29060/299.

Methods	A double‐blind, multicentre, randomised, flexible dose, parallel group study.
Participants	Male or non‐pregnant, non‐lactating female patients using adequate contraception were eligible if they were aged 18 to 65 years; were hospitalised; had a diagnosis of severe, unipolar depression (without psychotic symptoms), defined according to ICD‐10 criteria; and had a score of at least 24 points on the Hamilton rating scale for depression (HDRS‐17) at screening and at the baseline assessment.
Interventions	Paroxetine: 109 participants. Amitriptyline: 108 participants. Paroxetine dose range: 20‐50 mg/day. Amitriptyline dose range: 100‐250 mg/day.
Outcomes	Clinical Global Impression (CGI), Hospital Anxiety and Depression scale (HAD). Total dropout, dropout due to side effects. Number of patients experiencing at least one side effect, side‐effect profile.
Notes	Funding: paroxetine manufacturer.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "patients were randomized (1:1) to either paroxetine or amitriptyline".
Allocation concealment (selection bias)	Unclear risk	No information provided.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "double blind". No further details.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "double blind". No further details.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Quote: "the primary analysis was on the Intention‐to‐treat (ITT) data set at endpoint. No efficacy data was available for 15 of the randomized patients. The ITT analysis was therefore performed on 202 subjects of whom 102 were randomized to paroxetine and 100 to amitriptyline. The safety population included all randomized subjects".
Selective reporting (reporting bias)	Low risk	Outcomes data were reported.
Other bias	Unclear risk	Sponsorship bias cannot be ruled out.