Fluoxetine modulates motor performance and cerebral activation of patients recovering from stroke

Abstract

In order to determine the influence of a single dose of fluoxetine on the cerebral motor activation of lacunar stroke patients in the early phase of recovery, we conducted a prospective, double-blind, crossover, placebo-controlled study on 8 patients with pure motor hemiparesia. Each patient underwent two functional magnetic resonance imaging (fMRI) examinations: one under fluoxetine and one under placebo. The first was performed 2 weeks after stroke onset and the second a week later. During the two fMRI examinations, patients performed an active controlled motor task with the affected hand and a passive one conducted by the examiner with the same hand. Motor performance was evaluated by motor tests under placebo and under fluoxetine immediately before the examinations to investigate the effect of fluoxetine on motor function. Under fluoxetine, during the active motor task, hyperactivation in the ipsilesional primary motor cortex was found. Moreover, fluoxetine significantly improved motor skills of the affected side. We found that a single dose of fluoxetine was enough to modulate cerebral sensory-motor activation in patients. This redistribution of activation toward the motor cortex output activation was associated with an enhancement of motor performance.

Effect of Serotonin on Paired Associative Stimulation-Induced Plasticity in the Human Motor Cortex

“…In accordance, LTD is facilitated in animal models of depression, which was prevented by chronic application of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine (Holderbach et al, 2007). Besides depression, several studies have demonstrated that SSRIs improve motor functions in stroke patients (Chollet et al, 2011;Dam et al, 1996;Pariente et al, 2001) and in healthy individuals (Loubinoux et al, 1999;Loubinoux et al, 2002a;Loubinoux et al, 2002b;Loubinoux et al, 2005). Again, the physiological basis for this effect might be the impact of serotonin on plasticity.…”

Increased Lower Limb Spasticity but Not Strength or Function Following a Single-Dose Serotonin Reuptake Inhibitor in Chronic Stroke

“…17,26 One explanation may be assessment of lower extremity function in the present study, where direct cortical projections to lower versus upper extremity motor pools in humans are more limited, such that increased motor cortical excitability may not sufficiently increase descending commands to increase peak force output. However, patients with incomplete SCI demonstrate increases in strength, 30 suggesting that differences in tested populations may also contribute.…”

“…Previous data suggest that selective serotonin reuptake inhibitors (SSRIs) may mitigate weakness 17 and improve function poststroke. 18,19,20 In general, SSRIs facilitate 5-hydroxytryptamine (serotonin) (5-HT) transmission by decreasing presynaptic sequestration in axon terminals originating primarily from brainstem (raphe) projections.…”

“…22,23 While the central effects of 5-HT are complex, the net result on motor systems is excitatory. 24,25 In humans poststroke, most studies using SSRIs or other 5-HT reuptake inhibitors (eg, fluoxetine, paroxetine, venlafaxine) focus on the upper extremity and indicate enhanced cortical excitability and motor performance in subacute and chronic stroke (grip strength, rate of finger tap, and 9-hole peg test 17,20,26 ). Interestingly, with repeated SSRI administration, data from intact individuals demonstrate potential decreased motor cortical excitability, 27,28 while studies 19,29 with patients early poststroke undergoing rehabilitation indicate improved motor recovery.…”

Functional magnetic resonance imaging: A review of methodological aspects and clinical applications

“…But also the effects of drugs can be studied. Application of a single dose or a 1-week treatment with a selective serotonin-reuptake inhibitor increases the activeability of the motor system, including M1, measured with fMRI in normal subjects (102), as well as in stroke patients correlating with improvement of function (103).…”