Ketamine's dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders
Ketamine's dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders
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DOI：
10.1177/0269881117705089
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发表时间：
2017-10-01
影响因子：
4.1
通讯作者：
McNaughton, Neil
中科院分区：
文献类型：
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作者：
Glue, Paul;Medlicott, Natalie J.;McNaughton, Neil
N-甲基-D-天冬氨酸受体拮抗剂氯胺酮在难治性抑郁症、创伤后应激障碍和强迫症中具有快速起效活性。由于抑郁症和焦虑症的大脑网络活动相似，我们假设氯胺酮也可能在其他难治性焦虑症中起作用。我们采用单剂量递增研究设计（0.25、0.5、1 mg/kg皮下给药），每周一次，评价了氯胺酮在12例难治性广泛性焦虑症和/或社交焦虑症患者中的疗效和安全性，这些患者目前没有抑郁症。在给药后1小时内，患者报告焦虑减轻，持续长达7天。观察到抗焦虑作用、分离性副作用以及血压和心率变化的剂量-反应特征，0.25 mg/kg剂量组变化较小，较高剂量组变化逐渐增大且更持久。12例患者中有10例在0.5-1 mg/kg剂量下为治疗应答者。氯胺酮在该人群中安全且耐受性良好。氯胺酮可能是难治性广泛性焦虑症/社交焦虑症患者的潜在治疗选择。沿着其在难治性抑郁症、强迫症和创伤后应激障碍患者中的有效性，这些数据提出了一种有趣的可能性，即氯胺酮可能对以负面情绪状态为特征的疾病具有广泛的疗效，并且这些疾病可能具有共同的促发性神经生物学。
The N-methyl-D-aspartate receptor antagonist ketamine has rapid onset activity in treatment-resistant depression, post-traumatic stress disorder and obsessive compulsive disorder. Due to similarities in brain network activity in depression and anxiety disorders, we hypothesized that ketamine might also be active in other refractory anxiety disorders. We evaluated the efficacy and safety of ketamine in 12 patients with refractory generalized anxiety disorder and/or social anxiety disorder who were not currently depressed, using an ascending single dose study design (0.25, 0.5, 1 mg/kg administered subcutaneously) at weekly intervals. Within 1 h of dosing, patients reported reduced anxiety, which persisted for up to seven days. A dose-response profile was noted for anxiolytic effects, dissociative side effects, and changes in blood pressure and heart rate, with minor changes at 0.25 mg/kg, and progressively greater and more durable changes at the higher doses. Ten of 12 patients were treatment responders at 0.5-1 mg/kg. Ketamine was safe and well tolerated in this population. Ketamine may be a potential therapeutic alternative for patients with refractory generalized anxiety disorder/social anxiety disorder. Along with its demonstrated effectiveness in patients with treatment-resistant depression, obsessive compulsive disorder and post-traumatic stress disorder, these data raise the intriguing possibility that ketamine may have broad efficacy in disorders characterized by negative emotional states, and that these disorders may share a common precipitating neurobiology.