Prognosis for seizure recurrence in seizure-free patients after stopping antiepileptic drugs: A long-term population-based study of childhood-onset epilepsy
The decision to discontinue antiepileptic drugs (AEDs) in seizure-free patients has been problematic because the long-term risk of seizure relapse is not well understood. The literature reports that after AEDs are gradually withdrawn there is a substantial risk of seizure relapse, particularly during the first year. However, there also are potential problems associated with treating seizure-free patients indefinitely with AEDs. A further question that needs consideration is whether patients whose seizures relapse after their AEDs are discontinued return to seizure-free status once their AEDs are restarted.
In a recent publication, M. Spillanpää and D. Schmidt reported on a longitudinal 37-year population-based study of 148 patients from the time of diagnosis of epilepsy (Epilepsy & Behavior 2006;8:713-9). The researchers found a substantial risk of seizure relapse with planned and gradual withdrawal of AEDs when compared with continuous treatment, noting that “Relapse occurred within the first year for 36%, within the first 2 years in 46%, and within the first 3 years in 67%.” However they also observed that 24 of 25 patients who were not put back on AEDs, after seizure relapse, regained 5-year terminal remission, though this may have taken more than 10 years to achieve. The risk factors for seizure relapse after AED discontinuation were difficult to determine in this study given the limitations of a population-based long-term study.
We asked two experts how this study will impact their recommendations to patients. Questions included:
COMMENTS OF EPILEPSY EXPERTS
When in the course of treating adult patients with epilepsy do you start to consider discontinuation of AEDs?
Ilo E. Leppik: First I need to very carefully look at the etiology of the epileptic . If a person has an epileptic syndrome which has a history of remission, I would consider stopping the AEDs at that age at which remission is expected. For example, it is well known that (also called childhood epilepsy) remits before the teen-age years, so it would be about that time when I would consider stopping the treatment.
Other syndromes may be lifelong and I would not discontinue any epileptic drugs even though there have been no seizures for many years.
Persons who are very good candidates for stopping treatment are those who have had only a few seizures which have come under control quickly with AED treatment and, additionally, have no abnormalities and whose EEGs are normal.
Evelyn Tecoma: I start to consider the decision to discontinue AEDs between two and five years after the patient has become seizure free. But it is a highly individual decision. It is important to realize that even if a person's epilepsy is easy to control with medication, it does not mean that the underlying epilepsy has vanished. Therefore prior to discontinuing AEDs, we are going to consider the , including the seizure type, age at onset, family history, neurological exam, status, results of an , brain imaging, and the ease of achieving seizure control, all of which may influence the likelihood of seizure recurrence.
How will this study impact your recommendation regarding the discontinuation of AEDs in your seizure-free patients?
Ilo E. Leppik: The findings of this particular study provide further supporting evidence for the way I practice, and it will not really affect the way I practice.
Evelyn Tecoma: I do not think that the study will have a major impact on my practice. It is an interesting study because of the long term follow-up. However, this cohort of patients had seizure onset prior to age 15. Among other factors, seizure persistence throughout life differs in patients with seizure onset prior to adolescence and post-adolescence. This study does not provide that information - so the conclusions reflect the pooled risk of the two different populations.
What other factors will go into your recommendation?
Ilo E. Leppik: The three factors that influence my recommendations are:
Evelyn Tecoma: There are syndromes such as Benign Rolandic Epilepsy which are known to have a good prognosis for remission in adulthood, and others such as that have a lifelong high probability of recurrence off medication. In addition to the epilepsy syndrome, and factors mentioned above, I consider age, occupation, activities of living and the general impact of having a seizure recurrence. If the patient is employed, parenting, driving, highly functioning, the impact of recurrence could be life changing.
What points do you discuss with patients to arrive at the decision?
Ilo E. Leppik: When I have made a decision that a patient fits a profile that will result in a good outcome by stopping the medication – I discuss the risks and benefits with the patient. I do this usually after the patient is seizure-free for at least two years and is also completely free of other symptoms such as auras, which suggest that the patient is still having seizures.
Then we discuss the patient’s feeling about the risks and benefits of stopping medication. We would carefully evaluate social circumstances such as driving and the work situation. Then we would determine if having any seizures after discontinuation would pose any significant problems to the person with epilepsy. Many of my patients who are seizure-free and have had no side effects often wish to continue medication -- even those who are at very low risk for seizure relapse because they do not want to take the chance of having another seizure while driving or working.
Evelyn Tecoma: It is important for patient to be on board with the decision to discontinue AEDs, and to be aware of the possibility of relapse. The risk will never be zero. It is almost impossible to predict when a breakthrough seizure can occur. If feasible, we try to pick a time to discontinue AEDs when the patient may be able to stop driving; reduce their level of work or studies; and maximize their support systems in case they do have a breakthrough seizure. Some seizure types may have minimal consequences if they recur, but others can be severe and have life threatening consequences.
How will this study impact your recommendation regarding restarting AEDs in patients whose seizures relapse after AED discontinuation?
Ilo E. Leppik: I would certainly restart medication. For example, with regard to whether or not restarting AEDs help one return to baseline, it depends upon the syndrome. With Juvenile Myoclonic Epilepsy the person will go right back into remission. Others might have a few more seizures before going back into remission once again.
Evelyn Tacoma: I will continue to recommend restarting AEDs after relapse, with rare exceptions. This is a good time to talk with patients about the choice of medication, and consider the impact on cognition, fertility and teratogenicity, bone health, and the cosmetic side effects - gum problems, weight gain, hair loss, body hair growth (hirsutism) - as well as fine tremors. After restarting an AED appropriate for the epilepsy syndrome, I would expect the patient to go back into remission. If the patient does not regain seizure control, I would then reevaluate the epilepsy syndrome to verify the diagnosis and explore a progression of the underlying epilepsy.
Edited by: Rita Watson: 11/30/06
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