Schmidt Mark E, Fava Maurizio, Zhang Shuyu, Gonzales Jill, Raute Nancy J, Judge Rajinder
Lilly Research Laboratories, Indianapolis, Ind 46285, USA.
Psychother Psychosom. 2002 Jul-Aug;71(4):190-4. doi: 10.1159/000063643.
Although continuing antidepressant treatment after patients have responded to medication has been shown to greatly reduce the risk of relapse, this risk is not eliminated. A number of theories have been proposed to account for this apparent loss of efficacy. A common initial approach to managing relapse is to increase the dose of antidepressant. We prospectively evaluated the likelihood of response to increasing the fluoxetine doses in patients relapsing during a long-term efficacy study of two fluoxetine dosing regimens.
Patients meeting the DSM-IV criteria for major depressive disorder with modified HAMD17 scores > or =18 and CGI-severity scores > or =4 were treated for 13 weeks with open-label 20 mg/day fluoxetine in a multicenter US study. Responders (n = 501) were randomized to 20 mg fluoxetine daily, placebo, or 90 mg enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. If the patients relapsed during the continuation phase, they were offered a 25-week optional rescue treatment phase 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. The results of the rescue phase for the latter two groups who relapsed while on continuation treatment with fluoxetine are reported. Response was defined as a 50% reduction in the modified HAMD17 score since time of relapse and a CGI-severity score < or =2. Additional efficacy analyses included HAMD and CGI-severity changes from baseline to endpoint. Safety measures included assessment of treatment-emergent adverse events, vital signs, and laboratory measures.
Overall, patients relapsing during the continuation treatment responded to an increased dose (57% of the 40-mg-daily group and 72% of the enteric-coated 90-mg-twice-weekly group). Mean modified HAMD17 scores decreased from a mean of approximately 20 to below 8 and were maintained for up to 6 months in the responders. Thirty-five percent of patients either did not respond or initially responded but again relapsed after augmentation of medication.
The patients relapsing after initially responding to fluoxetine can benefit from an increase in fluoxetine dose. These results also generally support increasing dose as a first-line treatment strategy for a patient who has relapsed while taking a previously effective dose of an antidepressant. Increasing enteric-coated fluoxetine 90 mg once weekly to twice weekly appeared to be as well-tolerated and effective in restoring response as increasing a daily fluoxetine dose from 20 to 40 mg.
尽管已证明患者对药物产生反应后继续进行抗抑郁治疗可大幅降低复发风险，但该风险并未消除。人们提出了多种理论来解释这种明显的疗效丧失。处理复发的常见初始方法是增加抗抑郁药的剂量。在一项关于两种氟西汀给药方案的长期疗效研究中，我们前瞻性评估了复发患者增加氟西汀剂量后的反应可能性。
在美国一项多中心研究中，符合DSM-IV重度抑郁症标准、改良HAMD17评分≥18且CGI严重程度评分≥4的患者接受了为期13周的开放标签、每日20毫克氟西汀治疗。有反应者（n = 501）被随机分为每日20毫克氟西汀组、安慰剂组或每周90毫克肠溶包衣氟西汀组，进行为期25周的双盲维持治疗。如果患者在维持治疗阶段复发，他们将进入一个为期25周的可选挽救治疗阶段，在此期间研究药物剂量按以下方式增加：（1）服用安慰剂的患者重新开始每日20毫克氟西汀治疗，（2）每日服用20毫克氟西汀的患者剂量增加至每日40毫克，（3）每周服用90毫克剂量的患者剂量增加至每周两次、每次90毫克。报告了后两组在继续接受氟西汀治疗时复发的挽救治疗阶段的结果。反应定义为自复发时起改良HAMD17评分降低50%且CGI严重程度评分≤2。其他疗效分析包括从基线到终点的HAMD和CGI严重程度变化。安全措施包括评估治疗中出现的不良事件、生命体征和实验室指标。
总体而言，在维持治疗期间复发的患者对增加剂量有反应（每日40毫克组的57%和每周两次、每次90毫克肠溶包衣组的72%）。有反应者的平均改良HAMD17评分从约20降至8以下，并维持长达6个月。35%的患者要么无反应，要么最初有反应但在增加药物剂量后再次复发。
最初对氟西汀有反应后复发的患者可从增加氟西汀剂量中获益。这些结果总体上也支持将增加剂量作为服用先前有效剂量抗抑郁药时复发患者的一线治疗策略。将每周一次90毫克肠溶包衣氟西汀增加至每周两次似乎与将每日氟西汀剂量从20毫克增加至40毫克一样耐受性良好且能有效恢复反应。
