Epilepsy.com has a great section on antiepileptic drugs (AEDs), but I often have been asked for a brief summary document that pulls the information into one package. This summary represents the opinion of the author, Dr. Robert Fisher, who is an epilepsy specialist, and it is not necessarily the official drug description that can be found in the package insert. No drug companies have paid for or reviewed these opinions.
There is no formula to choose which seizure medicine to use for a particular patient. No one medicine dominates for effectiveness, and all have various side effects. Doctors and patients choose AEDs after considering which side effects should be avoided in particular cases, convenience of use, cost and physician experience. An important start is to know which AEDs work for which seizure types. The narrow spectrum AEDs mostly work for specific types of seizures (such as partial, focal, or absence, myoclonic seizures). Broad spectrum AEDs additionally have some effectiveness for a wide variety of seizures (partial plus absence myoclonic seizures). Some types of seizure are difficult to treat with any AED. (Go here to learn what these seizures types are).
|Narrow-spectrum AEDs:||Broad-spectrum AEDs:|
|- phenytoin (Dilantin)||- valproic acid (Depakote)|
|- phenobarbital||- lamotrigine (Lamictal)|
|- carbamazepine (Tegretol)||- topiramate (Topamax)|
|- oxcarbazepine (Trileptal)||- zonisamide (Zonegran)|
|- gabapentin (Neurontin)||- levetiracetam (Keppra)|
|- pregabalin (Lyrica)||- clonazepam (Klonopin)|
|- lacosamide (Vimpat)||- rufinamide (Banzel)|
|- vigabatrin (Sabril)|
- Brand vs. generic. Every medicine has a brand and a generic name. The generic usually is cheaper, sometimes by quite a lot. For medicines introduced in recent years, patent (or “market exclusivity”) protection may block the sale of generic versions. A generic medicine usually works well, but it may not generate the same blood levels as does the brand name or an alternative generic medicine. Therefore, with changes of pill manufacturers, the blood levels can change. This may produce breakthrough seizures or side effects. The most important concern when taking generic drugs is to be sure the tablets are made by the same manufacturer for each refill. Switching from one generic manufacturer to another could result in different amount of active drug in each pill. The current author supports the right of the patient and doctor to know about medication substitution and consider whether generic substitution is safe.
- Starting schedule: Many AEDs have to be started slowly to minimize side effects, event though this delays helping the seizures. The titration (starting) schedules are those of the author, and may be slower than is the schedule recommended in the package insert. Dosages are all for adults. Children are treated on the basis of their weight (mg per kg dosing basis).
- Monotherapy: Some AEDs have approval for monotherapy (to be used alone) and others only as adjunctive (add-on) therapy to another AED. This reflects what testing evidence has been presented to the FDA - not all AEDs have gone through the required two clinical studies to show effectiveness in monotherapy. AEDs not proven effective in monotherapy still probably work well as single medications and are used that way by epilepsy doctors on a case-by-case basis where the benefit seems to exceed the risk.
- Blood levels: Target blood levels are broad guides to clinical use. Actual blood levels differ for different laboratories. The desirable level depends upon the type and number of seizures, side effects, taking one vs. multiple drugs and other clinical factors.
- Side effects: Side effects listed below are a brief compilation of the most common and most worrisome, not a full list. Every seizure medicine can sometimes cause side effects of fatigue, dizziness, unsteadiness, blurry vision, stomach upset, headaches, and reduced resistance to colds, memory and thinking problems. Weight gain tends to occur with valproic acid (Depakote), gabapentin (Neurontin), pregabalin (Lyrica) and carbamazepine (Tegretol, Carbatrol). Weight loss tends to occur with topiramate (Topamax), zonisamide (Zonegran) and felbamate (Felbatol). These are not mentioned separately in each section, unless they are especially common with the medicine. Detailed information is provided by the pharmacy as a package insert for new prescriptions and refills.
- Effects on internal organs: All seizure medicines can cause problems with blood counts (white cells, red cells and platelets), or liver or other internal organs, so doctors usually order blood tests to screen for these problems. Blood can be tested when starting a medicine to get a baseline, after a few months on the drug, every few months to yearly thereafter, then at individually determined times. The package insert often has recommendations, but there are no universal rules about when to test blood. All seizure medicines can produce either mild or severe allergic reactions. One, called the hypersensitivity syndrome, produces fever, rash, fluid accumulation, swollen lymph nodes, possible liver injury and confusion
- Suicide warning: The US FDA has required a suicide warning on all seizure medications as a general class. All people taking them should be aware of and report any serious depression or suicidal thinking to their doctor, but the actual risk for suicide due to AEDs is quite low.
- Mechanism: Mechanisms of action in the brain for antiepileptic drugs are described in simple form: most AEDs have multiple mechanisms of action to block seizures.
- Not a cure: Although AEDs are called “antiepileptic,” they do not cure epilepsy, but just suppress seizures while the medications are in the body.
Individual Antiepileptic Drugs (AEDs), alphabetically
carbamazepine (Tegretol, Carbatrol): A favorite partial seizure medicine in the developed world. Carbamazepine affects sodium channels, and inhibits rapid firing of brain cells. Long-acting forms such as Carbatrol or Tegretol-XR can be given once a day. Potential side effects include GI upset, weight gain, blurred vision, low blood counts, low blood sodium (hyponatremia). Carbamazepine causes a rash rate of a few percent, sometimes even the dangerous rash called Stevens-Johnson syndrome. People of Asian descent with HLA-B*1502 antigen are more at risk. Typical adult dose is 400 mg tid. I start my patients with 200 mg bid and each week, and increase by 200 mg daily to about 400 mg three times a day. See information on carbamazepine and information about carbamazepine extended release.
clonazepam (Klonopin): Clonazepam is a member of the drug class known as benzodiazepines, to which diazepam (Valium), lorazepam (Ativan), clorazepate (Tranxene), alprazolam (Xanax) also belong. Benzodiazepines are used as anti-seizure drugs, sedatives, tranquilizers and muscle relaxants. Benzodiazepines increase the effectiveness of GABA, the brain’s main inhibitory neurotransmitter. Clonazepam is more long-acting against seizures than are diazepam or lorazepam. Side effects of clonazepam include sedation, thinking/memory impairment, mood changes, addiction. More so than most, its effects wear off over time. A typical adult dose is 0.5-1.0 mg three times a day. I usually start my patients with 0.5 mg at night, and if they are not too sleepy the next day, increase to 0.5 mg twice a day. A week later, if seizures persist, I will increase to 0.5 mg three times a day. See information on clonazepam.
gabapentin (Neurontin): Gabapentin has the reputation of being a safe but not particularly powerful AED. The effectiveness criticism probably is because it is often prescribed at too low a dose. The drug probably works by influencing transport of GABA and effects on calcium channels. It has no drug interactions, is not metabolized in the liver and it does not bind to blood proteins. Side effects are unsteadiness, weight gain, fatigue, dizziness. Typical adult dose is 300-600 mg three times a, but doses can be up to 1200 mg three times a day. I often start at 300 mg per day, sometimes in one dose or with 100 mg pills, and increase over a month or two to the full dose. Gabapentin often is used also for chronic pains of certain types. See information on gabapentin.
lacosamide (Vimpat): Lacosamide is a new (2009) antiepileptic drug , for partial and secondarily generalized seizures. It is chemically related to the amino acid, serine. Vimpat blocks sodium channels (but in a different way from other seizure medicines), and this block reduces brain excitability. Side effects include dizziness, headache, nausea or vomiting, double vision, fatigue, memory or mood problems. Vimpat may affect the internal organs, blood counts or heart rhythm, but these potentially serious side effects are infrequent. The recommended starting dose is 50 mg twice daily, increased each week by an extra 100 mg, to the recommended maintenance dosage of 100-200 mg twice a day. See information on lacosamide.
lamotrigine (Lamictal): A broad-spectrum alternative to VPA, with a better side effect profile. However, LTG may not be as effective for myoclonic seizures. Lamotrigine works by several mechanisms including blocking release of glutamate, the brain’s main excitatory neurotransmitter. It has the usual side effects of dizziness and fatigue, usually mild cognitive (thinking) impairment. Severe medical side effects are unusual. The practical side effect issue is rash, occurring in several percent of people who take it, especially if the dose is increased too fast. Therefore, it takes a couple of months to get up to the typical adult dose of 200 mg twice a day. I usually start my patients at low doses, adding one 25 mg pill daily each week on a two-times-a-day schedule until taking 100 mg twice a day. If there is no rash at that time, one is unlikely. I then switch my patients to 100 mg pills and increase to 200 mg twice a day over the next few weeks. This is slower than the package insert suggested starting dose, however, a slow starting dose is especially important if the patient also takes valproic acid (Depakote), to reduce risk for rash. Lamotrigine is also used for mood stabilization. See information on lamotrigine.
levetiracetam (Keppra): Levetiracetam is one of the more used medicines in seizure clinics because it probably is effective for a broad-spectrum of seizures types, has a relatively low incidence of causing thinking/memory problems, and can be started at 500 mg twice a day, which is an effective dose. It has no drug interactions, is not metabolized in the liver and it does not bind to blood proteins. The most common side effects are dizziness, fatigue, insomnia, but the more troublesome problem can be irritability and mood changes. This may occur to some degree in up to a third of those taking the medicine. A typical adult dose is 500 - 1500 mg twice a day. I usually start my patients with 250 mg twice a day and increase the next week to 500 mg twice a day, then the next week to 1000 mg in the am plus 500 mg in the pm, then the week after to 1000 mg twice a day. This is slower than the package insert suggested starting dose. See information on levetiracetam.
lorazepam (Ativan): Lorazepam is similar to clonazepam in dosage and action, but it is not as long-acting. It is usually used as a ‘rescue medication’ for patients who frequently have clusters of seizures. It works reasonably quickly when taken orally and anti-seizure effect lasts for 2-6 hours. Typical adult dose is 0.5-2.0 mg orally or as needed. A lorazepam concentrate, 2 mg per ml, can be taken as 1 ml liquid under the tongue in urgent situations. See information on lorazepam.
oxcarbazepine (Trileptal): Slightly different from carbamazepine, it is at least as effective, and may have fewer side effects, except for more risk for low blood sodium (hyponatremia). It is more expensive than generic carbamazepine. A typical adult dose is 600 mg twice a day. I start my patients with 150 mg twice a day, and increase by 150 mg daily each week. This is slower than the package insert suggested starting dose. An immediate switch from carbamazepine to full-dose oxcarbazepine is possible in some cases. See information on oxcarbazepine.
phenobarbital (Luminal): The old-timer: very inexpensive and effective in a single daily dose. Phenobarbital increases the effect of GABA, the main inhibitory neurotransmitter in the brain. Watch for sedation, thinking/memory problems and depression. Phenobarbital can cause long-term bone problems. Phenobarbital is mildly addictive and requires slow withdrawal. During pregnancy, there is a significant rate of birth defects. Typical adult dose is around 100 mg per day. I start my patients with 30 mg pills, 2 or 3 at bedtime, to allow for future dosage flexibility. The target serum level is 10-40 mcg per ml. See information on phenobarbital.
phenytoin (Dilantin): The most used AED by general physicians in the US, less so by epilepsy doctors, because of the side effects. Phenytoin alters brain cell sodium channels, which has the effect of limiting rapid firing of the brain cells. It is inexpensive. Common side effects are unsteadiness and moderate cognitive problems. There are long-term potential cosmetic (body/face hair growth, skin problems), and bone problems (osteoporosis). Phenytoin causes a rash rate of a few percent, sometimes even the dangerous rash called Stevens-Johnson syndrome. Typical adult dose is 300-400 mg per day, usually with 100 mg pills. Phenytoin can be started quickly in an emergency with intravenous administration, or a large dose of capsules if an immediate effect is required. Small changes in phenytoin dose can cause large changes in serum drug levels, so the blood levels can be hard to regulate. The target serum level is 10-20 mcg per ml. See information on phenytoin.
pregabalin (Lyrica): A relative of gabapentin, it may be better, and can be given twice a day. Some believe that it is more effective against seizures than is gabapentin. Pregabalin has no drug interactions, no liver metabolism, no protein binding, and similar side effects to gabapentin. Typical adult dose is 150 - 600 mg bid. I usually start my patients with 50 mg daily, adding 50 mg each week on a twice a day basis until taking 300 - 600 mg per day. This is slower than the package insert suggested starting dose, but avoid sedation. Pregabalin often is used also for chronic pains of certain types. See information on pregabalin.
rufinamide (Banzel, Inovelon in Europe): Banzel is approved for add-on treatment of children age 4 and older and adults with Lennox Gastaut Syndrome. This syndrome can include seizure types such as atonic (drop) seizures, tonic (stiffening) seizures, myoclonic (brief jerking) seizures, or staring (absence) seizures, as well as partial seizures. Banzel works on sodium channels in brain cells, in a way to make them less excitable. Common side effects include headache, dizziness, fatigue and sleepiness, double vision and tremor (trembling). People who have the “short QT syndrome,” a rare heart rhythm irregularity, should not take Banzel. The drug comes as 200 and 400 mg tablets. Children will usually be started at doses of approximately 10 mg/kg/day administered in two equally divided doses. Dosing can increase by adding additional 10 mg/kg amounts every two days, until the child is taking 45 mg/kg/day or a maximum of 3200 mg/day, divided into two doses each day. See information on rufinamide.
topiramate (Topamax): A good broad-spectrum AED (i.e., treats all types of seizures). Topiramate has several mechanisms, including blocking the enzyme carbonic anhydrase, which affects the acidity of brain tissue. More acidity (to a point) suppresses seizures. Side effects include thinking and memory problems in about 1/3rd, renal stones in 1-2%, rare cases of glaucoma (increased eye pressure) and weight loss. Typical adult dose is 150-200 mg twice a day. I usually start my patients with one 25 mg pill daily, adding another pill each week on a two-times-a-day schedule until taking 100 mg twice a day. If there are no significant side effects, I then switch my patients to 100 mg pills and increase to 200 mg twice a day over the next few weeks. Topiramate also is used for migraine headache prevention. See information on topiramate.
valproic acid (Depakote): This is the standard broad-spectrum AED (treats all types of seizures) and no other AED is more effective for generalized seizure types. VPA has effects on GABA (at least in very high doses), and a neurotransmitter called NPY to block seizures, and maybe also on calcium channels. VPA has significant side effects: weight gain, tremor, hair loss, GI upset, blood count decreases, hepatic or pancreatic injury, bone weakness over time (osteoporosis), birth defects in up to 10% (folic acid can help to prevent them). Typical adult dose is 250 mg - 500 mg three times a day, but dose can be higher. An extended release form can be taken once a day. See information on valproic acid.
vigabatrin (Sabril): At time of this writing, vigabatrin is approved in the US, but official package insert information has not become available. Vigabatrin is a “designer drug,” made to block metabolism of GABA, the brain’s main inhibitory neurotransmitter. Sabril has been used for over a decade in many countries, and it is effective for partial seizures, with or without secondary generalization. It also may be very effective for infantile spasms, a serious type of seizures in young children. Release in the US was delayed because the drug is toxic to the retina of the eye in up to 30% of people who take it long-term. This toxicity can result in permanent loss of peripheral vision. Regular vision testing is recommended for all people on this drug. A typical regimen begins with 500 mg twice a day, and can increase over a month or two to 1500 mg twice a day. See information on vigabatrin.
zonisamide (Zonegran): Zonisamide is rather similar in its coverage and side effects to topiramate, except glaucoma is not usually listed. Some find less cognitive impairment than with topiramate but this is individual and dose-dependent. Typical adult dose is 100-300 mg twice a day. I usually start my patients with one 25 mg pill daily, adding 25 mg each week on a two-times-a-day schedule until taking 100 mg twice a day. If there are no significant side effects, I then switch my patients to 100 mg pills and increase to 200 mg twice a day over the next few weeks. See information on zonisamide.
Others: acetazolamide (Diamox), diazepam rectal gel (Diastat), ethosuximide (Zarontin), felbamate (Felbatol), primidone (Mysoline), and tiagabine (Gabitril) can be searched individually on epilepsy.com.