Ibrahim 2012b.

Study characteristics
Methods	Double‐blind randomised controlled cross‐over trial
Participants	Diagnosis: DSM‐IV major depressive disorder; score ≥22 score on MADRS; an inadequate response to at least two therapeutic trials of an antidepressant N: 5 Age: not stated Sex: not stated Baseline depression severity: not stated
Interventions	12 days treatment MK‐0657 (N = 3) 1 mg capsules, 8 daily in the morning. Dose titrated; initial dose 4 mg/day, increased every 4 days by 2 mg/day until treatment‐limiting side effects or completion of the study. 8 mg/day was treatment target for all participants unless tolerability issues ensued Placebo (N = 2) capsules, same dose escalation as MK‐0657 Concomitant treatment: no, patients had a 2‐week drug‐free period before commencing treatment
Outcomes	MADRS Response rates (≥ 50% reduction in MADRS scores) Remission rates (< 10 on MADRS) HRSD BDI VAS HAMA BPRS CADSS YMRS SHAPS
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No details given on randomisation procedure other than quote:''randomised in a double‐blind manner''
Allocation concealment (selection bias)	Unclear risk	No details given on allocation concealment procedure
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: ''a double‐blind dummy design was used throughout the study''
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No details given on blinding of outcome assessment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Requested data reports dropout rates alongside each time point
Selective reporting (reporting bias)	Unclear risk	No results tables available in original publication. Data requested was provided when the author was contacted
Other bias	Low risk	No other potential sources of bias identified