COURSE OF TREATMENT RESISTANT DEPRESSION

本研究将评估难治性抑郁症患者的序贯治疗：首先，去甲替林试验;第二，在去甲替林失败试验中添加锂的抗抑郁疗效;第三，对于那些对去甲替林锂增加无反应的患者，使用反苯环丙胺加或不加锂。Nierenberg博士在进行抑郁症临床试验方面拥有丰富的经验，并进行了迄今为止唯一的研究，以评估接受锂强化治疗的抑郁症患者的纵向病程。患者将接受为期6周的去甲替林开放试验。无应答者将有资格参加为期六周的双盲安慰剂对照研究，在失败的去甲替林试验中加入锂。 接受安慰剂的患者将有资格添加锂6周。 去甲替林锂强化治疗失败的患者将有资格接受反苯环丙胺加安慰剂或反苯环丙胺加锂治疗8周。受试者年龄在18至60岁之间，患有无精神病的重性抑郁症，17项汉密尔顿抑郁量表评分>18，并且对于当前发作已经失败了1至5次充分的抗抑郁剂试验。 如果患者在去甲替林或锂的试验中失败，或者如果他们对去甲替林或锂不耐受，怀孕，有任何过敏或医疗条件，无法使用去甲替林或锂，在过去一年内有药物滥用或酒精滥用，或者急性自杀，则将被排除在外。

This study will assess sequential treatments for patients with treatment-resistant depression: first, a trial of nortriptyline; second, the antidepressant efficacy of the addition of lithium to the failed trial of nortiptyline; third, tranylcypromine with or without lithium for those patients who do not respond to lithium augmentation of nortriptyline. Dr. Nierenberg has extensive experience in conducting clinical trials in depression and has done the only study to date to assess the longitudinal course of depressed patietns who were treated with lithium augmentation. Patients will receive a six-week open-trial of nortriptyline. Nonresponders will then be eligible for a six-week double-blind placebo-controlled study of lithium added to the failed trial of nortriptyline. Patients who receive placebo will be eligible to have lithium added for six weeks. Patients who fail lithium augmentation of nortriptyline will be eligible to receive either tranylcypromine plus placebo or tranylcypromine plus lithium for another eight weeks. Subjects will be between the ages of 18 and 60, hve a major depression without psychosis with a 17-item Hamilton Depression Scale Score of >18, and have failed between 1 and 5 adequate antidepressant trials for the current episode. Patietns will be excluded if they have failed a trial of either nortripyline or lithium, or if they have been intolerant of either nortriptyline or lithium, are pregnant, have any allergies or medical conditions that preclude the use of either nortriptyline or lithium, have active drug or alcohol abuse within the past year, or are acutely suicidal.