Abstracts

Valproate (VPA) is widely regarded as the drug of choice in JME. To date, it has been the only antiepileptic drug (AED) to be consistently effective against myoclonic seizures that characterize JME as well as absence and primary generalized tonic-clonic seizure (PGTCS) that can also occur. Topiramate (TPM) may have an equally broad profile and therefore therapeutic potential in JME. In addition to double-blind, placebo-controlled trials proving TPM is effective in controlling PGTCS, smaller data sets suggest TPM is also effective against absence and myoclonic seizures. In our pilot study, patients with JME were randomized to open-label treatment with TPM or VPA.
Patients (12-65 yrs old; [ge]25 kg) with a confirmed diagnosis of JME were eligible if they had myoclonic seizures or at least one PGTCS in the 3 months before study entry. Patients could be untreated or, if treated, on monotherapy that was stable for at least 1 month before study entry. Patients were excluded if they were currently receiving VPA or TPM or had a past history in which VPA or TPM was discontinued due to adverse events. Following 2:1 randomization to TPM or VPA, study drug was titrated according to patient response over 14 weeks and maintained for an additional 12 weeks. Target TPM dose: 3-4 mg/kg/day, up to 9 mg/kg/day, for patients age 12-16 yrs; 200 mg/day, up to 600 mg/day, for patients [gt]16 yrs. Target VPA dose: 10 mg/kg/day for patients age 12-16 yrs; 750 mg/day for patients [gt]16 yrs; maximum, 60 mg/kg/day.
28 patients were enrolled. Of 19 patients randomized to TPM, 12 completed the study; discontinuations were due to adverse events (N=2), inadequate seizure control (2), lost to follow-up (2), and patient choice (1). Among 9 patients randomized to VPA, 7 completed; 1 patient discontinued due to adverse events and 1 for unspecified reasons. Mean dose among study completers was 897[plusmn] 375 mg/day VPA and 189[plusmn] 78 mg/day TPM. For the intent-to-treat population, median seizure reduction was 100% with both TPM and VPA. Baseline PGTCS, myoclonic, and absence seizure frequency was reduced 100% in 10/12 (83%), 9/14 (64%), and 2/2 (100%) TPM-treated patients, respectively, and in 3/4 (75%), 7/9 (78%), and 1/2 (50%) VPA-treated patients. Physician global evaluation of improvement in study completers was moderate/marked in 75% of TPM-treated patients and 71% of those receiving VPA. The most common adverse events (occurring in more than 2 patients) in the TPM group were headache (N=5) and concentration/attention difficulty (3). With valproate, the most common adverse events were fatigue (N=3), nausea (3), and alopecia (3). Mean change in baseline body weight among study completers: +5 kg with VPA; -4 kg with TPM (p[lt]0.001).
VPA and TPM appear to be similarly effective in JME. At the relatively modest dosages achieved when titrated to response, both agents are well tolerated, although VPA was associated with substantial weight gain.
[Supported by: Ortho-McNeil Pharmaceutical.]