Fu 2020.

Study characteristics
Methods	Phase 3 double‐ blind, randomised, placebo‐controlled, multi‐centre study
Participants	Diagnosis: DSM‐5 Major depressive disorder and active suicidal ideation with intent N: 226 Age: esketamine group M = 40.8 (SD = 13.17); placebo group M = 37.9 (SD = 12.54). Sex: esketamine group 68.8% female ; placebo group 66.1% female. Baseline depression severity: esketamine group MADRS M = 41.3 (SD = 5.87); Placebo group MADRS M = 41.0 (SD = 6.29).
Interventions	Patients were randomised to receive 84 mg esketamine nasal spray or matching placebo nasal spray administered twice weekly for 4 weeks. Concomitant medications: standard‐of‐care oral antidepressant(s) treatment was initiated or optimised for participants in both groups at the time of randomisation.
Outcomes	MADRS CGI‐SS‐r Remission Response Adverse events
Notes	Authors kindly provided additional data for remission rates according to this review's definition, MADRS and CGI‐SS‐r scores.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “Eligible patients were randomized (1:1), based on a computer‐generated randomization scheduled”.
Allocation concealment (selection bias)	Low risk	Quote:“Eligible patients were randomized (1:1), based on a computer‐generated randomization scheduled...Randomization was balanced using randomly permuted blocks and stratified by study center and type of standard‐of‐care antidepressant”.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Stated but not tested.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Stated but not tested. Likely unblinding of participants due to known dissociative effects of esketamine.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Participant attrition reported in supplementary figure 2. Withdrawals explained and balanced across groups.
Selective reporting (reporting bias)	Low risk	Trial registration available (NCT03039192). Outcomes reported as planned
Other bias	High risk	Funded by pharmaceutical company whom authors are employed by.