NCT00498173.

Study characteristics
Methods	8‐week parallel trial of atomoxetine versus placebo
Participants	Inclusion criteria: 5‐15 years of age diagnosis of ASD significant hyperactivity, inattention, or impulsivity as determined by a score on an investigator‐administered ADHD Rating Scale (ADHDRS)‐Home Version that is at least 1.5 standard deviations above the mean for age and sex parent/caregiver's primary complaint about the child is inattention, hyperactivity, and/or impulsivity ("ADHD" symptoms) symptoms present for 6 months prior to study entry psychotropic drug‐free for at least 2 weeks prior to starting study medication (or 5 weeks for fluoxetine (Prozac)) Exclusion criteria: weighs < 15 kg any another psychiatric disorder that may require a different treatment, including psychotic disorders, major affective disorders, obsessive compulsive disorder, panic disorder, or substance‐related disorders clinical diagnosis of Rett's disorder or childhood disintegrative disorder presence of extreme aggression or self‐injury currently taking an effective psychotropic drug currently using other medications that may be unsafe to take with atomoxetine (e.g. potent CYP 2D6 inhibitors, intravenous albuterol, monoamine oxidase inhibitors) inability to swallow study medication presence of a medical condition that would make treatment with atomoxetine unsafe (e.g. unstable hypertension or cardiac disease, asthma requiring frequent treatment with albuterol, narrow angle glaucoma, pregnancy, etc.) mental age of < 18 months previous adequate trial of atomoxetine previous evidence of hypersensitivity or an allergic reaction to atomoxetine clinically significant abnormalities in laboratory measures indicating an undiagnosed medical condition as determined by the study physician in discussion with the participant's primary care physician clinically significant abnormalities on ECG as determined by a pediatric cardiologist pregnant initiation of a new psychosocial intervention within 90 days prior to starting study medication. Participants who have recently had a significant change in their psychosocial interventions will not be eligible until this intervention has been stable for 90 days in order to avoid confounding results of the study. Stable interventions (e.g. speech and occupational therapy) will be allowed to continue during the course of the study. Minor changes in ongoing treatment (e.g., missed therapy sessions due to holiday/vacation planned break in therapy due to school holidays) will not be considered significant Location/setting: details not described Mean IQ: details not described Mean age: atomoxetine 9.3 years, placebo 8.4 years Gender: 54 male, 6 female Sample size: 60 Reasons for dropouts: no postbaseline ratings for 2 people in atomoxetine group and 1 in placebo group Baseline ABC‐I or other BoC scale: PedsQL atomoxetine 56.3 (18.8); placebo 60.5 (19.6) Concomitant medications: atomoxetine (34.5%) were taking concomitant medications; placebo 41.9% were taking concomitant medications Previous medications: details not provided
Interventions	Intervention (atomoxetine) for 8 weeks: available tablet strengths of atomoxetine: 5 mg, 10 mg, 25 mg, 40 mg. Week 1, participant takes 0.5 mg/kg/day; week 2, 0.8 mg/kg/day; week 3, 1.2 mg/kg/day. Potential exists for dose increase at week 4 to 1.8 mg/kg/day based on CGI improvement rating at week 4. Comparator (placebo) for 8 weeks: participants will receive blinded, matched placebo for 8 weeks. Dosage can be increased over the first 4 weeks of study participation and will then be held constant for the remainder of the 8‐week trial. Placebo tablets dosages: 5 mg, 10 mg, 25 mg, 40 mg
Outcomes	Primary outcomes: irritability using the ABC‐I (Aman 1985) AEs Secondary outcomes: acceptability/tolerability QoL using PedsQL (WHO 1998) Timing of outcome assessments: details not described
Notes	Study start date: July 2007 Study end date: August 2017 Source of funding: details not provided Conflicts of interest: details not provided
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Quote: "Sequential Assignment"
Allocation concealment (selection bias)	Unclear risk	Details not provided
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Only details provided were on the trial registry, "Masking: triple (participant, care provider, investigator)"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Only details provided were on the trial registry, "Masking: triple (participant, care provider, investigator)"
Incomplete outcome data (attrition bias) All outcomes	High risk	3 participants were not included in the analysis all due to "no post‐baseline ratings"
Selective reporting (reporting bias)	Unclear risk	Only relying on Clinical trials reg
Other bias	Unclear risk	Difficult to know without a published paper and protocol