ADJUNCTS TO FLUOXETINE TREATMENT OF DEPRESSION

我们提议对患有严重抑郁障碍的成年人进行为期五年的研究。 氟西汀治疗无效。我们想要解决基本的 临床问题：一旦氟西汀试验足够的持续时间和剂量 已经失败了，下一步应该尝试什么？应该增加……的剂量吗？ 氟西汀，或保持相同的剂量，并添加小剂量的 三环类抗抑郁药还是锂？我们的研究范围是比较 这三种不同的治疗策略在这一领域的疗效 非常需要对照研究。关键的临床问题是 使用辅助药物提供了任何额外的好处，因为 这一策略在临床医生中的普及和使用日益增多。一个 该研究的另一个目的是评估阿司匹林的安全性和耐受性。 这些治疗。 这项研究涉及超过48个月的500名主要疾病患者的登记 抑郁症患者将公开服用氟西汀20 mg/d，共8次 几周。受试者将从门诊患者样本中抽取 患有严重抑郁障碍，通过使用结构化的 DSM-III-R-患者版临床访谈(Spitzer等人，1989)， 并使用最初的17个条目的汉密尔顿抑郁量表(HAM-D-17) (哈密尔顿，1960)得分大于16。如果这些抑郁患者失败了 为了回应这个为期8周的氟西汀开放治疗，他们将 有资格参加为期四周的三臂双盲三人假人 研究的阶段，他们将被随机分为三个不同的阶段 治疗：氟西汀40-60毫克/天，氟西汀20毫克/天，地塞帕明25-50毫克 氟西汀20 mg，锂300-600 mg/d。难解到 治疗将被定义为未能达到50%或更高 Ham-D-17分数降低，Ham-D-17分数大于10 注册的时间。将会有一个预期的分层 患者的随机化基于这样一个事实，即他们将是 部分应答者或无应答者：部分应答者将被考虑 那些经历了->25%和&lt；50%的 Ham-D-17分数或Ham-D-17分数或Ham-D-17分数&lt；16；无 应答者将被认为是那些有不到25%的 他们的HAM-D-17评分从治疗开始就降低了，并且 Ham-D-17得分大于16分。 这项研究扩展了我们之前关于药物治疗策略的研究 治疗难治性抑郁症并检查三种药物的疗效 对抑郁人群的不同治疗方法 同样的抗抑郁剂的定义是前瞻性的，而不是历史的 或者追溯。

We are proposing a five-year study of adults with major depressive disorder refractory to treatment with fluoxetine. We want to address the basic clinical question: once a fluoxetine trial of adequate duration and dosage has failed, what should be tried next? Should one increase the dosage of fluoxetine, or maintain the same dosage and add either low-dose of a tricylic antidepressant or lithium? The scope of our study is to compare the efficacy of these three different treatment strategies in this area in great need of controlled research. The critical clinical issue is whether the use of adjunctive medications offers any additional benefit given the popularity and increasing use of this strategy by clinicians. An additional aim of the study is to assess the safety and tolerability of these treatments. The study involves the enrollment over 48 months of 500 patients with major depression who will be treated openly with fluoxetine 20 mg/day for 8 weeks. The subjects will be drawn from an outpatient sample of patients with major depressive disorder, diagnosed by the use of the Structured Clinical Interview for DSM-III-R - Patient Edition (Spitzer et al, 1989), and with an initial 17-item Hamilton Rating Scale for Depression (HAM-D-17) (Hamilton, 1960) score greater than 16. If these depressed patients fail to respond to this 8-week open treatment with fluoxetine, they then will become eligible for a four-week, three-arm, double-blind, triple-dummy phase of the study where they will be randomized to one of three different treatments: fluoxetine 40-60 mg/day, fluoxetine 20 mg and desipramine 25-50 mg/day, and fluoxetine 20 mg and lithium 300-600 mg/day. Refractoriness to treatment will be defined as a failure to achieve a 50% or greater reduction in the HAM-D-17 scores and a HAM-D-17 score greater than 10 at the time of enrollment. There will be a prospective stratification of the patients for the randomization based on the fact that they will be either partial responders or non responders: partial responders will be considered those patients who had experienced a > 25% and < 50% reduction in their HAM-D-17 score or have a HAM-D-17 score or have a HAM-D-17 score < 16; non responders will be considered those patients who have had a less than 25% reduction in their HAM-D-17 score from the beginning of treatment and have a HAM-D-17 score greater than 16. The study extends our previous research on drug therapy strategies for treatment-refractory depression and examines the efficacy of three different treatments in a depressed population whose refractoriness to the same antidepressant has been defined prospectively rather than historically or retrospectively.