Cerebral Blood Flow Changes After Treatment of Social Phobia with the Neurokinin-1 Antagonist GR205171, Citalopram, or Placebo

• Published in: Biological psychiatry (1969) 2005-07, Vol.58 (2), p.132-142
• Main Authors: Furmark, Tomas, Appel, Lieuwe, Michelgård, Åsa, Wahlstedt, Kurt, Åhs, Fredrik, Zancan, Stefano, Jacobsson, Eva, Flyckt, Karin, Grohp, Magnus, Bergström, Mats, Pich, Emilio Merlo, Nilsson, Lars-Göran, Bani, Massimo, Långström, Bengt, Fredrikson, Mats
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Anxiety - drug therapy; Anxiety - physiopathology; Anxiety disorders. Neuroses; Anxiety/drug therapy/physiopathology; Biological and medical sciences; Brain; Cerebrovascular Circulation - drug effects; Citalopram - pharmacology; Citalopram - therapeutic use; Citalopram/pharmacology/therapeutic use; Comparative Study; Double-Blind Method; Female; Humans; Male; Medical sciences; Medicin och hälsovetenskap; Neurokinin-1 Receptor Antagonists; Neuropharmacology; NK1 antagonist; Pharmacology. Drug treatments; Phobia; Phobic Disorders - drug therapy; Phobic Disorders - physiopathology; Phobic Disorders/drug therapy/physiopathology; Piperidines - pharmacology; Piperidines - therapeutic use; Piperidines/pharmacology/therapeutic use; Positron-Emission Tomography; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; rCBF; Serotonin Uptake Inhibitors - pharmacology; Serotonin Uptake Inhibitors - therapeutic use; Serotonin Uptake Inhibitors/pharmacology/therapeutic use; social anxiety; SSRI; substance P; Temporal Lobe - blood supply; Temporal Lobe - diagnostic imaging; Temporal Lobe/blood supply/radionuclide imaging; Tetrazoles - pharmacology; Tetrazoles - therapeutic use; Tetrazoles/pharmacology/therapeutic use
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2005.03.029

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. 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. 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. 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.