Wink 2018.

Study characteristics
Methods	5‐week cross‐over study of riluzole versus placebo
Participants	Inclusion criteria: 12‐25 years of age diagnosis of ASD based on ADOS‐2 criteria ABC‐I score of at least 18 at baseline concomitant medications (including those targeting irritability) were required to be stable for ≥ 5 half‐lives prior to baseline and throughout the study weighing at least 50 kg Exclusion criteria: "participants prescribed > 2 psychotropic drugs targeting irritability, taking medications with known interactions with riluzole or prescribed concomitant glutamatergic or GABA (A) modulating drugs." Location/setting: the USA Mean IQ: details not reported Mean age: 16.0 years Gender: 6/7 were male Sample size: 8 in total Number analysed: 7 in total Reasons for dropouts: "one participant withdrew due to worsening aggressive behavior necessitating adjustment of his concomitant psychotropic medications after receiving five doses of study drug." Baseline ABC‐I or other BoC scale: riluzole ABC‐I 24.29 (6.2); placebo 25.71 (7.3) Current or previous medications: participant 1: benztropine, clonidine, haloperidol, melatonin, propranolol; participant 2: chlorpromazine, guanfacine extended release, melatonin, naltrexone, olanzapine, sertraline, topiramate, zolpidem; participant 3: amphetamine/dextroamphetamine, guanfacine, melatonin, olanzapine, quetiapine, trazodone; participant 4: methylphenidate, quetiapine, sertraline, topiramate; participant 5: melatonin, propranolol, quetiapine, risperidone, vistaril; participant 6: buspirone, paliperidone; participant 7: melatonin, naltrexone, risperidone, sertraline, trazodone
Interventions	Intervention (riluzole): initially dosed at 50 mg/day. Dosing was then increased by 50 mg weekly to a maximum potential optimal dose of 200 mg/day (100 mg twice daily) by week 4. Comparator (placebo): initially dosed at 50 mg/day. Dosing was then increased by 50 mg weekly to a maximum potential optimal dose of 200 mg/day (100 mg twice daily) by week 4
Outcomes	Primary outcomes: irritability (Aman 1985) AEs Secondary outcomes: none reported Timing of outcome assessments: screening, baseline, weeks 3, 5, 7, and 12
Notes	Study start date: September 2013 Study end date: May 2015 Funding: "This study was funded by the Center for Clinical and Translational Science and Training at the University of Cincinnati via an Institutional Clinical and Translational Science Award, NIH/NCRR Grant No. 8UL1TR000077‐04" Conflicts of interest: "The authors declare that they have no interests that compete directly with this work, though LKW, CRT, RSC, EVP, and CAE do receive research support from various sources for other work". Trial registry: NCT02081027
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Participants were randomized by the CCHMC investigational pharmacy"
Allocation concealment (selection bias)	Unclear risk	Details not provided
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Participants, guardians, and investigators remained blind to study assignment throughout the study"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Participants, guardians, and investigators remained blind to study assignment throughout the study"
Incomplete outcome data (attrition bias) All outcomes	Low risk	The 7 participants who completed the trial were included in all the analyses.
Selective reporting (reporting bias)	Low risk	The ABC‐I and CGI were the only outcomes listed on the trials registry. They were reported in full.
Other bias	Low risk	No other bias sources identified