Piña‐Garza 2008.

Methods	Randomised, double‐blind, multi‐centre placebo‐controlled trial. Responder‐enriched design in which all patients received adjunctive lamotrigine during an open‐label phase (wherein dose was escalated to achieve optimal response); those who had a 40% or greater reduction in the frequency of partial seizures during the last 4 weeks of the optimisation period were randomly assigned to double‐blind treatment for up to 8 weeks with continued lamotrigine or placebo.
Participants	Total number enrolled = 38. Male or female infants aged 1 month to 24 months with at least 4 partial seizures (with or without generalisation) per month, uncontrolled by 1 AED and who showed 40% or greater reduction in seizure frequency during an initial open label phase. There were 19 subjects in each arm; median age was 13.5 months in lamotrigine arm and 14.2 months in placebo arm; median age of onset of epilepsy was 3 months and median duration of epilepsy was 9.1 months in lamotrigine arm and 8.5 months in placebo arm. Exclusion Criteria: subjects with progressive myoclonic epilepsy; progressive neurologic disease, seizures unrelated to epilepsy or resulting from drug withdrawal; use of felbamate, adrenocorticotropic hormone, previous use of lamotrigine, two AEDs as maintenance treatment, presence of hepatic dysfunction, having a functioning vagus nerve stimulator; or being on a ketogenic diet.
Interventions	Intervention group was continued on lamotrigine. Control group subjects had their lamotrigine dose tapered and changed to placebo. The maximum maintenance dose was 5.1 mg/kg/day for those on non–enzyme‐inducing AEDs or valproate and 15.6 mg/kg/day for those on enzyme‐inducing AEDs.
Outcomes	(1) Percentage of patients who had treatment failures during the double‐blind phase. (2) Cumulative percentage of patients who met escape criteria as a function of days on double‐blind study medication. Subjects were withdrawn from study if they met one of the following criteria: 50% increase in monthly partial seizure frequency compared with seizure frequency during the last 4 weeks of the open‐label optimisation period; a doubling of the highest consecutive 2‐day partial seizure count observed during the open‐label optimisation period; onset of a new and more severe seizure type; clinically significant worsening of non‐partial seizures that were also observed during the historical baseline phase or the open‐label optimisation period; the need to use any therapeutic intervention in addition to study medication to control seizures; or status epilepticus.
Notes	The protocol was amended midway through the study to randomly assign all patients with at least 40% reduction in seizure frequency, instead of planned inclusion of subjects with 40% to 80% reduction in seizure frequency. 43 subjects who had more than 80% reduction in seizure frequency before the protocol amendment were not included in the double‐blind study.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of randomisation not specified.
Allocation concealment (selection bias)	Unclear risk	Details not reported in the publication.
Blinding (performance bias and detection bias) All outcomes	Unclear risk	No information provided.
Incomplete outcome data (attrition bias)	Low risk	11 patients (8 in the lamotrigine group and 3 in placebo group) completed the double‐blind phase, 25 (9 in the lamotrigine group and 16 in placebo group) met escape criteria, and 2 (both in the lamotrigine group) prematurely withdrew because of protocol violations. The reasons for exclusion were reported.
Selective reporting (reporting bias)	Low risk	All expected and pre‐specified outcomes were reported. Protocol was not available.
Other bias	Unclear risk	This study was sponsored by GlaxoSmithKline, the manufactures of LTG.