The Australian-led AFFINITY (Assessment of Fluoxetine In Stroke Recovery) study has confirmed that SSRIs do not improve recovery after stroke.
While previous trials have given conflicting results, the randomised controlled trial involving 1280 patients found that oral fluoxetine 20 mg daily for six months after acute stroke did not improve functional outcome and was associated with higher rates of adverse effects such as bone fractures.
Published in Lancet Neurology, the study led by Professor Graeme Hankey, of the University of WA included patients from sites in Australia, New Zealand, and Vietnam who were randomised to treatment with fluoxetine of placebo.
At 6 months, the distribution of modified Rankin Scale (mRS) categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53).
And compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months.
The study authors said it had been thought that fluoxetine might improve neurological recovery and reduce disability after stroke because it had shown neuroprotective and neuroregenerative effects in preclinical models of acute brain ischaemia. The small FLAME study involving 118 patients had provided positive results but subsequent larger prospective RCTs such as the FOCUS and EFFECTS trials were negative.
They concluded that the AFFINITY trial had confirmed a lack of benefit of SSRIs in stroke recovery in ethnically diverse populations with a high rates of treatment adherence.
“These results do not support the use of fluoxetine to improve functional outcome after stroke,” they concluded.
“Based on the evidence, SSRIs should not be prescribed routinely to improve functional outcome after stroke because they are ineffective and increase serious adverse events.”
They added that further analysis of the data would examine the effects of SSRIs in specific patient subgroups such as those with hemiparesis, severe stroke, and cognitive impairment; and on specific outcomes.
“Until these results are available, further trials of fluoxetine for stroke recovery are not recommended.”
An accompanying commentary noted there is a wealth of evidence that SSRIs can increase the potential for activity-dependent plasticity in the adult brain, “most probably through a reduction of extracellular concentrations of GABA and an increase in BDNF expression.
Therefore SSRIs might only be helpful in stroke recovery when combined with a sufficient level of physical or behavioural training, the authors said.