Methods	24-week, double-blind, randomised, multicentre study.
Participants	Outpatients meeting DSM-IV criteria for Major Depressive Disorder and having a minimum score of 30 on Montgomery-Asberg Depression Rating Scale (MADRS) . Age range: 18-75 years. Exclusion criteria: bipolar disorder, psychotic disorder or features, obsessive-compulsive disorder, current eating disorders, mental retardation, any pervasive developmental disorder or cognitive disorder, or alcohol or drug abuse-related disorders within the past 12 months, a serious risk of suicide (a minimum score of 5 on item 10 of the MADRS) , concomitant behaviour therapy or systematic psychotherapy, pregnancy or breastfeeding, a history of lactose intolerance, a history of hypersensitivity or non-response to citalopram or escitalopram or duloxetine or with increased intra-ocular pressure, risk of acute narrow-angle glaucoma, use within the past 2 weeks of MAOI or RIMA, SSRIs (fluoxetine within 5 weeks), SNRIs, tricyclic antidepressants, tryptophan, psychoactive herbal remedies, any drug used for augmentation of antidepressant action or any other antidepressant drugs, oral antipsychotics and anti-manic drugs, dopamine antagonists, anxiolytics, any anticonvulsant drug, serotoninergic agonists, narcotic analgesics, cardiac glycosides, type 1c anti-arrythmics, oral anticoagulants, cimetidine, potent inhibitors of CYP2C19, CYP1A2, or medicinal products with a narrow therapeutic index predominantly metabolised by CYP2D6, use of ECT within the past 6 months
Interventions	Escitalopram: 232 participants. Paroxetine: 227 participants. Escitalopram dose: 20 mg/day. Paroxetine dose: 40 mg/day. Zolpidem, zolpiclone or zaleplon used episodically for insomnia were allowed
Outcomes	Primary Outcome: Change from baseline to week 24 in Montgomery-Asberg Depression Rating Scale Secondary Outcomes: Hamilton Depression Scale - 24 and 17 item, Hamilton Anxiety Scale, Clinical Global Impression - Improvement, Clinical Global Impression - Severity
Notes	Remission: a score equal or less than 12 on MADRS. This study was funded by escitalopram manufacturer
Risk of bias
Item	Authors’ judgement	Description
Adequate sequence generation?	Yes	Quote: “Patients …. were assigned to 24 weeks of double-blind treatment in a 1:1 ratio … according to a computer-generated randomisation list.”
Allocation concealment?	Yes	Quote: “The details of the randomisation series were unknown to any of the investigators and were contained in a set of sealed opaque envelopes. At each study centre, sequentially enrolled patients were assigned the lowest randomisation number available in blocks of 4.”
Blinding? All outcomes	Yes	Quote: “The medication was given as capsules of identical appearance, taste and smell. All study personnel and participants were blinded to treatment assignment for the duration of the entire study.”
Incomplete outcome data addressed? All outcomes	Yes	The prospectively defined primary end-point was the adjusted mean change in MADRS total score from baseline to Week 24, based on the intent-to-treat set (ITT) and using last-observation-carried-forward (LOCF) analysis
Free of selective reporting?	Yes