Mouti 2014.

Study characteristics
Methods	Parallel study of fluoxetine versus placebo
Participants	Inclusion criteria: aged 7.5‐18 years met criteria for an ASD based on the DSM‐4 or the ICD‐10 criteria a score of ≥ 6 on the total score of the CYBOCS at the time of screening. Exclusion criteria: any psychotropic medication (including typical and atypical anti‐psychotics, mood stabilisers, antidepressants, anti‐anxiolytics and stimulant medication including atomoxetine, monoamine oxidase inhibitor or pimozide, and St John's wort) or any use of such medication in the 3 months prior to the commencement of the trial concomitant administration of drugs that interact with the metabolism of fluoxetine (e.g. phenytoin and carbamazepine) co‐morbid significant medical conditions (e.g. unstable seizure disorder, cardiac disease, liver failure or renal failure) female participants of childbearing potential require a urine pregnancy test to exclude pregnancy Location/setting: 3 tertiary hospitals in Australia Sample size: 146 participants Number of withdrawals/dropouts: 31 in fluoxetine, 21 in placebo dropped out or did not complete treatment. Mean age: 11.2 years Gender: 124 boys, 22 girls IQ: 46/146 had an intellectual disability Baseline ABC‐I or other BoC: fluoxetine ABC‐I 18.57; placebo 17.87 Concomitant medications: 62/146 were on concurrent medications and a further 2 were receiving stimulant medications History of previous medications:details not provided
Interventions	Fluoxetine for 16 weeks: commenced at 4 or 8 mg/day for the first week depending on weight and then titrated to a maximum of 20 mg/day for children weighing < 40 kg or 30 mg/day if ≥ 40 kg Placebo for 16 weeks: equivalent placebo
Outcomes	Primary outcomes: irritability, measured using the ABC‐I subscale (Aman 1985) self‐injurious behavior, measured using the Repetitive Behavior Scale (Bodfish 2000) AEs Secondary outcomes: none reported Timing of outcome assessments: AEs assessed weekly and other primary outcomes at baseline and endpoint
Notes	Study start date: November 2010 Study end date: August 2017 Source of funding: "Drs Reddihough and Lee and Ms Orsini report receiving grants from NHMRC and the Royal Children's Hospital Foundation during the conduct of the study. Dr Hazell reports that his employer has received payment from Shire for speaker’s fees. Dr Whitehouse reports receiving grants from NHMRC during the conduct of the study." Conflicts of interest: none declared Comment: Study authors were contacted for further information and they emailed a separate published paper providing all the details (Reddinhough).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Details not provided
Allocation concealment (selection bias)	Low risk	Quote: "The randomization schedule was provided to the clinical trials pharmacist at each site, who arranged a sequential stock of trial medication for each stratum, labeled with only the study number, strata, and instructions for use"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "This schedule remained confidential throughout the study. The independent statistician retained a copy of the master randomization schedule to check for any discrepancies. Participants and their families, clinicians, and the research team assessing outcomes remained blind to the randomization schedule throughout the study."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "This schedule remained confidential throughout the study. The independent statistician retained a copy of the master randomization schedule to check for any discrepancies. Participants and their families, clinicians, and the research team assessing outcomes remained blind to the randomization schedule throughout the study."
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	A large number from each group withdrew from the trial (31 fluoxetine and 21 placebo) and "Twenty‐five percent of the participants did not provide data on the primary outcome (n = 21 and n = 16 in the fluoxetine and placebo groups, respectively) however where outcome data was reported at least once an ITT analysis was used. There was a chance baseline imbalance in some of the key behavioral measures of ASDs, indicating that the placebo group had a comparatively more severe behavioral phenotype than the fluoxetine group". LTFU fluoxetine group: 31 discontinued (20 parent or caregiver withdrew consent; 5 AEs; 2 clinician decisions to discontinue; 1 used other ineligible drugs; and 3 others withdrew for personal reasons) LTFU placebo group: 21 discontinued (12 parent or caregiver withdrew; 4 AEs; 2 clinician decisions to discontinue; 3 others withdrew for personal reasons)
Selective reporting (reporting bias)	Unclear risk	All scales mentioned in the protocol were reported in the final paper, however the subscales of the Repetitive Behaviour Scale were not reported, only the total score however, more information was provided by the study authors.
Other bias	High risk	Quote: "The active and placebo medication will be produced by Richard Stenlake Chemists (Bondi Junction, Australia)". "PH and MK have received payment from Eli Lilly (the manufacturer of fluoxetine) for participation in consultancies, advisory boards, speaker’s bureau, and the conduct of clinical trials"