Bembenek 2020.

Study characteristics
Methods	Study type: interventional (clinical trial) Actual enrolment 61 Allocation: randomised Intervention model: parallel assignment Masking: double (participant, care provider) Primary purpose: treatment
Participants	61 participants Country: Poland Setting: inpatient At randomisation number allocated: N = 61: fluoxetine (n = 30); placebo (n = 31) % male: fluoxetine (73.3%); placebo (58.1%) Age: mean age: fluoxetine = 66.6 ± 12.6; placebo = 66.35 ± 12.46 Subtype of stroke Total anterior circulation infarct: fluoxetine (40.0%); placebo (38.7%) Partial anterior circulation infarct: fluoxetine (23.3%); placebo (35.5%) Lacunar infarct: fluoxetine (6.7%); placebo (0.0%) Posterior circulation infarct: fluoxetine (20.0%); placebo (16.1%) Uncertain: fluoxetine (2%); placebo (2%) Severity of stroke: NIHSS, Median (IQR) fluoxetine (5 (3 to 8)); placebo (6 (4 to 8)) Inclusion criteria Age ≥ 18 years Ischaemic or haemorrhagic stroke confirmed by neuroimaging Within 2 to 15 days from the stroke onset Evidence of neurological deficit at randomisation Exclusion criteria Subarachnoid haemorrhage (unless secondary to intracerebral bleeding) High probability that the patient would not be available during follow‐up (e.g. another 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 Current use of drugs that cause significant interactions with fluoxetine: history of epileptic seizures; history of allergy to fluoxetine; suicide attempt or self‐ harm; hepatic impairment (ALT > 3 above the upper normal limit) and renal impairment (creatinine > 180 micromol/L)
Interventions	Fluoxetine 20 mg daily (1 capsule) for 6 months (180 capsules) vs placebo
Outcomes	The primary outcomes at 6 months mRS Secondary endpoints SIS at 6 months NIHSS at baseline, 6 and 12 months Brunnstrom scale at 6 month follow‐up Medical Research Council scale ay 6 month follow‐up BI at 6 and 12 month follow‐up EuroQol 5D‐5L MHI‐5 Overall recovery on a VAS Diagnosis of new depression Compliance with drug intake Treatment effects and the occurrence of possible adverse reactions are assessed up to 12 months
Funding source	POLPHARMA S.A. manufactured and donated fluoxetine and placebo for this study. Anna Członkowska, Jan Bembenek, and Katarzyna Kurczych were supported by statutory activity of the Institute of Psychiatry and Neurology, Warsaw, Poland
Notes	Recruitment 19 December 2014 and 13 March 201 8. Authors declared no conflicts of interest
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Patients were randomly assigned in a 1:1 ratio to receive either fluoxetine or a placebo, by use of a computer‐based permuted block randomisation
Allocation concealment (selection bias)	Low risk	Allocation was concealed (further information obtained from the study author Jan Bembenek to confirm this)
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Clinicians involved in randomisation and outcome assessments, the patients, and their families, were all masked so as to be unaware of treatment allocation. The placebo capsules were visually identical to the fluoxetine capsules, even when broken open."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Clinicians involved in randomisation and outcome assessments, the patients, and their families, were all masked so as to be unaware of treatment allocation"
Incomplete outcome data (attrition bias) All outcomes	Low risk	5 withdrew consent (8%) before 6 months but the withdrawals are balanced between groups (3 in the fluoxetine group and 2 in the control group) From personal communication with the author: a further 2 patients dropped out between 6 and 12 months
Selective reporting (reporting bias)	Low risk	Trial was registered and all outcomes were reported
Other bias	Low risk	The study appears to be free of other sources of bias