Lists of Antiepileptic Drugs | AED Page List/Topic Index | Common uses of Antiepileptic Drugs

1.  Class Acts

Like antidepressants anticonvulsants (ACs), or antiepileptic drugs (AEDs) - the terms are nearly interchangeable1 - are broken up into different classes based upon things like how your liver deals with them, chemical structure, and even how they work in your brain. Unlike antidepressants there is overlapping membership, classes that consist of a single drug, or a drug and subsequent drugs derived from it, and existing anticonvulsants will be added or removed from categories as the understanding of their pharmacodynamics and/or pharmacokinetics improved. Thus the taxonomy of AEDs is as complex and fungible as that of mushrooms.

The primary classifications of anticonvulsants are if they are benzodiazepines or non-benzodiazepine anticonvulsants. While some are used as AEDs, most benzos are prescribed only for anxiety and other conditions these days, so they get their own pages. Some, like Xanax (alprazolam), are not even approved by the FDA to treat epilepsy or any kind of seizure disorder. Unless otherwise specified the terms “antiepileptic drug” and “anticonvulsant” will refer to non-benzodiazepine anticonvulsants.

The next classifications are based on pharmacokinetics.

2.  Enzyme-inducing AEDs

The first is which AEDs induce CYP450 and/or UGT enzymes. Enzyme-inducing AEDs (EIAEDs) can have numerous drug-drug interactions, as well as deplete your body of vitamin D3. EIAEDs include:

  • Tegretol (carbamazapine)
  • Dilantin (phenytoin)
  • phenobarbital
  • primidone
  • Trileptal (oxacarbazepine)
  • Topamax (topiramate)
  • Sabril (vigabatrin)

Most of the time EIAEDs refers only to Tegretol, Dilantin, and phenobarbital, because:

  • primidone is converted to phenobarbital.
  • Trileptal’s induction of UGT enzymes is only moderate and it doesn’t do much in the way of CYP3A4/5 induction like Tegretol does.
  • Topamax induces some enzymes, but its effect is significant only at higher dosages.
  • Lamictal barely induces UGT enzymes, so it rarely makes a difference.
  • Why Sabril speeds up the clearance of some meds hasn’t been identified. Enzyme induction is assumed.
  • Anything else that may induce CYP or UGT enzymes is so rarely prescribed these days that any doctor who prescribes it had better know everything there is about that med.

Lots of other medications, both crazy and non-crazy meds, induce CYP450 and UGT enzymes. AEDs are singled out because epileptics have been given more than one med to control their seizures for over 150 years;2 so neurologists as a group are more aware of drug-drug interactions and how the slightest change in dosage can affect their patients’ symptoms than most other doctors.



3.  The Valproates/Enzyme-Inhibiting AEDs

Some doctors, researchers, et al. lump remaining AEDs into a category called non-Enzyme-inducing AEDs (non-EIAEDs), but the true flipside of enzyme induction is enzyme suppression, and I’ve found one crazy med that suppresses an enzyme - Provigil. However, enzyme inhibition is the functional opposite of induction. There is only one group of commonly-prescribed AEDs that inhibits UGT and CYP450 enzymes involved in the metabolism of any medications to any meaningful extent, and that’s the valproates:

  • Depakote (divalproex sodium or valproate semisodium)3
  • Depakene (valproic acid)
  • Stavzor (valproic acid delayed release)
  • Depacon 4 (valproate sodium or sodium valproate)5

For more information on CYP450 and UGT enzymes, enzyme induction and inhibition, see the pages on pharmacokinetics.

4.  Aromatic Anticonvulsants

The next group is the Aromatic Anticonvulsants. These meds don’t help you smell purty. Aromatic refers to aromatic hydroxylation, which is part of the process when these drugs are metabolized. With a very small percentage of people (somewhere between 1 in 1,500 to 1 in 10,000) the metabolism isn’t done correctly and a toxic substance (arene oxides) is left over instead of getting cleaned up. The leftover triggers anticonvulsant hypersensitivity syndrome, and that sucks donkey dong. Anticonvulsants with a particular chemical structure (similar to TCAs, and TCAs may trigger a similar reaction) are going to be converted into the problem toxin, but there’s no way (yet) of telling if someone won’t be able to properly metabolize the toxin once it is created. While the odds are a bad reaction of one of these drugs means a bad reaction to one or more, if not all of the others, someone may have a problem with just one of them.6 Or there may be one of them they can take.

  • Lamictal (lamotrigine)
  • Trileptal (oxacarbazepine)
  • Zonegran (zonisamide)
  • Tegretol (carbamazapine)
  • Dilantin (phenytoin)
  • phenobarbital (the data are mixed regarding primidone)
  • Felbatol (felbamate)

Stevens-Johnson Syndrome (SJS), a.k.a. The Lamictal Rash, is thought to be a component of anticonvulsant hypersensitivity syndrome. So if you got SJS, or any rash scary enough that you and/or your doctor thought it best to discontinue one or more of the above meds, the odds are you’ll get a rash from one or more of the others.



5.  All Other AED Classes

Finally we come to classifications of AEDs that are chemically related and/or work in similar ways. There may be only one drug per class because it is unique, or it is the only still on the market, or that ever made it to the market in the first place.

The classes Carbonic Anhydrase Inhibitors (CAI) and GABA Reuptake Inhibitors contain drugs that do only that, otherwise most AEDs would be classified as a GABA reuptake inhibitor, and Topamax and Zonegran would also be CAIs.

5.1  Bromides

The Bromides were the very first AEDs that actually worked, developed in the mid-19th century by Charles Locock, Charles Bland Radcliffe and Samuel Wilks.

  • potassium bromide was the first.
    • It is still used today, although as a second- or third-line veterinary AED.
    • Except in some developing nations, where it’s still used on people when nothing else works or is available.
  • There used to be a lot more bromides, including ammonia, arsenic, mercury, sodium, and the rather-effective gold7.
    • Except for a compound of gold and arsenic bromide, potassium bromide worked better than all the others.

5.2  Barbiturates

The Barbiturates were the first AEDs developed in the 20th century. More effective and tolerable than the bromides.

  • mephobarbital
  • Nembutal (pentobarbital sodium)
  • phenobarbital

5.3  Hydantoins

The Hydantoins were the first generation of what came to be known as modern AEDs. These are the ones still on the market. Dilantin (phenytoin) is still the benchmark against which any new AED is first compared for efficacy, much as any new mood stabilizer is compared with lithium or a new antipsychotic is compared with Thorazine.

  • Peganone (ethotoin)
  • Mesantoin (fosphentyoin)
  • Dilantin (phenytoin)

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5.4  Succinimides

Succinimides are an old group of meds that are rarely prescribed these days. They are mostly used to treat absence seizures that don’t respond to anything else.
  • ethosuximide
  • methsuximide
  • phensuximide

5.5  Carbamates

I’m pretty sure there were more Carbamates, and felbamate is the only one left that’s still on the US market.

  • Felbatol (felbamate)

5.6  Carbonic Anhydrase Inhibitors (CAIs)

Although available in the US, treating seizures is an off-label use of these meds. Carbonic Anhydrase Inhibitors (CAIs) are approved for epilepsy in other countries, such as in the UK. In any event they are third-line add-ons.

  • Diamox (acetazolamide)
  • sultiame

5.7  Dibenzapine Derivitives (carboxamides)

Dibenzapine Derivitives (carboxamides) are also known as Tegretol and its derivitives. And that one drug that looks like Tegretol.
  • Tegretol (carbamazapine)
  • Trileptal (oxacarbazepine)
  • eslicarbazepine
  • Banzel (rufinamide)

5.8  Fatty Acid Derivatives

At least Fatty Acid Derivatives have a similar mechanism of action, in that they are all very GABAergic meds.

5.9  GABA Analogues

I have no idea why the GABA Analogues class is still around. None of these meds is an analog for GABA. They all do something that increases the amount of, or otherwise enhances the GABA you have in your brain, but they don’t act like, nor are they a precursor for, GABA.8

  • Gabrene (progabide)
  • Sabril (vigabatrin)
  • Neurontin (gabapentin) and Lyrica (pregablain) were once considered GABA analogues.

5.10  GABA Reuptake Inhibitors

GABA Reuptake Inhibitors are just like any other reuptake inhibitors. Which is probably why Gabitril poops out.
  • Gabitril (tiagabine)
  • Neurontin (gabapentin)
  • Lyrica (pregablain) - although not everyone agrees on just how Neurontin and Lyrica work…

5.11  alpha-2-delta Ligands

With any luck alpha-2-delta Ligands will be Neurotin’s and Lyrica’s final classification.


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5.12  Functionalized Amino Acids (FAAs)

Functionalized Amino Acids are currently the hot new thing in AEDs, so with any luck there will be more.
  • Vimpat (lacosamide)

5.13  Sulfamate-Substituted Monosaccharides / Fructose Derivatives

If there is ever another Sulfamate-Substituted Monosaccharide/Fructose Derivative I bet it would make people lose weight.

5.14  Sulfonamides

If you are allergic to sulfa drugs, you need to stay away from Sulfonamides. You should also avoid Aromatic AEDs until you start running out of options.

  • Diamox (acetazolamide)
  • sulthiame
  • Zonegran (zonisamide)

5.15  Phenyltriazines / Triazines

As much as I love Lamictal, I seriously doubt anyone is even thinking about making another drug in the Phenyltriazines/Triazines class.


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5.16  Pyrrolidines

Pyrrolidines
  • Keppra (levetiracetam)
  • Keppra derivatives (e.g. brivaracetam) that UCB is working on.

5.17  Oxazolidinediones

Oxazolidinediones
  • trimethadione

6.  Non-Drug Epilepsy Treatment Options

Most of the time when reading about “non-drug treatments” for something it’s probably something you’d like to try before taking a medication. Not with epilepsy.

6.1  Taking Stuff Out (Surgery)

There are all sorts of fun surgical procedures available. They include:

  • Resection - cutting out the bit of your brain that is the source of the problem. This is done somewhere in a person’s temporal lobe more often than anywhere else.
    • Lobe resection - an entire lobe, roughly a quarter of your cerebrum, is removed.
  • Corpus callosotomy - disconnecting the major broadband communication route between the two hemispheres of your brain. The best part: it doesn’t stop seizures, it just makes them a lot less bad.
  • Multiple subpial transections - isolating multiple parts of someone’s brain. Like the corpus callostomy, but at specific locations. It also makes seizures less bad.
  • Functional hemispherectomy - literally splitting your brain into two separate organs. One step up from the corpus callosotomy, it physically separates the two hemispheres of your brain. Rarely done on anyone older than 12, although that may change.
  • Hemispherectomy - Removing half of your brain. Rarely done anymore, as the functional hemispherectomy is the preferred most-radical procedure.

6.2  Putting Stuff In

  • Vagus Nerve Stimulator (VNS) - the original pacemaker for the brain.
  • Deep Brain Stimulation - Lots of little pacemakers put in specific parts of your brain. Still experimental.

6.3  Other Treatments

  • Ketogenic Diet - It’s not just for kids anymore. The traditional one, where desert is a couple apple slices or, in its most extreme form, bacon9, is still for kids. Adults who were once on the ketogenic diet, or are responding partially to their meds, now have the option for a modified Atkins diet.

7.  AED equivalences

Given how there are so few AEDs in each class it’s little wonder few of them work the same way. Many people ask about AEDs/ACs that are equivalent, the way SSRIs are. Very few AEDs are:

  • The valproates are essentially interchangeable. There are some dosage adjustments required, as well as getting used to different side effects, but those are mostly for your gut and liver and not your brain. If need be you can substitute them one to one (e.g. 500mg of valproic acid equals 500mg of Depakote equals 500mg of your commie sodium valproate). See the valproates page for more details.
  • Trileptal is a derivative of Tegretol. They aren’t exactly alike, but they are close enough that switching from one to the other can be done without titration if absolutely necessary. 300mg of Trileptal (oxcarbazepine) = 200mg of Tegretol (carbamazepine USP). The US PI sheets (Trileptal’s full US prescribing information Tegretol’s full US prescribing information) are full of information about switching between the two.
  • Lyrica isn’t derived from Neurontin, but their mechanisms of action, whatever they may be, have always seemed similar.
  • Diamox and sulthiame are both carbonic anhydrase inhibitors, and neither is approved to treat epilepsy in the US.
  • Zonegran and Topamax have a vaguely similar chemical structure and a very similar mechanism of action. I’ve yet to figure out how much Topamax equals how much Zonegran.
  • I did find this 2004 report to the American Academy of Neurology and American Epilepsy Society that gives functional equivalents for some AEDs in treating partial and generalized seizures:

8.  References

  1. Trileptal’s full US prescribing information
  2. Tegretol’s full US prescribing information
  3. Efficacy and Tolerability of the New Antiepileptic Drugs, I: Treatment of New-Onset Epilepsy: Report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society. Epilepsia, 45(5):401–409, 2004. Jacqueline A. French, Andres M. Kanner, Jocelyn Bautista, Bassel Abou-Khalil, Thomas Browne, Cynthia L. Harden, et al.
  4. Anticonvulsant Hypersensitivity Syndrome: Implications for Pharmaceutical Care. Pharmacotherapy. 2007;27(10):1425-1439. KarenBeth H. Bohan, Pharm.D., Tarannum F. Mansuri, Pharm.D., Natalie M. Wilson, Pharm.D.
  5. Bromide, the first effective antiepileptic agent. J Neurol Neurosurg Psychiatry 2002;72:412 J M S Pearce
  6. Antiepileptic Drugs René H. Levy, Richard H. Mattson, Brian S. Meldrum, Emilio Perucca © 2003
  7. PDR: Physicians’ Desk Reference 2010 64th edition
  8. United States Dispensatory 15th edition. Dr. George B. Wood, Dr. Franklin Bache, H.C. Wood M.D., Joseph P. Remington Ph.G., Samuel P. Sadtler, Ph.D. F.C.S. © 1883 H.C. Wood M.D. published by J. B. Lippincott & Co.
  9. United States Dispensatory 19th edition. Dr. George B. Wood, Dr. Franklin Bache, H.C. Wood M.D., Joseph P. Remington Ph.G., Samuel P. Sadtler, Ph.D. F.C.S. Albert B. Lyons M.D., Horatio C. Wood Jr., M.D. © 1907 H.C. Wood M.D. published by J. B. Lippincott & Co.


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Lists of Antiepileptic Drugs | AED Page List/Topic Index | Common uses of Antiepileptic Drugs


1 Because some benzodiazepines aren't approved, and rarely, if ever prescribed off-label to treat epilepsy, not all anticonvulsants are AEDs. Similarly not all AEDs are in the anticonvulsant class of drugs, but only because they are being prescribed off-label. E.g. progesterone-based birth control.

2 Most modern AEDs are approved by the FDA to be used only with other AEDs. Topamax was the first AED in a long time to receive FDA approval to be used all by itself (monotherapy) to treat both partial and generalized seizures.
Potassium bromide is still in use after 150 years, primarily as a treatment for epileptic animals. Although it is the final straw you'd ever want to grasp at. Phenobarbital is over 100 years old and may be in front of some (relatively) newer meds to try if you're running out of options.

3 Divalproex sodium is used in the US and most places. Valproate semisodium is the official commie international nonproprietary name (INN), but I see divalproex sodium used far more often.

4 Or whatever it's called where you live.

5 Whichever it's called where you live. Abbott prefers valproate sodium, most everyone outside of the US uses sodium valproate.

6 Cross-sensitivity, or in English, having the same sort of bad reaction to a similar substance, runs in the neighborhood of 40 to 80% when it comes to people who took one aromatic AC and had the same bad reaction to another one.

7 If you thought the side effects of any medication you have taken or consider taking sucked, just imagine those of mercury bromide. These weren't patent medicines, they had the approval of what passed for the FDA in the late 19th century.

8 In case you forgot or didn't know: GABA can't cross the blood-brain barrier - i.e. any GABA you eat or inject will float around your blood stream but never be able to get into your brain. Which means any money you've spent buying GABA supplements has been a total waste. Camomile tea is a much cheaper placebo and far less likely to have something in it that isn't camomile that could be harmful. Not that GABA supplements would have anything harmful. Most of them are probably all cornstarch. Or may as well be.

9 I'm not making this up. There is an absolutely carb-free version of the ketogenic diet used for children who have seizures associated with syndromes that make your life seem like nothing but panda cubs crapping rainbows everywhere you look. They get to eat nothing but meat and eggs, drink only water, and still have to take AEDs. For one child I knew who was on this version of the diet bacon was treated as desert.


If you have any questions not answered here, please see the Crazymeds Antiepileptic Drug/Anticonvulsant discussion board. I welcome criticisms of the articles, notifications of bad links, site problems, consumer experiences with medications, etc. I’m not always able to write back.

Last modified on Tuesday, 19 April, 2016 at 22:24:59 by JerodPoorePage Author: Date created 21 November 2010

Classifications of Antiepileptic Drugs / Anticonvulsants by Jerod Poore is copyright © 2010 Jerod Poore


All drug names on this page and used throughout the site, are a trademark of someone else. Their PI sheets will probably have the name of the manufacturer and/or trademark owner (they’re not always the same company) at or near the very bottom. Or ask Google who the owner is. The way pharmaceutical companies buy each other and swap products like Monopoly™ real estate, the ownership of the trademark may have changed without my noticing. It may of changed hands by the time you finished reading this article.





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1 While there are plenty of books to help you with hypochondria, for some reason there’s not much in the way of websites. Then again, staying off of the Internet is a large part of curing/managing the disorder.

2 Remember kids, Microsloth operating systems are like TOS Star Trek movies with in that every other one sucks way, way more. With TOS Star Trek movies you don’t want to bother watching the odd-numbered ones. With Microsloth OS you don’t want to buy and install the even-numbered ones. Anyone who remembers ME and Vista knows what I mean.

3 Have I mentioned how open source operating systems for commercial applications is one of the dumbest ideas in the history of dumb ideas?* I don’t even need my big-ass rant any more. Heartbleed has made my case for me. And that’s just the one that got all the media attention. The very nature of an open source operating system makes security as much of an illusion as anonymity on teh Intergoogles. Before you flip out too much: the domain Crazymeds is hosted on uses a version of SSL that is not affected by the Heartbleed bug. That’s one of the many reasons why I pay a lot of money and keep this site on Lunarpages.

* Yes, I know I’m using open source browsers. I also test the site using the now-defunct IE and Safari browsers. Their popularity - and superiority - killed IE and Safari, so that’s why I rely on the open source browsers. It’s like brand vs. generic meds. Sometimes the generic is better than the brand.

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