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.

Capsulotomy for refractory anxiety disorders: long-term follow-up of 26 patients.

OBJECTIVE: The objective of the present study was to evaluate the long-term efficacy and safety of capsulotomy in patients with anxiety disorders. METHOD: Twenty-six patients who had undergone bilateral thermocapsulotomy were followed up 1 year after the procedure and after a mean of 13 years. Primary diagnoses were generalized anxiety disorder (N=13), panic disorder (N=8), and social phobia (N=5). Measures of psychiatric status included symptom rating scales and neuropsychological testing. Ratings were done by psychiatrists not involved in patient selection or postoperative treatment. A quantitative magnetic resonance imaging (MRI) evaluation was conducted to search for common anatomic denominators. Seventeen of the 23 patients who were alive at long-term follow-up were followed up in person, and one was interviewed by telephone; the relatives of these 18 patients were interviewed. RESULTS: The reduction in anxiety ratings was significant both at 1-year and long-term follow-up. Seven patients, however, were rated as having substantial adverse symptoms; the most prominent adverse symptoms were apathy and dysexecutive behavior. Neuropsychological performance was significantly worse in the patients with adverse symptoms. No common anatomic denominator could be found in responders in the analysis of MRI scans. CONCLUSIONS: Thermocapsulotomy is an effective treatment for selected cases of nonobsessive anxiety but may carry a significant risk of adverse symptoms indicating impairment of frontal lobe functioning. These findings underscore the importance of face-to-face assessments of adverse symptoms.