Open-label study enrolling patients age 12–65 years with a confirmed diagnosis of
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 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). 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%). Systemic toxicity was 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). TPM appears
to be a an effective alternative to VPA. Results are supported by recently published
data.
