Pharmaceuticals Inc., as well as the Andrews Foundation, the John and Barbara Vogelstein Foundation, and Finding a Cure for Epilepsy and Seizures (FACES) — a nonprofit organization affiliated with the NYU Comprehensive Epilepsy Center.
French also receives salary and research support from the Epilepsy Foundation and the Epilepsy Study Consortium. These organizations also covered fees for consulting or attending scientific advisory board meetings for Acadia Pharmaceuticals, Access Industries, Acuta Capital Partners, AfaSci, AgriThera, Alterity Therapeutics, Angelini Pharma, Autifony Therapeutics, Axonis Therapeutics, Beacon Biosignals, Biogen, Biohaven, Bloom Science, Bright Minds Biosciences, CAMP4, Capsida Biotherapeutics, Cerebral Therapeutics Inc., Cerecin Neurosciences, Cerevel Therapeutics, Ceribell, Cognizance Biomarkers, Cowen and Company, Crossject, EcoR1 Capital, Eisai Co., Encoded Therapeutics, Engrail, EpiMinder, Epitel, Équilibre BioPharmaceuticals Corp., Genentech, GRIN Therapeutics, Harmony Biosciences/Epygenix Therapeutics Inc., iQure Pharma, IQVIA, Janssen Pharmaceutica, Jazz Pharmaceuticals, Korro Bio, Leal Therapeutics, LivaNova, Longboard Pharmaceuticals, Marinus Pharmaceuticals, Modulight Bio, Neumirna Therapeutics, Neurelis, Neurocrine Biosciences, Neurona Therapeutics, NeuroPace, NeuroPro Therapeutics, Neuroventis, Neurvati, Noema Pharma, Ono Pharmaceutical Co., Otsuka, Ovid Therapeutics, Praxis Precision Medicines, PureTech Health, Rapport Therapeutics, Receptor Holdings Inc., RiverVest, Sage Therapeutics, SK Life Science, Stoke Therapeutics, Supernus Pharmaceuticals, Takeda Pharmaceuticals, Taysha Gene Therapies, Third Rock Ventures, UCB, uniQure, Ventus Therapeutics, Vida Ventures, and Xenon Pharmaceuticals Inc.
French has received additional research support from FACES, the One8 Foundation, the
National Institute of Neurological Disorders and Stroke, and Praxis Precision Medicines.
French serves on the editorial boards of "The Lancet Neurology" and "Neurology Today" and is the chief medical/innovation officer for the Epilepsy Foundation. She is the president and serves on the board of directors of the Epilepsy Study Consortium, and she has received travel/meal reimbursement related to research, advisory meetings, and presentation of results at scientific meetings from the Epilepsy Study Consortium, the Epilepsy Foundation, Biohaven Pharmaceuticals, Cerebral Therapeutics, Cowen and Company, Longboard Pharmaceuticals, Neumirna Therapeutics, Neurocrine Biosciences, NeuroPace, Neurvati, Praxis Precision Medicine, Rapport Therapeutics, SK Life Science, Takeda Pharmaceuticals, Ventus Therapeutics, and Xenon Pharmaceuticals Inc.
The terms and conditions of all of these relationships are being managed by NYU Langone.
Along with French, Ruben Kuzniecky, MD, at Northwell Health in New York City, and Daniel Lowenstein, MD, at the University of California, San Franscisco, are study co-senior authors and are co-principal investigators of the Human Epilepsy Project.
Other study co-investigators are Sarah Barnard, MD, MPH, and Zhibin Chen, PhD, at Monash University in Melbourne, Australia; Manisha Homes, M.D., at New York Medical College in Valhalla; Andres Kanner, M.D., at the University of Miami in Florida; and Manu Hegde, MD, PhD, at the University of California, San Franscisco.
