title: Impact of fluoxetine on the human brain in multiple sclerosis as quantified by proton magnetic resonance spectroscopy and diffusion tensor imaging.
abstract: The antidepressant fluoxetine stimulates astrocytic glycogenolysis, which serves as an energy source for axons. In multiple sclerosis patients fluoxetine administration may improve energy supply in neuron cells and thus inhibit axonal degeneration. In a preliminary pilot study, 15 patients with multiple sclerosis (MS) were examined by diffusion tensor imaging (DTI) and (1)H magnetic resonance spectroscopy (MRS) in order to quantify the brain tissue diffusion properties (fractional anisotropy, apparent diffusion coefficient) and metabolite levels (choline, creatine and N-acetylaspartate) in cortical gray matter brain tissue, in normal appearing white matter and in white matter lesions. After oral administration of fluoxetine (20 mg/day) for 1 week, the DTI and MRS measurements were repeated and after treatment with a higher dose (40 mg/day) during the next week, a third series of DTI/MRS examinations was performed in order to assess any changes in diffusion properties and metabolism. One trend was observed in gray matter tissue, a decrease of choline measured at weeks 1 and 2 (significant in a subgroup of 11 relapsing remitting/secondary progressive MS patients). In white matter lesions, the apparent diffusion coefficient was increased at week 1 and N-acetylaspartate was increased at week 2 (both significant). These preliminary results provide evidence of a neuroprotective effect of fluoxetine in MS by the observed partial normalization of the structure-related MRS parameter N-acetylaspartate in white matter lesions.
authors.affiliation: Department of Radiology, University Hospital Groningen, and University of Groningen, The Netherlands. p.e.sijens@rad.umcg.nl
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sijens
authors.forename: Jop P
authors.initials: JP
authors.lastname: Mostert
authors.forename: Roy
authors.initials: R
authors.lastname: Irwan
authors.forename: Jan Hendrik
authors.initials: JH
authors.lastname: Potze
authors.forename: Matthijs
authors.initials: M
authors.lastname: Oudkerk
authors.forename: Jacques
authors.initials: J
authors.lastname: De Keyser
mesh_terms: D001253:Astrocytes / Q000187:drug effects; D001369:Axons / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000188:drug therapy*; D011522:Protons; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D005473:Fluoxetine; D011522:Protons; D017367:Selective Serotonin Reuptake Inhibitors