Klerman 1974.

Methods	Design: 2 x 3 factorial design (high and low personal interaction versus amitriptyline, placebo, no treatment) Purpose: examine the effect of amitriptyline, placebo and psychotherapy treatment on relapse of depression
Participants	Patients: out‐patients with neurotic depression having improved markedly after 1 to 2 months amitrityline medication Baseline comparability: yes
Interventions	Placebo: ‐continuous treatment with tablets containing no amitriptyline (content NS) Untreated: ‐tablet treatment discontinued (observational group) Experimental: ‐continuous treatment with amitriptyline tablets (Co‐intervention: no)
Outcomes	Number of patients with relapse of depression Residual symptoms of depression Social adjustment
Notes	As the high and low personal interaction treatments showed no significant difference the 2 x 3 factorial design was collapsed into a three group parallel trial.
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	NS
Allocation concealment?	Unclear risk	NS
Blinding? Treatment provider	Low risk	'... in a double‐blind controlled manner..'
Blinding? Outcome assessor	Unclear risk	NS
Incomplete outcome data addressed? All outcomes	High risk	Drop‐out > 15% or NS
Free of selective reporting?	Unclear risk	No protocol available
Free of other bias?	Low risk
No signs of variance inequality or skewness?	Unclear risk	Not relevant (binary outcome)
Trial size > 49?	Low risk	N = 50
Clearly concealed allocation + trial size > 49 + drop‐out max 15%	High risk	Drop‐out > 15% or NS