title: Selective serotonin reuptake inhibitors to improve outcome in acute ischemic stroke: possible mechanisms and clinical evidence.
abstract: BACKGROUND
  Several clinical studies have indicated that selective serotonin reuptake inhibitors (SSRIs) administered in patients after acute ischemic stroke can improve clinical recovery independently of depression. Due to small sample sizes and heterogeneous study designs interpretability was limited in these studies. The mechanisms of action whereby SSRI might improve recovery from acute ischemic stroke are not fully elucidated.
  
  
  METHODS
  We searched MEDLINE using the PubMed interface to identify evidence of SSRI mediated improvement of recovery from acute ischemic stroke and reviewed the literature on the potential underlying mechanisms of action.
  
  
  RESULTS
  Among identified clinical studies, a well-designed randomized, double-blind, and placebo-controlled study (FLAME - fluoxetine for motor recovery after acute ischemic stroke) demonstrated improved recovery of motor function in stroke patients receiving fluoxetine. The positive effects of SSRIs on stroke recovery were further supported by a meta-analysis of 52 trials in a total of 4060 participants published by the Cochrane collaboration. Based on animal models, the mechanisms whereby SSRIs might ameliorate functional and structural ischemic-brain damage were suggested to include stimulation of neurogenesis with migration of newly generated cells toward ischemic-brain regions, anti-inflammatory neuroprotection, improved regulation of cerebral blood flow, and modulation of the adrenergic neurohormonal system. However, to date, it remains speculative if and to what degree these mechanisms convert into humans and randomized controlled trials in large populations of stroke patients comparing different SSRIs are still lacking.
  
  
  CONCLUSIONS
  In addition to the need of comprehensive-clinical evidence, further elucidation of the beneficial mechanisms whereby SSRIs may improve structural and functional recovery from ischemic-brain damage is needed to form a basis for translation into clinical practice.
authors.affiliation: Department of Neurology University Hospital Carl Gustav Carus Technische Universität Dresden Dresden Germany ; Department of Psychotherapy and Psychosomatic Medicine University Hospital Carl Gustav Carus Technische Universität Dresden Dresden Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Siepmann
authors.affiliation: Institute of Clinical Pharmacology University Hospital Carl Gustav Carus Technische Universität Dresden Dresden Germany.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Penzlin
authors.affiliation: Department of Neurology University Hospital Carl Gustav Carus Technische Universität Dresden Dresden Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Kepplinger
authors.affiliation: Department of Neurology Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts.
authors.forename: Ben Min-Woo
authors.initials: BM
authors.lastname: Illigens
authors.affiliation: Department of Psychotherapy and Psychosomatic Medicine University Hospital Carl Gustav Carus Technische Universität Dresden Dresden Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Weidner
authors.affiliation: Department of Neurology University Hospital Carl Gustav Carus Technische Universität Dresden Dresden Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Reichmann
authors.affiliation: Department of Neurology University Hospital Carl Gustav Carus Technische Universität Dresden Dresden Germany.
authors.forename: Kristian
authors.initials: K
authors.lastname: Barlinn
mesh_terms: D000818:Animals; D005473:Fluoxetine / Q000008:administration & dosage; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D020127:Recovery of Function; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*; D020521:Stroke / Q000188:drug therapy*
chemical_list: D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Acute ischemic stroke; SSRI; fluoxetine