Choosing a medication for epilepsy
By Dr. George Morris
Treating seizures with medicines has many aspects and there are many choices to be made. Treatment should stop seizures and have no
limiting side effects. When a person starts medication for seizure treatment, approximately 2/3 will find a medication that stops their
seizures and without undue side effects.
 Steps to finding the right epilepsy medication
- Your doctor confirms that there's a reasonable chance that your seizures will reoccur (not a 1-time event)
- Typically you will be referred to a specialist, who will run some tests, including an EEG and an MRI. If medication is deemed
appropriate, the specialist will prescribe one (see below for examples).
- If the seizures continue, or if there are too many side effects, the doctor will try a 2nd kind of
medication.
- If the seizures continue, or if there are still too many side effects, your doctor will re-evaluate your condition, possibly run
more tests, and determine if a different treatment approach would be more likely to work.
Issues of side effects with epilepsy medication
Unfortunately, side effects are a potential problem for medications and we will need to be vigilant for them. The most common side
effects from seizure medications include fatigue, slowed thinking processes, unsteadiness on one's feet and dizziness.
Seizure medications fundamentally work to suppress certain types of brain cell activity. Those types of brain cell activity are often
involved in the seizure process, but unfortunately some of them are present and necessary in other types of brain function. Those
include things constantly being adjusted such as thinking, alertness, our balance and the movement of our eyes. This is why the
medications that we use for epilepsy will frequently have all of these listed as potential side effects.
Each medication has side effects unique to that drug and depending on which medication is appropriate, you should discuss those
potential side effects with your doctor and decide which medication is best you.
Again, the goal is to choose a medication completely eliminating seizures, produce no limiting side effects, which is easy to take
and use, comes in many forms and is readily available. These are sometimes challenging goals, as no ideal medicine exists. An ideal
medicine taken daily has no interactions with other medications and is easily monitored in the blood stream. Sadly, there is no ideal
medication, but those are the features of an ideal medication, and the closer we can get to these goals, the better the care will
be.
So which epilepsy medication should I take?
We have to determine if the patient is experiencing partial seizures or generalized seizures. Partial seizures are the most common
seizure, and many of our medications have been tested and shown to be effective in treatment of partial seizures.
Medications are frequently described as older generation medication or part of the newer generation of seizure medications available
since the early 1990's. Older generation medications include medications like Dilantin (Phenytoin), Tegretol (Carbamazepine),
Phenobarbital, Mysoline (Primidone) and Depakote (Valproic Acid). These medications have been available for decades and have been most
commonly used for the treatment of partial seizures. Many physicians have learned to use the medications during their training and they
are familiar with their many positive and negative attributes.
Phenobarbital is the oldest of our currently used medications. It has been available since 1912 and has the
advantage of being able to be taken once daily and remaining relatively stable in the blood stream. It has the reputation of treating
generalized tonic and clonic seizures, but being less effective against partial seizures such as simple partial and complex partial
seizures. Phenobarbital has well recognized blood-testing levels and has not been identified to produce any long-term negative
consequences except lowering someone's thinking abilities and decreasing bone density. Phenobarbital's overall success is not as good in
the treatment of partial seizures as many other medications, and its use has slowly decreased in comparison to other medications. It is
available in pill and intravenous form and can frequently be used for short periods of time to eliminate ongoing seizures.
Dilantin (Phenytoin) is a unique medication discovered by a specific program looking for medications that can stop
seizures. It was the first of a long list of medications discovered by the National Institute of Health and its program to develop
seizure medications. Dilantin may be taken once daily, making it convenient, and is effective against partial and tonic-clonic seizures.
It is available both as a long-acting capsule, a chewable tablet for children, unstable syrup and IV form. It has long been used as
initial treatment for all types of seizures. Dilantin has many difficulties including an unpredictable change in the level with changes
in the amount taken, an interaction with many other medications including commonly used blood thinning agents, aspirin, and birth
control pills, a decrease in the bone density which does not respond to more calcium and vitamin D, and potential slowed thinking
difficulties. Still Dilantin remains the most commonly used medication for seizures due to significant familiarity to physicians.
Tegretol (Carbamazepine) has also been available for decades and is recognized as good treatment for partial
seizures. Tegretol comes in several forms including an elixir and sustained release capsules and tablets known as Tegretol XR and
Carbatrol. Tegretol must be taken at least twice per day and does interact with many medications, including some commonly used
antibiotics, birth control pills and other seizure medications. Tegretol has a pattern of producing excessive fatigue that sometimes
does not go away. Tegretol is not effective in generalized seizures such as absence and has been known to make them worse. Occasionally,
Tegretol can lower the amount of salt in the blood stream, although this has not been known to cause patients significant problems.
Depakote (valproic acid, divalproex) is the newest of the older generation medications. Depakote is available in
several forms including an elixir, immediate release tablet, several sustained release formulations and an intravenous form. Potentially
the first of a group of medications known for its ability to treat all seizure types, Depakote has become the drug of choice for
generalized types of seizures such as absence and generalized tonic and clonic seizures, and is effective in partial seizures. This
broad spectrum of activity is a principle strength for Depakote. Side effects include stress to the liver, weight gain related to
stimulation of the appetite, hair loss related to fragileness of hair fibers, and a tremor of the hands. Special attention regarding
Depakote and the reproductive system has been raised concerning its ability to produce a syndrome known as Polycystic Ovary Syndrome
leading to infertility in women. Issues about depression of male sexuality have also been raised with Depakote.
Newer epilepsy medications
Since the medications listed above have limitations, new medications were developed. The results of this 15-year focus resulted a
number of new medications, the new generation antiepileptic drugs. The attempt was to produce medications with fewer side effects and
fewer interactions with other medications. The initial treatment, where the greatest successes lie required minimizing the negative
aspects of the drug so therapy was more likely to succeed early.
Felbatol (Felbamate) is a drug which led these new generation medications with its release in the fall of 1993.
Felbatol's use is infrequent because 2 serious, life threatening side effects were identified: fatal hepatitis and aplastic anemia.
Occurring in a small portion of patients who were predominantly adult, these side effects required liver and bone marrow transplants and
have limited the use of Felbatol. Side effects include headache and insomnia and it does interact substantially with other seizure
medications including Dilantin, Tegretol and Phenobarbital. It is taken 3 times per day.
Neurontin (Gabapentin) is a drug indicated for partial onset seizures and is taken 3 times per day. It has been
shown to be an effective add-on choice to other medications and is easily done so with no drug interactions. Its side effects are
relatively few and studies have shown it useful in the elderly compared to Tegretol. Neurontin is not broken down but leaves by the
kidney, and so kidney function, when it is reduced, requires adjustment of the dose. Neurontin has been found to be useful in other
conditions and most of its uses currently are in the area of pain management.
Lamictal (Lamotrigine) was released the year after Neurontin in 1994. It showed effectiveness in partial seizures
and studies suggest a broad spectrum of activity for both partial and generalized seizures. Lamictal is taken twice daily and has some
interactions, particularly with Depakote. Principle benefits of Lamictal appear to be its low side effect rate. Lamictal's principle
difficulty is in the area of rash. When the concentration in the bloodstream increases too quickly, patients are prone to having a
diffuse body rash. Some of these rashes are allergic, but the majority are not. On a rare occasion these rashes can be life threatening
when associated with other problems, including liver and bone marrow difficulties. Lamictal has some considerable use outside of the
U.S. and was available overseas for a number of years. That means a significant number of birth exposures without a pattern of
significant malformation.
Topamax (Topiramate) is a drug indicated for the treatment of partial seizures, as well as with the treatment of
fairly severe epilepsies (Lennox Gastaut). Topamax is taken twice daily and has few interactions with seizure medications. Topamax also
shares the quality of Depakote and Lamictal in providing a benefit for multiple types of seizures in both the partial and generalized
category. Potentially one of Topamax's largest side effects can be viewed as a positive event. Topamax has the tendency to suppress
appetite, which may be a significant benefit. Other side effects of Topamax include a perception of slow thinking.
Gabitril (Tiagabine) is a medication used for the treatment of partial seizures, so its current use is limited. This
is a medication used 3 times daily that appears to have significant interactions with other medications. In the presence of medications
stimulating the liver, such as Dilantin and Tegretol, Gabitril levels are difficult to raise. Sedation and fatigue appear to be
Gabitril's most common side effects.
Keppra (levetiracetam) was approved in 2000 and shows effectiveness in the treatment of partial seizures. Taken
twice daily, Keppra has not been associated with interactions with other medications and its metabolism is relatively limited. Patients
find the medication easy to take and Keppra may be increased quickly. It is effective at its recommended starting dose. Keppra's
principle side effect is a reported difficulty with behavior disturbance. This behavior disturbance has been seen more frequently in
children but does not occur very often in any group.
Trileptal (Oxcarbazepine) was released for the treatment of seizures in 2000. It is chemically similar to the drug
Tegretol and is taken twice daily. Trileptal has few interactions with other medications. It is indicated for the treatment of partial
seizures. Trileptal's principle side effect is fatigue, a lowering of blood salt levels such as is seen with Tegretol, but is a
relatively rare phenomenon.
Zonegran (Zonisamide) is a drug that was originally released in Japan many years ago and is indicated for the
treatment of partial seizures. The Japanese literature suggests that Zonegran may have use in other seizure types including generalized
seizures. Zonegran may be taken once or twice daily and is generally well tolerated without significant side effects. There is a
potential cross-reaction between individuals who are allergic to Zonegran and Sulfa antibiotics. Zonegran's principle side effect is a
potential positive one with reductions in weight occurring in approximately 6% of patients.
Then patients say "Well, that's a lot of choices. Tell me the one I should take."
And I reply, we will pick the one you feel the most comfortable with and see how it works.
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