Epilepsy Update: Cash, Car Accidents, and Psychiatric Side Effects

Andrew N. Wilner, MD


May 23, 2014

This feature requires the newest version of Flash. You can download it here.

Greetings. I'm Dr. Andrew Wilner, reporting for Medscape from the 66th Annual Meeting of the American Academy of Neurology in Philadelphia, Pennsylvania. There are more than 2500 posters and platforms at this year's meeting. Because I only have a few minutes for this epilepsy update, I have chosen a few presentations that are directly relevant to clinical practice.

The first is an economic outcome in patients receiving antiepileptic drug adjunctive therapy, by Drs. Wang, Li, Powers, and Cavazos from the University of Texas at San Antonio.[1] The study authors looked at a retrospective claims database of 15,000 patients with partial-onset seizures, of which 1349 (9%) changed from monotherapy to polytherapy. They were then able to compare the polytherapy group with those who remained on monotherapy.

They found that there were fewer hospitalizations in the polytherapy group: 19% vs 28%. There were also fewer emergency room (ER) visits in the polytherapy group: 22% vs 30%. Both hospitalizations and ER visits for epilepsy reasons were tallied.

Furthermore, the monthly costs were lower for the polytherapy group: only $886 vs $1579 for the monotherapy group. This finding occurred despite the fact that patients in the polytherapy group were taking more medications.

In conclusion, more effective treatment -- in this case, 2 drugs vs 1 drug -- resulted in fewer hospitalizations for epilepsy, fewer ER visits for epilepsy, and lower costs.

The next presentation was titled "Virtual Car Accident Rates of Epilepsy Patients Are Significantly Increased by Interictal Generalized Spike Waves." The study authors were Drs. Krestel, Von Allmen, Liechti, Steinlin, Mathis, and Arto from Switzerland.[2]

There is a big debate about the importance of interictal epileptic activity when it comes to driving or other activities that require continuous concentration, and this study provides important information. The investigators created a laptop driving simulator game and programmed it so that crashes occurred if the reaction time of the subject was 1 second or longer.

Of 34 patients with generalized epilepsy and 12 patients with focal epilepsy, 5% of generalized interictal activity caused crashes and 1.2% of focal interictal activity caused crashes. Among the generalized interictal activity, 20% of classical spikes, 1.2% of sharp theta, and 0.8% of atypical spikes caused crashes. Classical spikes prolonged reaction time by 278 ms -- more than double that of the other types of spikes. Sharp theta prolonged reaction time by 84 ms, and atypical spikes prolonged reaction by 126 ms.

The study conclusion was that the presence of classical generalized spikes was associated with a prolonged reaction time and caused errors in the game, which suggests the possibility that car accidents in real life might occur with persistent interictal spikes. This has important implications for when patients may drive.

Traditionally, we look at seizure control but not necessarily interictal spikes, and this raises the question of what seizure control really is. The presence of interictal spikes and generalized spikes in particular may be important when making decisions about the safety of driving.

The last presentation that I will discuss was a summary of perampanel clinical studies: an analysis of psychiatric and behavioral events. The study authors were Drs. Ettinger, LoPresti, Yang, Williams, Zhou, Fain, and Laurenza.[3]

Perampanel has the trade name of Fycompa®. It is one of the newest epilepsy drugs that we have available. It is a noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist -- the only one that we have. However, it carries a boxed warning about serious psychiatric and behavioral issues.

The investigators looked at all of the phase 3 clinical trials and tried to assess to the degree to which these are real problems. They looked at the placebo group and the perampanel group. These statistics are for perampanel at all doses ranging from 2 to 12 mg.

Anxiety: placebo group, 1.1%; perampanel group, 2.8%

Aggression: placebo group, 0.5%; perampanel group, 1.6%

Anger: placebo group, 0.2%; perampanel group, 1.2%

Irritability: placebo group, 2.9%; perampanel group, 7%

All of these behavioral and psychiatric problems were at least double the frequency with perampanel compared with placebo. As might be expected, these problems tended to be worse during titration and at higher doses.

In conclusion, one should be vigilant for these behavioral and psychiatric problems when using perampanel, and in rare cases, it may be necessary to discontinue the drug.

Thank you very much for your attention to these brief epilepsy highlights from the 66th Annual Meeting of the American Academy of Neurology.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: