Drug Tolerability, Dosing Frequency Impacts Adherence in Epilepsy

Physicians shouldn't dismiss patients who claim they simply "forgot" to take their medication.

Administration of more well-tolerated drugs in simpler dosing regimens may help improve treatment adherence among people with epilepsy, results from a large cohort study indicate.

The study, published in Neurology, assessed treatment adherence among a large German cohort of adults with epilepsy. Adherence was measured using the medication possession ratio (MPR), with patients with an MPR <80% considered nonadherent.

A total of 31 317 patients with epilepsy were included in the analysis. The mean MPR was 81.1%; 64.7% of patients had an MPR of >80%, indicated good adherence. Those with good adherence to antiepileptic treatment were likely to be of West German residence (OR 1.23, P<.0001) and have a learning disability (OR 1.80, P<.0001). Based on drug-related factors, patients who used new vs old (OR 1.52, P<.0001) and branded vs generic antiepileptic drugs (OR 1.44, P<.0001) had better adherence. Levetiracetam was associated with the best adherence (OR 2.85, P<.0001) while valproate had the worst. Notably, 2 or more doses of antiepileptic drugs reduced treatment adherence (TID vs QD: OR 0.84, P= 0.005; BID vs QD: OR 0.86, P= .011).

In an accompanying editorial, Edward Faught, MD, of Emory University School of Medicine in Atlanta, GA, noted that the study identifies which patients are nonadherent, but not why, and raises the point that many patients may truly just forget to take their medications.

“If patients are asked, by far the most common excuse is forgetting — not side effects, not hopelessness, not overconfidence. Those reasons may be disguised by self-reporting, but maybe we should take patients at their word,” Dr Faught wrote. “In fact, there is evidence from studies of some diseases that intensive educational efforts are of limited value. Memory aids may be more effective. These can take the form of associating doses with daily routines (tooth-brushing, morning coffee), filling weekly pill boxes, strengthening associations (intention implementation intervention: having patients write down and repeat their planned routine), and electronic pill bottle recording.”

Coaxing an honest answer about adherence out of a patient requires a careful approach, Dr Faught advised, however teaching them what to do in the event of a missed dose is equally important, as nonadherence in epilepsy is associated with high rates of morbidity and mortality.


  1. Gollwitzer S, Kostev K, Hagge M, Lang J, Graf W, Hamer HM. Nonadherence to antiepileptic drugs in Germany: A retrospective, population-based study. Neurology. 2016; doi:10.1212/WNL.0000000000002791.
  2. Faught E. Epilepsy and nonadherence: Did you take your medicine? Neurology. 2016;87:1-2.