Umbricht 2020.

Study characteristics
Methods	Randomised, placebo‐controlled, double‐blind phase 2 trial.
Participants	Diagnosis: DSM‐IV‐TR Major Depressive Disorder N: 357 randomised Age: Placebo group M = 46 (SD=11.2); decoglurant 5 mg group M = 46.9 (SD = 10.7); decoglurant 15 mg group M = 46.9 (SD = 10.9), decoglurant 30 mg group M = 44.5 (SD = 13.1) Sex: Placebo group 40.7% female; decoglurant 5 mg group 69.7% female; decoglurant 15 mg group 71.6% female; decoglurant 30 mg group 63.8% female Baseline depression severity: placebo group MADRS M = 30.9 (SD=5.9); decoglurant 5 mg group MADRS M= 30.5 (SD = 5.8); decoglurant 15 mg group MADRS M = 30.9 (SD=5.7); decoglurant 30 mg group MADRS M = 31.2 (SD = 7.4).
Interventions	Participants were randomised to receive decoglurant (5mg, 15 mg, 30 mg) or placebo once daily for 6 weeks in addition to existing permitted medications.
Outcomes	MADRS Response Remission
Notes	Remission rate is not consistent with study definition.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation codes genereated and put into web‐based response system.
Allocation concealment (selection bias)	Low risk	Computer generated and stratified.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Fully blinded centralised raters. Trial registration states participants blinded too.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Blinded raters assessed MADRS score. Not clear how medications were concealed from participant and personelle. MADRS scores assessed by the centralised raters tended to be smaller than those assessed by site raters, particularly in the placebo group (page 5). Personnel and participants blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Reasons for missing data are explained, and not related to outcome. CONSORT diagram depicts participant flow through study. Similar numbers withdrew from each group. ITT analysis.
Selective reporting (reporting bias)	Low risk	Outcomes reported according to protocol outcomes. Trial registration NCT01457677, all expected outcomes reported.
Other bias	High risk	Sponsor bias ‐ pharma company.