Researchers at Seoul National University Bundang and Children’s Hospitals, Republic of Korea evaluated the long-term effectiveness and tolerability of ethosuximide (ESX), valproic acid (VPA), and lamotrigine (LTG) as initial monotherapies for patients with childhood absence epilepsy (CAE). CAE was diagnosed according to the criteria of Panayiotopoulos (2005) in a total of 128 patients, female preponderance 1.8:1, and mean age at onset of 6.5 years; 48 were assigned to the ESX group, 59 were treated with VPA and 21 with LTG. The mean follow-up duration was 3.4 years (range, 1-17 years). ESX and VPA starting dose was 10 mg/kg/day, and 1 mg/kg/day for LTG. The final maintenance doses were 23 mg/kg/day for ESX, 26 mg/kg/day for VPA, and 4.7 mg/kg/day for LTG. The seizure-free rate of ESX at 3 months was 84% and significantly higher than that of VPA (62%) and LTG (54%). At 6 months, the seizure-free rate of ESX (90%) was significantly higher than that of LTG (63%); the seizure-free rates of VPA and LTG groups at 6 months were not significantly different. After 9 months, there was no significant difference in seizure-free rates among the 3 drug groups, nor in rates of normalization of the EEG at 12 months (ESX, 77%; VPA, 83%; and LTG, 64%), retention rate through the treatment period, and adverse-event rates (ESX, 25%; VPA, 29%; and LTG, 14%). Frequent causes of AED withdrawal because of adverse events were GI complaints for ESX (10%), GI complaints (5%) and alopecia (7%) for VPA, and rash for LTG (5%).
ESX, VPA and LTG are equally effective in the long-term treatment of newly diagnosed CAE patients. The onset of efficacy is faster for ESX compared with VPA or LTG. 
COMMENT. A previous double-blind, randomized, controlled clinical trial comparing the 3 drugs, ESX, VPA and LTG, found that ESX and VPA were more effective than LTG after 4-5 months of treatment. Attentional dysfunction was more common with VPA than with ethosuximide . The present study, extending the period of observation to 9 months, finds no significant difference in long-term effectiveness or adverse event rates of ESX, VPA and LTG. Apparently, contrary to earlier conclusions, “older (ESX) is not better!” (Vining EPG. Pediatr Neurol Briefs 2010 March;24(3):19).