Ghaleiha 2015.

Study characteristics
Methods	Parallel trial of pioglitazone + risperidone versus placebo + risperidone
Participants	Inclusion criteria: male and female outpatients aged 4–12 years diagnosis of autism based on DSM‐4‐TR criteria and confirmed by an expert child psychiatrist based on behavioural observations and semi‐structured interviews with parents a score of at least 12 on the ABC‐I presenting with chief complaint of severely disruptive symptoms related to autism drug‐free for at least 6 weeks Location/setting: autism speciality clinic of the children's outpatient clinic of Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Iran Sample size: 22 in each group. Number of withdrawals/dropouts: 2 in each group withdrew consent Gender: treatment 15/20 male; placebo 17/20 male Mean age: treatment group 6.95 years; placebo 6.2 years IQ: not reported Baseline ABC‐I or other BoC: ABC‐I 18.25; placebo 19.00 Concurrent medications: not reported History of previous medications: treatment group: risperidone 15/20 participants, Ritalin (methylphenidate) 4, valproic acid 2, lamotrigine 1. Placebo: risperidone 16/20, Ritalin (methylphenidate) 6, valproic acid 2, lamotrigine 2 Exclusion criteria: any active medical condition, diagnosis of DSM‐IV axis I or II disorder, use of any psychotropics in previous 6 weeks, history of hepatic disease or seizure; having insulin‐dependent diabetes, liver disease, or congestive heart failure Number randomised: pioglitazone 22; placebo 22 Number analysed: pioglitazone 20; placebo 20
Interventions	Intervention (pioglitazone + risperidone) for 10 weeks: pioglitazone (Actos, Takeda/Eli Lilly) 30 mg/day (15 mg twice/day) fixed dose. Risperidone(Risperdal; Janssen Pharmaceuticals, Belgium) initial dose 0.5 mg/day increased by 0.5 mg every week to a maximum of 1 mg/day for participants weighing < 20 kg and 2 mg/day for those who were ≥ 20 kg Comparator (placebo + risperidone) for 10 weeks: placebo tablets with identical appearance. Risperidone (Risperdal; Janssen Pharmaceuticals, Belgium) initial dose 0.5 mg/day increased by 0.5 mg every week to a maximum of 1 mg/day for participants weighing < 20 kg and 2 mg/day for those who were ≥ 20 kg
Outcomes	Primary outcomes: irritability, measured using the ABC‐I (Aman 1985) AEs Secondary outcomes: none reported Timing of outcome assessments: baseline, week 5, week 10
Notes	Study start date: March 2012 Study end date: February 2014 Source of funding: "This study was supported by a grant from Tehran University ofMedical Sciences to Prof Shahin Akhondzadeh (grant number16043). The funding organization had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript and the decision to submit the paper for publication." Conflicts of interest: none declared Trial registry: IRCT201204081556N40
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomisation codes were generated by Microsoft Office excel software and each participant was assigned to one specific code"
Allocation concealment (selection bias)	Low risk	Quote: "Assignments were kept in confidential sealed opaque envelopes and were disclosed after the end of the study for statistical analysis"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The participants, parents and referring physicians were totally blinded to the assignments. Additionally, responsible individuals for administration of the medications, rating and statistical analysis were also blinded to the assignments.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The participants, parents and referring physicians were totally blinded to the assignments. Additionally, responsible individuals for administration of the medications, rating and statistical analysis were also blinded to the assignments.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Two of 22 were LTFU in both groups
Selective reporting (reporting bias)	Low risk	All data were reported.
Other bias	High risk	The contact author is also on the ethics committee at the university funding the study. The contact author is a peer‐reviewer for one of the journals in which some of their studies are published.