Moazen‐Zadeh 2018.

Study characteristics
Methods	10‐week parallel trial of simvastatin versus placebo
Participants	Inclusion criteria: male and female aged 4‐12 years diagnosis of AD based on the DSM‐4‐TR criteria ABC‐I subscale score of at least 12 Exclusion criteria: concomitant DSM‐4 axis I or II disorders active medical conditions severe intellectual disability making the diagnosis inconclusive based on prior records and clinical judgement seizure disorders history of alcohol/drug abuse tardive dyskinesia, history of antipsychotic medication or behaviour therapy within the past 6 months before the trial. Location/setting: speciality outpatient autism clinic at Roozbeh Psychiatry Hospital, Iran Sample size: 35 in each group Number of withdrawals/dropouts: 2 from each group (simvastatin: 1 no longer met criteria, 1 withdrew consent; placebo: 2 withdrew consent) Gender: 53 male, 13 female Mean age: simvastatin 7.06 years (2.33); placebo 7.61 (2.74) years IQ: details not provided Baseline ABC‐I or other BoC: ABC‐I simvastatin 20.97 (5.37); placebo 19.97 (7.24) Concomitant medications: children did not have a history of psychotropic drug use History of previous medications: children did not have a history of psychotropic drug use
Interventions	Intervention (simvastatin + risperidone): risperidone (Risperdal; Janssen Pharmaceuticals, Belgium) plus simvastatin (Osveh, Iran) for 10 weeks. Risperidone starting dose was 0.5 mg/day in 0.5 mg tablets, and in the absence of clinically significant AEs it was increased by 0.5 mg per week to the target dose of 1 mg/day for children weighing < 20 kg and 2 mg/day for those weighing at least 20 kg. Simvastatin was administered in the form of a 20 mg tablet/day for children < 10 years of age and a 40 mg tablet per day for those at least 10 years of age. Comparator (placebo + risperidone): risperidone (Risperdal; Janssen Pharmaceuticals, Belgium) plus placebo for 10 weeks. Risperidone starting dose was 0.5 mg/day in 0.5 mg tablets, and in the absence of clinically significant AEs it was increased by 0.5 mg/week to the target dose of 1 mg/day for children weighing < 20 kg and 2 mg/day for those weighing at least 20 kg. Placebo was administered in the form of a 20 mg tablet/day for children < 10 years of age and a 40 mg tablet per day for those at least 10 years of age.
Outcomes	Primary outcomes: irritability, measured using the ABC‐I subscale (Aman 1985) AEs Secondary outcomes: tolerability Timing of outcome assessments: baseline, weeks 5 and 10 (endpoint)
Notes	Study start date: February 2016 Study end date: December 2016 Funding: "This study was supported by a grant to Prof. Shahin Akhondzadeh (Grant number 30327) from Tehran University of Medical Sciences (TUMS)" Conflicts of interest: "No competing financial interests exist" Trial registry: IRCT201602041556N86
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computerised random number generator
Allocation concealment (selection bias)	Low risk	Sealed opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Simvastatin and placebo tablets were identical in shape, size, texture, colour, and taste, and they were dispensed in identical containers by an investigational drug pharmacist. Quote: "During the trial, the physicians, other healthcare personnel, participants, and parents were blinded to treatment assignments."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "During the trial, the physicians, other healthcare personnel, participants, and parents were blinded to treatment assignment"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No further statistical methods such as data imputation or ITT analysis were conducted for participants who were lost to follow‐up or dropped out.
Selective reporting (reporting bias)	Low risk	All outcomes on the trial registry were reported in the paper.
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.