Kent 2013.

Study characteristics
Methods	Parallel trial of risperidone versus placebo
Participants	Inclusion criteria: DSM‐4 diagnosis of autistic disorder and parent‐rated ABC‐I subscores of at least 18 aged 5‐17 years (inclusive) weighing at least 20 kg Exclusion criteria: previous or current DSM‐4 diagnosis of psychotic disorder or PDD determined neurological disorders moderate or severe extrapyramidal symptoms or tardive dyskinesia past lack of response to risperidone treatment girls who were pregnant or breastfeeding Setting: multicenter study including "16 clinical and investigative settings", USA Sample size: 66 (risperidone 31, placebo 35) Number of withdrawals/dropouts: placebo 8 (AE 0, LTFU 0, withdrew consent 1, insufficient response 6, medication noncompliance 1, other 0). Risperidone 6 (AE 1, LTFU 1, withdrew consent 3, insufficient response 0, medication noncompliance 0, other 1) Gender: placebo 31 male, 4 female; risperidone 28 male, 3 female Mean age: all were aged under 18 years IQ: not reported Baseline ABC‐I or other BoC: ABC‐I risperidone 28.0; placebo 28.9 Concomitant medications: participants were not allowed to be taking psychotropic medications for at least 1 week before baseline. Anticholinergics and antihistamines for the treatment of emergent extrapyramidal symptoms were restricted to the lowest dose and for the shortest duration possible. Similarly, hypnotic or sedative medications (lorazepam, 0.25–2 mg; or diphenhydramine up to 50 mg) were allowed if the patient had been stable on a particular dose for at least 30 days before study start. Antihistaminic drugs were the most commonly used concomitant medication; a higher percentage of participants in placebo (20%; n = 7) than risperidone group 3%, n = 1) were treated with these drugs. History of previous medications: not reported
Interventions	Intervention (risperidone) for 6 weeks: 1.25 mg/day children < 45 kg; or 1.75 mg/day children > 45 kg Comparator (placebo) for 6 weeks: placebo oral solution for 6 weeks
Outcomes	Primary outcomes: ABC‐I (change from baseline) and response rates (at least 25% improvement in ABC‐I scores)(Aman 1985) Improvement in irritability (defined as a minimum 25% improvement in ABC‐Irritability scores (Aman 1985) ) AEs Secondary outcomes: none reported Timing of outcome assessment: baseline and the 6 weeks (endpoint)
Notes	Study start date: December 2007 Study end date: March 2010 Source of funding: Johnson & Johnson Pharmaceutical Research & Development, LLC Conflicts of interest: "Dr Aman was an investigator for this study and has received research support or been a consultant for Janssen Research & Development, LLC, Bristol‐Myers Squibb, Pfizer, Forest Research, and Hoffman La Roche. Drs. Ness, Singh, Hough and Kent and Mr. Karcher are employees of Janssen Research & Development, LLC. Drs Ning and Kushner were employed by Janssen Research & Development, LLC during the design and conduct of this study. Dr Ning is currently employed by Purdue Pharma and Dr Kushner is at CFG Health Systems, LLC. All authors met ICMJE criteria and all those who fulfilled those criteria are listed as authors". Trial registry" NCT00576732
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "the randomisation was conducted by using randomly permuted blocks and was stratified by centre and baseline weight"
Allocation concealment (selection bias)	Low risk	Quote: "To maintain blinding, the study drugs supplied were identical in appearance and packed in identical child‐resistant containers."
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "Patients, parents or primary caregivers, and the site personnel were all blinded to treatment assignment."
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not mentioned apart from "site personnel were all blinded"
Incomplete outcome data (attrition bias) All outcomes	High risk	ITT analysis used Sedation not reported for high‐dose risperidone ‐ only low‐dose. LTFU: placebo (8): lack of efficacy (6); withdrew (1); protocol violation (1) risperidone low‐dose (5): adverse effects (1); withdrew (1); LTFU (1); other (2) risperidone high‐dose (6): adverse effects (1); withdrew (3); LTFU (1); other (1)
Selective reporting (reporting bias)	Unclear risk	All outcomes mentioned were reported however without a trial protocol it is difficult to know if other outcomes were originally measured but not reported. Data were collected at 4 days, and weeks 1, 2, 4 and 6, or at the time of early withdrawal but only endpoint data were reported.
Other bias	Unclear risk	Participants were recruited from the investigators' practices There were no apparent differences in age, gender, race, BMI, diagnosis, symptoms or baseline scores.