Niederhofer 2003.

Study characteristics
Methods	Cross‐over trial of tianeptine versus placebo
Participants	Inclusion criteria: met "ICD‐10 criteria for autistic disorder" no history of identified medical or neurological illnesses free of medication for at least 4 weeks (12 weeks for a single subject who had been taking fenfluramine) before beginning the study Exclusion criteria: history of medical or neurological illnesses taking regular medications in the month prior to the study Sample size: 7 in tianeptine group, 6 placebo (13 in total) Reason for withdrawals/dropouts: "a thirteenth subject entered the study but was dropped because of noncompliance with medication" Location/setting: Italy Mean age: 7.3 years Gender: all participants were male. Mean IQ: ranged from 35‐84 Baseline ABC‐I or other BoC: tianeptine ABC‐I 13.9; placebo 14.1 Concomitant medications: participants had been off medication for at least 1 month before the study. History of previous medications: "all these children had been treated with either methylphenidate, neuroleptics or desipramine before entry into the study. In each case, these medications had either not been effective or caused intolerable side effects."
Interventions	Intervention (tianeptine) for 12 weeks: 37.5 mg/day dose for 12 weeks Comparator (placebo) for 12 weeks: identical placebo tablets
Outcomes	Primary outcomes: irritability, measured using the ABC‐I subscale (Aman 1985) AEs Secondary outcomes: none reported Timing of outcome assessments: weekly ABC ratings and AEs
Notes	Study start date: 2002 Study end date: not reported Source of funding: not reported Conflicts of interest: none disclosed
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Details not provided
Allocation concealment (selection bias)	Unclear risk	Details not provided
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "subjects were randomly assigned by a nonrating clinician to begin tianeptine or placebo."
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	All raters were blind to drug order until ratings were completed. However, the authors note of "possible unblinding of parents and teachers because of side effects"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No details about participation and dropouts
Selective reporting (reporting bias)	Unclear risk	Adverse effects not reported. Without a trial protocol it is difficult to know if any outcomes were measured but not reported.
Other bias	Unclear risk	Details not provided