title: Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial.
abstract: BACKGROUND
  Hemiplegia and hemiparesis are the most common deficits caused by stroke. A few small clinical trials suggest that fluoxetine enhances motor recovery but its clinical efficacy is unknown. We therefore aimed to investigate whether fluoxetine would enhance motor recovery if given soon after an ischaemic stroke to patients who have motor deficits.
  
  
  METHODS
  In this double-blind, placebo-controlled trial, patients from nine stroke centres in France who had ischaemic stroke and hemiplegia or hemiparesis, had Fugl-Meyer motor scale (FMMS) scores of 55 or less, and were aged between 18 years and 85 years were eligible for inclusion. Patients were randomly assigned, using a computer random-number generator, in a 1:1 ratio to fluoxetine (20 mg once per day, orally) or placebo for 3 months starting 5-10 days after the onset of stroke. All patients had physiotherapy. The primary outcome measure was the change on the FMMS between day 0 and day 90 after the start of the study drug. Participants, carers, and physicians assessing the outcome were masked to group assignment. Analysis was of all patients for whom data were available (full analysis set). This trial is registered with ClinicalTrials.gov, number NCT00657163.
  
  
  RESULTS
  118 patients were randomly assigned to fluoxetine (n=59) or placebo (n=59), and 113 were included in the analysis (57 in the fluoxetine group and 56 in the placebo group). Two patients died before day 90 and three withdrew from the study. FMMS improvement at day 90 was significantly greater in the fluoxetine group (adjusted mean 34·0 points [95% CI 29·7-38·4]) than in the placebo group (24·3 points [19·9-28·7]; p=0·003). The main adverse events in the fluoxetine and placebo groups were hyponatraemia (two [4%] vs two [4%]), transient digestive disorders including nausea, diarrhoea, and abdominal pain (14 [25%] vs six [11%]), hepatic enzyme disorders (five [9%] vs ten [18%]), psychiatric disorders (three [5%] vs four [7%]), insomnia (19 [33%] vs 20 [36%]), and partial seizure (one [<1%] vs 0).
  
  
  CONCLUSIONS
  In patients with ischaemic stroke and moderate to severe motor deficit, the early prescription of fluoxetine with physiotherapy enhanced motor recovery after 3 months. Modulation of spontaneous brain plasticity by drugs is a promising pathway for treatment of patients with ischaemic stroke and moderate to severe motor deficit.
  
  
  BACKGROUND
  Public French National Programme for Clinical Research.
authors.affiliation: Neurology Department, Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Toulouse, France.
authors.forename: François
authors.initials: F
authors.lastname: Chollet
authors.forename: Jean
authors.initials: J
authors.lastname: Tardy
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Albucher
authors.forename: Claire
authors.initials: C
authors.lastname: Thalamas
authors.forename: Emilie
authors.initials: E
authors.lastname: Berard
authors.forename: Catherine
authors.initials: C
authors.lastname: Lamy
authors.forename: Yannick
authors.initials: Y
authors.lastname: Bejot
authors.forename: Sandrine
authors.initials: S
authors.lastname: Deltour
authors.forename: Assia
authors.initials: A
authors.lastname: Jaillard
authors.forename: Philippe
authors.initials: P
authors.lastname: Niclot
authors.forename: Benoit
authors.initials: B
authors.lastname: Guillon
authors.forename: Thierry
authors.initials: T
authors.lastname: Moulin
authors.forename: Philippe
authors.initials: P
authors.lastname: Marque
authors.forename: Jérémie
authors.initials: J
authors.lastname: Pariente
authors.forename: Catherine
authors.initials: C
authors.lastname: Arnaud
authors.forename: Isabelle
authors.initials: I
authors.lastname: Loubinoux
mesh_terms: D000208:Acute Disease; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009048:Motor Skills / Q000187:drug effects* / Q000502:physiology; D011446:Prospective Studies; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D005473:Fluoxetine