New study show direct link between depression and medication nonadherence

A new study led by Alan B. Ettinger, M.D., M.B.A., Director of the Epilepsy Center at Neurological Surgery, P.C. (NSPC), has found that many patients who fail to take their antiseizure medications are suffering from depression. Previous studies by Dr. Ettinger and others have found a high incidence of depression in people with epilepsy, but this is the first research to show a direct link between depression and medication nonadherence. The study will be published in the July 2014 issue of the journal Epilepsy & Behavior, and is available online ahead of publication.

"Our previous studies have shown that there are substantial consequences to missing doses of antiepileptic medications, even occasionally," said Dr. Ettinger. "We have also seen that depression impacts quality of life. Now we see that depression is a significant factor in drug nonadherence. This demonstrates that it is critical for physicians to screen their patients for depression, and to talk with them about the importance of taking all of their medications when scheduled."

Missing even one dose of an antiepileptic drug can cause breakthrough seizures, even in patients whose epilepsy is well controlled by medications. This can have devastating effects - including hospitalizations, falls and related injuries, and even death. Studies have shown that 30-50% of people with epilepsy don't adhere to their medication regimen.

"Other studies have shown a link between depression and failure to take medications in conditions such as hypertension and HIV, but little was previously known about the potential impact of depression on antiepileptic drug adherence," said Dr. Ettinger.

Among other factors thought to play a role in antiepileptic drug nonadherence are memory difficulties and medication side effects.

In the current study, researchers accessed a nationwide health plan/pharmacy database, and selected a sample of 10,000 epilepsy patients. 2,750 patients were randomly selected from this group and mailed an in-depth survey that included a number of validated questionnaires on medication adherence, depression status, seizure severity and frequency, and quality of life, among other factors. Questionnaires used in the survey included the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), which asks questions that are highly specific to epilepsy and is considered highly reliable. 465 patients completed and returned the survey. Claims data were analyzed with the widely used medication possession ratio (MPR), to measure drug adherence. (MPR represents the proportion of time that an individual was theoretically in possession of a medication.)

The researchers conducted a path analysis, a highly reliable and sophisticated type of statistical modeling, to determine the relationships between depression, drug adherence, seizure severity and quality of life. One key finding was that depression, as determined by the NDDI-E, was significantly correlated with an elevated risk of antiepileptic drug nonadherence. Depression, as measured by the NDDI-E and another survey instrument, was also associated with low quality of life scores. In addition, patients with depression were more likely to report having more severe seizures.

"We have known for a while that depression impacts patients' quality of life, and we know that it can be treated; now we know that there is a direct link to patient harm," said Dr. Ettinger, who works on a number of committees through the American Epilepsy Society to educate clinicians on the importance of depression screening.

Dr. Ettinger suggests that neurologists inquire about each patient's mood and quality of life, as well as medication adherence, during office visits. There are also brief questionnaires that patients can complete in the waiting room to indicate potential mental health issues. He also points out that some antiepileptic medications are now available in once-daily formulations (making it easier for patients to remember to take them), and that there are other medication adherence reminders now available, including smartphone alarm apps.

The study was funded by GlaxoSmithKline. The survey was administered and analyzed by OptumInsight, Inc.