FOCUS Trial Collaboration 2018.

Methods	Multicentre RCT Study type: interventional (clinical trial) Primary purpose: treatment
Participants	3127 participants Country: UK Setting: inpatient At randomisation number allocated: N = 3127: fluoxetine (n = 1564); placebo (n = 1563) % male: fluoxetine (62%); placebo (61%) Age: mean age: fluoxetine = 71·2 ± 12.4; placebo = 71·5 ± 12.1 Subtype of stroke: Total anterior circulation infarct: fluoxetine (20%); placebo (20%) Partial anterior circulation infarct: fluoxetine (36%); placebo (35%) Lacunar infarct: fluoxetine (20%); placebo (18%) Posterior circulation infarct: fluoxetine (12%); placebo (15%) Uncertain: fluoxetine (2%); placebo (2%) Severity of stroke: NIHSS, Median (IQR) fluoxetine (6 (3 to 11)); placebo (6 (3 to 11)) Time since stroke onset: mean days: fluoxetine 6.9 ± 3.6; placebo 7.0 ± 3.6 Inclusion criteria Age > 18 years Brain imaging consistent with intracerebral haemorrhage or ischaemic stroke Randomisation can be performed between 2 and 15 days after stroke onset Persisting focal neurological deficit is present at the time of randomisation Exclusion criteria Subarachnoid haemorrhage Unlikely to be available for follow up at 12 months Patient and/or carer unable to understand spoken or written English Other life‐threatening illness Pregnant or breast‐feeding or of child bearing age not taking contraception History of epileptic seizures Attempted suicide or self‐harm Allergy or contra indication to fluoxetine Taken a monoamine oxidase inhibitor in last 5 weeks Current or recent depression requiring treatment with selective serotonin reuptake inhibitor Already participating in a CTIMP
Interventions	Experimental: 20 mg orally once daily for 6 months Comparator: matching placebo orally once daily for 6 months
Outcomes	Primary outcome: mRS at 6 months Secondary outcome measures: Deaths from all causes at 6 and 12 months Modified Rankin scale at 12 months Stroke Impact Scale Euroquol 5D‐5L Mental Health Inventory 5 Vitality subscale of SF36 (as an assessment of fatigue) Diagnosis of depression Other adverse events Adherence to the trial medication Health and social care resources used during follow‐up
Funding source	MHRA approval granted. Start‐up phase funded by The Stroke Association. Main phase funded by NIHR
Notes	ISRCTN83290762. Recruitment 10 September 2012 to 31 March 2017. Authors declared no conflicts of interest
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were randomly assigned in a 1:1 ratio to receive fluoxetine or placebo, by use of a centralised randomization system."
Allocation concealment (selection bias)	Low risk	Quote: "Patients were randomly assigned in a 1:1 ratio to receive fluoxetine or placebo, by use of a centralised randomization system."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Patients, their families, and the health‐care team including the pharmacist, staff in the coordinating centre, and anyone involved in outcome assessments were all masked to treatment allocation by use of a placebo capsule that was visually identical to the fluoxetine capsules even when broken open."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Patients, their families, and the health‐care team including the pharmacist, staff in the coordinating centre, and anyone involved in outcome assessments were all masked to treatment allocation by use of a placebo capsule that was visually identical to the fluoxetine capsules even when broken open."
Incomplete outcome data (attrition bias) All outcomes	Low risk	For the primary outcome of mRS at 6 months data were available for fluoxetine n = 1553/1564 (99.3%) and placebo n = 1553/1563 (99.3%)
Selective reporting (reporting bias)	Low risk	The study protocol is available and all of the study's prespecified (primary and secondary) outcomes that are of interest in the review have been reported
Other bias	Low risk	The study appears to be free of other sources of bias