Treatment of SSRI-Resistant Depression in Adolescents

描述(由申请人提供)：这项为期两年、六个地点的竞争性更新比较了四种治疗SSRI抵抗型青少年抑郁症的策略。我们建议完成对400名12-18岁青少年的招募，这些青少年尽管对目前在社区实践中使用的一种SSRI抗抑郁药物(即氟西汀、西酞普兰、艾司匹兰、舍曲林)进行了充分的试验，但他们仍然患有抑郁症。在这个项目期间，我们将招募100名患有SSRI抵抗型抑郁症的青少年来完成我们的目标招募。临床可接受的应答率(定义为CDRS-R下降50%)、CDRS-R上抑郁症状减轻的斜率和单位改善的直接治疗费用将以2x2析因设计在4个细胞中进行比较：(1)在SSRI类别内切换(服用西酞普兰的患者切换至氟西汀；服用氟西汀的患者切换至西酞普兰；服用舍曲林的患者随机切换至氟西汀或西酞普兰)；(2)切换至不同类别的药物(文拉法辛)；(3)改用SSRI类药物加认知行为疗法(CBT)；(4)改用文拉法辛加认知行为疗法。SSRI的“适当治疗”被定义为8周的总治疗，其中至少4周相当于20毫克的氟西汀，至少4周相当于40毫克的氟西汀。为了进入研究，受试者在两周内的两个时间点进行评估，并且必须表现出足够的严重性(CDRS-R&>40，CGI-S&>4)和稳定性(CDRS在两周内下降&lt；30%)。符合这些标准的受试者将在目前的方案基础上逐渐减少。治疗的急性期为12周，在此期间，受试者可以接受最多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再接受12周的持续治疗。所有受试者，无论治疗依从性如何，都将在急性治疗结束时、治疗中点和治疗结束时进行评估，并在继续治疗结束后每6个月进行一次评估，为期一年。我们假设，在充分的临床反应和抑郁症状的下降率方面，文拉法辛优于SSRI Switch，CBT+药物优于单独用药，CBT+文拉法辛优于其他三种细胞。意义重大。由于40%的抑郁青少年对SSRI的初步治疗没有反应，这是一个常见和严重的公共卫生问题。到目前为止，入选的受试者是高危人群，在摄入时普遍存在慢性抑郁症和自杀倾向。这是现存的唯一一项针对SSRI抵抗型青少年抑郁症治疗的研究，将独特地提供有关治疗指南、不同抗抑郁药的相对安全性和有效性以及在这种情况的药物治疗中加入CBT的价值的信息。该网站的总部设在匹兹堡，匹兹堡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