Antidepressant efficacy of the antimuscarinic drug scopolamine - A randomized, placebo-controlled clinical trial
Antidepressant efficacy of the antimuscarinic drug scopolamine - A randomized, placebo-controlled clinical trial
复制标题
DOI：
10.1001/archpsyc.63.10.1121
复制
发表时间：
2006-10-01
影响因子：
--
通讯作者：
Drevets, Wayne C.
中科院分区：
文献类型：
--
作者：
Furey, Maura L.;Drevets, Wayne C.
背景：需要改进的治疗药物，更快速，更有效地治疗抑郁症是至关重要的。在一项初步研究中，我们评估了胆碱能系统在抑郁症认知症状中的作用，并意外地观察到与安慰剂相比，抗毒蕈碱药物氢溴酸东莨菪碱（4 μ g/kg静脉注射）给药后抑郁症严重程度迅速降低（P= .002）。随后，设计了一项临床试验，以更具体地评估东莨菪碱的抗抑郁疗效。目的：评估东莨菪碱作为一种潜在的抗抑郁药。设计：进行了两项研究：一项双盲，安慰剂对照，剂量探索研究，随后是一项双盲，安慰剂对照，交叉临床试验。设置：国家精神卫生研究所。患者：符合DSM-IV复发性重性抑郁障碍或双相情感障碍标准的18 - 50岁的抑郁症门诊患者。在39名符合条件的患者中，19名被随机分组，18名完成了试验。干预措施：多次会议，包括安慰剂或氢溴酸东莨菪碱（4 μ g/kg）静脉输注。个体被随机分配至安慰剂/东莨菪碱或东莨菪碱/安慰剂序列（3个安慰剂疗程的系列和3个东莨菪碱疗程的系列）。治疗间隔3 ~ 5天。主要结果测量：采用Montgomery-Asberg抑郁评定量表和汉密尔顿焦虑评定量表进行精神病学评估，以评估东莨菪碱对抗抑郁和抗焦虑的反应。与安慰剂相比，东莨菪碱给药后观察到抑郁和焦虑评定量表评分降低（两者均P <0.001）。东莨菪碱/安慰剂组在东莨菪碱给药后，抑郁和焦虑量表评分也相对于基线降低（P <0.001），并且这些影响在接受安慰剂时持续存在。两组在东莨菪碱给药后第一次评估时均有显著改善（P
Context: The need for improved therapeutic agents that more quickly and effectively treat depression is critical. In a pilot study we evaluated the role of the cholinergic system in cognitive symptoms of depression and unexpectedly observed rapid reductions in depression severity following the administration of the antimuscarinic drug scopolamine hydrobromide ( 4 mu g/kg intravenously) compared with placebo ( P= .002). Subsequently a clinical trial was designed to assess more specifically the antidepressant efficacy of scopolamine.Objective: To evaluate scopolamine as a potential antidepressant agent.Design: Two studies were conducted: a double-blind, placebo-controlled, dose-finding study followed by a double-blind, placebo-controlled, crossover clinical trial.Setting: The National Institute of Mental Health.Patients: Currently depressed outpatients aged 18 to 50 years meeting DSM-IV criteria for recurrent major depressive disorder or bipolar disorder. Of 39 eligible patients, 19 were randomized and 18 completed the trial.Interventions: Multiple sessions including intravenous infusions of placebo or scopolamine hydrobromide (4 mu g/kg). Individuals were randomized to a placebo/ scopolamine or scopolamine/ placebo sequence (series of 3 placebo sessions and series of 3 scopolamine sessions). Sessions occurred 3 to 5 days apart.Main Outcome Measures: Psychiatric evaluations using the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale were performed to assess antidepressant and antianxiety responses to scopolamine.Results: The placebo/ scopolamine group showed no significant change during placebo infusion vs baseline; reductions in depression and anxiety rating scale scores ( P < .001 for both) were observed after the administration of scopolamine compared with placebo. The scopolamine/ placebo group also showed reductions in depression and anxiety rating scale scores ( P < .001 for both) after the administration of scopolamine, relative to baseline, and these effects persisted as they received placebo. In both groups, improvement was significant at the first evaluation after scopolamine administration ( P