Nations 2012 (part II).

Study characteristics
Methods	Double‐blind randomised controlled trial
Participants	Diagnosis: DSM‐IV major depressive disorder; score ≥ 9 but ≤ 20 on QIDS‐C N: 30 Age: Org 26576 100 mg group M = 38.3 (SD = 14.4); Org 26576 400 mg group M = 35.6 (SD = 12.8); placebo group M = 31.1 (SD = 6.5) Sex: Org 26576 100 mg group 40% female; Org 26576 400 mg group 40% female; placebo group 50% female Baseline depression severity: Org 26576 100 mg group QIDS‐C = 15.0 (SD = 2.5); Org 26576 400 mg group QIDS‐C = 15.3 (SD = 1.1); placebo group QIDS‐C = 17.0 (SD = 1.9)
Interventions	28 days treatment Org 26576 100 mg twice daily (N = 10) Org 26576 400 mg wice daily (N = 10) Placebo (N = 10) Indistinguishable capsules containing placebo, 50 or 100 mg Org 26576 Concomitant treatment: no, patients were taking no other psychotropic medication throughout study
Outcomes	MADRS CGI‐S CGI‐I Response rate (≥ 50% reduction in MADRS scores) Remission rate (MADRS score ≤ 10) Cognitive functioning and social acuity Neuroendocrine parameters and BDNF EEG Bioanalysis
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: ''Patients in Part II were randomized to receive Org 26576 100 mg BID, Org 26576 400 mg BID, or placebo in a 1:1:1 ratio''
Allocation concealment (selection bias)	Unclear risk	No information on allocation concealment provided
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	No information on blinding provided, other than 'double‐blind'
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information on blinding of outcome assessment provided
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Endpoint data uses LOCF, unsure when dropout occurred
Selective reporting (reporting bias)	Unclear risk	Protocol unavailable. Data for all time points reported
Other bias	Low risk	No other potential sources of bias identified