Improving Outcomes in Pharmacotheraphy of Social Phobia

改善社交恐惧症药物治疗的效果

• 批准号: 7126934
• 负责人: MICHAEL VAN AMERINGEN
• 金额: $ 21.08万
• 依托单位: MCMASTER UNIVERSITY
• 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/7126934
• 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

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（也称为社交恐惧症）是社区中最常见的精神疾病之一，与受影响个体的显著痛苦和功能障碍有关。广泛性社交焦虑障碍（GSAD）的高患病率（保守估计为4-5%）和大量伴随的发病率使其成为一个严重的公共卫生问题。虽然目前可用的治疗GSAD是有效的，大多数患者仍然残留症状后，初步的心理或心理药物干预。临床医生经常面临这样的问题，下一步该怎么做，这些患者，但有没有经验得出的数据，以指导临床实践的“下一步”策略，以改善结果的相对好处。缺乏此类数据是推进这一领域知识和患者护理的重大障碍。 鉴于药物治疗在精神病和初级保健环境中的广泛使用，以及在稀少的研究环境之外，基于经验的心理社会疗法的相对缺乏，我们提出了一项为期5年的研究，以系统地评估替代药物治疗策略在GSAD患者中的相对疗效，尽管初始SSRI药物治疗仍有症状。此外，我们还将检查响应的预测因素（例如，发病年龄、病程、合并症）对初始SSRI治疗的反应以及对所研究策略的不同反应的预测因素。我们还将研究是否多态性在充分研究的基因，影响血清素和/或儿茶酚胺代谢影响GSAD的治疗反应。该研究包括一项双盲、安慰剂对照、随机试验，以比较添加苯二氮卓类药物（氯硝西泮）或改用替代抗抑郁药（文拉法辛缓释剂）对GSAD患者的相对益处，这些患者在10周单独舍曲林试验后仍有症状。三个研究中心各入组163例患者（总计N = 490）：马萨诸塞州总医院焦虑和创伤应激相关疾病中心 医院、加州圣地亚哥大学焦虑症项目和麦克马斯特大学焦虑症诊所。采用CMSD机制是为了利用每个研究中心以往对GSAD患者进行系统评价和治疗的经验，并确保及时招募足够数量的受试者。 这项研究将提供系统的，前瞻性的数据在一个欠研究的领域-改善焦虑症患者的结果。因此，它直接涉及对相当一部分人口产生不利影响的一个关键公共卫生问题。