Cognitive enhancers as adjuncts to psychotherapy - Use of D-cycloserine in phobic individuals to facilitate extinction of fear
Cognitive enhancers as adjuncts to psychotherapy - Use of D-cycloserine in phobic individuals to facilitate extinction of fear
复制标题
DOI：
10.1001/archpsyc.61.11.1136
复制
发表时间：
2004-11-01
影响因子：
--
通讯作者：
Davis, M
中科院分区：
文献类型：
--
作者：
Ressler, KJ;Rothbaum, BO;Davis, M
背景：治疗精神疾病的传统药理学方法侧重于纠正假定的生化异常。然而，有些疾病，特别是焦虑相关的疾病，例如特定的恐惧症，有一个情绪学习的组成部分，他们可以与心理治疗促进。目的：为了确定是否D-环丝氨酸（DCS），一种N-甲基-D-天冬氨酸受体的部分激动剂，以前已被证明可以改善啮齿动物的恐惧消退，设计：随机、双盲、安慰剂对照试验，研究DCS与安慰剂治疗结合精确控制的暴露模式。设置：参与者从一般社区招募到一个research clinic.Participants：28名被诊断患有恐高症的受试者的结构化临床访谈DSM-IVwere enrolled.Interventions：在我们获得恐惧的预处理措施后，受试者接受了2次行为暴露治疗，使用虚拟现实暴露在虚拟玻璃电梯内的高度。在2次虚拟现实暴露治疗之前，接受安慰剂或DCS单次给药。受试者、治疗师和评估员对治疗条件是盲目的。受试者返回治疗后1周和3个月的措施，以确定恐高症symptoms.Main Outcome Measures的存在和严重程度：包括在虚拟环境中的恐高症的措施，在真实的世界中的恐高症的措施，和整体改善的一般措施。一个客观的措施，恐惧，皮肤电波动，也包括在虚拟暴露于高度。症状进行了评估，自我报告和独立的评估员在约1周和3个月posttreatment.Results：暴露疗法与DCS相结合，导致显着较大的减少恐高症症状的所有主要结果的措施。在虚拟环境中，接受DCS的受试者与接受安慰剂的受试者相比有显著的改善（治疗后1周，P小于或等于0.001; 3个月后，P小于或等于0.05）。接受DCS的受试者在虚拟暴露期间治疗后皮肤电导波动也显示出显著更大的降低（P小于或等于.05）。此外，与接受安慰剂的受试者相比，接受DCS的受试者在现实世界恐高症症状的一般测量方面有显著更大的改善（恐高症回避[P小于或等于.02]，恐高症焦虑[P小于或等于.01]，对高度的态度[P小于或等于.04]，临床总体改善[P小于或等于.01]，和自我暴露于真实世界高度的次数[P小于或等于0.1]）;治疗早期改善明显，并在3个月时保持。这些试验数据为使用DCS急性给药作为暴露的辅助手段提供了初步支持-基于心理治疗，以加速有助于纠正精神病理学的联想学习过程。
Background: Traditional pharmacological approaches to treating psychiatric disorders focus on correcting presumed biochemical abnormalities. However, some disorders, particularly the anxiety-related disorders exemplified by specific phobia, have an emotional learning component to them that can be facilitated with psychotherapy.Objective: To determine whether D-cycloserine (DCS), a partial agonist at the N-methyl-D-aspartate receptor that has previously been shown to improve extinction of fear in rodents, will also improve extinction of fear in human phobic patients undergoing behavioral exposure therapy.Design: Randomized, double-blind, placebo-controlled trial examining DCS vs placebo treatment in combination with a precisely controlled exposure paradigm.Setting: Participants were recruited from the general community to a research clinic.Participants: Twenty-eight subjects with acrophobia diagnosed by the Structured Clinical Interview for DSM-IV were enrolled.Interventions: After we obtained pretreatment measures of fear, subjects were treated with 2 sessions of behavioral exposure therapy using virtual reality exposure to heights within a virtual glass elevator. Single doses of placebo or DCS were taken prior to each of the 2 sessions of virtual reality exposure therapy. Subjects, therapists, and assessors were blind to the treatment condition.-Subjects returned at 1 week and 3 months posttreatment for measures to determine the presence and severity of acrophobia symptoms.Main Outcome Measures: Included were measures of acrophobia within the virtual environment, measures of acrophobia in the real world, and general measures of overall improvement. An objective measure of fear, electrodermal skin fluctuation, was also included during the virtual exposure to heights. Symptoms were assessed by self-report and by independent assessors at approximately 1 week and 3 months posttreatment.Results: Exposure therapy combined with DCS resulted in significantly larger reductions of acrophobia symptoms on all main outcome measures. Subjects receiving DCS had significantly more improvement compared with subjects receiving placebo within the virtual environment (1 week after treatment, Pless than or equal to.001; 3 months later, Pless than or equal to.05). Subjects receiving DCS also showed significantly greater decreases in posttreatment skin conductance fluctuations during the virtual exposure (Pless than or equal to.05). Additionally, subjects receiving DCS had significantly greater improvement compared with subjects receiving placebo on general measures of real-world acrophobia symptoms (acrophobia avoidance [Pless than or equal to.02], acrophobia anxiety [Pless than or equal to.01], attitudes toward heights [Pless than or equal to.04], clinical global improvement [Pless than or equal to.01], and number of self-exposures to real-world heights [Pless than or equal to0.1]); the improvement was evident early in treatment and was maintained at 3 months.Conclusion: These pilot data provide initial support for the use of acute dosing of DCS as an adjunct to exposure-based psychotherapy to accelerate the associative learning processes that contribute to correcting psychopathology.