Fava Maurizio, Schmidt Mark E, Zhang Shuyu, Gonzales Jill, Raute Nancy J, Judge Rajinder
Depression Clinical and Research Program, Massachusetts General Hospital, Boston, Mass 02114, USA.
Psychother Psychosom. 2002 Jul-Aug;71(4):195-9. doi: 10.1159/000063644.
Anecdotal reports concerning mood disorder patients suggest restarting drug treatment in patients who prematurely discontinue it may be associated with a diminished chance of response upon rechallenge. We evaluated the likelihood of response to reinitiation of fluoxetine treatment in patients relapsing after switching to placebo during a long-term efficacy study of two different dosing regimens of fluoxetine.
Patients who met the DSM-IV major depressive disorder criteria with modified HAMD17 scores > or =18 and CGI-Severity scores > or =4 were treated with open-label 20 mg/day fluoxetine for 13 weeks in a multicenter US study. Responders (n = 501) were randomized to placebo, 20 mg fluoxetine daily, or 90 mg enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. Patients relapsing during the continuation phase were offered 25 weeks of double-blind rescue treatment during which the study medication dose was increased as follows: (1) patients on placebo had treatment with fluoxetine 20 mg/ day reinitiated; (2) patients on fluoxetine 20 mg/day had their dose increased to 40 mg/day, and (3) patients on a 90-mg weekly dose had their dose increased to 90 mg twice a week. Only the results of the rescue phase for the group who relapsed while on continuation treatment with placebo are reported here. Analyses included percentage of responders (50% reduction of modified HAMD17 and CGI-Severity < or =2) and assessments of change from baseline to endpoint (HAMD, CGI-Severity). Safety measures included assessment of vital signs, laboratory measures, and treatment-emergent adverse events.
Of 122 patients assigned to placebo, 57 (47%) relapsed during continuation treatment. Fifty-five (96%) of these elected to enter double-blind rescue treatment. Overall, patients who relapsed upon switching to placebo responded well to reinitiation of fluoxetine (62%). The mean modified HAMD17 score decreased from 20 to less than 9 and was maintained for up to 6 months. Thirty-eight percent of patients either did not respond or initially responded but again relapsed after reinitiation of medication.
This study suggests that patients who, after an initial response to fluoxetine, relapse upon switching to placebo have a relatively high probability of responding to the reinitiation of fluoxetine treatment. These results challenge the view that the efficacy of an agent prematurely discontinued is diminished when such an agent is restarted. They also generally support reinitiation of the same antidepressant as a 'first-line' treatment strategy in patients who relapsed after stopping a previously effective antidepressant.
有关情绪障碍患者的传闻报告表明，在过早停药的患者中重新开始药物治疗可能与再次用药时反应机会减少有关。在一项针对两种不同剂量方案氟西汀的长期疗效研究中，我们评估了在换用安慰剂后复发的患者重新开始氟西汀治疗后产生反应的可能性。
在美国一项多中心研究中，符合DSM-IV重度抑郁症标准且改良HAMD17评分≥18分和CGI-严重程度评分≥4分的患者接受为期13周的开放标签20mg/天氟西汀治疗。反应者（n = 501）被随机分配接受安慰剂、每日20mg氟西汀或每周90mg肠溶包衣氟西汀，进行为期25周的双盲持续治疗。在持续治疗阶段复发的患者接受为期25周的双盲挽救治疗，在此期间研究药物剂量按以下方式增加：（1）接受安慰剂治疗的患者重新开始使用20mg/天氟西汀治疗；（2）接受20mg/天氟西汀治疗的患者剂量增加至40mg/天，（3）接受每周90mg剂量治疗的患者剂量增加至每周两次90mg。这里仅报告在接受安慰剂持续治疗时复发的组的挽救阶段结果。分析包括反应者百分比（改良HAMD17降低50%且CGI-严重程度≤2）以及从基线到终点的变化评估（HAMD、CGI-严重程度）。安全措施包括生命体征评估、实验室检测和治疗中出现的不良事件。
在分配接受安慰剂治疗的122例患者中，57例（47%）在持续治疗期间复发。其中55例（96%）选择进入双盲挽救治疗。总体而言，换用安慰剂后复发的患者重新开始氟西汀治疗后反应良好（62%）。改良HAMD17评分的平均值从20降至低于9，并维持长达6个月。38%的患者要么无反应，要么最初有反应但在重新开始用药后再次复发。
本研究表明，在最初对氟西汀有反应后换用安慰剂复发的患者重新开始氟西汀治疗有相对较高的反应概率。这些结果挑战了这样一种观点，即过早停用的药物重新使用时疗效会降低。它们还总体上支持在停用先前有效的抗抑郁药后复发的患者中重新开始使用同一种抗抑郁药作为“一线”治疗策略。
