Fankhauser 1992.

Study characteristics
Methods	Cross‐over trial of clonidine versus placebo
Participants	Inclusion criteria: aged 5‐33 years DSM‐III‐R diagnosis of an autistic disorder no medication use in the 2 weeks before the study Exclusion criteria: a history of schizophrenia or profound intellectual disability unstable medical condition requiring medication abnormal laboratory results Location/setting: USA Sample size: 9 in total (cross‐over) Number of withdrawals/dropouts: 2 from clonidine group Gender: all male Mean age: 12.9 years IQ: not reported Baseline ABC‐I or other BoC: baseline RFRLRS (affectual responses: 1.02) Concurrent medications: 0% History of previous medications: 0%
Interventions	Intervention (clonidine): weekly patch delivering approximately 0.005 mg/kg /day for 4 weeks Comparator (placebo): transdermal placebo patch for 4 weeks
Outcomes	Primary outcomes: irritability, measured using the RFRLRS (Freeman 1986) Secondary outcomes: tolerability Timing of outcome assessment: baseline, 2 weeks, 4 weeks
Notes	Study start date: not reported Study end date: not reported Source of funding: Boehringer Ingelheim Pharmaceuticals supplied the patches Conflicts of interest: none declared Trial registry: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not stated
Allocation concealment (selection bias)	Unclear risk	Details not provided
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not stated
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not stated
Incomplete outcome data (attrition bias) All outcomes	High risk	2 of 9 participants were lost to follow‐up, 1 because of irritability and sedation while on clonidine LTFU: 2 unexplained
Selective reporting (reporting bias)	High risk	AEs were not reported.
Other bias	Unclear risk	This was highly divergent sample (5‐33 years) with low sample numbers (9)