Skip to main content
. 2021 Nov 15;2021(11):CD009286. doi: 10.1002/14651858.CD009286.pub4

AFFINITY 2020.

Study characteristics
Methods Multicentre
Study type: interventional (clinical trial)
Allocation: randomised
Intervention model: parallel assignment
Masking: quadruple (participant, care provider, investigator, outcomes assessor)
Primary purpose: treatment
Participants 1280 participants
Country: Australia (n = 532), New Zealand (n = 42), and Vietnam (n = 706)
Setting: inpatient
At randomisation number allocated: N = 1280: fluoxetine (n = 642); placebo (n = 638)
% male: fluoxetine (64%); placebo (62%)
Age: mean age: fluoxetine = 63.5± 12.5; placebo = 64.6 ± 12.2
Subtype of stroke

  • Total anterior circulation infarct: fluoxetine (9%); placebo (9%)

  • Partial anterior circulation infarct: fluoxetine (49%); placebo (52%)

  • Lacunar infarct: fluoxetine (21%); placebo (105%)

  • Posterior circulation infarct: fluoxetine (114%); placebo (103%)

  • Uncertain: fluoxetine (2%); placebo (1%)


Inclusion criteria

  • Age > 18 years

  • Clinical diagnosis of stroke 2 to 15 days previously

  • Brain imaging consistent with ischaemic or haemorrhagic stroke (including normal CT brain scan)

  • Persisting measurable focal neurological deficits causing a functional deficit at the time of randomisation


Exclusion criteria:

  • History of epileptic seizures

  • History of bipolar disorder

  • History of drug overdose or attempted suicide

  • Ongoing treatment with any selective serotonin reuptake inhibitor

  • Allergy or contra‐indication to fluoxetine

  • Use of medications that may interact seriously with fluoxetine

  • Not available for follow‐up over the next 365 days e.g. no fixed home address

  • Life‐threatening illness (e.g. advanced cancer) that is likely to reduce 365‐day survival

  • Pregnant, breast‐feeding or of child‐bearing potential and not using contraception

  • Enrolled in another interventional clinical research trial involving an investigational product (medicine) or device
Interventions Fluoxetine 20 mg once daily or matching placebo capsules for 6 months
Outcomes Primary outcome

  • Functional outcome as measured by the mRS at 180 days after randomisation


Secondary outcomes at 180 and 365 days after randomisation

  • Survival

  • Mood (PHQ‐9)

  • Cognitive function (TICSm)

  • Communication (SIS)

  • Motor function (SIS)

  • Overall health status (SIS)

  • Health‐Related Quality of Life (HRQoL) (EuroQol)

  • Functional recovery (smRSq) at the 365‐day assessments

  • New diagnosis of depression requiring treatment with antidepressants

  • Fatigue (vitality domain of the SF‐36)

  • Serious adverse events at any time during follow‐up including new stroke, acute coronary syndrome, epileptic seizures, fall, new fractures or death
Funding source The AFFINITY trial was funded by the Australian NHMRC Project Grant 1059094. The minimisation algorithm was provided by The Stroke Research Group, Division of Clinical Neuroscience, University of Edinburgh, Edinburgh, UK
Notes ACTRN12611000774921Recruitment January 11, 2013, and June 30, 2019. GJH has received grants from the NHMRC of Australia, Vetenskapsrådet (The Swedish Research Council), and UK National Institute for Health Research Technology, during the conduct of the study; and personal fees from the American Heart Association, outside of the submitted work. MLH, CE‐B, LB, and TL have received grants from the NHMRC of Australia during the conduct of the study. CSA has received grants from the NHMRC of Australia, and grants and personal fees from Takeda, outside of the submitted work. All other members of the writing group declare no competing interests.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Quote: " The patient’s clinician entered the patient’s baseline data into a secure, password‐protected, centralised, web‐based randomisation system that checked the data for completeness and consistency and generated a unique study identification number and treatment pack number corresponding to fluoxetine or placebo in a 1:1 ratio."
Allocation concealment (selection bias) Low risk Quote: " All patients, carers, investigators, and outcome assessors were masked to the allocated treatment by use of placebo capsules that were visually identical to the fluoxetine capsules even when broken open. Success of masking was not assessed."
Blinding of participants and personnel (performance bias)
All outcomes Low risk Quote: "All patients, carers, investigators, and outcome assessors were masked to the allocated treatment by use of placebo capsules that were visually identical to the fluoxetine capsules even when broken open. Success of masking was not assessed."
Blinding of outcome assessment (detection bias)
All outcomes Low risk Quote: "All patients, carers, investigators, and outcome assessors were masked to the allocated treatment by use of placebo capsules that were visually identical to the fluoxetine capsules even when broken open. Success of masking was not assessed."
Incomplete outcome data (attrition bias)
All outcomes Low risk Less than 5% dropped out or died and there is no compelling evidence of a difference between the 2 groups
Selective reporting (reporting bias) Low risk All outcomes in protocol were reported
Other bias Low risk The study appears to be free of other sources of bias