Escitalopram promotes recovery from hand paresis in cortical sensori-motor stroke: a randomized, double-blind, placebo-controlled longitudinal study

Abstract Background Selective serotonin reuptake inhibitors (SSRIs) have been proposed to support post-stroke motor recovery, but evidence for domain-specific behavioral effects and associated neural mechanisms remains limited. This study examined whether early escitalopram administration influences recovery of within-hand motor dexterity following first-ever sensorimotor stroke affecting the pre- or postcentral gyrus. Methods In a double-blind, placebo-controlled trial, participants were randomized to receive escitalopram or placebo during the first three months post-stroke. Motor dexterity was assessed behaviorally and with fMRI using an imitation-based task requiring observation and execution of grasp–regrasp movements. Measurements were acquired at baseline, three months, and nine months. Behavioral effects were analyzed using nonparametric statistics and a complementary permutation framework to assess robustness under small-sample conditions. Results The escitalopram group showed greater improvement in Jebsen–Taylor Test subtest 1 from baseline to three months and in finger gaiting from three to nine months, with both effects supported by permutation testing. fMRI revealed increased activation in a left-hemispheric premotor–opercular–striatal network (OP6, BA44, anterior insula, posterior putamen) and in right premotor subarea 6v3 during motor execution in the escitalopram group. The placebo group, by contrast, exhibited increased activity in the left mediodorsal thalamus at nine months, consistent with compensatory recruitment. Conclusion Although based on a small, highly specific cohort, the findings suggest that early escitalopram administration may facilitate recovery of fine motor control by supporting normalization of task-relevant cortical and subcortical networks. The placebo group’s delayed recovery pattern, characterized by thalamic overactivation, is compatible with compensatory executive engagement. Larger studies are needed to confirm these preliminary but mechanistically informative results.