Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo.
2005 (English)In: Biol Psychiatry, ISSN 0006-3223, Vol. 58, no 2, 132-42 p.Article in journal (Other scientific) Published
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.
Place, publisher, year, edition, pages
2005. Vol. 58, no 2, 132-42 p.
Adult, Anxiety/*drug therapy/physiopathology, Cerebrovascular Circulation/*drug effects, Citalopram/*pharmacology/therapeutic use, Comparative Study, Double-Blind Method, Female, Humans, Male, Phobic Disorders/*drug therapy/physiopathology, Piperidines/*pharmacology/therapeutic use, Positron-Emission Tomography, Receptors; Neurokinin-1/antagonists & inhibitors, Research Support; Non-U.S. Gov't, Serotonin Uptake Inhibitors/*pharmacology/therapeutic use, Temporal Lobe/blood supply/radionuclide imaging, Tetrazoles/*pharmacology/therapeutic use
IdentifiersURN: urn:nbn:se:uu:diva-19636PubMedID: 16038684OAI: oai:DiVA.org:uu-19636DiVA: diva2:47408