Enhancing Panic and Smoking Reduction Treatment with D-Cycloserine

描述(由申请人提供)：美国约有900万至1500万吸烟者在一生中符合至少一种焦虑症的标准(Kessler等人，2005年)，这些人经历了戒烟的重大挑战(Piper等人，2010a；Zvolensky等人，2008年)。然而，很少有人注意焦虑症患者，特别是有恐慌症病史的吸烟者的烟草使用情况。这一群体的研究尤其重要，因为研究表明，他们的戒烟率明显低于没有恐慌症发作史的吸烟者，而且他们对安慰剂、单一戒烟和联合戒烟药物治疗的反应相同(Piper等人，2010a)。目前这项研究的目标是在认知行为程序(Cbt)中加入d-环丝氨酸(Dcs)和pil安慰剂的效果进行初步测试，cbt的目标是焦虑敏感、痛苦 吸烟维持中的不容忍和恐慌发作。拟议的项目直接建立在我们的基础和临床研究以及相应的试点工作上：(A)烟草与恐慌的关系；(B)针对恐慌和焦虑倾向的吸烟者的强化认知-行为干预(CBT)；以及(C)加强CBT以减少恐慌。该项目旨在获得初步的效果大小，并对我们的专门行为小组方案--恐慌和减少吸烟治疗(PSRT)--与DSC联合治疗与PSRT+安慰剂进行比较--的假定机制进行初步测试。PSRT计划将拦截暴露、认知结构调整和心理教育练习与标准戒烟策略和尼古丁替代疗法相结合。有恐慌症发作的成年吸烟者(n=80)将被招募并随机分配到(1)PSRT+DC或(2)PSRT+避孕药安慰剂。主要结果指标为戒烟后2周、4周、8周、10周、16周和24周的时点戒烟率、首次戒烟时间和再次吸烟时间。建议的调节因素包括恐慌症发作、痛苦不耐受、焦虑敏感、尼古丁戒断症状和负面影响。这些变量将在基线、治疗期间每周以及戒烟后2、4、8、10、16和24周进行评估。这项拟议的研究代表着将基础研究转化为治疗尼古丁依赖的策略的关键和重要阶段。这项调查通过测试一种综合干预措施来解决一个重要的公共卫生问题-由基础研究提供信息-这可能导致对有风险的吸烟者进行更有效和高效的治疗，同时隔离解释机制。预期的发现应该：(1)指导恐慌和焦虑-吸烟关系的理论概念化方面的进展；(2)为将DC添加到对患有恐慌症发作的吸烟者的心理社会/行为和药物戒烟综合干预中提供初步效果大小数据，从而为大规模后续试验提供必要的数据。

DESCRIPTION (provided by applicant): Approximately 9-15 million smokers in the U.S. meet criteria for at least one anxiety disorder during their lifetime (Kessler et al., 2005) and these persons experience significant challenges quitting tobacco (Piper et al., 2010a; Zvolensky et al., 2008). Yet, little attention has been given to the maintenance of tobacco use among persons with anxiety disorders, and in particular, smokers with a history of panic attacks. This group is especially important to study because research shows that they have significantly lower quit rates than smokers with no history of panic attacks, and that they respond the same to placebo, single cessation, and combination cessation pharmacotherapy (Piper et al., 2010a). The goal of the current research is to pilot test the efficacy of the addition of d-cycloserine (DCS) versus pil placebo to a cognitive-behavioral program (CBT) targeting the role of anxiety sensitivity, distress intolerance, and panic attacks in smoking maintenance. The proposed project builds directly from our basic and clinical research as well as corresponding pilot work on (a) tobacco-panic relations; (b) intensive cognitive-behavioral intervention (CBT) for panic- and anxious-prone smokers; and (c) DCS enhancement of CBT for panic reduction. The project aims to obtain initial effect sizes and perform an initial test of putative mechanisms of our specialized behavioral group protocol, Panic and Smoking Reduction Treatment (PSRT), combined with DCS as compared to PSRT plus placebo. The PSRT program integrates interceptive exposure, cognitive restructuring, and psycho education exercises with standard smoking cessation strategies and nicotine replacement therapy. Adult smokers (n = 80) with panic attacks will be recruited and randomly assigned to either: (1) PSRT plus DCS or (2) PSRT plus pill placebo. Primary outcome measures will be point prevalence abstinence, time to first smoking lapse, and time to smoking relapse, assessed at 2, 4, 8, 10, 16, and 24 weeks after quit date. Proposed mediators include panic attacks, distress intolerance, anxiety sensitivity, nicotine withdrawal symptoms, and negative effect. These variables will be assessed at baseline, weekly during the treatment phase, and at 2, 4, 8, 10, 16, and 24 weeks after quit date. The proposed study represents a crucial and important stage in translating basic research to strategies for treating nicotine dependence. The investigation addresses an important public health issue by testing an integrated intervention --- informed by basic research --- that may lead to a more effective and efficient treatment for at-risk smokers while simultaneously isolating explanatory mechanisms. The expected findings should: (1) guide advances in the theoretical conceptualization of the mechanisms involved in panic- and anxiety-smoking relations; and (2) provide initial effect size data for the addition of DCS to an integrated psychosocial/behavioral and pharmacological smoking cessation intervention for smokers with panic attacks, and thus provide the necessary data for a large-scale follow-up trial.