Jacobson 1990.

Methods	4‐week (according to abstract) or 6‐week (according to Organon and review by Bech 2001), double‐blind, randomised, flexible‐dose trial, number of study centres not reported, but mentioned that there was only 1 investigator, placebo wash‐out with exclusion of placebo responders
Participants	Psychiatric outpatients meeting DSM‐III criteria for a major depressive episode (single or recurrent), baseline 17‐item HAM‐D ≥ 18 Age: no data Sex: no data Exclusion criteria: ≥ 25% decrease in total HAM‐D score during the placebo wash‐out period, history of schizophrenia or other psychoses, atypical depression, adjustment disorder, drug or alcohol abuse, drug overdose in the previous 4 months, active suicidal tendencies; patients with clinically relevant renal, cardiovascular, respiratory or cerebrovascular diseases, prostatic hypertrophy, narrow‐angle glaucoma, urinary retention, unstable diabetes, seizure disorder or clinically relevant EEG changes; no ECT in the previous 3 months, adequate dose of an antidepressant (≥ 150 mg amitriptyline or equivalent for at least 6 weeks) in the month preceding the trial; women of childbearing potential without adequate contraception, mothers either breastfeeding or 6 months post partum
Interventions	Amitriptyline: 48 participants Placebo: 48 participants Amitriptyline dose (mean dose last week of therapy): 115.1 mg/d
Outcomes	17‐item HAM‐D, MADRS, CGI, ZDS, PDI, Drug account (primary outcome not defined)
Notes	The information we used was from the abstract, the review by Bech 2001 and from data we received from Organon 3‐arm, dose finding study comparing mirtazapine with amitriptyline and placebo Sponsor: Organon, The Netherlands
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote "lists for randomisation were centrally prepared using random number tables, and the randomisation was blinded for the investigator"
Allocation concealment (selection bias)	Low risk	Quote "...capsules packed in coded packages."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: medication "prepared as indistinguishable capsules packed in coded packages"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: medication "prepared as indistinguishable capsules packed in coded packages", double‐blind trial, no further information
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	The number of participants might be slightly different from the number of patients randomised (the number of participants for amitriptyline is 48 in Bech 2001 and 47 in the data set provided by Organon)
Selective reporting (reporting bias)	Unclear risk	Insufficient information
Other bias	Unclear risk	Insufficient information