Fluoxetine does not improve outcomes after stroke

Many people experience disability after a stroke, such as weakness in the arm or leg, or problems with language and communication. The antidepressant drug fluoxetine has been used to reduce disability following a stroke but it is unclear how effective it is.

The first of three large-scale trials into the impact of fluoxetine in stroke patients is called FOCUS (Fluoxetine or control under supervision). This study found that fluoxetine has no beneficial impact. In fact, it was linked to an increase in falls and fractures. Fewer people experienced depression when taking fluoxetine, but this effect disappeared when the drug was stopped.

Future detailed analyses could reveal whether specific groups of patients may benefit more, or have lower risks from taking fluoxetine after a stroke.

What’s the issue?

Fluoxetine is a commonly prescribed antidepressant that is part of a group of drugs called selective serotonin reuptake inhibitors (SSRIs). A study in 2011, FLAME (Fluoxetine for motor recovery after acute ischaemic stroke) suggested that fluoxetine might reduce the movement loss experienced by stroke survivors. A Cochrane review in 2012 reported similar findings, but stated that many of the studies included were biased and so firm conclusions could not be reached.

There may be some negative effects associated with taking fluoxetine or other SSRIs. Observational studies have suggested there is an increased risk of fracture in people who take SSRIs, but there have been no large-scale trials comparing SSRIs with placebos.

International guidelines do not give clear advice on fluoxetine after stroke. Researchers designed FOCUS, to conclusively determine whether fluoxetine reduces disability after a stroke.

What’s new?

A large scale trial, FOCUS, found that fluoxetine does not improve outcomes six or twelve months after stroke.

More than 3,000 patients were recruited. Half took fluoxetine for six months, while the other half took a placebo (dummy pill). Patients started taking the tablets within two weeks of having a stroke and were followed up six and twelve months afterwards.

Compared to those in the placebo group, patients who had taken fluoxetine:

  • showed no improvements in mobility
  • were less likely to start experiencing depression (13% vs 16.9%) but this difference disappeared after they stopped taking the drug
  • were more likely to have a seizure (3.7% vs 2.6%)
  • were nearly twice as likely to have a bone fracture (2.9% vs 1.5%)

Why is this important?

International guidelines can now be updated to make it clear that fluoxetine does not improve outcomes for stroke patients.

Many patients and doctors may be unaware of the increased risk of falls and fractures among people taking SSRIs. This could be particularly important for older people and stroke patients and should be considered when choosing treatment for people with depression.

What’s next?

Two other large studies had similar findings. The AFFINITY (Assessment of fluoxetine in stroke recovery) and EFFECTS (Efficacy of fluoxetine: a randomised controlled trial in stroke) trials were carried out in Australasia/Vietnam and Sweden respectively.

The three studies included a total of 6,000 patients. Data from all patients will be combined and analysed to see whether patients’ characteristics such as their age or sex, or the health-care setting, makes a difference. These results will help doctors and patients make more informed decisions about the use of fluoxetine.


You may be interested to read

The full paper: Dennis M, and others. Fluoxetine to improve functional outcomes in patients after acute stroke: the FOCUS RCT. Health Technology Assessment. 2020; 24

The AFFINITY trial: AFFINITY Trial Collaboration. Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial. The Lancet Neurology. 2020;19:651-660

The EFFECTS trial: EFFECTS Trial Collaboration. Safety and efficacy of fluoxetine on functional recovery after acute stroke (EFFECTS): a randomised, double-blind, placebo-controlled trial. The Lancet Neurology. 2020;19:661-669

The FLAME trial which originally suggested fluoxetine could be beneficial to stroke patients: Chollet F, and others. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. The Lancet Neurology. 2011;10:123-130

The Cochrane study: Mead G, and others. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database Syst Rev 2012;11:CD009286


This project was funded by the NIHR Health Technology Assessment programme.



Study author

I’m not surprised by either outcome. Most things we try in medicine and most things we try in stroke, turn out to be ineffective. I am rarely convinced by smaller trials that have gone before.

Analysis of individual patient data will give us more precise estimates of the effect of the drug. It may turn out that there are other adverse or beneficial effects which are small but potentially worthwhile. It will allow us to look at whether particular types of patient are prone to the adverse effects of fluoxetine. This will allow us to select patients who are at low risk for the adverse effects of fluoxetine and also identify those at higher risk.

Patients who have had a stroke and have then developed depression and want to take an SSRI, need to know about the side effects.

Martin Dennis, Professor of Stroke Medicine, Centre for Clinical Brain Sciences, University of Edinburgh

Consultant Neurologist

The lack of benefit of fluoxetine on the majority of patients is a robust finding. The authors are appropriately cautious in their interpretation of the possible reduction in the incidence of depression.

The trial confirms that fluoxetine is associated with a significant increase in the risk of fractures in stroke patients. Doctors should take this into account and warn patients of this side effect if they are considering prescribing fluoxetine.

Martin Brown, Professor of Stroke Medicine, Institute of Neurology, University College London, and Consultant Neurologist, University College Hospital

Conflicts of Interest

None declared.