Kim 2017.

Study characteristics
Methods	Multicentre Study type: interventional (clinical trial) Intervention model: parallel assignment Primary purpose: prevention
Participants	478 participants Country: South Korea Setting: inpatient. at neurology departments in 17 university hospitals throughout South Korea At randomisation number allocated: N = 478, escitalopram (n = 241); placebo (n = 237) % male at baseline: unclear Age at baseline: unclear Subtype of stroke at baseline: unclear Severity of stroke at baseline: unclear Time since stroke onset: acute ischaemic stroke or intracerebral haemorrhage within the previous 21 days Inclusion criteria Age > 20 years Patients with acute stroke (ischaemic stroke or cerebral haemorrhage) confirmed by neuroimaging within 21 days after stroke onset Patients with haemorrhagic transformation of infarcted tissue will not be included, but if investigators judge the risk of bleeding is small (i.e. reduced amount of blood in follow‐up neuroimaging) those patients can be enrolled Patients with mRS ≥ 2 on screening Patients without definite history of depression Patients who fulfil the following criteria in the K‐MADRS test: The combined score of the 9th question (pessimistic thoughts) and the 10th question (suicidal idea) ≤ 7 The score of the 10th question < 6 Patients without serious communication problem Consent Exclusion criteria MRS 0 or 1 on screening History of depression or have taken antidepressants Diagnosis of bipolar disorder or other psychiatric disorders Severe dementia or aphasia and unable to communicate Taken migraine medication on screening or expected to take migraine medication frequently due to severe migraine Suicidal ideation on screening test or those who express their wish to be treated for depression Depression requiring treatment diagnosed by physician SSRI medication required for other reasons Taken antiepileptic drugs on screening History of traumatic brain injury, brain tumour, or other brain disease (except stroke) within 30 days prior to screening Uncommon causes of stroke (e.g. subarachnoid haemorrhage, venous thrombosis, arteriovenous malformation, or Moyamoya disease) Bleeding diathesis, haemophilia, or thrombocytopenia Severe concomitant illness (e.g. liver disease, renal disease, malignancy) Patients with abnormal blood tests, renal insufficiency, heart failure Pregnant or breastfeeding Participating in another clinical (interventional) trial Withdrawal criteria: not stated
Interventions	Experimental: escitalopram: first week 5 mg, 2nd week ~ 12 week: 10 mg Comparator: "sugar pill". First week 5 mg, 2nd week ~ 12 week: 10 mg
Outcomes	Primary outcomes collected at 3 months Occurrence rate of depression (MADRS score ≥ 16) Secondary outcomes Prevention of depression at 3 months Prevention of emotional incontinence (modified Kim's criteria) at 3 and 6 months Prevention of anger proneness (modified Spielberger trait anger scale) at 3 and 6 months Recovery of neurologic dysfunction (NIHSS, mRS, BI, motor function test from Hemispheric Stroke Scale at 3 months) Improvement of cognitive function (MoCA) at 3 and 6 months Improvement of quality of life (Stroke Specific Quality of Life scale) at 3 and 6 months Improvement of caregiver burden (Sense of Competence Questionnaire scores) at 3 and 6 months
Funding source	Dong‐A Pharmaceutical Company, grants from the Ministry for Health, Welfare, and Family Affairs, South Korea
Notes	NCT01278498 Baseline demographic and clinical characteristics for each group not presented, but rather the baseline demographic and clinical characteristics for those completing the trial (i.e., a subset of all those randomised at baseline) are presented Dates study conducted: January 2011 to December 2015 Declarations of Interest: none reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Eligible patients were enrolled by investigators at each centre, and randomly assigned in a 1:1 ratio using a web‐based system to the escitalopram group or the placebo group after being assigned a subject number. Randomisation was done with random permuted blocks of sizes four to six, and was stratified by centre. The placebo was identical in appearance to escitalopram"
Allocation concealment (selection bias)	Low risk	Quote: "Eligible patients were enrolled by investigators at each centre, and randomly assigned in a 1:1 ratio using a web‐based system to the escitalopram group or the placebo group after being assigned a subject number. Randomisation was done with random permuted blocks of sizes four to six, and was stratified by centre"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "The placebo was identical in appearance to escitalopram" Quote: "The individual treatment code was stored separately by the main medical statistician (E‐JL) and two designated statisticians. All investigators including interviewers and assessors of the outcome, participants, and care providers were masked to treatment assignment throughout the study. The code could be unblinded only with the approval of the steering committee."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "All investigators including interviewers and assessors of the outcome, participants, and care providers were masked to treatment assignment throughout the study. The code could be unblinded only with the approval of the steering committee."
Incomplete outcome data (attrition bias) All outcomes	High risk	The following participants were excluded from the 'full analysis set' post‐randomisation from both escitalopram group and placebo group: did not take at least 1 dose of study medication (escitalopram = 4, placebo = 6) did not undergo at least 1 assessment of the primary endpoint (escitalopram = 27, placebo = 36) Reasons for attrition were reported (withdrew consent, violated protocol, considered for treatment for depression, death). Numbers were similar in both groups At 12 weeks, escitalopram group 67/241 (28%) attrition and placebo 73/237(31%) attrition Attrition much greater than 5% It is not clear how missing data were imputed for the intention‐to‐treat analysis; Quote: "we used latest available records for analysis."
Selective reporting (reporting bias)	Low risk	The study protocol is available and all the study's prespecified (primary outcomes and secondary outcomes) that are of interest in the review have been reported in the prespecified way.
Other bias	High risk	The baseline data presented in table 1: comparison of data at baseline between control group and the treatment group are not true baseline characteristics (i.e. at randomisation). The data presented in table 1 are the baseline characteristics of all those completing the trial which is a subgroup of all participants randomised. We cannot tell if there is whether there was any baseline imbalance in important demographic or clinical characteristics