Singh 2016 b.

Study characteristics
Methods	Double‐blind, randomised, placebo‐controlled trial
Participants	Diagnosis: DSM‐IV‐TR recurrent major depressive disorder without psychotic features N: 30 Age: esketamine .20 mg/kg group M = 44.7 (SD = 13.38); esketamine.40 mg/kg group M = 41.8 (SD = 11.63); placebo group M = 42.7 (SD = 10.89) Sex: esketamine .20 mg/kg group 56% female; esketamine.40 mg/kg group 64% female; placebo group 60% female Baseline depression severity: esketamine .20 mg/kg group MADRS score M = 33.1 (SD = 3.55); esketamine.40 mg/kg group MADRS M = 33.7 (SD = 5.82); placebo group MADRS score M = 33.9 (SD = 4.15)
Interventions	On day 1, patients were randomsly assigned to receive an IV infusion of .20mmg/kg or.40mmg/kg esketamine or placebo (.9% saline solution) over 40 minutes. On day 4 (second dose), responders received the same treatment as day 1. For those on placebo, non‐responders were randomly assigned to .20mmg/kg or.40mmg/kg esketamine. Non‐responders who received 20mmg/kg or 40mmg/kg on day 1 received esketamine 40mmg/kg on day 4.
Outcomes	MADRS Response (reduction of >50% in the MADRS total score on days 2, 3, or 4) QIDS‐SR CGI‐S CGI‐I PGI‐S PGI‐C TEAEs Clinical laboratory tests 12‐lead ECG Vital signs Physical examinations C‐SSRS CADSS BPRS MGH‐CPFQ
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Central randomization was implemented based on a computer generated randomization schedule prepared by the sponsor before the study. The randomization was balanced by using randomly permuted blocks and was stratified by study center".
Allocation concealment (selection bias)	Unclear risk	Quote: "Before dosing, the unblinded pharmacist at each study site contacted the randomization center and provided the required subject information. The randomization center assigned a randomization number to the subject and informed the unblinded pharmacist at the site about the assigned treatment"
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Stated but not tested.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "During the study, the subject was assessed by qualified trained site raters who were blinded to the subject’s treatment"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Reasons for participant withdrawal noted on page 426
Selective reporting (reporting bias)	Low risk	Clinical trials registration available online (NCT01640080). All outcomes reported in paper.
Other bias	High risk	Potential bias due to funding being provided by a pharmaceutical company, Janssen Research & Development.