Marcus Ronald N, McQuade Robert D, Carson William H, Hennicken Delphine, Fava Maurizio, Simon Jeffrey S, Trivedi Madhukar H, Thase Michael E, Berman Robert M
Bristol-Myers Squibb, Wallingford, CT 06492, USA.
J Clin Psychopharmacol. 2008 Apr;28(2):156-65. doi: 10.1097/JCP.0b013e31816774f9.
Nonresponse to one or more antidepressants is common and an important public health problem. This study evaluated the efficacy and safety of adjunctive aripiprazole or placebo to standard antidepressant therapy (ADT) in patients with major depressive disorder who showed an inadequate response to at least 1 and up to 3 historical and 1 additional prospective ADT. The study comprised a 7-28-day screening, an 8-week prospective treatment, and a 6-week randomization phase. During prospective treatment, patients experiencing a major depressive episode (17-item Hamilton Rating Scale for Depression total score > or = 18) received single-blind adjunctive placebo plus clinicians' choice of ADT (escitalopram, fluoxetine, paroxetine controlled-release, sertraline, or venlafaxine extended-release). Subjects with inadequate response were randomized to adjunctive placebo (n = 190) or adjunctive aripiprazole (n = 191) (starting dose 5 mg/d, dose adjustments 2-20 mg/d, mean end-point dose of 11.0 mg/d). The primary efficacy endpoint was the mean change in Montgomery-Asberg Depression Rating Scale total score from end of prospective treatment phase to end of randomized treatment phase (last observation carried forward). Mean change in Montgomery-Asberg Depression Rating Scale total score was significantly greater with adjunctive aripiprazole than placebo (-8.5 vs -5.7; P = 0.001). Remission rates were significantly greater with adjunctive aripiprazole than placebo (25.4% vs 15.2%; P = 0.016) as were response rates (32.4% vs 17.4%; P < 0.001). Adverse events occurring in 10% of patients or more with adjunctive placebo or aripiprazole were akathisia (4.2% vs 25.9%), headache (10.5% vs 9.0%), and fatigue (3.7% vs 10.1%). Incidence of adverse events leading to discontinuation was low (adjunctive placebo [1.1%] vs adjunctive aripiprazole [3.7%]). Aripiprazole is an effective and safe adjunctive therapy as demonstrated in this short-term study for patients who are nonresponsive to standard ADT.
对一种或多种抗抑郁药无反应的情况很常见，是一个重要的公共卫生问题。本研究评估了阿立哌唑或安慰剂辅助标准抗抑郁治疗（ADT）对重度抑郁症患者的疗效和安全性，这些患者对至少1种、最多3种既往及1种额外的前瞻性ADT反应不佳。该研究包括一个7 - 28天的筛查期、一个8周的前瞻性治疗期和一个6周的随机化阶段。在前瞻性治疗期间，经历重度抑郁发作（17项汉密尔顿抑郁量表总分≥18） 的患者接受单盲辅助安慰剂加临床医生选择的ADT（艾司西酞普兰、氟西汀、帕罗西汀控释片、舍曲林或文拉法辛缓释片）。反应不佳的受试者被随机分为辅助安慰剂组（n = 190）或辅助阿立哌唑组（n = 191）（起始剂量5mg/d，剂量调整为2 - 20mg/d，平均终点剂量为11.0mg/d）。主要疗效终点是蒙哥马利 - 阿斯伯格抑郁量表总分从前瞻性治疗阶段结束到随机治疗阶段结束（末次观察结转） 的平均变化。辅助阿立哌唑组蒙哥马利 - 阿斯伯格抑郁量表总分的平均变化显著大于安慰剂组（-8.5对-5.7；P = 0.001）。辅助阿立哌唑组的缓解率显著高于安慰剂组（25.4%对15.2%；P = 0.016），有效率也是如此（32.4%对17.4%；P < 0.001）。辅助安慰剂或阿立哌唑治疗中，10%或更多患者出现的不良事件有静坐不能（4.2%对25.9%）、头痛（10.5%对9.0%）和疲劳（3.7%对10.1%）。导致停药的不良事件发生率较低（辅助安慰剂组[1.1%]对辅助阿立哌唑组[3.7%]）。在这项短期研究中，对于对标准ADT无反应的患者，阿立哌唑是一种有效且安全的辅助治疗药物。
