Introduction: How Is Epilepsy Treated?

If you are diagnosed with epilepsy, the first question you and your doctor will face is whether treatment is necessary. In most cases the answer will be yes. Typically there is a significant risk of further seizures, and these seizures would interfere in some way with your life. In rare cases, however, the chance of another seizure may be so small that treatment is not recommended. For some, seizures may be subtle and tolerable. For instance, a seizure could be only a brief vision or feeling without change in alertness. In these cases treatment may not be required.

In most cases, however, your doctor will recommend treatment, which almost always means an anti-seizure drug. Surgical treatment may be beneficial in selected cases.

Drugs for Epilepsy

The choice of drugs for epilepsy depends first on the type of seizures you have. Most patients have what is termed partial epilepsy, meaning that the seizure starts in a particular spot on the brain. It may spread and involve other areas, or even the entire brain (a generalized tonic-clonic, or grand mal, seizure). Most available drugs treat partial epileptic seizures.
The other category of seizures is called generalized because the seizure appears to start everywhere at once. Important seizure types in this category are absence (petit mal) seizures, tonic seizures (consisting of sudden stiffening all over), and myoclonic seizures (in which the patient experiences a sudden jerk of the entire body, which can occur repeatedly). Some drugs that treat partial seizures can make generalized seizures worse, but other drugs treat both partial and generalized seizures.

The Old School
Potassium bromide was the first effective drug used for epilepsy and was developed in the mid-nineteenth century. It helped to control seizures but caused such severe sedation and long-term toxicity that it is no longer in use.

Phenobarbital: Phenobarbital was introduced early in the twentieth century and is still used today, primarily for partial seizures. It is in the barbiturate class and therefore can cause sedation, although most patients become tolerant to this over time. Phenobarbital is only available as a generic drug. The usual daily adult dose is 90 to 200 milligrams, taken in a single dose. A related drug, primidone (Mysoline), was introduced in 1954.

Phenytoin: Phenytoin (Dilantin) has been used since 1938, primarily to control partial seizures. It is a lot less sedating than phenobarbital and was thus a big advance at the time. Some people may still experience tiredness, particularly at high doses. Dizziness and double vision can occur as well. Over time, phenytoin causes increased hair growth and coarsening of facial features. It also can worsen osteoporosis, and interferes with oral contraceptives. Therefore, I prefer to use other drugs in young women. The usual daily adult dose is 300 to 400 milligrams, taken in a single dose.

Carbamazepine: Like phenobarbital and phenytoin, carbamazepine is used primarily to control partial seizures. Introduced in 1974, carbamazepine (Tegretol) is less sedating than phenobarbital and does not cause the cosmetic changes that phenytoin can. There are now two extended release formulations of carbamazepine: Tegretol XR and Carbatrol. Both allow twice daily dosing. It usually takes about a week to get onto a full dose of carbamazepine. Like phenytoin, it interferes with oral contraceptives. The usual daily adult dose is 800 to 1,600 milligrams, taken in two doses (if extended-release - Tegretol XR or Carbatrol).

Ethosuximide: Ethosuximide (Zarontin) is an unusual medicine in that it only works for absence (petit mal) seizures.
Valproic acid: Valproic acid (Depakote, Depakene) also works for absence seizures, and additionally for other types of generalized seizures and partial seizures. It is the only one of the older medications that is really broad-spectrum, meaning it works for most seizure types. Important side effects include weight gain, tremor, and (particularly in small children) a small risk of liver problems. The usual daily adult dose is 1,000 to 3,000 milligrams, taken in two or three doses.

The New School
The 1990s witnessed an explosion of new medications for epilepsy that gave doctors and patients many more options for treatment. But the differences between the drugs can be difficult to appreciate for doctors and patients who are unfamiliar with them. Many general practitioners and general neurologists tend to use the older, more familiar drugs. The drugs discussed below are widely prescribed in epilepsy centers, and in general, they are considerably more expensive than the older drugs (with the exception of valproic acid).

Felbamate: When it was introduced in 1993, felbamate (Felbatol) was the first new drug for epilepsy in almost fifteen years. It was different from other medications at the time-rather than sedating, it was stimulating; rather than causing weight gain, it caused weight loss. It is a broad-spectrum drug and works for most types of epilepsy. Unfortunately, within a year of its release, some relatively rare, but serious complications became apparent: A few patients acquired aplastic anemia (ceasing of blood cell production), while others had liver failure. Because of these complications, felbamate is now generally prescribed only when other drugs fail. It is still available and can be very effective in some hard-to-control patients. The usual daily adult dose is 2,400 to 3,600 milligrams, taken in two or three doses.

Gabapentin: Gabapentin (Neurontin) is probably the safest drug for epilepsy, though it only works for partial seizures. It is easy to use and generally very easy to tolerate, even at high doses. Furthermore, it does not interact with other medications. Gabapentin is also widely used for pain control and for certain psychiatric diseases. The usual daily adult dose is 1,800 to 3,600 milligrams, taken in three or four doses.

Lamotrigine: Lamotrigine (Lamictal) is also a very well tolerated drug that has few interactions with other drugs. Like felbamate, it is a broad-spectrum drug. It is considerably safer than felbamate however, and is frequently prescribed when valproic acid does not work or causes side effects. Because lamotrigine can cause a rash (which can be serious if left untreated), it must be started slowly over about six weeks. The rash is most common in small children and in patients who are also taking valproic acid. The daily adult dose varies from 100 to 500 milligrams, depending on other drugs being taken, and is taken in one or two doses.

Topiramate: Topiramate (Topamax) is another broad-spectrum drug, and it also has to be started slowly. Some patients will experience slow thinking or speech difficulty, particularly if it is started rapidly. A rare complication is kidney stones. The usual daily adult dose is 200 to 400 milligrams, taken in two doses.
Tiagabine: Tiagabine (Gabitril) is often limited by stomach problems, and for this reason, it is started very slowly (over six to eight weeks). Tiagabine is used only for partial seizures, and the usual daily adult dose is 32 to 56 milligrams, taken in two or three doses.

Levetiracetam: One of the newest medications for epilepsy, levetiracetam (Keppra) promises to be a very safe drug that does not interact with other medications. It is a broad spectrum drug with relatively few side effects. One of its biggest advantages is that it can be taken at full dose immediately. The usual daily adult dose is 1,000 to 3,000 milligrams, taken in two doses.

Oxcarbazepine: Oxcarbazepine (Trileptal) is also a new drug. It is chemically similar to carbamazepine (Tegretol) but, because the body breaks it down differently, it may have fewer side effects in some patients. It sometimes causes a drop in sodium which is rarely problematic. Oxcarbazepine is useful only for partial seizures. The usual daily adult dose is 600 to 2,400 milligrams, taken in two or three doses.

Zonisamide: The latest drug approved for epilepsy in this country, Zonisamide (Zonegran) has been available in Japan for more than ten years. It is a broad-spectrum medication, and is started at 100 milligrams per day. It can be taken either once or twice a day, and the typical daily dose is 100-600 mg. The most important side effects are nausea, tiredness, and dizziness; these are often improved if taken with food.

Choosing the Drug for You

Once you and your doctor decide that you need an anti-epilepsy drug, the choice of drug will depend on many factors. The first is the seizure type, as described above. In most cases, there are a number of possible choices.

I typically start treatment with either carbamazepine or phenytoin. These are tried-and-true, effective medications that are usually well tolerated. Both are relatively inexpensive. Both may be started fairly quickly, and their tolerability and effectiveness can be determined. If the first drug is not satisfactory, it is perfectly reasonable to try another. There are times when I would not use these first; for instance, I tend not to use phenytoin in young women because of cosmetic side effects (particularly hair growth) if I anticipate they will need to use it for a long time. Also, in older and medically complicated patients, it may make more sense to use one of the newer drugs.

If the first drug is not effective or not tolerated, I will usually try one of the newer ones, rather than phenobarbital (because of sedation) or valproic acid (due to weight gain, tremor, and sedation). Gabapentin and lamotrigine are good second choices; oxcarbazepine, levetiracetam, and zonisamide are also being used more commonly. It is rarely a good idea to try using two medications together before trying at least two alone, and at the maximum dose tolerated.

Generic Drugs Versus Brand Name

Most doctors will specify brand names for epilepsy drugs. While with many medications the use of generics is acceptable, using the brand may be critical for epilepsy drugs. Most have what we call a narrow therapeutic window. That means the difference between an effective dose and a dose that causes side effects is very small. Because dose per pill can fluctuate in generic medicines, epileptic patients may receive too little medicine one day, causing seizures, and too much the next, causing side effects such as double vision or sedation. In general, it is better to stay with brand name drugs or, if not, with the same generic drug manufacturer.

Special populations

There are several considerations for children with epilepsy. First, there are several types of childhood epilepsy that may not require treatment. While a rare seizure in an adult can be devastating (for instance, if the patient is driving), the same seizure in a child may not interfere with life as much as taking a medication every day could. That decision, however, should always be carefully discussed with a doctor. We know that certain medications can cause dangerous side effects in young children. Examples include rash with lamotrigine and liver failure with valproic acid. Most of the newer drugs have now been approved for use in children. Gabapentin, is often used in this group because it is probably safer than the other agents.

Women of childbearing age

There are two important considerations in choosing a drug for women of childbearing age: effects during pregnancy and ability to use oral contraceptive medications. Phenobarbital, carbamazepine, phenytoin, and topiramate increase the rate of metabolism of oral contraceptives. Therefore, there is a higher risk of contraceptive failure, even if a stronger pill is used. Valproic acid, gabapentin, lamotrigine, and levetiracetam do not interfere with oral contraceptives.

The older anticonvulsants all slightly increase the risk of birth defects. These risks are considered small, and in general they are smaller than the risk of seizures during pregnancy. The risk is decreased by taking folic acid (a vitamin) before becoming pregnant. Therefore, all women of childbearing age who take anticonvulsants should also take folic acid. The risk of the newer agents is not known, although it is clear that risks are not greater than for older drugs and there is suggestion of fewer problems. Because there is no strong evidence that one drug is any better or worse during pregnancy, the best treatment for a woman with epilepsy in her childbearing years is the drug that best controls her seizures. A single drug should always be used rather than two or more, if at all possible.

Older patients

Older patients are, in general, more sensitive to the sedation and dizziness caused by some anti-epileptic drugs. They are also more likely than younger patients to have other illnesses requiring medication. For this reason, it often makes more sense to use a drug that does not interfere with other drugs (e.g., gabapentin, lamotrigine, or levetiracetam). These three drugs are also less likely to cause side effects than the older agents. Seizures in older people are typically easy to control, so effective doses may be lower than those required in younger individuals.

Medically complicated patients

If you are taking drugs for other medical illnesses, or if you have liver or kidney problems, these may be important factors in choosing a medicine. Gabapentin, lamotrigine, and levetiracetam do not really affect other medications, so these might be a better choice for you. You may need lower doses if you have liver failure because your body will not break down certain drugs as fast as a healthy person. If you have kidney problems, you may also need lower doses of some medications.

Some anticonvulsants are used for illnesses other than epilepsy. For example, valproic acid, gabapentin, and (to a lesser extent) topiramate and zonisamide are used to treat migraine headaches. Valproic acid, gabapentin, lamotrigine, and, less often, carbamazepine, are used in some psychiatric illnesses. For this reason, if I have a patient with epilepsy who also has migraines, I am more likely to prescribe valproic acid or gabapentin because it could improve both problems.

Drugs in Development

There are a number of new medicines being studied for epilepsy, and some will certainly be on the market in the next few years. So far there is no one best drug, but with more options, there is a better chance of finding the best medicine for you. There are still many things about epilepsy we don't understand; for some people, finding the best treatment still involves a certain amount of trial and error.

The Ketogenic Diet

The primary alternative medical treatment for epilepsy is the ketogenic diet. The origins of this diet may actually be historical; the Bible actually says that Jesus cured an epileptic child with "prayer and fasting." Doctors learned that some kinds of seizures, particularly in children, improved with fasting. The reason for this is that the brain is forced to use a different fuel, called ketones, when there is no sugar available. The ketogenic diet is very strict and limits the intake of sugar and carbohydrates severely so that the body (and the brain) runs on ketones. It is a tough way to live, and it does not seem to work very well in adults. The ketogenic diet is sometimes used in children if drugs don't work.

Conclusion

Remember that the goal in using epilepsy drugs is to gain complete control of your seizures without side effects. You and your doctor need to work toward getting as close to that goal as possible. If you still have seizures that interfere with your life, you may need a higher dose or a different medicine. If you have no seizures but you feel tired, unsteady, dull, or otherwise not at your best, you may also do better on a different medicine. With the variety of seizure drugs now available, freedom from both seizures and side effects is becoming a reality for more patients all the time.