TREATMENT OF SSRI RESISTANT DEPRESSION IN ADOLESCENTS

一项为期5年、包含6个互锁R01应用程序的6点研究，旨在研究400名青少年抗ssri抑郁症的治疗方法。受试者为DSM-IV重度抑郁症患者，目前正在接受治疗，尽管治疗至少6周，其中至少2周使用更高剂量（40mg）的帕罗西汀或氟西汀，其余时间使用适当剂量（20mg）。我们关注这两种SSRIs是因为它们是这类药物中最常用的药物，也是仅有的两种被证明对治疗青少年抑郁症有效的药物。在初步评估后，青少年将以更高剂量的SSRI观察另外2周，然后重新评估。在这段时间内无明显反应（CDRS-R下降等于或小于20%）的患者将逐渐退出当前的方案并加入方案。这400名受试者将被分配到四种情况中的一种，在12周内交付。临床可接受的治疗缓解率（定义为CGI-I等于或小于2，CDRS-R下降等于或大于50%）将在2x2因子设计中比较4个细胞：(1)SSRI类切换（帕罗西汀组切换到氟西汀组，氟西汀组切换到帕罗西汀组）；(2)切换到不同的类别或药物（文拉法辛）；(3)切换SSRI类并接受认知行为治疗（CBT）；(4)改用不同类型的药物（文拉法辛）加CBT。表现出临床可接受反应的受试者将接受与急性期相同干预措施的额外12周的继续治疗。无应答者将接受12周的开放治疗。所有受试者将在持续期后随访12个月，无论治疗依从性如何。我们假设会有药物效应（文拉法辛优于SSRI转换），CBT效应（CBT +药物优于单独药物），CBT +文拉法辛优于其他3种细胞。此外，我们假设在CBT治疗的细胞中复发率和复发率会更低。参与研究的6个地点和受试者人数分别是：布朗大学（n=40）、达拉斯（n=80）（本次申请的地点）、加尔维斯顿（n=80）、俄勒冈州（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.