Improving Outcomes in Pharmacotherapy of Social Phobia

改善社交恐惧症药物治疗的效果

• 批准号: 7126935
• 负责人: MURRAY B. STEIN
• 金额: $ 30.17万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-28 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7126935
• 关键词: antidepressants; benzodiazepines; catecholamines; clinical research; combination chemotherapy; comorbidity; cooperative study; disease /disorder onset; disease /therapy duration; drug metabolism; drug resistance; genetic polymorphism; human subject; human therapy evaluation; mental disorder chemotherapy; patient oriented research; pharmacogenetics; phobias; psychopharmacology; serotonin inhibitor; sertraline; venlafaxine; antidepressants; benzodiazepines; catecholamines; clinical research; combination chemotherapy; comorbidity; cooperative study; disease /disorder onset; disease /therapy duration; drug metabolism; drug resistance; genetic polymorphism; human subject; human therapy evaluation; mental disorder chemotherapy; patient oriented research; pharmacogenetics; phobias; psychopharmacology; serotonin inhibitor; sertraline; venlafaxine

DESCRIPTION (provided by applicant): Social anxiety disorder (also referred to as social phobia) is among the most common psychiatric conditions in the community, and is associated with significant distress and dysfunction in affected individuals. This combination of high prevalence (conservatively 4-5%) and substantial attendant morbidity in generalized social anxiety disorder (GSAD) positions it as a serious public health problem. Although currently available treatments for GSAD are efficacious, most patients remain residually symptomatic after initial psychosocial or psychopharmacological intervention. Clinicians regularly face the question of what to do next for these patients, but there are no empirically derived data available to guide clinical practice regarding the relative benefits of "next step" strategies to improve outcome. The absence of such data is a substantial barrier to advancing knowledge and patient care in this area. Given the extensive use of medication treatment in psychiatric and primary care settings and the relative dearth of availability of empirically based psychosocial therapies outside of rarified research settings, we are proposing a 5-year study to systematically assess the relative efficacy of alternate pharmacologic treatment strategies in patients with GSAD remaining symptomatic despite initial SSRI pharmacotherapy. In addition, we will examine predictors of response (e.g., age at onset, duration of illness, comorbidity) to initial SSRI therapy and predictors of differential response to the strategies under study. We will also examine whether polymorphisms in well-studied genes that influence serotonin and/or catecholamine metabolism influence response to treatment in GSAD. The study comprises a double-blind, placebo controlled, randomized trial to compare the relative benefits of the addition of a benzodiazepine (clonazepam), or a switch to an alternative antidepressant (venlafaxine extended-release), for patients with GSAD who remain symptomatic after a 10-week trial of sertraline alone. One hundred sixty-three patients will be entered at each of the three sites (total N = 490): the Center for Anxiety and Traumatic Stress Related Disorders at the Massachusetts General Hospital, the Anxiety Disorders Program at the University of California San Diego, and the Anxiety Disorders Clinic at McMaster University. The CMSD mechanism is being employed to take advantage of each of the sites' previous experience with the systematic evaluation and treatment of individuals with GSAD and to ensure timely recruitment of an adequate number of subjects. This study will provide systematic, prospectively derived data in an understudied area - that of improving outcomes in patients with anxiety disorders. It thus directly addresses a critical public health issue that adversely affects a substantial proportion of the population.

描述（由申请人提供）：社交焦虑症（也称为社会恐惧症）是社区中最常见的精神病病之一，并且与受影响的个体的严重困扰和功能障碍有关。高流行率（保守的4-5％）和广义社交焦虑症（GSAD）的大量伴随发病率的结合将其定位为严重的公共卫生问题。尽管目前对GSAD的可用治疗是有效的，但在初始的心理社会或心理药理干预后，大多数患者仍然存在残留症状。临床医生经常面临这些患者接下来要做什么的问题，但是没有经验得出的数据可用于指导有关“下一步”策略的相对好处以改善预后的临床实践。缺乏此类数据是在这一领域推进知识和患者护理的重大障碍。 鉴于在精神病和初级保健环境中广泛使用药物治疗，以及在稀有研究环境之外基于经验的基于经验的心理社会疗法的可用性，我们提议一项为期5年的研究，以系统地评估GSAD替代药物治疗策略的相对效率，尽管该策略使GSAD降低了初始SSRI药物药物治疗，但仍有症状。此外，我们将研究对初始SSRI治疗的反应预测因素（例如，发病时代，疾病持续时间，合并症）以及对所研究策略的差异反应的预测指标。我们还将研究影响5-羟色胺和/或儿茶酚胺代谢的良好基因中的多态性是否影响GSAD治疗的反应。该研究包括一项双盲，安慰剂控制的随机试验，以比较苯并二氮卓类药物（氯硝西ep剂）的相对好处，或切换到替代性抗抑郁药（Venlafaxine Extended-Release）的替代性抗抑郁药（对于单独进行10周的均可症状试验后仍然有症状的GSAD患者）的相对益处。将在三个部位中的每个站点中输入一百六十三名患者：马萨诸塞州一般性的焦虑与创伤性应力相关疾病中心 医院，加州大学圣地亚哥分校的焦虑症计划以及麦克马斯特大学的焦虑症诊所。 CMSD机制被用来利用每个站点以前对具有GSAD的人进行系统评估和治疗的经验，并确保及时招募足够数量的受试者。 这项研究将在研究不足的领域提供系统的，前瞻性的数据 - 改善焦虑症患者的结局。因此，它直接解决了一个关键的公共卫生问题，该问题会对人口的很大一部分产生不利影响。