Treatment of SSRI-Resistant Depression in Adolescents

描述（由申请人提供）：这项为期两年，六个站点的竞争性更新比较了治疗ssri抗性青少年抑郁症的四种策略。我们建议招募400名12-18岁的青少年，尽管对目前在社区实践中使用的一种SSRI抗抑郁药（即氟西汀、西酞普兰、艾司西酞普兰、舍曲林）进行了充分的试验，但他们仍然感到抑郁。在这个项目期间，我们将招募100名患有ssri抵抗性抑郁症的青少年来完成我们的目标招募。临床可接受的缓解率（定义为CGI-I < 2、CGIS < 3和> CDRS-R减少50%）、CDRS-R抑郁症状减少的斜率和单位改善的直接治疗成本将在2x2因子设计中进行比较：(1)SSRI类切换（西酞普兰组切换到氟西汀；氟西汀组切换到西酞普兰；舍曲林组随机切换到氟西汀或西酞普兰）；(2)改用不同类别的药物（文拉法辛）；(3) SSRI类转换加认知行为治疗（CBT）；(4)改用另一类药物（文拉法辛）加CBT。用SSRI进行“充分治疗”的定义是：总治疗时间为8周，其中至少4周的氟西汀剂量相当于20毫克，至少4周的氟西汀剂量相当于40毫克。为了进入研究，受试者在间隔2周的两个时间点进行评估，并且必须证明足够的严重程度（CDRS- r bbb40, CGI-S bbb4）和稳定性（两周内CDRS下降< 30%）。符合这些标准的受试者将从目前的方案中逐渐交叉递减。急性期治疗为12周，在此期间，受试者可接受高达40毫克的氟西汀或西酞普兰，或225毫克的文拉法辛。表现出临床可接受反应的受试者将接受额外12周的继续治疗。所有受试者，无论治疗依从性如何，将在急性治疗开始、中点和结束时进行评估，并在继续治疗结束后的1年内每6个月进行一次评估。我们假设，在充分的临床反应和抑郁症状下降率方面，文拉法辛优于SSRI转换，CBT +药物优于单独用药，CBT +文拉法辛优于其他三种细胞。的意义。因为40%的抑郁青少年对SSRI的初始治疗没有反应，这是一个普遍而严重的公共卫生问题。到目前为止，纳入的受试者都是高危人群，在摄入时普遍存在慢性抑郁症和自杀倾向。这是目前唯一一项针对抗ssri青少年抑郁症治疗的研究，它将为治疗指南、不同抗抑郁药的相对安全性和有效性以及将CBT加入药物治疗的价值提供独特的信息。该网站位于匹兹堡，同时也是该研究的数据协调中心

DESCRIPTION (provided by applicant): This two-year, six-site, competitive renewal compares four strategies for the treatment of SSRI-resistant adolescent depression. We propose to complete our recruitment of 400 adolescents, aged 12-18, who continue to be depressed despite an adequate trial of one of the SSRI antidepressants currently used in community practice (i.e., fluoxetine, citalopram, escitalopram, sertraline). During this project period, we will empanel 100 adolescents with SSRI-resistant depression to complete our target recruitment. The rates of clinically acceptable response (defined as a CGI-I < 2, CGIS < 3, and > 50% decrease in the CDRS-R), slope of decrease of depressive symptoms on the CDRS-R, and direct cost of treatment per unit of improvement will be compared across the 4 cells in a 2x2 factorial design: (1) switch within SSRI class (those on citalopram switch to fluoxetine; those on fluoxetine switch to citalopram; those on sertraline switch randomly to either fluoxetine or citalopram); (2) switch to a different class of agent (venlafaxine); (3) switch within SSRI class plus receive cognitive behavior therapy (CBT); and (4) switch to a different class of agent (venlafaxine) plus CBT. "Adequate treatment" with an SSRI is defined as > 8 weeks of total treatment, at least 4 weeks of which were at the equivalent of 20 mg of fluoxetine, and at least 4 weeks of which were at the equivalent > 40 mg of fluoxetine. In order to enter the study, subjects are assessed at two points in time 2 weeks apart, and must demonstrate sufficient severity (CDRS-R > 40, CGI-S > 4) and stability (decline in CDRS over two weeks < 30%). Subjects meeting these criteria will be cross-tapered gradually from their current regimen. The acute phase of treatment is 12 weeks, during which subjects can receive up to 40 mg of fluoxetine or citalopram, or 225 mg of venlafaxine. Subjects who show a clinically acceptable response will receive continuation treatment for an additional 12 weeks. All subjects, regardless of treatment compliance, will be assessed at intake, midpoint, and the end of acute treatment, and every 6 months thereafter for 1 year after the end of continuation treatment. We hypothesize that, with regard to adequate clinical response and rate of decline of depressive symptoms, venlafaxine will be superior to SSRI switch, CBT + medication will be superior to medication alone, and that CBT + venlafaxine will be superior to the other three cells. Significance. Because 40% of depressed adolescents do not respond to initial treatment with an SSRI, this is a common and serious public health problem. Subjects empaneled thus far are a high-risk group, with prevalent chronic depression and suicidality at intake. This is the only extant study to address the treatment of SSRI-resistant adolescent depression, and will be uniquely informative about treatment guidelines, the relative safety and efficacy of different antidepressants, and the value of adding CBT to medication treatment for this condition. This site is based in Pittsburgh, which also serves as the Data Coordinating Center for the study