Few robust studies
There are few robust studies in this field (19). With regard to adults, two studies exist in which seizure-free patients were randomised either to discontinuation or continued treatment.
A prospective, open randomised study of 1 013 patients who had been seizure-free for at least two years found recurrence in 41 % two years after discontinuation, compared to 22 % in the group that continued to receive treatment (13).
The second study, a Norwegian randomised, double-blind study, included 160 patients who had been seizure-free on monotherapy for at least two years. They were randomised to discontinuation (n = 79) or continued treatment (n = 81). After 12 months, 15 % of those in the discontinuation group and 7 % in the group receiving continued treatment experienced seizure recurrence. In an open follow-up study, 89 % of patients who were randomly selected for continued treatment chose to discontinue the drug. After 41 months, seizures had recurred in 27 % of those who had discontinued treatment (7).
The explanation for the relatively low percentage of recurrence in this study compared to that of the first study may be that the inclusion criteria in the later study were more stringent. Both studies found that the risk of seizures in those patients who discontinued antiepileptic drugs was twice as high as in those who continued.
A meta-analysis based on 25 observational studies reported seizure recurrence in 25 % after one year and in 29 % two years after discontinuation (20). An American guideline based on 17 observational studies concluded with a similar rate after discontinuation of 31.2 % for children and 39.4 % for adults (21).
Regarding children, an overview is available based on 12 observational studies of more than 2 500 children. This showed seizure recurrence in 4 – 33 % of the children one year after discontinuation and in 9 – 39 % after two years. The variation in recurrence rate is probably attributable to differences in the type of epilepsy, its aetiology, and additional disorders in the children included in the study. The risk of seizure recurrence was highest in the first 12 months (22).
A Cochrane review based on five studies of altogether more than 900 children concluded that there was a 34 % increased risk of seizure recurrence if the child had been seizure-free for less than two years, compared with those who discontinued drug use after more than two years of freedom from seizures. The risk of recurrence with early discontinuation was further increased if the child had focal seizures, developmental delay and/or a pathological EEG result (23).
In the case of pharmacoresistant epilepsy, that is, in patients with intractable seizures after trying two relevant antiepileptic drugs, other forms of treatment should be considered. Of those who are found to be suitable for resective epilepsy surgery following a thorough assessment, around 60 % are seizure-free after temporal lobe resection, while 30 – 40 % are seizure-free after extratemporal surgery (24). The majority of those who are seizure-free two years after the surgery continue to be so in subsequent years. However, some experience seizure recurrence after many seizure-free years, even with continued use of antiepileptic drugs (24, 25).
No randomised controlled studies have been conducted on patients who discontinue antiepileptic drugs after epilepsy surgery. Several of the observational studies in this field show selection bias – usually those with the best prospects for continued freedom from seizures are selected for discontinuation (25).