Abstract
Background.
Although recent evidence has shown a new role of fluoxetine in motor
rehabilitation, results are mixed. We conducted a randomized clinical
trial to evaluate whether combining repetitive transcranial magnetic
stimulation (rTMS) with fluoxetine increases upper limb motor function
in stroke.
Methods. Twenty-seven hemiparetic patients within 2
years of ischemic stroke were randomized into 3 groups: Combined (active
rTMS + fluoxetine), Fluoxetine (sham rTMS + fluoxetine), or Placebo
(sham rTMS + placebo fluoxetine). Participants received 18 sessions of
1-Hz rTMS in the unaffected primary motor cortex and 90 days of
fluoxetine (20 mg/d). Motor function was assessed using Jebsen-Taylor
Hand Function (JTHF) and Fugl-Meyer Assessment (FMA) scales.
Corticospinal excitability was assessed with TMS.
Results. After
adjusting for time since stroke, there was significantly greater
improvement in JTHF in the combined rTMS + fluoxetine group (mean
improvement: −214.33 seconds) than in the placebo (−177.98 seconds, P = 0.005) and fluoxetine (−50.16 seconds, P
< 0.001) groups. The fluoxetine group had less improvement than
placebo on both scales (respectively, JTHF: −50.16 vs −117.98 seconds, P = 0.038; and FMA: 6.72 vs 15.55 points, P
= 0.039), suggesting that fluoxetine possibly had detrimental effects.
The unaffected hemisphere showed decreased intracortical inhibition in
the combined and fluoxetine groups, and increased intracortical
facilitation in the fluoxetine group. This facilitation was negatively
correlated with motor function improvement (FMA, r2 = −0.398, P = 0.0395).
Conclusion.
Combined fluoxetine and rTMS treatment leads to better motor function
in stroke than fluoxetine alone and placebo. Moreover, fluoxetine leads
to smaller improvements than placebo, and fluoxetine’s effects on
intracortical facilitation suggest a potential diffuse mechanism that
may hinder beneficial plasticity on motor recovery.
, Leon Morales-Quezada, MD, PhD*, Polyana Vulcano de Toledo Piza, MD*
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