Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo.
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.
Furmark
Tomas
T
Department of Psychology, Uppsala University, Uppsala, Sweden. tomas.furmark@psyk.uu.se
Appel
Lieuwe
L
Michelgård
Asa
A
Wahlstedt
Kurt
K
Ahs
Fredrik
F
Zancan
Stefano
S
Jacobsson
Eva
E
Flyckt
Karin
K
Grohp
Magnus
M
Bergström
Mats
M
Pich
Emilio Merlo
EM
Nilsson
Lars-Göran
LG
Bani
Massimo
M
Långström
Bengt
B
Fredrikson
Mats
M
D000328:Adult; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D015283:Citalopram / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010698:Phobic Disorders / Q000188:drug therapy* / Q000503:physiopathology; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D049268:Positron-Emission Tomography; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013702:Temporal Lobe / Q000098:blood supply / Q000000981:diagnostic imaging; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use
D015283:Citalopram; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D017367:Selective Serotonin Reuptake Inhibitors; D013777:Tetrazoles; C103207:vofopitant