TREATMENT OF SSRI RESISTANT DEPRESSION IN ADOLESCENTS

青少年 SSRI 抵抗性抑郁症的治疗

• 批准号: 6166150
• 负责人: KAREN D WAGNER
• 金额: $ 32万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-26 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6166150
• 关键词: adolescence (12-20); clinical research; cognitive behavior therapy; combination therapy; cooperative study; drug administration rate /duration; drug resistance; fluoxetine; human subject; human therapy evaluation; longitudinal human study; major depression; mental disorder chemotherapy; paroxetine; serotonin inhibitor

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 less than or equal to 20 percent) 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 less than or equal to 2 and greater than or equal to 50 percent 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 of agent (venlafaxine); (3) switch within SSRI class plus receive cognitive behavior therapy (CBT), and; (4) switch to a different class of agent (venlafazine) 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), Galveston (n=80), the site of this application, Oregon (n=80), UCLA (n=40), and Pittsburgh (n=80), with the latter being the coordinating site for the overall study.

拟开展一项为期 5 年、6 个地点的研究，由 6 个相互关联的 R01 应用组成，以研究 400 名青少年对 SSRI 耐药性抑郁症的治疗。 受试者将是患有 DSM-IV MDD 的患者，目前正在接受治疗，尽管治疗至少 6 周，但仍然处于抑郁状态，其中至少 2 周服用较高剂量（40mg）的帕罗西汀或氟西汀，其余时间服用足够剂量的帕罗西汀或氟西汀。剂量（20毫克）。 我们重点关注这两种 SSRIs，因为它们是此类药物中最常用的药物，也是唯一两种已被证实可治疗青少年抑郁症的药物。 初步评估后，将使用较高剂量的 SSRI 对青少年进行另外 2 周的观察，然后进行重新评估。 那些在这段时间内没有表现出明显反应的患者（CDRS-R 下降小于或等于 20%）将逐渐减少当前的治疗方案并进入方案。 这 400 名受试者将被分配到四种情况之一，并在 12 周内进行交付。 临床上可接受的治疗反应率（定义为 CGI-I 小于或等于 2 且 CDRS-R 下降大于或等于 50%）将在 2x2 析因设计中的 4 个细胞之间进行比较：（ 1) SSRI类别内的转换（服用帕罗西汀的患者改用氟西汀；服用氟西汀的患者改用帕罗西汀）； (2)改用不同类别的药物（文拉法辛）； (3) 转换 SSRI 类别并接受认知行为治疗 (CBT)，并且； (4)改用不同类别的药物（文拉法嗪）加CBT。 表现出临床上可接受的反应的受试者将接受额外 12 周的持续治疗，并采用与急性期相同的干预措施。 无反应者将接受 12 周的开放治疗。 无论治疗依从性如何，所有受试者将在继续阶段后随访 12 个月。 我们假设会有药物效应（文拉法辛优于 SSRI 开关）、CBT 效应（CBT + 药物优于单独药物），并且 CBT + 文拉法辛优于其他 3 个细胞。 此外，我们假设经过 CBT 处理的细胞的复发率和复发率会较低。参与的六个地点和要登记的受试者数量是：布朗（n=40）、达拉斯（n=80）、加尔维斯顿（n=80）、本申请地点、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。