Stroke is a very common disease that leads to disability in around half of its survivors.1 It has been believed that fluoxetine, a selective serotonin-reuptake inhibitor (SSRI), could improve neurological disability and combat disability after a stroke. However, the literature on the topic has not been convincing so far – a meta-analysis of trials that were at low risk for bias did not find an effect of SSRIs on disability scores or functional independence.2,3 That is why an international collaboration of researchers initiated three large clinical trials to investigate the SSRI fluoxetine in stroke recovery. The UK‑based FOCUS study, the first of the three clinical trials, was published in 2019 and showed that fluoxetine did not improve functional outcomes in stroke patients.4 Last month, the results of the Sweden-based EFFECTS study and the Australia-, New Zealand- and Vietnam-based AFFINITY study were published in The Lancet Neurology showing similar outcomes.2,3
Fluoxetine did not improve functional outcomes in two trials
In both the EFFECTS and the AFFINITY studies, adult patients with a clinical diagnosis of acute stroke were randomly assigned to receive either oral fluoxetine or placebo for 6 months.2,3 The primary outcome was their functional status, measured by the modified Rankin Scale (mRS) at 6 months. In the AFFINITY study (N=1280), there was no statistical difference in mRS category distribution after 6 months between fluoxetine and placebo (P=0.53).2 The same outcome was observed in the EFFECTS study (N=1500), in which fluoxetine did not affect the primary mRS outcome compared with the placebo group (P=0.42).3 These results confirmed the results of the FOCUS study, proving that fluoxetine does not help to improve functional recovery after acute stroke.
Fluoxetine increased risk of severe adverse events
Even though researchers found that patients on fluoxetine had a lower incidence of new diagnoses of depression in the EFFECTS study, the results of the AFFINITY study could not confirm this finding.2,3 Furthermore, in both studies, fluoxetine led to some major side effects. In the EFFECTS study, patients on fluoxetine experienced significantly more bone fractures and hyponatraemia compared with patients on placebo; in the AFFINITY study, the fluoxetine group had significantly more falls, bone fractures, as well as epileptic seizures.
Not recommended for stroke recovery
The authors state that “collectively, these trials [FOCUS, AFFINITY and EFFECTS] provide compelling evidence that fluoxetine does not improve functional outcome after stroke.”2 The studies generally provide strong evidence, which is partly attributed to their large, ethnically-diverse patient numbers. In the future, the authors are still planning to perform an individual patient data meta-analysis of the three trials to strengthen their conclusion.2 Nevertheless, they already concluded that SSRIs should not be prescribed to stroke patients to improve functional outcomes due to their ineffectiveness and risk for serious adverse events.