Troost 2005.

Study characteristics
Methods	Parallel discontinuation trial of risperidone versus placebo
Participants	Inclusion criteria: aged 5‐17 years weighed at least 15 kg mental age of at least 18 months required to demonstrate clinically significant tantrums, aggression, self‐injurious behaviour, or a combination ineffective medications were gradually withdrawn in a 7‐28‐day wash‐out period. In the case of comorbid ADHD, stimulants were allowed to be continued, provided that no changes in dose during the study would occur. Exclusion criteria: on effective psychotropic drug treatment for disruptive behaviour Location/setting: "study participants were recruited from Groningen and Utrecht University Child and Adolescent Psychiatry Centres", the Netherlands Sample size: 24 Number of withdrawals/dropouts: Gender: 22/24 were male Mean age: risperidone 9 years; placebo 8 years IQ: mental age of ≥ 18 months Baseline ABC‐I or other BoC: ABC‐I risperidone 11.1, placebo 12.7 Concomitant medications: provided that no changes in dose during the study would occur. Anticonvulsants used for the treatment of a seizure disorder were permitted if the dose had been stable for at least 4 weeks and the patient was seizure‐free for at least 6 months. 20/24 were not taking any medications concurrently. 3 were on stimulants and 1 was on stimulants and anticonvulsants. History of previous medications: 19/24 had not received any prior psychotropic drugs, 3 had been on stimulants, 1 on antipsychotics and 1 on a stimulant and anticonvulsant.
Interventions	Intervention (risperidone) for 8 weeks: risperidone mean daily dose of 1.8 mg/day or maximum daily dose of 2.5 mg (children weighing < 45 kg) or 3.5 mg (children ≥ 45 kg) Comparator (placebo) for 8 weeks: "for the placebo group, entry doses were reduce by 25% per week for 3 consecutive weeks. After full placebo substitution, the placebo group remained on placebo for 8 weeks."
Outcomes	Primary outcomes: irritability, measured using the ABC‐I subscale (Aman 1985) rate of relapse (defined as 25% increase in ABC‐I scores), measured in % Secondary outcomes: none reported Timing of outcome assessments: weekly during the discontinuation phase
Notes	Study start date: details not reported Study end date: details not reported Source of funding: "Korczak Foundation" ‐ EBMH publication Conflicts of interest: "Dr. Buitelaar is a paid consultant to or has received support from Janssen Cilag BV, Abbott, VCB, Shire, Medice, and Eli Lilly; Dr. Minderaa is a paid consultant to Eli Lilly and Janssen Cilag BV; and Dr. Scahill is a paid consultant to Janssen Pharmaceutica Inc., Bristol‐Myers Squibb, and Pfizer."Study medications were donated by Janssen Cilag BV." Trial registry: not reported.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The randomisation sequence was generated by an outside vendor and was stratified by investigational site.
Allocation concealment (selection bias)	Low risk	Risperidone and placebo were supplied by the pharmacist at each site as matching capsules in identical packages.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Patients, parents and evaluators all were unaware of assignment to placebo or risperidone.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Patients, parents and evaluators all were unaware of assignment to placebo or risperidone.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Sedation was not reported as an AE. No LTFU reported by the study authors. ITT analysis: an ITT analysis was used for all participants enroled by using the LOCF for all measures.
Selective reporting (reporting bias)	High risk	The ABC‐I scores were reported in full for both the open‐label and discontinuation phases of the trial. However, the CGI scores were only reported at baseline.
Other bias	High risk	Dr. Buitelaar is a paid consultant to or has received support from Janssen Cilag BV, Abbott, VCB, Shire, Medice, and Eli Lilly; Dr. Minderaa is a paid consultant to Eli Lilly and Janssen Cilag BV; and Dr. Scahill is a paid consultant to Janssen Pharmaceutica Inc., Bristol‐Myers Squibb, and Pfizer. Only 8/24 with autism were in discontinuation phase despite title mentioning ASD. Baseline ABC‐I was relatively low.