Robinson 2008.

Study characteristics
Methods	Study design: 3‐arm parallel randomised controlled clinical trial (note: the third study‐arm problem‐solving therapy was not extracted due to no suitable control group) Sample size: 200 Method of randomisation: permuted blocks randomisation scheme; sample size randomly divided into block sizes of 3, 6, and 9; within each block random assignment to numbers of 1, 2, or 3 (the three treatment arms) Method of concealment: centralised Blinding: double‐blind Analysis: intention‐to‐treat Date the study was conducted: July 2003 ‐ October 2007
Participants	Location: USA Total N randomised: 176 but we excluded the third study‐arm problem‐solving therapy (n = 59) resulting in N = 117 Intervention n: 59 (64 % male; age M = 61, SD = 14) Control n: 58 (64 % male; age M = 64, SD = 13) Inclusion criteria: no depression at baseline; hemispheric, brainstem, or cerebellar (including Ischaemic or haemorrhagic) stroke in the preceding 3 moths; age 50‐90 Diagnostic criteria ‐ long‐term physical condition: stroke is diagnosed by clinical and neurological findings consistent with either hemispheric, brainstem, or cerebellar stroke Diagnostic criteria ‐ depression: depression is diagnosed according to DSM‐IV and assessed by the HAM‐D (17‐item version; a cut‐off score > 11 implies depression) Exclusion criteria: severe comprehension deficits (inability to complete part 1 of the Token Test); impaired decision‐making capacity (neuropsychological testing); alcohol or substance abuse or dependence according to DSM‐IV (within the last past 12 months); acute coronary syndromes; neurodegenerative disorders; life‐threatening heart or respiratory failure; renal or hepatic failure; severely disabling musculoskeletal disorder; cancer, and neurodegenerative disorders such as idiopathic Parkinson disease or Alzheimer disease; occurrence of stroke secondary to complications from an intracranial aneurysm, arterial‐venous malformation, intracranial tumour or neoplastic process; stroke during the course of myocardial infarction, aortic dissection, or revascularization surgery; stroke due to complications of an intracranial aneurysm, arteriovenous malformation, or neoplastic disease History of depression: intervention: n = 3 placebo: n = 3
Interventions	Intervention: escitalopram: < 65 years: daily dose of 10 mg at morning ≥ 65 years: daily dose of 5 mg at morning Control: matched placebo Duration of treatment: 12 months Length of follow‐up: 18 months (at baseline, 3, 6, 9, 12, and 18 months) Other study arms: problem‐solving therapy 6 treatment sessions (weeks 1, 2, 3, 4, 6, and 10) and 6 reinforcement sessions (16, 20, 24, 28, 32, 40, and 48 weeks) n = 59 (51 % male; age = 67, SD = 11)
Outcomes	Primary outcome: incidence of depression ‐ diagnosis: diagnosis according to DSM‐IV assessed by SCID‐I adverse events: total numbers of adverse events measured by a standardized checklist developed for the study Secondary outcome: incidence of depression ‐ cut‐off: HDRS‐17 cut‐off score >12 (note: we only reported the primary outcome: incidence of depression assessed by diagnosis) severity of depression: HDRS‐17 cost‐effectiveness: N/A cost‐utility: N/A
Notes	Language: English Funding: National Institute of Mental Health (NIMH) grant R01 MH‐65134; NIMH grant funds were use to purchase all of study medications. All of the authors received salary contributions from the grant supporting this study. Over the past five years, Dr Robinson reports serving as a consultant to the former Hamilton Pharmaceutical Company and Avanir Pharmaceutical Company; receiving support or honoraria from Lubeck, Forest Laboratories, and Pfizer; being on the speakers’ bureau for Forest Laboratories and Pfizer; and receiving grant support from the National Institute of Mental Health. Dr Small reports that he conducted a research study funded by Northstar Neuroscience that was unrelated to this prevention study. Dr Arndt reports inheriting Pfizer stock, which he owned from January 6, 2005, to December 23, 2006, and receiving grant support from the National Institute of Mental Health. The former Hamilton Pharmaceutical Company and Avanir Pharmaceutical Company had no financial interest in this prevention study. Declaration of interest: no other authors reported any financial disclosures
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"...using a permuted blocks randomisation scheme Specifically, at the beginning of the study, the targeted sample size was divided randomly (200 patients) into block sizes of 3, 6, and 9 and within each block patients were randomly assigned 1 of the 3 treatments using computer‐generated random numbers of 1, 2, or 3..." (p. 4)
Allocation concealment (selection bias)	Low risk	"patients were centrally randomised...by a team member who was not involved in any evaluation..." (p. 4)
Blinding of participants and personnel (performance bias) All outcomes	Low risk	low risk for escitalopram: "the examiners were unaware of each patient’s treatment assignment and double‐blinded assessments were done for escitalopram and placebo" (p. 5)
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	no information specified
Incomplete outcome data (attrition bias) All outcomes	High risk	numbers randomised: escitalopram: n = 59; placebo: n = 58; total: N = 117 number of drop‐outs at 12 months: escitalopram: n = 7; placebo: n = 5; total: N = 12 number of drop‐outs at 18 months: escitalopram: n = 25; placebo: n = 25; total: N = 50 (note: no information specified, drop‐outs were calculated by comparing the data of the two corresponding publications conducted by Robinson 2008 and Mikami 2011). numbers analyzed post‐intervention at 12 months: escitalopram: n = 52; placebo: n = 53; total: N = 105 numbers analysed at follow‐up 18 months: escitalopram: n = 34; placebo: n = 33; total: N = 67 reasons for drop‐out: at 12 months (p. 14): escitalopram: death, intercurrent disease, could not be reached, protocol violation; placebo: could not be reached, adverse events, intercurrent disease, protocol violations at 18 months (Mikami et al. 2011): escitalopram: no information specified; placebo: no information specified note: Even though Mikami et al. 2011 published further data (12 months to 18 months) on the study conducted by Robinson et al. 2008, analyses were conducted independently from preceding results. Information on drop‐outs between 12 and 18 months are not available. Information on depression scores of the re‐evaluated sub‐sample are also not available.
Selective reporting (reporting bias)	High risk	no protocol available; trial registration included the Stroke Impact Scale which was not reported on
Other bias	Low risk	no