Loo 2002.

Methods	Eight‐week, double‐blind, randomised multicentre study.
Participants	Seven hundred and eleven patients (238 males, 33.5%; 473 females, 66.5%; mean age 42.3 years) in 102 centres located in Belgium, France and the UK were included in this study. There was no significant difference between groups at inclusion for demo‐graphic characteristics or disease factors: 67.1% of patients met DSM‐IV criteria for a recurrent major depressive disorder, 33.5% of patients had an episode of severe intensity.
Interventions	Patients were to take orally one capsule twice daily: one in the morning, one in the evening. Following a placebo run‐in period of 1 week, patients were randomised in double‐blind conditions to receive fixed doses of agomelatine (1mg, 5mg or 25mg in the evening capsule), paroxetine 20 mg (in the morning capsule) or placebo. Concomitant treatment with psychotropic drugs was not allowed with the exception of benzodiazepines at restricted doses. High potency benzodiazepines, such as alprazolam and triazolam, were not permitted. Drugs which were thought to be able to influence study evaluations by acting on patient’s mood or circadian rhythms, such as b‐blockers, central a‐blockers,non‐steroidal anti‐inflammatory drugs and exogenous melatonin,were not allowed.
Outcomes	The Hamilton rating scale for depression (HDRS) and the Clinical Global Impression (CGI) were assessed at baseline, and at weeks 1, 2, 4, 6and 8.The Montgomery and Asberg Depression Rating Scale (MADRS) and the Hamilton rating scale for anxiety (HAM‐A) were assessed at baseline, and at weeks 4 and 8. Total dropout, dropout due to side effects, dropout due to inefficacy. Number of patients experiencing at least one side effect, side‐effect profile.
Notes	In this Cochrane Review data referring to dichotomic outcomes were add up together, data referring to continuous outcomes were matched together as suggested by the Cochrane Handbook (Table 7.7.a: Formulae for combining groups).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "patients were randomized". No further details.
Allocation concealment (selection bias)	Unclear risk	No information provided.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "double blind conditions". No further details.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "double blind conditions". No further details.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Primary measure of efficacy was based on the Intention‐to‐treat (ITT) population, defined as "patients who has received at least one post‐randomization capsule and had a baseline measurement and at least one post‐baseline measurement".
Selective reporting (reporting bias)	Low risk	Outcomes data were reported.
Other bias	Unclear risk	Sponsorship bias cannot be ruled out.