Fluoxetine increases cerebral white matter NAA/Cr ratio in patients with multiple sclerosis

Neurosci Lett. 2006 Jul 10;402(1-2):22-4. doi: 10.1016/j.neulet.2006.03.042. Epub 2006 Apr 27.


Axonal degeneration in multiple sclerosis (MS) may be caused by mitochondrial dysfunction and is associated with decreased levels of N-acetylaspartate (NAA) as measured with 1H-magnetic resonance spectroscopy (MRS). Fluoxetine stimulates astrocytic glycogenolysis, which serves as an energy source for axons. Eleven patients with MS received fluoxetine orally 20 mg a day during the first week, and 40 mg a day during the second week. The mean NAA/Creatine ratio in cerebral white matter of the MS patients increased from 1.77 at baseline to 1.84 at the end of the second week (p=0.007). These findings show evidence for a reversible axonal dysfunction in patients with MS and provide a rationale for investigating whether fluoxetine has neuroprotective effects in MS.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Antidepressive Agents, Second-Generation / administration & dosage*
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Creatine / metabolism*
  • Female
  • Fluoxetine / administration & dosage*
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / pathology*


  • Antidepressive Agents, Second-Generation
  • Fluoxetine
  • Aspartic Acid
  • N-acetylaspartate
  • Creatine