Willemsen‐Swinkels 1995.

Study characteristics
Methods	Cross‐over trial of naltrexone versus placebo
Participants	Inclusion criteria: aged 18‐46 years meet the DSM‐III‐R criteria for autistic disorder social impairment had to be more serious than could be expected on the basis of the level of intellectual disability Exclusion criteria: details not provided Location/setting: the Netherlands Sample size: 33 Number of withdrawals/dropouts: one 28‐year old woman (with autism and self‐injurious behaviour) "manifested an acute and severe increase in SIB and acting out behavior. She had to be isolated for several weeks, and her condition improved only gradually after naltrexone treatment was stopped and lithium treatment was instituted" Gender: 27 men, 6 women Mean age: 29 years IQ: details not provided Baseline ABC‐I or other BoC: not an outcome Concomitant medications: details not provided History of previous medications: details not provided
Interventions	Intervention (naltrexone) for 4 weeks: after 2 weeks of placebo capsule taken once daily, naltrexone hydrochloride was given at 100 mg (mean 1.61 (0.24) mg/kg) in 1 dose at the start of week 3. For the remainder of that week, the participant received a placebo capsule every morning. From week 4, naltrexone was given at 50 mg per day for 4 weeks. This was followed by a 4‐week washout period then cross‐over to continue on placebo. Comparator (placebo) for 4 weeks: matching placebo tablets
Outcomes	Primary outcomes: AEs Secondary outcomes: none reported Timing of outcome assessments: participants were observed twice at baseline, 6 and 24 h after the single‐dose administration, and after 2 and 4 weeks of daily treatment
Notes	Study start date: not reported Study end date: not reported Source of funding: Janusz Korczak Foundation, Huizen 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	Unclear risk	Details not provided apart from "double‐blinding used"
Blinding of outcome assessment (detection bias) All outcomes	High risk	Treatment doses were changed for second cross‐over phase after review of outcome measures, implying that assessors or investigators knew which group was being given naltrexone in first phase ‐ i.e. not blinded
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	1 participant didn't complete trial due to AEs detailed ‐ data were excluded due to early discontinuation (week 2 of 16)
Selective reporting (reporting bias)	High risk	Self‐injurious behaviour was measured using the ABC‐Stereotypies subscale. The authors mention that "it included three items on SIB". Incorrect. The ABC‐Stereotypies subscale does not.
Other bias	High risk	Active treatment was provided in part by employee of pharmaceutical company. Nature of funding support unclear. Participant details were not provided in terms of age, gender, diagnosis, rate of SIB etc, in addition to incorrectly claiming to have assessed SIB using the ABC