Campbell 1993.

Study characteristics
Methods	3‐week parallel trial of naltrexone versus placebo
Participants	Inclusion criteria: hospitalised aged 2‐7 years diagnosed as having ASD infantile onset (before 36 months of age) according to the DSM‐III‐R criteria Exclusion criteria: “children with identifiable causes of autism (eg. congenital rubella, inborn errors of metabolism, etc.), tardive or withdrawal dyskinesia or those who had other associated movement disorders (eg. Tourette's syndrome, chorea), systemic disease (renal, vascular), history of cardiac disease or nephrosis, seizure disorder or history of seizure disorder, history of hyperthyroidism or hypothyroidism, concurrent administration of any psychoactive medication, hypersensitivity to naltrexone, and opioid dependence”. Location/setting: pediatric inpatient clinic, Bellevue Hospital Centre, USA Sample size: 41 participants (naltrexone 23, placebo 18) Number of withdrawals/dropouts: 4 from naltrexone group "because error was made in labelling the blood samples for naltrexone levels." Gender: 34 boys, 7 girls Mean age: 4.9 years IQ: naltrexone group mean adaptive developmental quotient was 56.8; placebo group mean adaptive developmental quotient was 44.9 Baseline ABC‐I or other BoC: not reported Concomitant medications: 0% History of previous medications: not reported
Interventions	Intervention (naltrexone) for 3 weeks: naltrexone maximum 1.0 mg/kg/day Comparator (placebo) for 3 weeks: placebo equivalent
Outcomes	Primary outcomes: AEs Secondary outcomes: none reported Timing of outcome assessment: once/week an hour after drug administration
Notes	Study start date: not reported Study end date: not reported Funding source: "supported in part by USPHS grants MH‐32212 and MH‐18915 from the NIMH, the Hirschell and Deanna E. Levine Foundation, and the Marion O. and Maximilian E. Hoffman Foundation, Inc Conflicts of interest: none declared Trial registry: not reported
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	Unclear risk	Details not provided
Blinding of outcome assessment (detection bias) All outcomes	Low risk	These ratings were done independently by 2 child psychiatrists (CPRS; CGI) and a research nurse (Nurses' Global Impressions [NGIl and Aggression Rating Scale) who were all blinded to the child's treatment condition. "The teacher, also blinded, rated the children in the classroom."
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	45 children completed the study; the data of 4 were not analysed because error was made in labeling the blood samples for naltrexone levels
Selective reporting (reporting bias)	Unclear risk	Several scales were used to measure outcomes and all were reported on, however only comparisons between baseline and endpoint were given (as F values and P values) and the aggression scale reported as absent/mild etc
Other bias	High risk	Quote: "New York Health and Hospitals Corporation, I.E. du Pont de Nemours & Company for supplying naltrexone (Trexan) and matching placebo tablets and for supporting in part the statistical analyses"