A double blind placebo RCT to investigate the effects of serotonergic modulation on brain excitability and motor recovery in stroke patients

J Neurol. 2009 Jul;256(7):1152-8. doi: 10.1007/s00415-009-5093-7. Epub 2009 Mar 22.


Motor excitability is increased in both hemispheres in stroke patients during motor recovery. Pharmacologically controlled changes of cortical excitability might be beneficial for synaptic plasticity and therefore facilitate functional recovery after a brain lesion. In particular, it has been suggested that antidepressant drugs can modulate motor excitability. Several recent reports suggest the possibility of monitoring pharmacological effects on brain excitability through transcranial magnetic stimulation (TMS). The aim of this study was to investigate motor area excitability in patients with stroke after oral administration of citalopram. We conducted a prospective randomised placebo controlled study. Twenty patients with unilateral stroke were included in the study: ten patients treated by antidepressive drug and ten patients with placebo. A selective serotonergic drug (citalopram) or a placebo was administered using a mean dosage of 10 mg/day in combination with physiotherapy. Motor cortex excitability was studied by single and paired transcranial magnetic stimulation. TMS recording was tested before (T1) and 1 month after (T2) beginning drug treatment. Patients treated by the serotonergic drug, compared to patients that received a placebo, showed a significant improvement in neurological status as measured by NIHSS and a decrease of motor excitability over the unaffected hemisphere, while no differences were observed over the affected hemisphere. Our findings suggest that treatment with serotonergic drugs can bring about a significant decrease of the motor cortex excitability in stroke patients with effects on both the affected and unaffected hemispheres associated with a better motor recovery.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Aged
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / physiopathology
  • Citalopram / administration & dosage*
  • Dominance, Cerebral / drug effects
  • Dominance, Cerebral / physiology
  • Double-Blind Method
  • Evoked Potentials, Motor / drug effects
  • Evoked Potentials, Motor / physiology
  • Extremities / innervation
  • Extremities / physiopathology
  • Female
  • Functional Laterality / drug effects
  • Functional Laterality / physiology
  • Humans
  • Male
  • Middle Aged
  • Movement Disorders / drug therapy*
  • Movement Disorders / etiology
  • Movement Disorders / physiopathology
  • Paresis / drug therapy*
  • Paresis / etiology
  • Paresis / physiopathology
  • Recovery of Function / drug effects
  • Recovery of Function / physiology
  • Serotonin / metabolism*
  • Serotonin Uptake Inhibitors / administration & dosage*
  • Stroke / drug therapy*
  • Stroke / physiopathology
  • Transcranial Magnetic Stimulation
  • Treatment Outcome


  • Serotonin Uptake Inhibitors
  • Citalopram
  • Serotonin