TREATMENT OF SSRI RESISTANT DEPRESSION IN ADOLESCENTS

一项为期5年、6个部位的研究，包括6个相互关联的R01应用程序，被提议在400名青少年中研究SSRI抵抗抑郁症的治疗。受试者将是那些患有DSM-IV MDD的人，目前正在治疗中，尽管至少治疗了6周，但仍然抑郁，其中至少2周是较高剂量(40毫克)的帕罗西汀或氟西汀，其余的是适当剂量(20毫克)。我们将重点放在这两种SSRI上，因为它们是这类药物中最常用的药物，也是唯一两种已被证明有效治疗青少年抑郁症的药物。在初步评估后，将观察青少年在更高剂量的SSRI额外2周，然后重新评估。那些在这段时间内没有显着反应(CDRS-R的降幅等于或低于2O%)的人将从目前的方案逐渐减少，并加入方案。这400名受试者将被分配到四种情况中的一种，在12周内分娩。采用2x2析因设计比较4个细胞对治疗的临床可接受缓解率(定义为CGI-I等于或小于2，且CDRS-R等于或大于50%)：(1)SSRI类内的切换(服用帕罗西汀的患者改用氟西汀；氟西汀的患者改用帕罗西汀)；(2)切换至不同的类别或制剂(文拉法辛)；(3)SSRI类内的切换加接受认知行为疗法(CBT)，以及；(4)切换到不同类别的制剂(文拉法辛)加CBT。表现出临床可接受反应的受试者将额外接受12周的持续治疗，干预措施与急性期相同。无反应者将接受为期12周的开放治疗。无论治疗依从性如何，所有受试者都将在持续阶段后接受12个月的随访。我们假设有药物效应(文拉法辛优于SSRI开关)，CBT效应(CBT+药物优于单独用药)，CBT+文拉法辛优于其他3种细胞。此外，我们假设CBT处理的细胞的复发率和复发率会更低。参与研究的六个地点和登记的对象数量是：布朗(n=40)，达拉斯(n=80)，本申请的地点，加尔维斯顿(n=80)，俄勒冈(n=80)，加州大学洛杉矶分校(n=40)和匹兹堡(n=80)，后者是整个研究的协调地点。

A 5-year, 6-site study, consisting of 6 interlocking R01 applications is proposed to study the treatment of SSRI-resistant depression in 400 adolescents. Subjects will be those with DSM-IV MDD, currently in treatment, and still depressed despite at least 6 weeks of treatment, at least 2 weeks of which are at a higher dosage (40mg) of either paroxetine or fluoxetine and the remainder at an adequate dosage (20 mg). We focus on these two SSRIs because they are most commonly used drugs in this class, and the only two for which efficacy has been demonstrated for the treatment of adolescent depression. After an initial assessment, the adolescents will be observed at the higher dosage of SSRI for an additional 2 weeks and then be reassessed. Those who show no significant response over that time (decrease in CDRS-R equal to or less than 2O%) will be tapered from their current regimen and entered into the protocol. These 400 subjects will be assigned to one of four conditions to be delivered over 12 weeks. The rate of clinically acceptable response to treatment (defined as a CGI-I equal to or less than 2 and equal to or greater than 50% decrease in the CDRS-R) will be compared across the 4 cells in a 2x2 factorial design: (1) switch within SSRI class (those on paroxetine switch to fluoxetine; those on fluoxetine switch to paroxetine); (2) switch to a different class or 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. Subjects who show a clinically acceptable response will receive 12 additional weeks of continuation treatment with the same intervention as in the acute phase. Non-responders will be offered 12 weeks of open treatment. All subjects will be followed up for 12 months after the continuation phase, regardless of treatment compliance. We hypothesize that there will be a medication effect (venlafaxine superior to SSRI switch), a CBT effect (CBT + medication superior to medication alone), and that CBT + venlafaxine superior to the other 3 cells. In addition, we hypothesize that the rate of relapse and recurrence will be lower in the CBT treated cells. The six sites participating and the number of subjects to be enrolled are: Brown (n=40), Dallas (n=80), the site of this application, Galveston (n=80), Oregon (n=80), UCLA (n=40), and Pittsburgh (n=80), with the latter being the coordinating site for the overall study.