CL3‐023.

Methods	Double‐blind, randomised study.
Participants	Male and female adults, 18‐70 years of age, with a diagnosis of Major Depressive Disorder according to DSM‐IV criteria. Hamilton Depression Rating Scale (HDRS) total score > or = 22 at screening and baseline.
Interventions	Paroxetine: 20 mg/day. Agomelatine: 25 mg/day.
Outcomes	Change from baseline to endpoint at HDRS, remission, sexual functions.
Notes	Funding: by industry.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The randomisation of treatments (agomelatine, placebo, fluoxetine or paroxetine) was non‐adaptive, non‐centralised, and balanced with a 1:1:1 ratio. There was no stratification and permutation blocks were of fixed size = 6".
Allocation concealment (selection bias)	Unclear risk	No information provided.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Double blind. Quote: "Agomelatine, placebo and fluoxetine (or paroxetine) were disguised in tablets or capsules (or tablets) of identical appearance and taste".
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Double blind. Quote: "Agomelatine, placebo and fluoxetine (or paroxetine) were disguised in tablets or capsules (or tablets) of identical appearance and taste".
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient information.
Selective reporting (reporting bias)	Unclear risk	Insufficient information.
Other bias	Unclear risk	Sponsorship bias cannot be ruled out.