Soorya 2021.

Study characteristics
Methods	6‐month parallel trial of memantine versus placebo
Participants	Inclusion criteria: verbal outpatients aged 6‐12 years clinical diagnosis of PDD based on the DSM‐4 criteria, or a diagnosis of ASD based on the DSM‐5 criteria required to have difficulty with motor skills as per caregiver report during the psychiatric intake interview. stable on all nonpharmacologic treatments for 3 months before randomisation and stable on up to 2 concomitant psychotropic medications 30 days before randomisation CGI‐S score of ≥ 4 (i.e. moderately ill) ABC‐I subscale score of < 17 Exclusion criteria: born prior to 35 weeks' gestational age any primary psychiatric diagnosis other than autism at screening history of ADHD, bipolar disorder, psychosis, post‐traumatic stress disorder, schizophrenia, or major depressive disorder medical history of neurological disease, including, but not limited to, epilepsy/seizure disorder (except simple febrile seizures), movement disorder, tuberous sclerosis, fragile X, and any other known genetic syndromes, or known abnormal MRI/structural lesion of the brain a medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well‐being evidence or history of malignancy or any significant haematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease planning to initiate or change pharmacological or nonpharmacologic interventions during the course of the study on d‐cycloserine or riluzole on agents that alkalinise the urine (acetazolamide, potassium citrate, and sodium bicarbonate), received treatment with memantine in the past with no response history of hypersensitivity reaction to dextromethorphan, amantadine, or any other NMDA receptor antagonists unable to tolerate venipuncture procedures for blood sampling might not be suitable for the study in the Investigator's opinion weigh < 20 kg (to meet FDA approvals) positive pregnancy test Location/setting: 2 outpatient clinics in the USA Sample size: 23 in total (memantine (12); placebo (11)) Reasons for withdrawals/dropouts: 5 in memantine group discontinued (AEs (1), time constraints (1), lack of efficacy (2), LTFU (1)); 3 in placebo group discontinued (time constraints (1), AEs (2)) Gender: 20 male, 3 female Mean age: approximately 9.5 years across both groups IQ: approximately 77 across both groups Baseline ABC‐I or other BoC scale: ABC‐I was < 17 at baseline Concomitant medications: "stable on up to two concomitant psychotropic medications 30 days before randomization" Previous medications: details not provided
Interventions	Intervention (memantine) for 6 months: "memantine will be initiated at 3 mg. The dose will be increased every week by 3 mg for a maximum of 12mg for subjects weighing ≥ 60kg, 9mg for subjects weighing ≥ 40 kg but <60 kg, and 6 mg for subjects weighing ≥ 20 kg but < 40kg." Comparator (placebo): equivalent placebo for 6 months
Outcomes	Primary outcomes: AEs Secondary outcomes: tolerability Timing of outcome assessments: every 2 weeks
Notes	Study start date: December 2011 Study end date: October 2015 Funding:"No funding was received for this article." Conflicts of interest: study medication was provided through an in‐kind contribution from Forest Pharmaceuticals. Most of the study authors received consultation fees or other support from pharmaceutical companies.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information on how the sequence was generated. Quote: "Participants (n = 23), ages 6–12, were randomized at a 1:1 ratio to treatment with memantine or placebo by the study pharmacist at the Icahn School of Medicine at Mount Sinai (original coordinating site)."
Allocation concealment (selection bias)	Unclear risk	Randomisation process unclear, pharmacist may have known the next allocation Quote: "Participants (n = 23), ages 6–12, were randomized at a 1:1 ratio to treatment with memantine or placebo by the study pharmacist at the Icahn School of Medicine at Mount Sinai "
Blinding of participants and personnel (performance bias) All outcomes	Low risk	All participants and investigators were blind to group assignment until the blind was broken by the study statistician at the end of the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	All participants and investigators were blind to group assignment until the blind was broken by the study statistician at the end of the study.
Incomplete outcome data (attrition bias) All outcomes	High risk	Large attrition from treatment group (near 50%), denominator unclear for outcomes reported
Selective reporting (reporting bias)	Low risk	Appears to match registry
Other bias	High risk	Study medication was provided through an in‐kind contribution from Forest Pharmaceuticals.