Your physician will adjust the dosage of seizure medicine that you take (that is, how much of each medicine you take and when you take it) according to how well your seizures are controlled and whether you experience any troublesome side effects. The way that a seizure medicine (also called an "antiepileptic drug" or "AED") works with each individual's body is a bit different. Therefore, your doctor may want to test the levels of medication in your blood from time to time to find out how your body absorbs and eliminates each type of medicine. This information can suggest ways in which seizure control can be improved and side effects of the medicine can be reduced by adjusting the amount of medicine you take and the timing of when you take it. These levels also may tell the doctor whether you have been taking the medicine as prescribed (what doctors call "compliance").
These tests of blood levels can cause problems, though, if the doctor pays too much attention to the numbers on the chart and too little attention to you as the patient. Based on experiences with many patients, doctors are taught that certain numerical levels for each type of medicine are considered "therapeutic" (most likely to be effective). Other levels are believed to be too low to be effective; these are called "subtherapeutic" levels. If the level is so high that injury or ill effects are thought to be likely, that level is called "supratherapeutic." Each person's body is different, however, so the best way to prescribe a seizure medicine may not always fit the general rules. If the level of a medication in your blood is in the "subtherapeutic" range, that does not necessarily mean that a seizure is likely to occur. A therapeutic level may not mean that you are fully protected. And a supratherapeutic level is not always harmful.
Each antiepileptic medication has a "half-life," which is the length of time that it takes for its level in your blood to decrease by one-half. These vary widely from medication to medication. The half-lives of common seizure medicines can be as short as 2 hours and as long as 100 hours, depending on the individual medicine and some other factors. If you take a particular medication regularly for a period about five times as long as its half-life, its level in your blood will reach a state of equilibrium called the "steady state level." The levels in your blood produced by each dose are then consistent, and measurements taken should be meaningful. Usually the doctor will want to measure a "trough level," taken shortly before the morning dose. The doctor also may want to know the "peak level," usually measured 1 to 4 hours after the highest dose of the day. Because peak levels are sometimes used to assess adverse effects that might be the result of high levels of medication in the blood (called toxicity), peak levels also may be taken at the time that suspected toxic effects occur.
If you have had only one or two seizures, you are likely to get good seizure control from low doses of seizure medicine, which produce low levels in your blood. Sometimes when the lab report shows this "subtherapeutic level," however, the doctor thinks about increasing the dose right away. This may or may not be the right thing to do, depending on your individual situation. For example, a 39-year-old businesswoman with two seizures that occurred during sleep will probably get good seizure control from low doses of Tegretol or Carbatrol (carbamazepine), such as 300 mg of an extended-release form, which she takes twice a day. After taking this dosage for 2 weeks, the trough level in her blood may be low, at 5.5 mcg/mL. This level probably will decline even more over the next several weeks because this medication can stimulate its own metabolism (an effect called autoinduction). Some doctors would increase the dose, aiming for a so-called low therapeutic level. This logic is reasonable. Others might leave the dose unchanged, even if the level in her blood fell into the subtherapeutic range, since low levels are often effective. The decision about raising the dose should reflect the woman's situation. Because both of her seizures took place while she was sleeping, if she had another one, it probably would also occur during the night -- but not definitely. If she desperately does not want to have another seizure and has no side effects, a dose increase is reasonable. The larger dose probably should be given at bedtime, considering the time when her seizures occur and her desire to avoid daytime drowsiness. But if she is already complaining about tiredness and loss of mental sharpness, the dose should not be increased. (Some might argue for a decrease!) In either case, this woman should be informed about the blood level and the factors involved in considering a dose change.
Two factors should guide dosage changes: toxicity (side effects) and efficacy (how well the medicine controls seizures). Efficacy is often impossible to predict accurately. You want protection against seizures at the lowest effective dose. Unfortunately, there is no way to determine this dose. The doctor's experience, and sometimes trial and error, must be used. No matter how much you and the doctor want to avoid an "error"—a seizure or side effect—sometimes they are inevitable.
The following guidelines are helpful in adjusting the dosage of seizure medicines:
If you have a "breakthrough" seizure (one that occurs after a period of control), measuring the level of the seizure medicine in your blood can help the doctor to identify factors that may have contributed to that event, such as missed pills, lack of sleep, or a fever or other illness. Missed doses may be more easily detected by measuring blood levels if the medicine is one with a long half-life. For example, consider a college student who stops taking her seizure medicine. Several months later she has a seizure. If she immediately starts taking her medicine again as prescribed (perhaps with an extra pill or two for insurance), the level in her blood when it's tested 2 days later at the student health service might show a level of Tegretol that's in the therapeutic range because the half-life is short. If she had been taking Dilantin (phenytoin) or phenobarbital, on the other hand, the level would be extremely low because these medicines have long half-lives.
When interpreting the blood levels of your seizure medicines and adjusting dosage, your doctor also should consider the time of day that seizures and side effects occur. For example, a 45-year-old man was seizure-free for 3 years, during which time he took 350 mg of Dilantin at bedtime. A trough level of 14.5 mcg/mL was recently measured. Then he had a tonic-clonic seizure at 9:30 one evening, while he was awake. The neurologist increased the dose to 400 mg at bedtime and several weeks later the morning trough level was 19 mcg/mL. Two months later, however, the man had another seizure. When the level of phenytoin in his blood was measured at 9 PM, it was 4.5 mcg/mL, very low. Although the textbooks list the half-life of Dilantin as 24 hours, in this man it was shorter. His problem was solved by taking the medicine twice a day, not increasing the dose.
In another example, a 6-year-old girl with benign rolandic epilepsy received 200 mg of an extended-release form of carbamazepine twice a day, at 8 AM and 8 PM. Once every 4 to 6 weeks she had a partial seizure with facial twitching for 45 seconds, usually around 9 PM. (She went to bed at 8:30.). Her morning trough level was 5.8 mcg/mL. When the time for her evening dose was changed to 7 PM (allowing time for the medicine to be absorbed and reach a higher level when she was prone to seizures), her seizures were controlled. Another strategy would have been to increase the evening dose and lower the daytime dose because seizures in children with benign rolandic epilepsy usually occur in the transition into or out of sleep.
Sometimes it is hard to distinguish between symptoms related to minor, very brief seizures, anxiety, or side effects of seizure medicines. One hint is that side effects often start 30 minutes to 2 hours after a dose of medication is taken and last for more than 15 minutes. (They can be delayed if you take enteric-coated tablets.) If symptoms first appear shortly after a new medicine is started or the dose is increased and they persist for many hours, they are probably side effects. Ideally, the blood level of the medication should be tested if you have a possible side effect. You should also examine your dosing schedule and realistically consider how much you deviate from it. Do the symptoms occur when you take your medicine on an empty stomach or when you take two doses close together?
Some people are exquisitely sensitive to seizure medicines. They may have trouble with even very low doses and low blood levels. Usually they are sensitive only to one or two antiepileptic medications, but a few people are sensitive to most of them. If you are one of these people, the control of your seizures may be limited by how much medication you can tolerate. A few people cannot tolerate even low doses of the medicines that usually are least troublesome. Psychological factors may play a role. Restarting the seizure medicine at extremely low doses and increasing gradually may help. Some of these people also do better with newer medicines such as Neurontin (gabapentin) and Lamictal.
Topic Editor: Steven C. Schachter, M.D.
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