|Volume 7, Issue 1 January 2011
Happy New Year! As we survey the therapeutic choices for seizures in 2011, there are numerous antiepileptic medications (AEDs) currently approved in the United States. These medications are arbitrarily divided into two groups; first (AEDs approved prior to 1993) versus second generation AEDs (those drugs approved 1993 and later). First generation AEDs include agents phenobarbital, phenytoin, ethosuximide, carbamazepine, valproic acid, primidone and the benzodiazepinesólorazepam, diazepam and clonazepam. Second generation AEDs are felbamate, gabapentin, lamotrigine, tiagabine, topiramate, levetiracetam, zonisamide, oxcarbazepine, vigabatrin, rufinamide, lacosamide, and pregabalin. The question that I am most often asked by both my patients and from other physicians is which medication is my favorite? The question is deceptively simple. Because the answer, of course, is based on a number of different factors which include matching the right drug to seizure type, the drug's mechanism of action, its interactions with other medications and most importantly, what are the expected side effects?
Side-effects are what often determines whether a drug treatment is going to be successful or whether it is going to be failure from the start. A given response to an AED can be unique as the individual taking the drug. It is important to remember one basic fact, all drugs have side effects. All one has to do is spend some time on the FDA website to realize the number of potential side-effects that can occur with the use of any AED. So how does one choose between these adverse effects? Oftentimes, it is trying to predict which side-effect is potentially tolerable to an individual versus those which are not. I will try to briefly summarize in this column some of the more commonly encountered side effects which often make a difference to the individual with seizures.
There are many adverse effects commonly noted with first generation AEDs. Double vision, is often seen with carbamazepine and phenytoin use. Weight gain is associated with valproic acid. Conversely, weight loss is seen with ethosuximide. Reversible tremor to the degree that it can mimic Parkinson's disease and hair loss can often be noted with the use of valproic acid. Rash occurs with carbamazepine and phenytoin use. Gum enlargement, otherwise known as gingival hyperplasia is a common effect of long term phenytoin exposure. Low sodium levels, otherwise known as hyponatremia is seen with carbamazepine. Blood changes, such as diminished white cell counts can be seen with carbamazepine and phenytoin which could reduce one's ability to fight infection. A decrease in platelets (important for blood clotting) is a concern with valproic acid. Osteoporosis has been reported to occur with long-term use of carbamazepine, phenobarbital, phenytoin and primidone. Tiredness or sleepiness is commonly noted with phenobarbital and the benzodiazepines. These effects must be taken into account when making a decision as to which drug to use.
Second generation AEDs are not immune to adverse effects. For instance, weight gain is associated with the use of gabapentin and pregabalin whereas weight loss is associated with, felbamate, zonisamide and topiramate. There can be difficulty with word recall associated with the use of topiramate. Behavioral changes such as moodiness or irritability is commonly seen with the use of levetiracetam. Dizziness is a common side-effect that is noted with increasing doses of oxcarbazepine and lacosamide. Low sodium or hyponatremia is seen with oxcarbazepine. If an individual has a first-degree relative, i.e., sibling or parent with a history of renal stones, topiramate and zonisamide can potentially cause renal stones in the individual as well. Rash has been reported to occur with lamotrigine, particularly if the dose is increased quickly. There can be EKG changes that occur with the use of lacosamide or rufinamide. Peripheral visual field loss is a serious manifestation of vigabatrin use and topiramate should not be used in persons with glaucoma. Meaningful decreases in white and red blood cell counts have been noted with felbamate exposure.
In summary, there are a lot of different adverse effects that can be associated with the use of various AEDs. It is essential to be aware of these common adverse effects that occur in patients so that one can ask their physician for another option that does not cause that particular side-effect. It is only by an open and honest dialogue between a healthcare professional and an individual with epilepsy that good solutions can come about and positive change can occur to insure good quality of life.
How can Epilepsy Therapy Project help?
The Epilepsy Therapy Project's main mission is to advance and accelerate the discovery of new therapies that can quickly be brought from the laboratory to the patient in as short a time as possible. Finding new treatments that have the fewest side-effects and are most tolerable is one of the most important aspects of the work of the Epilepsy Therapy Project and in turn, Epilepsy.com. Our hope and our goal for 2011 is to find new ways in which to bring these treatments to the patient as fast as one can so as to best help bring hope and control of the patient's seizures in the best manner possible.
MARK YOUR CALENDAR!
Upcoming grant cycles, epilepsy-related Hallway Conversations, conferences, symposia, and events include:
Meet ETP in Miami!
April 27-29, 2011
Antiepileptic Drug and Device Trials XI Conference
Turnberry Isle Resort
Program Goals: This is the eleventh conference focusing on issues related to antiepileptic drug (AED) development from preclinical discoveries through clinical evaluations. In 2010 the antiepileptic drug pipeline has many interesting compounds. Yet, the path to development of a new antiepileptic drug has become riskier and more difficult. At this juncture, it is important that we reevaluate development strategies, to ensure that it is optimized for the current environment. There is always opportunity to learn from the past as we move into the future. This symposium will bring together representatives from academia, industry, the NIH, and the FDA to review what has been learned and to discuss strategies to enhance AED development.
AED2 XI Conference is Sponsored by: The Epilepsy Study Consortium in collaboration with the New York University Medical Center, the University of Pennsylvania Epilepsy Center and the Epilepsy Therapy Project
SPRING 2011 GRANT OPPORTUNITIES:
Letters of Intent due: March 2nd, 2011. If LOI is accepted, full proposals are due April 13th, 2011.
Learn more / Apply for Funding here
Applicants are encouraged to review ETP's Funding Portfolio
Read recent press releases issued by the Epilepsy Therapy Project
December 30, 2010: Epilepsy Therapy Project Expands Scope of "My Epilepsy Diary" Online tool. Read it here.
December 10, 2010: Epilepsy Organizations Award Grants for Novel Technologies to Improve Treatment, Monitoring and Detection of Epilepsy.
Read it here.