Fast track — ArticlesFluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial
Introduction
Thrombolysis with alteplase given within the first few hours of an ischaemic stroke has long been the only treatment recognised to improve the spontaneous recovery of neurological functions. However, we have learnt over the past decade, by use of neuroimaging and electrophysiological techniques, that spontaneous recovery of neurological functions is associated with a large intracerebral reorganisation of the damaged human brain.
Various interventions, such as monoaminergic drugs, have been shown to modulate brain plasticity after a stroke and to reduce the residual neurological deficit and subsequent disability.1, 2, 3 Amphetamines have enhanced recovery in animal models of acute brain lesions, whereas neuroleptic drugs or benzodiazepines have reduced it.1, 2, 3 Little evidence exists for the efficacy of serotonin-reuptake inhibitors in studies of animals, but these inhibitors have an acute neuroprotective action on the ischaemic brain and promote hippocampal neurogenesis.4, 5, 6 In clinical trials of amphetamine in patients with stroke, either no positive effect was noted on the recovery of motor function or the results were contradictory.7, 8, 9, 10, 11 The few small clinical trials of serotonin-reuptake inhibitors that have been reported (table 1) all suggest that drugs of this type might have a positive effect.13, 14, 15, 16 Use of functional MRI in other studies showed that single doses of fluoxetine and paroxetine overactivated motor cortices compared with placebo in both healthy individuals and patients with stroke, and use of transcranial magnetic stimulation showed that cortex overactivation was associated with drug-induced cortex hyperexcitability.12
In the fluoxetine in motor recovery of patients with acute ischaemic stroke (FLAME) trial, we aimed to test whether a 3-month treatment with fluoxetine would enhance motor recovery when given early after an ischaemic stroke to patients with moderate to severe motor deficits.
Section snippets
Participants
Patients who had an acute ischaemic stroke within the past 5–10 days that caused hemiparesis or hemiplegia were prospectively enrolled from nine stroke units in France. Those who were aged between 18 years and 85 years and who had Fugl-Meyer motor scale (FMMS) scores of 55 or less at baseline were eligible for inclusion.
Patients were excluded if they had severe post-stroke disability (National Institutes of Health stroke scale [NIHSS] score >20), substantial premorbid disability, or a
Results
Between March 14, 2005, and June 9, 2009, 118 patients were prospectively enrolled. The two groups were well balanced in terms of baseline and demographic characteristics and stroke severity (table 2). However, mean age was slightly higher and previous history of stroke was more frequent in the fluoxetine group than in the control group. FMMS score at inclusion was higher in the fluoxetine group than in the placebo group (table 2). NIHSS, mRS, and MADRS mean scores did not differ in the two
Discussion
We noted a positive effect on motor recovery in patients with acute ischaemic stroke who were treated with fluoxetine for 3 months. This effect, assessed as a change in FMMS score between day 0 and day 90, was noticeable in the FMMS subscores for both the upper and the lower limb at day 90. By contrast, no effect was noted with NIHSS at day 90. However, NIHSS motor component score at day 90 was lower in the fluoxetine group than in the placebo group, in agreement with the data for FMMS scores.
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