Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo

Biol Psychiatry. 2005 Jul 15;58(2):132-42. doi: 10.1016/j.biopsych.2005.03.029.

Abstract

Background: Evidence is accumulating that pharmacological blockade of the substance P preferring neurokinin-1 (NK1) receptor reduces anxiety. This study compared the effects of an NK1 receptor antagonist, citalopram, and placebo on brain activity and anxiety symptoms in social phobia.

Methods: Thirty-six patients diagnosed with social phobia were treated for 6 weeks with the NK1 antagonist GR205171 (5 mg), citalopram (40 mg), or matching placebo under randomized double-blind conditions. GR205171 was administered for 4 weeks preceded by 2 weeks of placebo. Before and after treatment, regional cerebral blood flow (rCBF) during a stressful public speaking task was assessed using oxygen-15 positron emission tomography. Response rate was determined by the Clinical Global Impression Improvement Scale.

Results: Patients improved to a larger extent with the NK1 antagonist (41.7% responders) and citalopram (50% responders), compared with placebo (8.3% responders). Within- and between-group comparisons showed that symptom improvement was paralleled by a significantly reduced rCBF response to public speaking in the rhinal cortex, amygdala, and parahippocampal-hippocampal regions. The rCBF pattern was corroborated in follow-up analyses of responders and subjects showing large state anxiety reduction.

Conclusions: Short-term administration of GR205171 and citalopram alleviated social anxiety. Neurokinin-1 antagonists may act like serotonin reuptake inhibitors by attenuating neural activity in a medial temporal lobe network.

Publication types

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

MeSH terms

  • Adult
  • Anxiety / drug therapy*
  • Anxiety / physiopathology
  • Cerebrovascular Circulation / drug effects*
  • Citalopram / pharmacology*
  • Citalopram / therapeutic use
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Neurokinin-1 Receptor Antagonists
  • Phobic Disorders / drug therapy*
  • Phobic Disorders / physiopathology
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use
  • Positron-Emission Tomography
  • Serotonin Uptake Inhibitors / pharmacology*
  • Serotonin Uptake Inhibitors / therapeutic use
  • Temporal Lobe / blood supply
  • Temporal Lobe / diagnostic imaging
  • Tetrazoles / pharmacology*
  • Tetrazoles / therapeutic use

Substances

  • Neurokinin-1 Receptor Antagonists
  • Piperidines
  • Serotonin Uptake Inhibitors
  • Tetrazoles
  • Citalopram
  • vofopitant