An ischemic stroke follows the obstruction of a vessel carrying blood to the brain. It is the third most prevalent cause of death and the second most prevalent cause of handicap among adults in France where it affects around 130,000 new patients every year. This affliction is the target of a national plan supported by the Ministry for Health. Researchers report that fluoxetine (Prozac) increases motor recovery following a stroke. The results of this study were published in The Lancet Neurology.
Ischemic stroke causes sometimes irreversible damage to the brain because none (or very few) of the nerve cells renew themselves and their death through oxygen privation results in loss of brain functions. Hemiplegia (paralysis of one side of the body) and hemiparesis (weakness in one half of the body) are the most frequent handicaps to occur following a stroke.
Several preliminary studies had suggested that serotonin recapture inhibitors could improve motor function following a stroke. In 2001, this team demonstrated on a small number of patients that fluoxetine was able to improve motor function by increasing the activation and excitability of neurons in the cerebral motor areas. This initial study led to the performance of a clinical trial.
The objective of the FLAME trial (Fluoxetine for motor recovery after acute ischemic stroke) was to determine if fluoxetine could increase motor function recovery in a larger group of patients.
Between March 2005 and June 2009, 118 patients who were hospitalized for hemiplegia at nine neurovascular units in France took 20 mg of fluoxetine per day (59 patients) or a placebo (59 patients) over the three months following the occurrence of an ischemic stroke. All the patients benefited from re-education. Motor tests were carried out at the start and finish of the three months of treatment. This evaluation of motor function included both performance of simple movements of the upper and lower limb (bending and extension of fingers, wrist, foot, etc.) as well as more complex gestures (placing the hand on the back, catching an object, etc.) which are included on a motor evaluation test scale validated by the scientific community.
Proven motor recovery
In the days and months following a stroke, all the patients spontaneously recovered some of their capabilities. However, the extent of functional recovery remains unpredictable.
Nevertheless, a larger improvement in motor function was observed among patients taking fluoxetine than among those taking the placebo. This improvement included the level of motor function recovery in both the arm and leg. Generally, regression of paralysis was greater among patients taking fluoxetine than among individuals taking the placebo.
After three months of treatment, the number of patients who were independent in their daily life (walking, toilet, common gestures, displacement, etc.) was higher for those taking fluoxetine than the placebo.
Overall, the treatment was well tolerated and side effects were limited. Transitory digestive problems were observed most frequently when taking fluoxetine, but the occurrence of nervous depression proved more frequent among those taking a placebo, suggesting that fluoxetine can prevent post-stroke depression syndromes.
For François Chollet and his collaborators, “The positive effect of the drug on the motor recovery of these patients suggests that the action of fluoxetine on neuron plasticity, rather than on blood vessels, constitutes a new therapeutic channel following acute strokes”. They add, “Fluoxetine is a relatively well-tolerated drug which is already in the public domain and therefore the cost is reasonable.”
Developments are to be expected in the near future. The long-term effects need to be evaluated as do the optimum prescription duration, the effect on neurological functions other than the motor functions, and the possibility, in particular, of treating cerebral hemorrhage. All this suggests that the question of marketing authorization will arise in the short or medium term.
This trial was supported by CHU de Toulouse using public financing from the PHRC (French national clinical research programme).
Material adapted from Inserm.
Reference / Abstract
François Chollet, Jean Tardy, Jean-François Albucher, Claire Thalamas, Emilie Berard, Catherine Lamy, Yannick Bejot, Sandrine Deltour, Assia Jaillard,Philippe Niclot, Benoit Guillon, Thierry Moulin, Philippe Marque, Jérémie Pariente, Catherine Arnaud, & Isabelle Loubinoux. “Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial.” The Lancet Neurology, Published Online January 10, 2011 DOI: 10.1016/S1474-4422(10)70314-8
Additional Researcher Background Information
Neurology Department (F Chollet MD, J Tardy MD,J-F Albucher MD, J Pariente MD) and Clinical Epidemiology Unit (E Berard MD, C Arnaud MD), Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Toulouse, France;
Institut des Sciences du Cerveau de Toulouse (INSERM, CNRS, Université de Toulouse), Toulouse, France (F Chollet, J Tardy, J-F Albucher, J Pariente, P Marque MD, I Loubinoux PhD);
Université de Toulouse, Université Paul Sabatier INSERM, Imagerie Cérébrale et Handicaps Neurologiques UMR 825, Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Purpan, Toulouse, France (F Chollet, J Tardy, J-F Albucher, J Pariente, P Marque);
Unité Mixte de Recherche INSERM U558/Université Toulouse III, Toulouse, France (E Berard, C Arnaud);
Clinical Investigation Centre INSERM CIC-9302 and Department of Clinical Pharmacology, Université de Toulouse, Toulouse, France (C Thalamas MD);
Service de Neurologie, Hôpital Sainte-Anne, Paris, France (C Lamy MD);
Service de Neurologie, Hôpital Général, Dijon, France (Y Bejot MD);
Service des Urgences Cérébro-Vasculaires, Hôpital Pitié Salpêtrière, Paris, France (S Deltour MD);
Centre d’Investigation Clinique, Hôpital Michalon, Grenoble, France (A Jaillard MD);
Centre Hospitalier René Dubos, Pontoise, France (P Niclot MD);
Service de Neurologie, Hôpital Nord Laennec, Nantes, France (B Guillon MD); and
Centre Hospitalier Universitaire de Besançon, Besançon, France (T Moulin MD)