20% of Refractory Epilepsy Patients May Be Nonadherent to Treatment

November 5, 2019

Study results suggest that as many as 20% of patients may be nonadherent to medication regimens, with youth having the strongest association with intentional nonadherence.

Oliver Henning, MD

New study results suggest that as many as 20% of patients with refractory epilepsy are not adherent to medication regimens, either as a result of intentional or unintentional actions.

The study, led by Oliver Henning, MD, division of clinical neuroscience, National Center for Epilepsy in Norway, featured 333 consecutive adult patients with refractory epilepsy who were given an anonymous survey during in- and outpatient settings (mean age, 37 years; range, 17­—72). Ultimately, 22% admitted to forgetting medications as scheduled either “sometimes” or “often,” while 19% reported that they “rarely,” “sometimes,” or “often” intentionally did not adhere to their prescribed antiepileptic treatment plan. Non‐adherence was found not to be associated with any specific drug.

In epilepsy, adherence remains a challenge—and one with critical concerns surrounding it. James Wheless, MD, professor and chief of pediatric neurology, Le Bonheur Children’s Hospital, University of Tennessee Health Science Center, who was not part of the study, recently told NeurologyLive that the need to adhere to medication regimens is “critical” due to the risks associated with poor adherence.

“If I’m treating my seasonal allergies and I forget to take my antihistamine, I might sneeze more, but the risk is not so high,” Wheless explained. “If I have seizure medicine that I’m supposed to take every day and I forget a couple of days, then it’s high risk. If I have a seizure while I’m driving or at work—it’s a whole different risk factor.”

Henning and colleagues noted that younger age (mean 32.7 years [SD, 11.94]; mean difference, 6.44; 95% CI, 3.038—9.832; P <.001) and depression (mean difference, 1.41; 95% CI, 0.289—2.530; P = .014), as measured by the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), were significantly correlated with unintentional nonadherence. The independent variables associated with unintentional nonadherence included a NDDI-E score ≥15 (odds ratio [OR], 2.03; 95% CI, 1.060—3.903; P = .033) and being younger than the median age (OR, 2.309, 1.222—2.309; P = .010).

Intentional non&#8208;adherence, however, was only associated with younger age (mean, 33.7 [SD, 11.71]; mean difference, 5.17; 95% CI, 1.532—8.800; P = .005). Being younger than the median age was the only independent factor that was significantly associated with intentional nonadherence (OR, 2.46; 95% CI, 1.252—4.808; P = .009).

No significant differences were identified between men and women with regard to nonadherence. As well, neither intentional or unintentional nonadherence was associated with seizure type, seizure frequency (daily or weekly versus less frequently), monotherapy, different antiepileptic drugs used in monotherapy, polytherapy (≥3 or more agents), NDDIE score >14, or adverse event profile score >44.

“In contrast to other studies, we did not find a high score of adverse events to be a risk factor,” Henning and colleagues wrote. Along with the other factors which were not significantly associated with nonadherence, they noted that “this is not necessarily dependent on the number of antiepileptic drugs in use which could explain [the] findings.”

Henning and coauthors noted that these data highlight the importance of monitoring nonadherence and implementing measures to improve adherence and point out that acknowledging variable adherence as a factor contributing to variability and poor seizure control is paramount. For patients with epilepsy, nonadherence to agreed antiepileptic treatment can result in seizure relapse, and at worst sudden unexpected death in epilepsy.

“In conclusion, about one-fifth of patients with refractory epilepsy admitted that they did not adhere to the agreed drug treatment plan, either intentionally or unintentionally,” Henning and colleagues concluded. “Measures to reduce non&#8208;adherence in this patient group may improve seizure control and should be tailored to address both unintentional and intentional lack of adherence.”


Henning O, Lossius MI, Lima M, et al. Refractory epilepsy and non-adherence to drug treatment. Epilepsia Open. Published online October 28, 2019. doi: 10.1002/epi4.12367.