• Neurology Clinical Trials
• Cerebrovascular Disease
• Ischemia

François Chollet, MD, Centre Hospitalier Universitaire de Toulouse, Toulouse, France, presented data from the Multicenter Randomized Double-Blind Placebo-Controlled Trial with Fluoxetine on Motor Rehabilitation After Acute Ischemic Stroke (FLAME; NCT00657163) trial, showing that in patients with severe motor deficit resulting from ischemic stroke, early use of fluoxetine in addition to physiotherapy enhances motor recovery after 3 months.

Animal studies indicate that serotonergic neurons can modulate motor output [Jacobs BL and Fornal CA. Curr Opin Neurobiol 1997], exert a neuroprotective effect in the postischemic brain [Lim CM et al. J Neurosci Res 2009], and promote hippocampal neurogenesis after stroke [Li WL et al. J Neurosci Res 2009]. Similar results have been reported in a few small clinical trials [Pariente J et al. Ann Neurol 2001; Dam M et al. Stroke 1996; Zittel S et al. Neurorehabil Neural Repair 2008; Gerdelat-Mas A et al. Neuroimage 2005].

FLAME was a double-blind, placebo-controlled trial of 118 patients with hemiparesia or hemiplegia that resulted from ischemic stroke and a Fugl-Meyer motor scale score (FMMS; a validated scale exclusively testing motricity in an analytical and global manner) ≤55 from nine stroke centers in France. Subjects were randomly assigned to once-daily treatment with fluoxetine 20 mg (n=59) or placebo (n=59), starting 5 to 10 days after stroke onset and continuing for 3 months. All subjects also received physiotherapy and standard care. The primary study endpoint was change in FMMS score between baseline and Day 90. Secondary outcomes included score changes in the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Montgomery-Åsberg Depression Rating Scale (MADRS) between baseline and Day 90.

Subjects in the fluoxetine group were slightly older than those in the placebo group (mean age 66.4 years vs 62.9 years) and more likely to have had a prior stroke (16.9% vs 6.8% of placebo subjects). Baseline mean FMMS score was 13.4 (+8.8) and 17.1 (+11.7) in the placebo and fluoxetine groups, respectively, a significant difference that was adjusted for in the analysis.

FMMS score progression at Day 90 was significantly (p=0.003) greater in the fluoxetine group (+34.0; 95% CI, 29.7 to 38.4) than in the placebo group (+24.3; 95% CI, 19.9 to 28.7), with the majority of benefit being seen for the upper limb part of the scale (+22.9 for fluoxetine; +13.1 for placebo; p=0.002; Table 1). Overall, there was no difference in NIHSS or MADRS score between the two groups; however, when only the motor portion of the NIHSS was considered, there was a significant (p=0.012) improvement, favoring fluoxetine. The number of independent patients (mRS score of 1–2) was significantly higher in the fluoxetine group at Day 90 than in the placebo group (26.3% [n=15] vs 8.9% [n=5]; p=0.015; Table1). Fluoxetine was well tolerated; a slight, positive effect on mood was detected, as indicated by a reduction in mean adjusted MADRS score (−0.1 [SD= –2.1 to 1.9]).

Prof. Chollet noted that although the FLAME trial was limited by its small size, the short-term nature of the trial and the fact that it was conducted in a group of patients who were specifically selected for having a severe motor deficit render the study treatment a new and promising therapeutic approach. The treatment target is neural plasticity, for which the only existing validated treatment is arterial deocclusion with IV thrombolytic agents. Fluoxetine is well tolerated and can potentially be given to a large cohort of patients at a reasonable cost and without the need for advanced treatment facilities.

• © 2011 MD Conference Express