By Robert S. Fisher, M.D., Ph.D.
Editor-in-Chief

Your doctor has prescribed antiepileptic drugs (AEDs). Perhaps you are holding a first-time prescription, or perhaps you have been taking them for 30 years. Either way, once you are on AEDs, is there an exit strategy? Or are AEDs forever?

As with so many aspects of epilepsy care, the answers depend upon individual circumstances. Some people are given AEDs to cover them over a few months of an acute illness that provoked a seizure, and then the treatment may comprise only a few months. At the other extreme is therapy for a potentially life-long hereditary condition, such as juvenile myoclonic epilepsy, which tends not to disappear. Most treatment plans fall in the middle, not brief, but also not forever.

Obviously, there are both pros and cons to stopping therapy. On the pro side is reduction in side effects or the possibility of future side effects from the AEDs. Not all side effects are immediately evident. Chronic loss of bone density, predisposing to osteoporosis and fractures, occurs silently over decades, particularly with the older AEDs such as Dilantin (phenytoin), Tegretol (carbamazepine) and Depakote (valproic acid). Some people, who do not notice that their thinking and memory is impaired by sedative medicines, such as phenobarbital, feel much sharper once they are off the medicine. Many seizure medicines interact with other drugs, making general medical care more complex. AEDs can be expensive. And important for some is the bother of having to remember to take the pills, to pack them, and to renew them every month. Even the idea of needing medicine and the associated stigma is philosophically distasteful to some people.

Arrayed against this long list of potential benefits of stopping AEDs is one big “con” – the increased risk of having a seizure. From such a seizure, you may incur injury, or even in the worse case SUDEP, the rare tragedy of sudden unexplained death in epilepsy. You may embarrass yourself, or put your job at risk. And a seizure may precipitate suspension of your driving license. If fact, many doctors, including me, advise not to drive when tapering that last AED, for at least three months from the start of the taper. Perhaps for these reasons, the majority of the seizure-free adults studied in the British Medical Research Council Drug Withdrawal study (Chadwick et al. 1996) chose to remain on AEDs. The risk to lifestyle of children caused by withdrawing AEDs may be less than that to adults, because of the lack of driving and employment issues in children.

Should a seizure be prevented at all cost, because one seizure renders the next more likely? As claimed over a century ago by Sir William Gowers: ". . . the tendency of the disease [epilepsy] is toward self-perpetuation; each attack facilitates the occurrence of the next by increasing the instability of the nerve elements." (Gowers 1881). The modern view, although still somewhat controversial, is that treatment of the seizure does not influence the long-term prognosis (Sander 1993; Shinnar and Berg 1996). Therefore, there is probably little long-term risk of an attempted AED withdrawal leading to worsening seizure disorder. However, it may be a struggle to regain seizure control once it is lost, and it may take some time to do so.

How often does withdrawal succeed? Relapse rates among various published studies range from 12 – 63% (Britton 2002), with the most definitive study being the Medical Research Council study of over 1013 patients (MRC Study Group, British Medical Journal 1993): 22% of patients who continued antiepileptic drug treatment had a recurrence of seizures within two years, compared to 41% who slowly stopped treatment. A study of 531 patients with epilepsy (Lamdhade and Taori 2002) showed these factors to be associated with seizures coming back: seizure onset late in life, seizures for more than three years, more than 30 total seizures, a positive family history of epilepsy, focal neurological deficits such as partial numbness or paralysis, epilepsy-associated findings on the electroencephalogram (EEG), and underlying ongoing structural or genetic causes for having seizures. Not predictive of whether tapering AEDs would succeed were gender, seizure frequency, and number of AED drugs used. A study (Specchio et al. 2002) compared outcome for 225 patients who chose to discontinue AEDs, versus 105 patients who chose to continue therapy. All had been seizure-free for at least two years. Overall, 50% of the patients who stopped medications had a seizure, versus 28% who remained on treatment. Calculated relative risk was 2.9-fold greater for patients coming completely off medicines. The probability of being seizure-free was 88% at 6 months, 82% at 24 months, 80% at 36 months, and 68% at 60 months.

As a rule of thumb, if you have been seizure-free for 2-5 years, have none of the negative risk factors mentioned above, and you go off your AEDs, you have about a two-thirds chance of remaining seizure-free for another five years. Conversely, 1-in-3 will have a seizure with medication discontinuation. Be aware also of small seizures, such as the simple partial, complex partial or absence (petit mal) episodes. You should be free of these as well before tapering medications, not just the big, obvious seizures.

When do seizures return after AED withdrawal? One study (Berg and Shinnar 1994) showed that patients seizure-free on AEDs for 2-4 years remained seizure-free at one year 75% of the time and seizure-free at two years 71% of the time, after discontinuing the medications. In this analysis, 60-80% of the recurrences occurred within one year. In a study from Turkey (Aktekin 2006), the probability of having a seizure after tapering AEDs was 29% at 1 month, 14% at 3 months, 4% at 6 months, 7% at 12 months, 18% at 24 months, and 7% at 36 months. Most of the risk of having a seizure is within the first two years of stopping medicines, and most of that risk is probably within the first few months. Unfortunately, there is no time when you can conclude you are “home free.” Seizures can come back many years after withdrawing AEDs. The longer you go without a seizure, the smaller the chances that they will return.

How quickly should medications be tapered? Anecdotal experience from patient-initiated discontinuations, and from experiences in epilepsy monitoring units (Yen et al. 2001), suggest that severe seizures or even status epilepticus can result from immediate discontinuation of therapeutic doses of medications. Tennison and coworkers (1994) randomized children being withdrawn from AEDs to a 6-week or 9-month course of taper, after at least two-years of freedom from seizures. The groups did not differ in relapse rates, thereby favoring the easier 6-week course. However, patients on barbiturates and benzodiazepines were not adequately represented in this series, and additional caution is warranted for these drugs. Do not stop your seizure medications suddenly unless there is an emergency need to stop. It could be dangerous to stop suddenly! Work with your doctor to design a tapering schedule.

One randomized, controlled study from Norway (Lossius and colleagues, 2008) emphasized the trade-off. People whose AEDs were tapered after being seizure-free for two years improved their neuropsychological test scores compared with those who stayed on medicines. But those who tapered AEDs had a 2.5-fold increased risk of having a seizure.

In conclusion, antiepileptic medication taper can be worthwhile after at least 2-5 years of freedom from seizures. Patients should not have an ongoing structural brain abnormality (for example, a tumor or stroke) or genetic predisposition for seizures, should not have had major prior problems withdrawing from medications, and should not have epilepsy-like activity on a recent EEG. If an adult, they must be willing to refrain from driving for at least three months from the start of the taper (some doctors argue for longer), and must be willing to accept about a one-third risk of relapsing with a seizure. If, on the other hand, the patient worries about seizures more than about medications, then continuation of AEDs likely will minimize the risk for future seizures. This is another area in which the clinician can be an educator, and the patient a decision-maker. Ultimately, it is your choice.