ATLANTA ― Depression not only makes epilepsy more difficult to treat, it may also increase the risk of developing the condition later in life, according to research presented at the American Epilepsy Society Annual Meeting.
While depression and epilepsy have long been linked, the relationship between them has remained unclear. Two new studies provide further evidence that the connection runs both ways and that mental health may play a critical role in treatment success and brain health.
- People with both conditions face greater epilepsy treatment challenges and poorer outcomes than people with epilepsy who don’t have depression, according to a national analysis of more than 90,000 insurance claims.
- People with depression are about 2 ½ times more likely to be diagnosed with epilepsy at a later point than those without depression, according to a systematic review and meta-analysis of eight studies.
“These findings highlight the importance of early detection of both conditions and coordinated care between mental health and neurology professionals,” said Howard P. Goodkin, MD PhD, FAES, president of the American Epilepsy Society. “The bottom line is good depression care supports brain health.”
Depression linked to early treatment failure in people with newly diagnosed epilepsy
Among more than 90,000 people with newly diagnosed epilepsy, those with depression were 40% more likely to fail their first antiseizure medication (ASM) within the first few months, meaning they stopped taking the drug, switched to a different drug or supplemented it with another drug.
“People with epilepsy are known to be at higher risk for mood disorders, but our study uncovers new information that those with depression are more likely to fail their first treatment,” said Samuel W. Terman, MD, MS, lead author of the study and assistant professor of neurology at the University of Michigan, Ann Arbor. “We didn’t assess why a person stopped or changed treatments, but it is likely that the initial treatment either was not tolerated or not effective enough.”
Researchers analyzed data from people with newly diagnosed epilepsy from 90,738 insurance claims starting Jan. 1, 2016, based on Medicare claims (ending Dec. 31, 2022) and the Inovalon MORE2 closed claims database (ending Dec. 31, 2023). They determined 21,388 (24%) also had a diagnosis of depression.
In addition to being more likely to fail their first ASM within a few months, those with epilepsy and depression were more likely to have other mental health issues:
- Anxiety (65% with depression vs. 24% without depression)
- Sleep disorders (42% vs. 21%)
- Psychosis (20% vs. 8%)
- Bipolar disorder (18% vs. 8%)
People with both conditions also had higher rates of cardiovascular and systemic conditions, including lung diseases (such as chronic obstructive pulmonary disease), diabetes, kidney disease and heart failure.
“Depression could affect epilepsy treatment in various ways, such as influencing a person’s motivation to continue medication, making their complex drug regimen too challenging or magnifying side effects. Or they may have other neurological conditions that may worsen seizures or medication tolerance,” said Dr. Terman. “This underscores the importance of integrating mental health care into epilepsy treatment to keep patients on effective therapies longer and improve outcomes.”
In future studies, researchers should assess how factors such as income, health problems and the type of medication affect the link between depression and epilepsy treatment success, Dr. Terman noted.
Increased risk of epilepsy diagnosis after depression
A separate analysis of eight studies found that people with depression are about 2 ½ times more likely to be diagnosed with epilepsy at a later point. However, most people with depression will not develop epilepsy.
“Our findings show a consistent association that suggests an increased risk of developing epilepsy after depression, but they do not show that depression causes epilepsy,” said Ali Rafati, MD, MPH, lead author of the study and postdoctoral research fellow at Johns Hopkins University School of Medicine, Baltimore. “We need to learn more about the biological connection, but the link between depression and epilepsy could be related to shared brain networks, stress and inflammation pathways and sleep issues.”
Researchers analyzed eight studies comparing epilepsy incidence in people with and without depression. While older, smaller studies did not show an association, two recent, large-scale studies of more than 11,000 people confirmed the association and pattern of depression diagnosis followed by a higher rate of epilepsy diagnosis later.
“Health care professionals who treat depression should be aware that neurological symptoms can occasionally overlap, and if a patient reports episodes that might resemble seizures, such as sudden confusion, unresponsiveness or unusual movements, it may be best to refer them for neurological assessment,” said Churl-Su Kwon, MD, MPH, FRSPH, senior author of the study and assistant professor of neurological sciences at Columbia Mailman School of Public Health, New York.
*** AES 2025 news releases may contain updated data that does not match what is reported in the abstract.
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