Missing or skipping a dose of medicine is a major cause of breakthrough seizures. Anything that we can do to simplify a patient’s dosing regimen is going to help. Of course, it is important to tell our patients that they should always take their medicine as prescribed, but we also need to appreciate what happens in their everyday lives. How often can a person truly say that they have taken each and every dose of their antibiotic even after they are feeling better, or that they have taken each and every dose of an antihypertensive medication exactly at the time that they were supposed to take it? The difference is that missing 1 dose of an antibiotic is not going to necessarily make a huge impact, but significantly delaying even just 1 dose of a seizure drug can spark a generalized tonic-clonic seizure that may result in a call to 911, a hospital admission, and the implementation of driving restrictions.

Treatment that forgives naturally occurring behavior is vitally important. Some of the third-generation drugs, such as perampanel and eslicarbazepine, for instance, have longer half-lives that enable them to be administered once daily. Perampanel has the longest half-life of the newer-generation agents at 105 hours. The next longest half-life other than phenobarbital is zonisamide at approximately 60 hours. Having a longer half-life means that, if a dose is missed or is significantly delayed, a patient’s serum levels are not going to decrease as rapidly as they will with drugs such as immediate-release (IR) levetiracetam or lamotrigine, which have half-lives of less than 30 hours (6-8 hours for levetiracetam and 29 hours for lamotrigine) and must be dosed twice daily. Extended-release (XR) formulations of second-generation drugs, such as levetiracetam XR or lamotrigine XR, can be taken just once daily rather than twice daily. Unfortunately, not all of these drugs are available to everyone. XR formulations often cost more than IR formulations, and some insurance companies require patients to provide proof of side effects or compliance issues with the IR formulation before they will approve an XR formulation. So, it is still occasionally a battle to get patients the XR versions of generic antiepileptic drugs. With regard to other sources of nonadherence, it is important to discuss not only the social consequences with our patients (eg, driving restrictions, risk of accidents, risk of injury), but also the risk of death. Noncompliant patients—especially those with generalized tonic-clonic seizures—are more likely to experience sudden unexpected death in epilepsy (SUDEP). It is always surprising to me how few patients know about SUDEP until I share it with them in the office. We need to do a better job of educating our patients about the risks of seizures to help with compliance. We also must ask our patients about the side effects they are experiencing, as many individuals may not share this information without being asked and these side effects could lead to future issues with compliance.