New Antiepileptic Drugs

INTRODUCTION

Two new antiepileptic drugs (AEDs) have had recent FDA approval. The first medication to be discussed is clobazam (band name = Onfi). This drug is currently available. The second AED is ezogabine (brand name = Potiga). Ezogabine is not yet available in pharmacies, but should be available soon.

The purpose of this article is to provide educational information on these medications. Please note- for specific treatment with these AEDs, please discuss with your clinician.

CLOBAZAM (BRAND NAME = ONFI)

What kind of medication is Onfi?

Onfi is an AED. It works by binding to GABA receptors in the brain. By binding to GABA receptors, seizure activity is reduced. Onfi fits into the class of drugs known as benzodiazepines. Other benzodiazepines that you may have heard of: lorazepam (brand name = Ativan) and diazepam(brand name =valium).

What types of seizures does Onfi help?

Works on seizures seen in patients with Lennox-Gastaut Syndrome (LGS). LGS seizures can be very severe. Seizure types associated with LGS:

  • Generalized tonic-clonic seizure: Old terminology is “grand mal seizure.” This is probably the most recognizable seizure type- patient will collapse to the ground, body will stiffen, full body shaking activity is seen.
  • Atypical absence seizure: Old terminology is “petit mal seizure.” Patient will stare and be unresponsive.
  • Myoclonic seizures: brief jerks of parts of body. For example, brief, sudden and fast jerk of an arm or leg. Can be a single jerk or a series of jerks.
  • Atonic seizures: Muscles lose tone- as if all strength in muscles is lost. Can be very sudden in onset. Can result in falls with injury. The reason for the injuries makes sense. If I fall to the ground, I can protect myself by bracing my fall with my arms. With atonic seizures, patients can fall on their face-unable to protect themselves because their muscles are not responding.
  • Tonic seizures: Muscles suddenly increase in tone—muscles go stiff. This can be very intense and sudden.This can also result in falling and injury.

Important side effects: sedation/sleepiness, coordination problems, breathing problems, slurred speech, change in behavior- such as aggressive behavior,  and nausea. There are other side effects- this is a brief list of some the more common or more important side effects. It is hoped that with slow increases in the medication, side effects can be minimized or not occur.

What happens if I stop Onfi abruptly?

This can lead to withdrawal symptoms. Symptoms of withdrawal include tremor, feeling anxious and possibly seizures.

Common dosing of Onfi:

Start at 5mg once or twice per day. Starting dose and titration depends on weight (children vs adult) and other clinical factors. Can be titrated up to 20mg twice per day in some patients.

EZOGABINE (BRAND NAME = POTIGA)

What kind of medication is Potiga?

Potiga is an AED. It improves seizure control by increasing the current through potassium channels in the brain’s neurons. The increase in flow through this channel reduces the excitability of the brain- this can reduce seizure activity (remember, a seizure is often due to abnormal electricity coming from the brain).

What types of seizures does Potiga help?

It has been approved for use in focal onset seizures. These are seizures that start in one part of the brain, and then propagate. For example, a seizure starting in the temporal lobe would be a focal seizure. Such a seizure may start with an aura- a feeling of nausea, for example. The seizure could then spread to cause confusion and unresponsiveness.

Important side effects: dizziness, sleepiness, inability to empty the bladder, change in cardiac conduction (QT interval lengthening), and change in behavior- including hallucinations. There are other side effects. These are just a sampling of some the important side effects. It is hoped that with slow increases in the medication, side effects can be minimal or not noted at all.

Common dosing of Potiga:

The medication is to be taken three times per day. The goal is to titrate up to a dose of 600mg to 1200mg per day (total daily dose).

References

Introduction to Potiga via [Epilepsy.com]

Dr. White has been practicing as a full-time epileptologist since 1999. His practice focuses on optimizing the diagnosis and treatment of patients with seizure disorders. Dr. White’s special interests include patient education, improving the side-effect profile of seizure medications, and epilepsy surgery.

18 Responses to “New Antiepileptic Drugs”

  1. Hopefully these new AED’s will give some people the seizure control they are looking for but haven’t yet found! I’ve been reading about one not yet approved called Perampanel, and if I’m reading it correctly it has a half-life of 70 hours, needs to be administered only once per day, and can be taken before bed. It seems like Perampanel may have been a marketplace competitor with Ezogabine, but the latter was approved first? (PharmaWatch: CNS; Sep2011, Vol. 10 Issue 9, p5-5, 1p). Still, no AED’s without side effects – always benefit vs risk. Speaking of side effects, I think I remember that Depakene and Depakote can cause tremor as a side effect. Is it understood what exactly happens to cause the tremor? Are there other AED’s that can cause that as well?

    As always, thanks for your time, and for delivering updates in an easy-to-read yet informative manner. 🙂

  2. I agree with your comments- it is always weighing risks and benefits. Although the newer AEDs have good side effect profiles, all AEDs can result in serious side effects in individual patients. I really try hard to go into detail about both sides of equation- side effects and benefits in terms of seizure control. To do it right, it is often a lengthy conversation. Nevertheless, having an informed patient is extremely important.

    Depakote/Depakene can, as you say, cause tremor. As a matter of fact, it is one of the most common and important side effects of Depakote. The mechanism is not completely understood. Depakote appears to have affects on the basal ganglia. The basal ganglia is part of the brain that controls coordinated movements. Disorders of the basal ganglia can cause tremor. For example, patients with Parkinsons Disease will often have an obvious tremor. This is due to dysfunction in the basal ganglia. It has been suggested that Depakote may produce changes on neurotransmitters (chemicals in neurons) in the basal ganglia that produce tremor (an effect on neurotransmitters such as GABA or dopamine). Other possibilities include effecting neurotransmitters in the cerebellum.

    Again, thank you for your thoughtful comments. It is obvious that your reading is extensive. I am hopeful that your questions and comments will continue to help us with the educational part of our website and Facebook (you have already helped!).

    Thank you!

  3. I’m really concerned about the antiepileptic drugs.. My son has been on about all of them with horrific side-effects. Watching his diet has been our best effort to stop his seizures.. All the dyes and preservatives that they put in our food is killing us slowing. Some like my son our more sensitive so it affects them sooner than later.. I just think hiding the conditions instead of finding the cause is some of the problem. The doctors have just told us they don’t know why our son has seizures and most people with epilepsy don’t know the reason. And, we should be happy he doesn’t have a brain tumor or something like that.
    Our son has had seizures for 13 years and we will never give up finding the reason he is having them. With Gods help and research on what is causing them so we can stop him for what ever is causing them is the course we are choosing.
    No this doesn’t make the medical field happy but I really don’t care. We don’t want to hide the condition we want it cured!!! So we need to find the cause….
    The doctors keep saying its too hard to watch what you eat and to do so much research. Give me a break. These are our children and God gave them to us to raise and protect. We should do everything in our power to do that. Yes, it’s hard but doable.
    Just my opinion. Drugs aren’t always the answer!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
    Thank you for letting people post their opinions.

    Smile,
    Kristi

    • Thank you for your comments Kristi. I completely agree that an important goal of research is to cure epilepsy, rather than just suppress the symptoms with seizure medications. An example I often use- if my brain gets an infection, an antibiotic can treat the infection- truly cure it. Unfortunately, seizure medications are not a cure. They can control seizures in most patients. Unfortunately, there are still patients who we cannot control with medications. I agree, some seizure medications have very significant side effects. You also make a good point about how some people are sensitive to medication side effects. Such patients may require alot of work and attention from the doctors, other staff and family to get the best possible outcome– well worthwhile when/if success is acheived. Again, thank you for your comments! James White, MD

  4. Hi Kristi-

    I’m curious as to whether you’ve been able to make a definitive connection between specific foods/dyes/preservatives and an increase/decrease in seizure activity in your son? Has he been tested for food allergies? I found an article (from Epilepsia, 2008) that addresses diet-triggered seizures. I’m sure you’ve probably already read this or something like it, but here’s the link if you’re interested: http://depts.washington.edu/neurolog/seminars/journalclub/20081217_all.pdf

    As far as medications go I understand you being wary of side effects and the idea of “treating the symptom and not finding the cause” (My background is in alternative medicine). In my 15 years of experience, I’ve seen a lot of pretty amazing things happen through the use of proper nutrition and supplements. I’ve also seen a lot of unsubstantiated claims and what could only be called quackery. When my husband started having seizures after a brain tumor removal, I did a lot of research, hoping to find a way to cope with the seizures without the worry of long term effects of medication, while in the meantime he was started on a single medication. His seizures worsened and grew in frequency. He eventually ended up in the hospital for over a week, suffering from non-stop seizures. While he was in the hospital, a fourth med was added into what he was already taking, and on this current combo he has been seizure free for almost 12 years. 🙂 He’s not without side effects (mild) and the long term effects of being on the meds are starting to show. However, the meds have given him a better quality of life and have allowed him freedoms that he wasn’t able to attain when he was having seizures. Maybe your son would have better luck on some of the newer AED’s, IF a cause cannot be determined.

    Don’t give up hope – keep searching! My experience, while limited only to my husband’s case, has taught me there are many unknowns when it comes to epilepsy, and that there’s a place for both ideologies when it comes to finding a solution. I’ll be hoping that you find the answers you are looking for and your son can soon be seizure free!

    Deb T.

  5. I have just recently started taking Topamax and it works great for Me

  6. Deb: As always, your comments are extremely helpful. The information you provide is well researched. Also, getting the perspective of the patient/family is incredibly valuable. Thank you! James White, MD.

  7. Yes Deb, Thank you for the information. Natalie, Please be very careful with Topamax !!!! It took my sons speech away and he has word search problems now… Not saying it won’t help Just Please be very careful!! Smile, Kristi

  8. Alice Halldorson May 1, 2012 at 12:02 pm

    Deb–

    Could you tell me what the combination (4 meds you mentioned) and how much was needed to finally stopped your husbands seizures, please? Thnx. Alice

    • Hi Alice-

      My husband is currently taking Dilantin (2 different strengths), Neurontin, Tegretol, and Keppra. It was the addition of the Keppra that eventually controlled his seizures. Over the course of 6 months the dose was slowly increased to 6000 mg/day, while at the same time we observed a gradual decrease in seizure activity. He remains on that amount of Keppra today, which I believe is higher than most people take. (Dr. White, please feel free to correct me if I’m wrong.) Of course everybody responds differently to each med, and he was able to tolerate higher doses and multiple meds better than some.

      However, as time went on his side effects got pretty bad (his Dilantin levels were always high) and we slowly and periodically decreased the amount he was taking of the Dilantin. (It goes without saying this reduction in dosage was done under the Dr.’s care). The decrease in Dilantin was what was needed to get the major side effects under control. The long-term effects of being on the meds are what we are starting to tackle now, and we approach this challenge the same way we did the seizures, day by day and with a lot of research! 😉

      Deb T.

  9. I oldest son has grand mal seizures and he has been changed to Kempra and seizure free in almost in a year. I youngest son has seizures and has been on Trilepthal for about 5 years and my husband has been on Trilptal for ten years and he has the ones partial complex. I was wondering if you get immune to the medications because I ask the physician about changing the medication. This is a concern of mine

    • Excellent question Margaret. I,of course, am not able to comment specifically on your family (as you know, in order to make specific comments, I would need to do a thorough history and exam. I realize you are probably well aware–but it is important to remind our readers–and me!–to not diagnose or treat online). For most patients, the effect of the seizure medication does not wear off. I there is good seizure control, that good control tends to continue. There is a situation that arises for some patients called the “honeymoon” effect. It is,fortunately, uncommon. This “honeymoon” is where there is excellent seizure control for a period of time- can be months or even longer. The seizures then return. It can be very frustrating (that is can really be an understatement!). Imagine if you are seizure free. You are about to get your drivers license–and bam–you are hit with a seizure. And then, the seizures continue. It is not a well understood phenemona. Something seems to happen to the effect of the seizure medications on the neuron receptors–the beneficial effects seem to change. As I said, fortunately it is uncommon. Great question. Thank you! James White, MD

  10. I am a patient of generalised epilepsy since last 30 years. It started when I was 15years old. There is distant family history also. Nearly every year I used to have seizures. But since last 3 years there was no seizure which made docs to withdraw tergitol (450mg) within 6 months of time. I was also taking lamictal along with tergitol which was 100mg/day. Hence doc increased the lamictal dose to 300mg/day within 2months and withdrew tergitol. Since the withdrawal of tergitol I m getting seizures again that too with inc frequency within one month. Pls guide me with meds and it’s withdrawal.

  11. I was taking 3 AED along with Onfi since 2005 before approved by FDA buying it from Bayamas and Canada, noting my partial seizures reduced from 20/month to average of 4 monthly since on Onfi. I then reduced and eliminated Keppra & Zonegran, currently taking Onfi and Lyrica without seizures increasing and preventing side effects by taking alternative & complementary medicine.
    When now taking half the amount of AEDs mostly controlled by Onfi and practicing neurofeedback to remain relaxed, I’m trying to decide to start either with Fycompa (Perampanel) or Ezogabine in order to fully control partial seizures 100% without having to cause severe side effects such as blindness. Which do you think can make a good adjunctive medicine along with Onfi and Lyrica?

  12. Hi i was wanting to know if you have heard of using
    Tritepal and keppra together for untraceable epilepsy

  13. Elizabeth Pelaez June 22, 2014 at 8:29 pm

    Hi I have autistic son 26 he had seizer wend he was 18 month to 5 years was a drop seizer I tried tegrtol but was make him aggressive istop no more m3diction he was free seizer to 21 years and them he start to drop and after shaking we tried different medic but his seizers come worse dr startto add medication keppra topamax clobazam and now he start fycompa he still drop he only 1/2dosis fycompan some one now about fycompa work for drop seizers . His seizer are better he dont shake any more but I am very worry for the drop to many Isured he used helmet kneed pads and baskbasketball running shoes to protect him

  14. Hi is there any medications specially for dravet syndrome ?

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