Smith 1993.

Methods	Randomised, double‐blind, cross‐over study. Two treatment arms: 1 placebo, 1 lamotrigine. Pre‐randomisation baseline = 4 weeks. Treatment I and II = 18 weeks each. Washout = 6 weeks.
Participants	Single centre UK study. 81 participants with drug‐resistant partial epilepsy (33 men and 48 women). 41 were randomised to lamotrigine and 40 to placebo in the initial treatment phase. The age range was 15 to 67 years (mean 33.7); duration of epilepsy ranged from 4 to 45 years (mean 21). The mean age at onset was 11.8 years (<1 to 52 years). Maximum number of other AEDS permitted was 2.
Interventions	Add‐on lamotrigine or placebo. Lamotrigine dose up to 400 mg/day. Median daily dose was 300 mg. Participants on valproate received lower doses.
Outcomes	(1) 50% responder rates. (2) Withdrawal from study for any reason. (3) Adverse effects. (4) Health‐related quality of life (HRQL).
Notes	HRQL model was completed by 40 to 54 of 81 participants.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer generated random permuted blocks.
Allocation concealment (selection bias)	Low risk	Partecipants were allocated sequentially numbered, sealed packages containing either lamotrigine or placebo.
Blinding (performance bias and detection bias) All outcomes	High risk	Patients (46/73) and investigators (52/73) were able to identify lamotrigine treatment. Identical tablets and packaging were used. Prepacked coded medication dispensed by pharmacy.
Incomplete outcome data (attrition bias)	Unclear risk	No participants were excluded from analysis. 9 people withdrew from the study; 6 receiving lamotrigine and 3 receiving placebo. The reasons for exclusion were reported. Patients who discontinued prematurely did not complete the HRQOL measure at the time of discontinuation, the exclusion of treatment failures may introduce a bias in favour of lamotrigine.
Selective reporting (reporting bias)	Low risk	Protocol unavailable, but appears all expected and pre‐specified outcomes were reported.
Other bias	Unclear risk	This study was sponsored by GlaxoSmithKline, the manufactures of LTG.

AED: antiepileptic drug

LTG: lamotrigine