CREATE 2007.

Study characteristics
Methods	RCT design: 2 x 2 factorial trial Total N randomised: 284 Length of follow‐up: no follow‐up Analysis: ITT with last‐observation‐carried‐forward applied for missing data
Participants	Location: Canada Number of study centres and setting: 9 hospitals with patients being referred from physicians, responded to media advertisements or targeted posters CAD criteria: evidence of CAD based on hospital chart, evidence of a previous hospitalisation for acute MI, or coronary angiographic evidence of 50% or more blockage in at least 1 major coronary artery, or previous revascularisation; patients were not randomised less than 1 week following discharge Depression criteria: current major depressive episode based on the SCID with at least 4 weeks' duration; baseline score of > 19 on the HAM‐D Other entry criteria: adult patients (18 years or older), stable CAD according to physician's clinical judgement Exclusion criteria: coronary bypass surgery planned during the next 4 months, CCS angina class = 4, bipolar disorder, major depression with psychotic features, or evidence of substance abuse or dependency during the previous 12 months, serious suicide risk based on clinical judgement, use of antidepressants, lithium, or anticonvulsants for mood disorder, currently undergoing any form of psychotherapy, absence of response to a previous adequate trial of citalopram or IPT, 2 previous unsuccessful trials of treatment for depression for the index episode, lifetime history of early termination (< 8 weeks) of citalopram because of adverse events or side effects, lifetime history of early termination (< 8 weeks) of 2 other SSRI antidepressants because of adverse events or side effects, significant cognitive problems, depression due to a general medical condition based on clinical judgement, participation in other trials, inability to speak English or French, unable or unwilling to comply with the study regimen Treatment 1 N: 142 (31.0% female, mean age: 59.0 (SD: 9.81)) Treatment 2 N: 142 (23.2% female, mean age: 57.9 (SD: 9.15)) Control 1 N: 142 (18.3% female, mean age: 57.3 (SD: 8.35)) Control 2 N: 142 (26.1% female, mean age: 58.4 (SD: 9.16)) Comparability of groups: significantly more women in IPT compared to CM groups
Interventions	Treatment 1: IPT + citalopram (20 mg/d to 40 mg/d, tablets) + CM. IPT provided weekly dealing with common problems in CAD patients, including interpersonal conflicts, life transitions, grief, loss, and social isolation (ineligible for this review) Treatment 2: citalopram (20 mg/d to 40 mg/d, tablets) + CM with 20‐ to 25‐minute visits including information about depression and medication use, reassurance, and encouragement of adherence to medication and the study protocol, review of side effects and progress Control 1: IPT + CM + placebo (ineligible for this review) Control 2: placebo administration matched to citalopram condition + CM Duration of treatment: 12 weeks
Outcomes	Outcomes: depression symptoms (HAM‐D, also BDI‐II), depression remission (HAM‐D ≤ 8), depression response (50% reduction on HAM‐D), cardiovascular vital signs (BP, HR), platelet biomarkers (P‐selectin), ECG waves, pharmacological side effects Other outcomes: Interpersonal Relationships Inventory (IPRI), Functional Performance Inventory (FPI), biomarkers (nitric oxide)
Funding	Canadian Institute of Health Research; Fondation du Centre Hospitalier de l'Université de Montréal; Fondation de l'Institut de Cardiologie de Montréal Other support: citalopram and matching placebo donated by Lundbeck Canada Inc
Notes	Factorial design did not allow for 2 randomised comparisons of main effects: 1) IPT vs CM, 2) citalopram vs placebo. Only citalopram vs placebo was included in this review.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Comment: Computer generated block randomisation
Allocation concealment (selection bias)	Low risk	Quote: "Concealed in sequentially numbered, site‐specific, sealed opaque envelopes stored at the coordinating center until randomization" (p. 369)
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Comment: therapists, patients, site psychiatrists, telephone raters for primary outcome, and other personnel blinded to assignment regarding citalopram treatment
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Comment: therapists, patients, site psychiatrists, telephone raters for primary outcome, and other personnel blinded to assignment regarding citalopram treatment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: intention‐to‐treat (ITT) analysis with last‐observation‐carried‐forward
Selective reporting (reporting bias)	Low risk	Comment: primary and secondary outcomes reported in accordance with the study protocol (ISRCTN15858091)
Other bias	Low risk	Comment: no indication of other bias