Combining Fluoxetine and rTMS in Poststroke Motor Recovery: A Placebo-Controlled Double-Blind Randomized Phase 2 Clinical Trial

作者：Camila Bonin Pinto, León Morales-Quezada, Polyana Vulcano de Toledo Piza, Dian Zeng, Faddi G. Saleh Velez, Isadora Santos Ferreira, Pedro Henrique Marques de Lucena, Dante Duarte, Fernanda Lopes, Mirret M. El-Hagrassy, Luiz Vicente Rizzo, Erica C. Camargo, David J. Lin, Nicole Mazwi, Qing Mei Wang, Randie M. Black‐Schaffer, Felipe Fregni · 发表于：Neurorehabilitation and neural repair · 年份：2019 · 被引用次数：31 · 研究领域：Transcranial Magnetic Stimulation Studies、Stroke Rehabilitation and Recovery、Muscle activation and electromyography studies

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 fa...