Zarate 2006a.

Study characteristics
Methods	Double‐blind randomised controlled cross‐over trial
Participants	Diagnosis: DSM‐IV major depressive disorder; HRSD‐21 ≥18; at least two adequate lifetime antidepressant trials that failed, as assessed by the Antidepressant Treatment History Form N: 18 Age: M = 46.7 (SD = 11.2) Sex: 66.7% female Baseline depression severity: ketamine group HRSD = 24.89; placebo group HRSD = 24.44
Interventions	1 single IV infusion Ketamine (N = 9) 0.5 mg/kg infused over 40 minutes Placebo (N = 9) 0.9% saline infused over 40 minutes Concomitant treatment: No, patients had a 2‐week drug‐free period before commencing treatment
Outcomes	HRSD Response rate (≥ 50% reduction in HRSD scores) Remission rate (HRSD score ≤ 7) BDI BPRS YMRS VAS
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: ''Patients were randomly assigned to the order in which they received the 2 infusions via a random‐numbers chart''
Allocation concealment (selection bias)	Unclear risk	No details given on allocation concealment
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	Quote: ''Double‐blind'' no further details given
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Study reports dropouts
Selective reporting (reporting bias)	Unclear risk	Protocol unavailable. Data reported matches methods
Other bias	Low risk	No other potential sources of bias identified