Yamasue 2020.

Study characteristics
Methods	6‐week parallel trial of oxytocin versus placebo
Participants	Inclusion criteria: male aged 18‐54 years diagnosis of autism, Asperger's or PDD‐NOS based on DSM‐4‐TR verbal IQ > 85 and full IQ > 80 measured using the Wechsler Adult Intelligent Scale‐III Exclusion criteria: primary psychiatric diagnosis other than those listed in the inclusion criteria, mood or anxiety disorders change in medication or psychotropics in the month prior to the study currently treated with > 2 psychotropics currently receiving medication for ADHD history of oxytocin treatment hyper‐sensitive to oxytocin history of seizures or traumatic brain injury with loss of consciousness > 5 minutes history of alcohol disorders, abuse or addiction Location/setting: The University of Tokyo Hospital, Nagoya University Hospital, Kanazawa University, and University of Fukui Hospital in Japan Sample size: 53 were randomised to oxytocin and 53 to placebo groups Number of withdrawals/dropouts: 2 in oxytocin group were LTFU, 1 withdrew due to tumoural swelling of breast; 1 LTFU in placebo group due to worsening of repetitive behaviours Gender: all participants were male Mean age: 18‐54 years, mean age oxytocin 27.6 years, mean age placebo 26.3 years IQ: details not provided Baseline ABC‐I scores or other BoC: baseline scores not reported Concomitant medications: "12 continued their psychotropic medications throughout the period (4 antidepressants, 4 antipsychotics, 2 anticonvulsants (mood stabilizers), 2 hypnotics)". Previous medications: details not provided
Interventions	Intervention (oxytocin): 24 IU (Syntocinon Spray; Novartis, Switzerland) in the morning and afternoon for 6 consecutive weeks Comparator (placebo): 24 IU in the morning and afternoon for 6 consecutive weeks
Outcomes	Primary outcomes: AEs Secondary outcomes: tolerability Timing of outcome assessments: baseline and week 6 (endpoint)
Notes	Study start date: January 2015 Study end date: March 2016 Funding: "the Strategic Research Program for Brain Sciences from Japan Agency for Medical Research and Development" Conflicts of interest: "Neither the funder nor the sponsor, the Strategic Research Program for Brain Sciences from Japan Agency for Medical Research and Development, had any involvement in the data collection, analyses, writing, or interpretation of the study. However, the sponsor participated in the discussion regarding which sites should be included in the trial and how to best interpret the results" Trial registry: JPRN‐UMIN000015264
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Participants were randomly assigned to receive oxytocin or placebo at a one‐to‐one ratio using a computer‐generated minimization design."
Allocation concealment (selection bias)	Low risk	"The registration, allocation, and data management procedures were defined separately... The following procedures were performed by the individual in charge of allocating and coding the test drug... confidentiality of the test drug allocation code table until the end of the trial and until the inclusion of each participant was fixed The registration, allocation, and data management procedures were defined separately."
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Details not provided
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Apart from "double blinded" no further details were provided.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Number of dropouts described don't add up to difference in randomised/analysed (see fig 1)
Selective reporting (reporting bias)	Low risk	All outcomes listed on trials registry were reported in the paper or journal website.
Other bias	High risk	The sponsor participated in the discussion regarding which sites should be included in the trial and how to best interpret the results

ABC: Aberrant Behaviour Checklist; ABC‐I: Aberrant Behaviour Checklist Irritability subscale; ADHD: Attention Deficit Hyperactivity Disorder; ADI‐R: Autism Diagnostic Interview‐Revised; ADOS‐2: Autism Diagnostic Observation Schedule, 2nd edition; AE: adverse effects; ASD: autism spectrum disorder; BoC: behaviours of concern; BSE: Behavioral Summarized Evaluation; CARS: Childhood Autism Rating scale; CBCL: Child Behaviour Checklist; CGI‐S: Clinical Global Impression Scale—Severity; CPRS: Conners' Parent Rating Scale; CYBOCS‐PDD: Children's Yale‐Brown Obsessive Compulsive Scale modified for pervasive developmental disorders; DSM‐4:Diagnostic and Statistical Manual of Mental Disorders(4th edition );DSM‐4 (TR):Diagnostic and Statistical Manual of Mental Disorders(4th edition ‐ text revision); DSM‐5:Diagnostic and Statistical Manual of Mental Disorders(5th edition); ECG: electrocardiogram; EEG: electroencephalogram; ICD‐10: International Classification of Diseases‐10; IQ: intelligience quotient; ITT: intention‐to‐treat; IU: International Units; LOCF: last observation carried forward; LTFU: lost to follow‐up; MAOI: monoamine oxidase inhibitor; MDMA: 3,4‐methylenedioxy‐methamphetamine; MRI: magnetic resonance imaging; MSEL: Mullen Scales of Early Learning; NAC: N‐acetylcysteine; PedsQL: Pediatric Quality of Life inventory; PDD‐NOS: pervasive developmental disorder not otherwise specified; QoL: quality of life; RCT: randomised controlled trial; RFRLRS: Ritvo Freeman Real Life Rating Scale; SD: standard deviation; SNAP: Swanson, Nolan and Pelham; SSRI: selective serotonin reuptake inhibitor; TSO:Trichuris suis ova; WHO: World Health Organization; WHOQOL: World Health Organization Quality of Life scale