McDougle 1996.

Study characteristics
Methods	Parallel trial of fluvoxamine versus placebo
Participants	Inclusion criteria: ASD diagnosis based on DSM‐III and ICD‐10 "moderate" symptoms as defined by global severity of illness on CGI psychotropic drug‐free for at least 6 weeks before the start of the trial Exclusion criteria: met DSM‐III‐R criteria for schizophrenia or had psychotic symptoms abused illicit substances within the previous 6 months notable medical condition, including seizure disorder women with positive serum pregnancy test results Location/setting: a neuroscience research centre at the Connecticut Mental Health Center, New Haven, and the Adult Pervasive Developmental Disorders Clinic at the same neuroscience research centre, USA Sample size: fluvoxamine 15; placebo 15 Number of withdrawals/dropouts: none reported Gender: 27 men, 3 women Mean age: 30.1 years IQ: not reported Baseline ABC‐I or other BoC: aggression (Brown Aggression Scale; Brown 1979) fluvoxamine 9.3, placebo 12.3 Concomitant medications: participants were required to be psychotropic drug‐free before the trial History of previous medications: not reported
Interventions	Intervention (fluvoxamine for 12 weeks): started at 50 mg every night. "The dosage could then be increased by 50 mg daily every 3 or 4 days to a maximum dosage of 300 mg/day, as tolerated, if maximal clinical response was not obtained. Thus, the maximum dosage of fluvoxamine was attained within 3 weeks, and patients received this dose for at least 9 weeks." maximum 300 mg/day Comparator (placebo for 12 weeks): equivalent placebo, "lactose in identical‐looking tablets"
Outcomes	Primary outcomes: AEs aggression (measured using the Brown Aggression Scale (Brown 1979)) Secondary outcomes: none reported Timing of outcome assessments: baseline, 4, 8 and 12 weeks
Notes	Study start date: September 1990 Study end date: December 1993 Source of funding: "this work was supported by a National Alliance for Research on Schizophrenia and Depression Young Investigator Award (Dr McDougle), the State of Connecticut Department of Mental Health and Addiction Services, The Korczak Foundation for Autism and Related Disorders, and grants MOI RR06022‐33, P50 MH30929‐18, HD 0300827, and POI MH25642from the National Institutes of Health, Bethesda, Md. Fluvoxamine and financial support were provided by Solvay Pharmaceuticals, Marietta, Ga". Conflicts of interest: none declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Details not provided
Allocation concealment (selection bias)	Unclear risk	Details not provided
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "The prescribing psychiatrist (C.J.M.), the nurse (S.T.N.) who performed the behavioral ratings, the patients, and all family and other members of the patients' treatment teams were unaware of drug assignment"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "The prescribing psychiatrist (C.J.M.), the nurse (S.T.N.) who performed the behavioral ratings, the patients, and all family and other members of the patients' treatment teams were unaware of drug assignment.". Apart from that it was not described how the outcome assessors were blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants were accounted for and included in the analysis. Quote: "All patients who complete at least two weeks of drug treatment will be included in the analysis. The final rating scores of any patient who terminates the study prematurely will be carried forward to the end of the study."
Selective reporting (reporting bias)	Low risk	All outcomes were reported.
Other bias	Unclear risk	No significant differences were seen in age, sex distribution, Autism Behavior Checklist scores, or full‐scale IQ scores between the 2 groups.