Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo
Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo
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DOI：
10.1016/j.biopsych.2005.03.029
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发表时间：
2005-07-15
影响因子：
10.6
通讯作者：
Fredrikson, M
中科院分区：
文献类型：
--
作者：
Furmark, T;Appel, L;Fredrikson, M
背景：越来越多的证据表明，药物阻断P物质偏好的神经激肽-1（NK 1）受体可以减轻焦虑。本研究比较了NK 1受体拮抗剂，西酞普兰，和安慰剂对大脑活动和焦虑症状在social phobia.Methods：36例诊断为社交恐惧症的患者进行了治疗6周的NK 1拮抗剂GR 205171（5毫克），西酞普兰（40毫克），或匹配的安慰剂随机双盲条件下。GR 205171给药4周，然后给药2周安慰剂。治疗前后，局部脑血流量（rCBF）在一个紧张的公开演讲任务进行了评估，使用氧-15正电子发射断层扫描。反应率由临床总体印象改善Scale.Results：患者改善到更大的程度与NK 1拮抗剂（41.7%的反应者）和西酞普兰（50%的反应者），与安慰剂（8.3%的反应者）相比。组内和组间比较表明，症状的改善是由显着减少rCBF反应公开演讲的鼻皮质，杏仁核，和副丘脑campal-hippocampal区域。的rCBF模式得到证实，在后续分析的响应者和主题显示大的状态焦虑reduction.Conclusions：短期管理GR 205171和西酞普兰缓解社交焦虑。神经激肽-1拮抗剂可能通过减弱内侧颞叶网络中的神经活动而发挥5-羟色胺再摄取抑制剂的作用。
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.