Strupp 2003.

Methods	Pharmacological interventions for acquired downbeat nystagmus Allocation: double‐masked Masking: double‐masked Exclusions: 1 (chronic alcohol use) Losses: 0 Design: cross‐over RCT
Participants	Country: Germany Dates of recruitment: March 2002 to September 2002 Number of participants randomised: 18 Age: 50‐85 years Gender: 9 female, 9 male Aetiologies: Arnold‐Chiari malformation (1), degeneration (4), cerebellar ataxia (1), stroke (3), unknown (8) Ocular motility condition: acquired downbeat nystagmus Inclusion criteria: pure downbeat nystagmus, downbeat nystagmus with associated central vestibular or ocular motility disorders Exclusion criteria: epileptic seizures, cardiac arrhythmia, taking drugs affecting the central nervous system or vestibular system
Interventions	Intervention: 3,4‐diaminopyridine Dose: 20 mg Control: lactose placebo Duration: 1 day of intervention, 1‐2 weeks for wash‐out period, 1 day of control
Outcomes	Measurements: 2‐dimensional video‐oculography, perceived motion of target, drug effects by participant recall Timepoints: Baseline, 1 day and 2 weeks Adverse events: Transient minor perioral or digital paraesthesia, nausea
Notes	Health economic costs: not reported Quality of life measures: not reported Funding: not specified Declaration of interests: not specified Trial registration ID: not specified
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "With use of a computer‐generated randomization list"
Allocation concealment (selection bias)	Low risk	Quote: "Code envelopes were kept by the investigator during the trial and returned unopened to the monitor after termination of the study. The blind was maintained until data analysis had been completed."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Capsules with 20 mg of 3,4‐DAP and lactose or placebo (a capsule with lactose alone) were manufactured and delivered by the pharmacy of the University of Munich (Klinikum Grosshadern). The shape and color of the capsules with 3,4‐DAP or placebo were identical."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Capsules with 20 mg of 3,4‐DAP and lactose or placebo (a capsule with lactose alone) were manufactured and delivered by the pharmacy of the University of Munich (Klinikum Grosshadern). The shape and color of the capsules with 3,4‐DAP or placebo were identical." Quote: "Code envelopes were kept by the investigator during the trial and returned unopened to the monitor after termination of the study. The blind was maintained until data analysis had been completed."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "Seventeen patients (nine men; aged 50 to 85 years) with DBN were included in the study; one patient had to be excluded because of chronic alcohol consumption even on the day of the planned examination" Judgement comment: this excluded participant appeared to be excluded before randomisation. All 17 participants completed the study.
Selective reporting (reporting bias)	Unclear risk	No access to study protocol or trials registry entry.
Other bias	High risk	Additional 'Risk of bias' assessment for cross‐over study Was the cross‐over design suitable: probably Was there a carry‐over effect: uncertain, no analysis done. Was only first period data are available: no, first period data not available Was the analysis correct: unclear, no estimates of effect reported Comparability of results with those from parallel‐group trials: no parallel group trials