Naritoku 2007.

Methods	Double‐blind, randomised, parallel‐group, placebo‐controlled multi‐centre global study. Screening phase of up to 2 weeks during which eligibility was determined; an 8‐week baseline phase serving to exclude from randomisation patients who did not meet the minimum seizure frequency criterion; a 7‐week, double‐blind escalation phase during which lamotrigine XR (Extended Release) was introduced and titrated to its target dose; and a 12‐week, double‐blind maintenance phase during which dosage of study medication and concomitant AED were maintained.
Participants	International multi‐centre study from North and South America, Europe, and Asia. Uncontrolled partial seizures (at least 8 partial seizures in 8 weeks with at least one partial seizure during each 4‐week period of the baseline phase). Male and female patients 12 years of age or older with partial seizures with or without generalisation who were treated with a stable regimen of one or two AEDs for at least 4 weeks before starting the baseline phase. Total number enrolled = 243; (121 to treatment arm; 123 to placebo arm); 93% were aged between 16 and 65 years; mean age in lamotrigine group = 35.8 (12.7) and in placebo group = 37.5 (14.4) years. Males constituted 47% of participants in lamotrigine group and 53% of participants in placebo group. Exclusion criteria included: presence of primary generalized seizures, status epilepticus during or within 24 weeks before the start of the baseline phase, chronic treatment with three or more AEDs, current or previous use of lamotrigine, current use of felbamate or adherence to a ketogenic diet, and pregnancy or planned pregnancy during the study or within 3 weeks after the last dose of study medication.
Interventions	Treatment group received lamotrigine XR (Extended Release); other group received identical placebo. Dosage of lamotrigine XR was escalated gradually up to 200 mg/day in those receiving valproate, 300 mg/day in those receiving valproate and an enzyme inducing AED, and up to 500 mg/day in those receiving enzyme inducing AEDs without valproate.
Outcomes	(1) Seizure frequency. (2) Adverse events (3) Withdrawals from study. US subjects had following additional assessments: Profile of Mood States (POMS), Center for Epidemiologic Studies‐Depression Scale (CES‐D), research version of the Neurological Disorders Depression Inventory‐Epilepsy (NDDI‐E), Quality of Life in Epilepsy‐31‐P (QOLIE‐31‐P), Liverpool Adverse Experience Profile (AEP), Seizure Severity Questionnaire (SSQ), and Epworth Sleepiness Scale (ESS).
Notes
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	24 subjects withdrew from treatment group and 16 from placebo group. The reasons for exclusion were reported.
Selective reporting (reporting bias)	Low risk	There was no protocol available to check a priori outcomes,but appears all expected and pre‐specified outcomes were reported.
Other bias	Unclear risk	This study was sponsored by GlaxoSmithKline, the manufactures of LTG.