Document Detail

Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo.
MedLine Citation:
PMID:  16038684     Owner:  NLM     Status:  MEDLINE    
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.
Tomas Furmark; Lieuwe Appel; Asa Michelgård; Kurt Wahlstedt; Fredrik Ahs; Stefano Zancan; Eva Jacobsson; Karin Flyckt; Magnus Grohp; Mats Bergström; Emilio Merlo Pich; Lars-Göran Nilsson; Massimo Bani; Bengt Långström; Mats Fredrikson
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological psychiatry     Volume:  58     ISSN:  0006-3223     ISO Abbreviation:  Biol. Psychiatry     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-07-25     Completed Date:  2005-10-20     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0213264     Medline TA:  Biol Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  132-42     Citation Subset:  IM    
Department of Psychology, Uppsala University, Uppsala, Sweden.
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MeSH Terms
Anxiety / drug therapy*,  physiopathology
Cerebrovascular Circulation / drug effects*
Citalopram / pharmacology*,  therapeutic use
Double-Blind Method
Phobic Disorders / drug therapy*,  physiopathology
Piperidines / pharmacology*,  therapeutic use
Positron-Emission Tomography
Receptors, Neurokinin-1 / antagonists & inhibitors
Serotonin Uptake Inhibitors / pharmacology*,  therapeutic use
Temporal Lobe / blood supply,  radionuclide imaging
Tetrazoles / pharmacology*,  therapeutic use
Reg. No./Substance:
0/Piperidines; 0/Receptors, Neurokinin-1; 0/Serotonin Uptake Inhibitors; 0/Tetrazoles; 59729-33-8/Citalopram; K08BK043YS/vofopitant

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