COURSE OF TREATMENT RESISTANT DEPRESSION

对抗抑郁药的治疗耐药性发生在高达20%的主要 抑郁症，可导致持续性残疾发病率，可能会增加 自杀的风险，但令人惊讶的是，研究仍然不足。 长期 本研究的目的是提高对治疗的认识， 抗抑郁症（TRD），以便可以更多地使用现有的治疗方法 有效地 第一个具体目标是测试方法的可靠性，以评估 治疗阻力 没有方法可以区分"耐药性" 从"不耐受"到"充分的抗抑郁药试验"。 第二 具体目的是确定锂的急性和长期疗效 与安慰剂增强去甲替林（NT）相比。 没有研究表明 有系统地跟踪锂强化（LiAug）反应者 前瞻性地。 第三个具体目标是比较急性和长期 单用反苯环丙胺（TCP）与TCP加锂治疗慢性乙型肝炎远期疗效比较 对NT的LiAug治疗无效的患者。 没有研究表明 给予LiAug失败的患者系统的下一次治疗， 纵向跟随他们。 第四个具体目标是制定一个 TRD患者对LiAug和TCP反应的预测量表。 没有 有一种方法可以预测任何抗抑郁药的反应。 实验设计和具体方法是：1）评估 McLean医院抗抑郁治疗记录的可靠性 精神科医生使用独立的访谈和未压缩的记录20 患有DSM-III-R、非精神病、单极的连续住院和门诊患者 抑郁症，有或没有抑郁症，谁失败了一个或多个 抗抑郁药试验; 2）比较6周试验的疗效， 在为期6周的NT前瞻性失败试验中添加锂剂与安慰剂 （N = 100）在门诊与上述诊断相同的患者中; 在前瞻性研究中， 随机化，为期8周的试验，上述受试者的LiAug失败， 去甲替林 将定期对受试者进行随访，最多3 年;和4）开发对LiAug反应的预测工具 和TCP使用预测变量和共病条件。 这四部分研究的重要性在于，临床医生将能够 使用开发的方法来评估治疗耐药性;急性和 LiAug和TCP的长期疗效以及TRD的自杀风险将被 确定;将开发TRD的LiAug和TCP预测因子， 可以改善未来的TRD研究。

Treatment resistance to antidepressants occurs in up to 20% of major depressions, can result in persistent disabling morbidity, may increase the risk of suicide, but remains surprisingly understudied. The long term objective of this study is to improve the understanding of treatment resistant depression (TRD) so that available treatments can be used more effectively. The first specific aim is to test the reliability of a method to evaluate treatment resistance. No method is available to differentiate "resistance to" from "intolerance of" adequate antidepressant trials. The second specific aim is to determine the acute and long term efficacy of lithium versus placebo augmentation of nortriptyline (NT). No study exists that has systematically followed lithium augmentation (LiAug) responders prospectively. The third specific aim is to compare the acute and long term efficacy of tranylcypromine (TCP) alone versus TCP plus lithium for the patients who fail to respond to LiAug of NT. No study exists that gives patients who failed LiAug the next treatment systematically and then follows them longitudinally. The fourth specific aim is to develop a predictor scale for response to LiAug and TCP for patients with TRD. No method exists to predict response to any antidepressant. The experimental design and specific methods are: 1) assessment of reliability of the McLean Hospital Antidepressant Treatment Record by five psychiatrists using independent interviews and uncondensed records of 20 consecutive in- and outpatients with DSM-III-R, non-psychotic, unipolar depression, with or without melancholia, who had failed one or more antidepressant trials; 2) comparison of the efficacy of a six week trial of lithium versus placebo added to a prospective failed six week trial of NT (N = 100) in outpatients with the same diagnosis as above; 3) comparison of lithium plus TCP 60 mg daily versus placebo plus TCP in a prospective, randomized, eight week trial with the above subjects who failed LiAug of nortriptyline. Subjects will be followed at regular intervals up to three years; and 4) development of a predictive instrument for response to LiAug and TCP using predictor variables and comorbid conditions. The importance of this four part study is that clinicians will be able to use the methods developed to assess treatment resistance; the acute and long term efficacy of LiAug and TCP, and risk of suicide for TRD will be determined; and predictors for LiAug and TCP for TRD will be developed that can improve future TRD research.