To evaluate the effectiveness of topiramate monotherapy or add-on therapy in patients with juvenile myoclonic epilepsy

Objective/methods: Open-label study enrolling patients age 12–65 years with a confirmed diagnosis of uvenile myoclonic epilepsy (JME) (myoclonic jerks and PGTCS or an EEG with generalized epileptiform abnormalities consistent with a clinical diagnosis of JME), age of disease onset between 8–26 years. Patients had to have myoclonus and/or >1 PGTCS within the 3-month retrospective baseline. Eligible patients were randomized (2:1) to 26 weeks treatment with topiramate monotherapy (TPM) (target, 3–4mg/kg/day; maximum, 9mg/kg/day) or VPA (target, 10mg/kg/day; maximum, 60mg/kg/day or 750mg/day if >16 years of age). 12 patients had one baseline AED. Seizure frequency, tolerability, and patient and physician evaluations of response were recorded during each visit (Baseline and Weeks 4, 8, 14, and 26).

Results: 28 patients were randomized to TPM (N=19; median age, 15 years; range, 9–42) or VPA (N=9; median age, 16 years; range, 12–34). 12/19 patients receiving TPM and 7/9 patients receiving VPA completed the study; mean dose among completers was 189±78mg/day and 897±375mg/day, respectively. At the end of the study, all patients but one patient achieved TPM (OXC) or VPA monotherapy. Reasons for discontinuation in the TPM group included adverse events (N=2), patient choice (N=1), or lost to follow-up (N=1); two patients discontinued VPA due to adverse events or other reasons. During the 3-month maintenance phase, seizure-free rates were 47% in patients receiving TPM and 33% in those receiving VPA. Seizure-free rates for myoclonic, PGTCS, and absence seizures in the TPM and VPA groups were 7/14 (50%) vs. 6/9 (67%), 8/12 (67%) vs. 3/4 (75%), and 2/2 (100%) vs. 1/2 (50%), respectively. Physician and patient global evaluation of improvement, alertness, and improvement in seizure severity were similar in both treatment groups (TPM, 75%; VPA, 71%). Neurotoxicity scores over time were similar, but systemic toxicity scores were higher with VPA. Most TPM-treated patients lost (mean, 4.1kg), while patients receiving VPA gained weight (mean, 5kg); the between group difference was statistically significant (p≤0.001).

Conclusion: TPM appears to be an effective alternative to VPA in patients with JME, with less systemic toxicity. These results are supported by recently published data from randomized controlled trials