A pilot study of the effects of chronic paroxetine administration on hippocampal N-acetylaspartate in generalized anxiety disorder

J Psychopharmacol. 2010 Aug;24(8):1175-81. doi: 10.1177/0269881108101796. Epub 2009 Feb 9.


The neural basis of generalized anxiety disorder (GAD) is poorly characterized. The effect of chronic administration (12 weeks) of paroxetine, a selective serotonin reuptake inhibitor, on N-acetylaspartate (NAA), a marker of neuronal viability, was evaluated in adults with GAD using proton magnetic resonance spectroscopic imaging ((1)H MRSI) at 1.5 T. We hypothesized that, pretreatment abnormalities in hippocampal NAA/creatine (NAA/Cr) would normalize with symptomatic improvement. Nine GAD patients (mean age = 41.7 year; 4 females) received 12 weeks of open-label paroxetine treatment, flexibly dosed up to 60 mg/day. Clinical outcome was assessed with the Hamilton Anxiety Rating Scale (HAM-A). Multislice ( 1)H MRSI scans were performed at unmedicated baseline and following 6 and 12 weeks of treatment. Ten untreated healthy volunteers (HVs) (mean age = 37.1 year; 4 females) received scans at the same intervals. All patients achieved remission (HAM-A <or= 7) by week 12. Compared to HVs, GAD patients showed persistently lower levels of bilateral hippocampal NAA/Cr (17.7% mean decrease; Cohen's d = 1.29) that were maintained across all three time points, despite marked symptom improvement. This pilot study failed to support an association between a hippocampal neuronal marker and anxiolytic response to paroxetine, and suggests further investigation of potential trait-like hippocampal abnormalities in GAD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / metabolism
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Creatine / metabolism
  • Female
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Humans
  • Male
  • Middle Aged
  • Neurons / drug effects
  • Neurons / metabolism*
  • Paroxetine / administration & dosage
  • Paroxetine / adverse effects
  • Paroxetine / pharmacology*
  • Pilot Projects
  • Psychiatric Status Rating Scales
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Time Factors
  • Treatment Outcome


  • Serotonin Uptake Inhibitors
  • Aspartic Acid
  • Paroxetine
  • N-acetylaspartate
  • Creatine