Fisher 2001.

Methods	Randomised, double‐blind, placebo‐controlled, parallel‐group study in the US No formal baseline period Treatment period: 7 days
Participants	Aged ≥ 12 years (range 12‐82 years) Multicentre study in the US 720 participants randomised. Initially 320 per dose initiation regimen. Finally, 280 slow initiation regimen and 294 rapid initiation, after withdrawals and exclusions for not fulfilling pre‐protocol criteria. All participants with a recent history of focal seizures, with or without secondary generalisation with either inadequate seizure control on 1 or 2 anticonvulsants or had been judged to be unable to tolerate therapeutic dosages of these drugs (reaching maximum tolerated dose of ≥ 1 anticonvulsant). 280 slow initiation regimen, 294 rapid initiation regimen Slow initiation; 44.6% male, rapid initiation: 44.2% male
Interventions	Slow initiation: 300 mg day 1, 600 mg day 2, then 900 mg/day Rapid initiation: 2‐day placebo lead‐in followed by 900 mg/day Total evaluated treatment period: 7 days
Outcomes	Reports of fatigue, dizziness, somnolence and ataxia
Notes	Study did not have a baseline period and only measured adverse outcomes over a 7‐day period (day 3 (equivalent to 3rd day of active study medication for slow initiation group and first day for rapid initiation group) and day 7)), therefore unable to include in meta‐analysis.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation schedule that assigned each participant number to either the slow group or the rapid group in a one‐to‐one manner
Allocation concealment (selection bias)	Low risk	Number‐specific blister packs
Blinding (performance bias and detection bias) All outcomes	Low risk	Matching placebo, all participants had a 2‐day lead‐in phase that was unknown to investigator and participant
Incomplete outcome data (attrition bias) All outcomes	High risk	Per‐protocol analysis stated to include participants who met the criteria for evaluation (not ITT analysis). 781 enrolled, only 574 analysed for 3 reasons: inadequate methods, inadequate reasons and reasons for withdrawal.
Selective reporting (reporting bias)	Low risk	Appeared all expected and prespecified outcomes were reported
Other bias	High risk	Trial sponsored by Parke Davis Study appeared free of other sources of bias