Medical Treatment of Epilepsy
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
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
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
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.
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
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 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
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
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.