Ravindran Arun V, Kennedy Sidney H, O'Donovan M Claire, Fallu Angelo, Camacho Fernando, Binder Carin E
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
J Clin Psychiatry. 2008 Jan;69(1):87-94. doi: 10.4088/jcp.v69n0112.
To evaluate the efficacy, safety, and tolerability of adjunctive osmotic-release oral system (OROS) methylphenidate in outpatients with major depressive disorder (MDD) receiving a stable oral antidepressant regimen.
This multicenter, double-blind, randomized, placebo-controlled, parallel-group, 5-week trial enrolled 145 subjects who met DSM-IV-TR criteria for MDD and who had failed 1 to 3 previous antidepressant monotherapies (including current antidepressant) of adequate dose and duration. Augmentation therapy was initiated with 18 mg of OROS methylphenidate and increased to a maximum dose of 54 mg of OROS methylphenidate until an optimal dose was achieved. Efficacy scales included the Montgomery-Asberg Depression Rating Scale (MADRS), 7 atypical items from the 31-item Hamilton Rating Scale for Depression, the Clinical Global Impressions-Severity of Illness (CGI-S) scale, the CGI-Improvement scale (CGI-I), the Sex Effects scale, the Multidimensional Assessment of Fatigue (MAF) scale, and the Apathy Evaluation Scale (AES). Subjects were recruited at 17 community and academic centers across Canada. The study was conducted from June 8, 2005, to April 18, 2006.
There was no statistically significant difference between the groups at endpoint on the MADRS. OROS methylphenidate was superior to placebo in improving apathy and fatigue as measured by the AES and the MAF. Statistically significant differences using mixed-model analysis were observed on the AES at all visits and at endpoint (p = .01) and on the MAF (p < .01). No differences were observed on other secondary measures, including the CGI-I and CGI-S. There were no clinically significant findings on electrocardiogram.
OROS methylphenidate did not demonstrate statistical significance on the MADRS at endpoint. Apathy and fatigue were significantly improved with OROS methylphenidate treatment, which was well tolerated with minimal side effects.
ClinicalTrials.gov identifier NCT00246233.
评估在接受稳定口服抗抑郁药物治疗方案的重度抑郁症（MDD）门诊患者中，辅助使用渗透泵控释口服系统（OROS）哌甲酯的疗效、安全性和耐受性。
这项多中心、双盲、随机、安慰剂对照、平行组、为期5周的试验纳入了145名符合DSM-IV-TR标准的MDD患者，这些患者之前接受过1至3种足够剂量和疗程的抗抑郁单药治疗（包括当前使用的抗抑郁药）但治疗失败。以18毫克OROS哌甲酯开始增效治疗，并增加至最大剂量54毫克OROS哌甲酯，直至达到最佳剂量。疗效量表包括蒙哥马利-阿斯伯格抑郁评定量表（MADRS）、汉密尔顿抑郁评定量表31项中的7项非典型条目、临床总体印象-疾病严重程度（CGI-S）量表、CGI-改善量表（CGI-I）、性别效应量表、疲劳多维评估（MAF）量表和淡漠评估量表（AES）。研究对象在加拿大17个社区和学术中心招募。研究于2005年6月8日至2006年4月18日进行。
在终点时，两组在MADRS上无统计学显著差异。通过AES和MAF测量，OROS哌甲酯在改善淡漠和疲劳方面优于安慰剂。在所有访视和终点时，使用混合模型分析在AES上观察到统计学显著差异（p = 0.01），在MAF上也观察到统计学显著差异（p < 0.01）。在其他次要指标上未观察到差异，包括CGI-I和CGI-S。心电图上未发现具有临床意义的结果。
在终点时，OROS哌甲酯在MADRS上未显示出统计学显著差异。OROS哌甲酯治疗可显著改善淡漠和疲劳，耐受性良好，副作用最小。
ClinicalTrials.gov标识符NCT00246233。
