TREATMENT OF SSRI RESISTANT DEPRESSION IN ADOLESCENTS

一项为期5年的6个研究中心的研究，包括6个联锁R 01应用程序，拟研究400名青少年SSRI耐药抑郁症的治疗。受试者将是那些患有DSM-IV MDD，目前正在接受治疗，并且尽管至少6周的治疗仍然抑郁的受试者，其中至少2周是以较高剂量（40 mg）的帕罗西汀或氟西汀，并且其余的是以足够剂量（20 mg）。我们关注这两种SSRIs，因为它们是这类药物中最常用的药物，也是唯一两种被证明对治疗青少年抑郁症有效的药物。在初步评估后，青少年将在较高剂量的SSRI下再观察2周，然后重新评估。在这段时间内未显示出显著应答（CDRS-R降低等于或小于20%）的患者将从其当前方案中逐渐减少并进入方案。这400名受试者将被分配到四个条件之一，在12周内交付。临床上可接受的治疗应答率在2x2析因设计中，将在4个细胞中比较CGI-I（定义为CGI-I等于或小于2且CDRS-R降低等于或大于50%）：（1）SSRI类别内的转换（接受帕罗西汀治疗的患者转为氟西汀治疗;接受氟西汀治疗的患者转为帕罗西汀治疗）;（2）转换为不同的类别或药物（3）在SSRI类别内转换并接受认知行为治疗（CBT），以及;（4）转换为不同类别的药物（文拉法辛）加CBT。表现出临床可接受应答的受试者将接受额外12周的持续治疗，并接受与急性期相同的干预。无应答者将接受12周的开放治疗。所有受试者将在继续阶段后随访12个月，无论治疗依从性如何。我们假设会有药物效应（文拉法辛上级优于SSRI转换）、CBT效应（CBT +药物上级优于单独药物）以及CBT +文拉法辛上级优于其他3种细胞。此外，我们假设复发率和复发率在CBT处理的细胞中会更低。参与研究的6家临床试验机构和入组的受试者数量为：Brown（n=40）、达拉斯（n =80）（本申请的临床试验机构）、加尔维斯顿（n = 80）、俄勒冈州（n=80）、UCLA（n=40）和匹兹堡（n=80），后者是整个研究的协调临床试验机构。

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.