Hansen 2012.

Study characteristics
Methods	Study design: randomised (2‐arm parallel randomised controlled clinical trial) Sample size: 11594 Method of randomisation: centrally prepared randomisation blocks Method of concealment: us of the consecutive number of the study medication Blinding: double‐blind Analysis: intention‐to‐treat Date the study was conducted: November 2004 ‐ December 2007
Participants	Location: Denmark Total N randomised: 240 (one patient was excluded due to protocol violation) Intervention n: 120 (63 % male; age M = 65, SD = 12) Control n: 119 (63 % male; age M = 64, SD = 12) Inclusion criteria: acute coronary syndrome (ACS) and no depression at baseline; age > 18 Diagnostic criteria ‐ long‐term physical condition: diagnosis of ACS based on symptoms, electrocardiogram and cardiac enzymes according to contemporary guidelines Diagnostic criteria ‐ depression: depression diagnosis assessed by SCAN interview and confirmation by a psychiatrist Exclusion criteria: current depression as determined by a structured interview and confirmed by a psychiatrist; use of antidepressants or antipsychotics; previous intolerance to SSRI; severe, life‐threatening medical conditions; severe heart failure; current alcohol or substance abuse, psychosis or dementia; participation in other intervention trials; pregnancy and lactation; linguistic difficulties History of mental disorder: Intervention n = 20 (16.7 %); Control n = 18 (15.1 %)
Interventions	Intervention: escitalopram ≤ 1 week: daily dose of 5 mg weeks 2 to 52 weeks: daily dose of 10 mg Control: matched placebo Other treatment: aspirin, clopidogrel, beta‐blockers, digoxin, angiotensin‐II antagonists, ACE inhibitors, statins, calcium antagonists, long acting nitrates, diuretics, benzodiazepines, hypnotic drugs, antidiabetics, eltroxin and antacids Duration of treatment: 12 month Length of follow‐up: 12 month (at baseline, 2, 8 and approximately 15, 22, 29, 36, 43, and 50 weeks) Other study arms: no
Outcomes	Primary outcome: incidence of depression ‐ diagnosis: diagnosis according to ICD‐10 (moderate or severe) assessed by SCAN interview adverse events: total number of adverse events measured by the Side Effect Rating Scale Secondary outcome: incidence of depression ‐ cut‐off: N/A severity of depression: HDS (note: only baseline means were reported) cost‐effectiveness: N/A cost‐utility: N/A
Notes	Patients were screened for depression by study investigators using the HDS at all assessments. In case of positive screening (cut‐off score ≥ 13), investigator increased the dose of study medication to 20 mg patients were seen at an extraordinary visit (approximately 14 days later) by a psychiatrist to diagnose a depressive episode according to ICD‐10 Language: English Funding: The Danish Hearts Foundation (01‐1‐9‐F13‐22884), Danish Medical Research Council (22‐02‐0221) and H. Lundbeck Ltd. The sponsors of the study had no role in study design, manuscript draft or decision to submit the manuscript. Declaration of interest: The authors declare that they have no competing interests.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"randomization was done in centrally prepared randomization blocs unknown to the investigators." (P. 12)
Allocation concealment (selection bias)	Low risk	"the allocation sequence was implemented using the consecutive number of the study medication." (P. 12)
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"investigators, nurses, outcome assessors as well as included patients remained blinded to group assignment during the entire intervention and data analysis." (p.12)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"investigators, nurses, outcome assessors as well as included patients remained blinded to group assignment during the entire intervention and data analysis." (p.12)
Incomplete outcome data (attrition bias) All outcomes	High risk	numbers randomised: escitalopram: n = 120; placebo: n = 120; total: N = 240 note: n = 1 participant was excluded due to protocol violation; total: N = 239 number of drop‐outs at 12 months: escitalopram: n = 35; placebo: n = 30; total: N = 65 numbers analysed post‐intervention: escitalopram: n = 85; placebo: n = 89; total: N = 174 reasons for drop‐out: "among the 65 (27.2%) patients who did not complete the study period, 55 (23%) withdrew their consent or dropped out within the first 6 months (28 patients within first 4 weeks). No significant differences between treatment groups in the number or the time for treatment stop were found" (P. 13) "during the study period there were no serious adverse events related to study medication. Four patients (1.7%) died while still on trial medication, 3 in the escitalopram group and 1 in the placebo group (P = 0.62). Among the 13 patients withdrawing from the study due to possible side effects, 8 were in treatment with escitalopram and 5 with placebo (P = 0.61)" (P. 14) no further information specified
Selective reporting (reporting bias)	High risk	protocol available only one of the two pre‐specified primary outcomes was reported; no information on HDS scores except for dosage increase of medication due to HDS ≥ 13 (N = 9) no further information specified on side effects: "The incidence of most of the 48 symptoms contained in the UKU side effect scale did not differ between groups, and no single symptom was more common in any group for more than one visit." (P. 14) "1 patient excluded du to protocol violation" (fig.1, P. 13)
Other bias	Low risk	no