Belsito 2001.

Study characteristics
Methods	Placebo‐controlled trial of lamotrigine versus placebo
Participants	Inclusion criteria: "children 3‐11 years with a primary diagnosis of autistic disorder, either with early signs or following regression after a period of normal development were enrolled." Exclusion criteria included "children with autistic disorder associated with comorbid medical etiologies, such as Fragile X syndrome or metabolic disorders" Location/setting: John Hopkins medical institutions Sample size: 35 Number of withdrawals/dropouts: lamotrigine 5; placebo 2 Gender: 33 boys, 2 girls Mean age: median age 5.8 (1.75) IQ: not reported Baseline ABC‐I scores or other BoC: not reported Concomitant medications: not reported History of previous medications: not reported
Interventions	Intervention (lamotrigine) for 18 weeks: 0.5 mg/kg lamotrigine twice daily titrated to a maximum of 5.0 mg/kg twice daily over 12 weeks or placebo twice daily Comparator (placebo) for 18 weeks: "participants received a placebo twice daily prepared in identically appearing tablets (shape, size, color, and taste)"
Outcomes	Primary outcomes: irritability, measured as change in ABC‐ I subscale scores (Aman 1985); AEs Secondary outcomes: none reported Timing of outcome assessment: baseline, 4, 8, 12 and 18 weeks
Notes	Study start date: not reported Study end date: not reported Funding source: Glaxo Wellcome 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	Quote: "the blinded sequence by which each patient received lamotrigine or placebo was determined by randomization at the end of baseline evaluations. Subjects were randomised via a computer‐generated cluster method which made user‐selected block assignments. Within each block, an equal number of patients received placebo or drug".
Allocation concealment (selection bias)	Low risk	Quote: "Codes were accessible to the investigational drug pharmacists and to the appointed safety committee".
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not described apart from, "Codes were accessible to the investigational drug pharmacists and to the appointed safety committee."
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described apart from, "Codes were accessible to the investigational drug pharmacists and to the appointed safety committee."
Incomplete outcome data (attrition bias) All outcomes	High risk	22% LTFU ‐ lamotrigine: 4 children (3 due to insomnia, and 1 due to increased stereotypies; 2 LTFU in placebo group: 1 increased stereotypies, and 1 for increased echolalia
Selective reporting (reporting bias)	High risk	The paper reports that outcome measures were completed at baseline, 4, 8, 12 and 18 weeks. Results were only presented graphically. Paper reports to measure changes in ABC‐I and other subscales however "changes in irritability, lethargy, and hyperactivity were also insignificant between the groups" and only P values provided.
Other bias	Unclear risk	Quote: "The trial was supported by GlaxoWellcome".