Hagerman 2018.

Study characteristics
Methods	6‐month trial of sertraline versus placebo
Participants	Inclusion criteria: documentation of ASD as verified using both DSM‐5 and ADOS‐2 criteria age between 24 and 72 months stable medications (including antiepileptics, antipsychotics, and clonidine) in the 2 months prior to enrolment concurrent enrolment in at least 1 community or school intervention for ASD Exclusion criteria: changes in concomitant medications and interventions were discouraged unless medically necessary during the trial current or past SSRI treatment diagnosis of the fragile X syndrome full mutation, or any other serious co‐morbid medical disorders affecting brain function and behaviour, including uncontrolled seizures Location/setting: USA Sample size: 58 (32 sertraline, 26 placebo) Number of withdrawals/dropouts: sertraline (8, 2 lost to follow‐up, 6 withdrew consent); placebo (5, 1 lost to follow‐up, 4 withdrew consent) Gender: details not provided Average age (SD) : 4.3 (0.8) and 3.7 (1.1) years in the sertraline and placebo groups IQ range: details not provided Baseline ABC‐I or other BoC: N/A Concurrent medications: sertraline (9.38%); placebo (7.69%) History of previous medications: details not provided
Interventions	Intervention: the study drug was administered orally in liquid form (20 mg/mL), and dose was assigned based on age at enrolment: participants under 4 years received sertraline or placebo liquid in a dose of 2.5 mg/day (0.125 mL) for the duration of the trial, and participants ≥ 4 years received 5.0 mg/day (0.25 mL). Comparator: placebo was administered orally in liquid form for 6 months.
Outcomes	Primary outcomes: AEs Secondary outcomes: tolerability
Notes	Study start date: April 2015 Study end date: July 2018 Funding: "This project was supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under grant number R40MCH 27701". Conflicts of interest: "RH has carried out treatment studies in fragile X syndrome and autism spectrum disorder by Roche, Novartis, Neuren, Marinus, Alcobra, and Curemark and has also consulted with Zynerba and Fulcrum. FT received funds from Asuragen, Roche, and Zynerba. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest". Trial registry: NCT02385799
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "The UC Davis Investigational Drug Services independently carried out randomization". No information on sequence generation
Allocation concealment (selection bias)	Low risk	Quote: "The UC Davis Investigational Drug Services independently carried out randomization"
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Apart from "double‐blinded" no further details were 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	Low risk	Dropout < 20% and reasons reported
Selective reporting (reporting bias)	Low risk	Same primary outcomes as trial reg (MSEL expressive language raw score and age equivalent combined score)
Other bias	Low risk	No other sources of bias identified