May, 2010 - Summary of Epilepsy Research Highlights at the 2010 American Academy of Neurology Meeting in Toronto, Canada
Joseph I. Sirven, M.D.
To all of our Epilepsy.com readers and listeners, it is now a new month and new updated information is currently available on Epilepsy.com for which we are very excited to share with you. Over the past few weeks, the American Academy of Neurology convened its annual meeting in Toronto, Ontario, Canada, where 200 epilepsy-based abstracts were presented and discussed on the latest research from investigators from around the world. I am happy to report on some of the highlights from this meeting which you may find useful to your practice. Here I report on 8 different presentations that struck a cord in me primarily because they represented various areas of active investigation or concerns and are representative of the latest information available on these topics.
Given that a new health care law has been signed in the US, any issue that pertains to quality care or the costs of delivering care is quite germane to the current ongoing topic of health care in the United States. In one study by Forlenza and colleagues, they assessed the market scan database of Medicaid claims from 7 states pertaining to 13,355 individuals. They assessed whether maintaining a given drug regimen or changing it (either discontinuing or adding an antiepileptic drug to a drug regimen) impacts the cost of delivering care. They found that increased visits and increased services were noted for individuals where they did not follow the course of care, particularly those who were either discontinued or added an antiepileptic drug to their care. This is important information as we strive to understand variables that drive health care costs and value in determining the best health care delivery model for individuals with epilepsy.
In a second study, which addresses the topic of generic agents, Krauss et. al addressed the issue of bioequivalency which are at the center of the debate for approval of generic formulations of antiepileptic drugs. In his analysis, he conducted a meta-analysis of bioequivalence studies for 147 generic antiepileptic drug formulations incorporating 258 reports. The authors concluded that most bioequivalency studies involve only healthy adults, which is quite different from the population for which these drugs will be utilized for, which are individuals with epilepsy. In addition, he noted that there was minor variation between brand and generic antiepileptic drugs, but there was greater variability among particular antiepileptic drugs, especially those with low solubility. For instance, oxcarbazepine had a variation of 33% between generic and brand drug with regards to specific pharmacokinetic parameters. In general, the study helped to again frame the issue that much more work is needed in order to understand the impact of a generic drug and its introduction into the market as compared to a brand agent.
Two presentations could potentially change the practice of epilepsy as it pertains to therapeutic drug levels and assessing whether a drug can be instituted before initiating it in a given group of patients. For instance, in a study by Rajappa and colleagues, they studied the HLA-B1502 genetic marker for carbamazepine-induced Stevens-Johnson syndrome. Their study confirmed earlier reports that the presence of this pharmacogenomic marker predicts carbamazepine-induced Stevens-Johnson syndrome. Moreover, the authors concluded that any Southeast Asian individual for which carbamazepine is initiated; this test should be done due to its consistent association with this serious condition. This testing recommendation is new and would reflect a change in standards of practice.
In an unrelated study, Dr. Leppik and colleagues looked at intra-individual variability of carbamazepine and valproic acid concentrations in elderly nursing home residents. A significant intra-individual variability of carbamazepine and valproic acid was noted such that valproic acid levels can vary up to 460% and carbamazepine 240% within a given individual over the course of the day. The salient point of this investigation are that single measurements may not be enough to determine whether a dose change is necessary given that these levels are so variable. Dosing decisions should not be based on a sole measurement as is often the case in clinical practice.
A topic that we have discussed often on Epilepsy.com is that of the new FDA suicide warning for all antiepileptic drugs. This was the subject of a recent JAMA manuscript reaffirming the link between suicide risk and antiepileptic drugs. One particular presentation helped to address this issue, but in a practical manner. In a study by Kanner and colleagues, they assessed rapid screening for anxiety and major depressive disorders and its link to suicide risk in an outpatient neurology clinic with individuals with epilepsy. Of 765 patients evaluated, they utilized 3 instruments which helped to gauge the level of suicide risk. These instruments may be quite useful for clinicians to hone in on suicide potential and will help to identify which individuals are of concern. In sum, although the black box warning is quite a frightening thing for patients, at the end it is likely that the warning will help to galvanize physicians to be more proactive in depression and suicide screens than perhaps they had been in the past.
A frequent topic on hallway conversations is antiepileptic drug teratogenicity and the impact of these therapies on newborn infants. Two particular studies help to provide more information on this topic. In a followup analysis of the NEAD Study, Drs. Meador et al showed an analysis of 199 children of women with epilepsy who had been treated with carbamazepine, lamotrigine, phenytoin or valproic acid. These individuals were followed and assessed with IQ by age 3. They then stratified those who had been breast fed versus those who had not and looked for differences in neurodevelopmental outcome based on IQ. There was no evidence of adverse effects of breast feeding during antiepileptic drug therapy and cognitive outcomes were not different between these groups. The authors continue to caution that larger numbers of patients need to be studied before any conclusions can be drawn.
In a related topic, Isojarvi and colleagues evaluated lacosamide, which was recently released and introduced to the U.S. market, and looked at 49 clinical trials for pregnancy outcomes. Of the 10 pregnancies that they identified, there was no evidence of major congenital malformations. Although this is promising information for lacosamide, we still do not know the full reality of what may or may not be the safety risk with this particular agent or other recently released antiepileptic drugs until larger populations of pregnant women are evaluated. The study serves as a reminder that all physicians should encourage their pregnant patients to join a pregnancy registry.
Recently, the FDA Advisory Panel approved the introduction of deep brain stimulation for the management of refractory epilepsy. Another device presented a subset analysis for efficacy for refractory partial epilepsy at the meeting. In the study presented by Salanova and investigators, they assessed individuals who had refractory mesial temporal lobe epilepsy implanted with an RNS ( responsive neurostimulation) for seizure improvement in the randomized double blind trial of the device. The investigators reported a 37% seizure reduction as compared to placebo. This is important because this is another medical device that is potentially approvable by the FDA and it is important to understand its effectiveness and when that efficacy is likely to be seen.
We hope that you find this brief report of only a handful of 200 abstracts presented useful to you and your patients. For further information, I refer you to the American Academy of Neurology web site and look under the epilepsy abstracts in conducting any searches of materials presented at this year’s meeting. In addition to this report, we continue with our hallway conversations in the month of May. Two of these hallway conversations directly pertain to some of the information that I have presented in this brief summary. On May 5, 2010, Dr. Andrew Herzog from Beth Israel Deaconess in Boston, Massachusetts, discusses the new birth control registry database which has just recently opened. This is a fascinating topic and will help to answer some questions with regards to women of child bearing potential and epilepsy-related treatments.
On May 17, 2010, we choose to go to a whole different spectrum of the population and Dr. Ilo Leppik joins us to discuss seizures in the institutionalized older adult patient. Dr. Leppik is a past President of the American Epilepsy Society and is an international expert on this topic. He will sit down and talk about the uses of antiepileptic drugs in the older adult in addition to some of the research that he recently presented with regards to the dramatic variability that is observed in the older adult when it comes to serum therapeutic levels. Lastly, the Pediatric subcommittee of the American Epilepsy Society Nonepileptic spells (NES) taskforce presents a brief monograph on NES across the lifespan that I am certain you will find helpful.
We hope that you find this and all of the material that is located on Epilepsy.com useful for both you and your patients. We hope you enjoy the month of May and you join us for upcoming hallway conversations and other epilepsy. Com activities.
Joseph Sirven, M.D.
© 2013 Epilepsy.com. All rights reserved.