Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents

Not enough evidence to show which drugs are best for treating seizures in children and adolescents with absence epilepsy

Epilepsy is a disorder where seizures are caused by abnormal electrical discharges from the brain. Absence epilepsy involves seizures that cause a sudden loss of awareness. It often starts in childhood or adolescence. Three antiepileptic drugs are often used for absence epilepsy: valproate; ethosuximide and lamotrigine. Valproate can lead to weight gain, and may cause fetal abnormalities. The review found some evidence that individuals taking lamotrigine are more likely to be seizure free than those using placebos. No difference in effectiveness has been found between valproate and ethosuximide, but more research is needed.

Authors' conclusions: 

Although ethosuximide, lamotrigine and valproate are commonly used to treat people with absence seizures we have insufficient evidence to inform clinical practice, and the few trials included in this review were of poor methodological quality and did not have sufficient number of participants. More trials of better quality are needed.

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Background: 

This is an updated version of the original Cochrane review published in Issue 3, 2003.

Absence seizures are brief epileptic seizures which present in childhood and adolescence. They are characterised by sudden loss of awareness and an electroencephalogram (EEG) typically shows generalised spike wave discharges at three cycles per second. Ethosuximide, valproate and lamotrigine are currently used to treat absence seizures. This review aims to determine the best choice of anticonvulsant for a child with typical absence seizures.

Objectives: 

To review the evidence for the effects of ethosuximide, valproate and lamotrigine as treatments for children and adolescents with absence seizures, when compared with placebo or each other.

Search strategy: 

We searched the Cochrane Epilepsy Group's Specialised Register (November 2009), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2009), MEDLINE (1950 to November week 3, 2009) and EMBASE (1988 to March 2005). No language restrictions were imposed. In addition, we contacted Sanofi Winthrop, Glaxo Wellcome (now GlaxoSmithKline) and Parke Davis (now Pfizer), manufacturers of sodium valproate, lamotrigine and ethosuximide respectively.

Selection criteria: 

Randomised parallel group monotherapy or add-on trials which include a comparison of any of the following in children or adolescents with absence seizures: ethosuximide; sodium valproate; lamotrigine or placebo.

Data collection and analysis: 

Outcome measures were: (1) proportion of individuals seizure free at 1, 3, 6, 12 and 18 months post randomisation; (2) people with a 50% or greater reduction in seizure frequency; (3) normalisation of EEG and/or negative hyperventilation test and (4) adverse effects. Data were independently extracted by two review authors. Results are presented as relative risks (RR) with 95% confidence intervals (95% CI).

Main results: 

Five small trials were found, four of them were of poor methodological quality. One trial (29 participants) compared lamotrigine with placebo using a response conditional design. Individuals taking lamotrigine were significantly more likely to be seizure free than participants taking placebo during this short trial. Another trial compared lamotrigine with sodium valproate, the study lacked power to detect the difference in efficacy. Three studies compared ethosuximide, but because of diverse study designs and populations studied, we decided not to pool results in a meta-analysis. None of these studies found a difference between valproate and ethosuximide with respect to seizure control, but confidence intervals were wide and the existence of important differences could not be excluded.