A second reason for uncontrolled seizures, assuming a correct diagnosis of epilepsy, is suboptimal treatment, equivalent in our metaphor to the wrong key. Common reasons for suboptimal treatment are listed in Table 3.

Using the wrong medication. Many seizure medicines have useful actions against a number of different seizure types. But some medicines are not right for some types of seizures. Carbamazepine (Tegretol), for example is usually good for treating complex partial seizures, but not absence seizures. Ethosuximide (Zarontin) is good for absence, but not complex partial seizures. Since absence and complex partial seizures can occasionally be confused with each other, there is a chance for using an ineffective medicine.

Inadequate doses of medicine. People vary widely in their response to seizure medicines. Every medicine has a suggested dosage range, but that range is too high for some and too low for others. If a dose that is too high for an individual is employed, toxic side effects will result. A dose that is too low leads to seizures. Therefore, some cases of uncontrolled seizures become controlled when the medication daily dosages are increased. Having said this, it is just as important to note that many people can be controlled on low doses of AEDs (3), which leads to less medication toxicity. Measurement of blood levels of antiepileptic drugs (AEDs) sometimes helps to guide therapy, but levels are not as important as a careful inquiry about side effects and seizure control. The newer seizure medicines often have fewer side effects than do the older seizure medicines. Information about the seizure medicines can be found here on epilepsy.com (4).

Polypharmacy and toxicity. Polypharmacy is the employment of several medications at once to treat the same condition. Some people require more than one drug to control their epilepsy, but additional AEDs rarely lead to complete freedom from seizures. Two important studies, one by Mattson and colleagues (5) and the other by Kwan and Brodie (6) suggest that if a person is not seizure-free on a good dosage of a single AED, then adding a second will make them seizure-free only about 10% of the time. The second drug may help, but not usually to the point of complete control. Two drugs have more side effects than does one drug, and three drugs more than two. Patients taking polypharmacy may have so many side effects that it is difficult to increase dosage for any of their AEDs to an effective level. Furthermore, polypharmacy can lead to drug interactions (7) that limit effectiveness or increase side effects of another drug. Therefore, one good treatment for refractory seizures in people taking polypharmacy is a streamlining of medicines. This may seem counterintuitive in the face of ongoing seizures, but here “less can be more,” especially if it lowers overall levels of side effects and allows an increase in the drug that is most effective. This process of streamlining can be stormy, with an unpleasant period of both seizures and side effects until the new, improved regimen is established.

Missing doses (poor compliance). Missing medication is a cause of breakthrough seizures. Almost everyone forgets to take pills, especially if the pill schedule is complicated. In the medical field, this is called "poor compliance." Refer to epilepsy.com (8) for more information on compliance and strategies for remembering to take epilepsy medicine. It can make a real difference!

Complicating factors (illness, sleep deprivations, extreme stress). Complicating or precipitating factors for seizures can make them more difficult to control. These again vary with the individual. Individual precipitating factors include alcohol, exercise, flashing lights or certain patterns, general illness, heavy breathing (hyperventilation), lowering dose of medicines, taking certain medications, the menstrual cycle, missing medications, missing sleep, recreational drugs, and stress. All too often, a seizure breakthrough is preceded by one of these, or other personally relevant, factors.

Continue on to True Intractable Epilepsy

Topic Editor: Robert S. Fisher, MD, PhD
Last Reviewed: April 21, 2009