Ninan Philip T, Hassman Howard A, Glass Steven J, McManus Frank C
Department of Psychiatry, Emory University School of Medicine, 1841 Clifton Road, Suite 400 North, Atlanta, GA 30329, USA.
J Clin Psychiatry. 2004 Mar;65(3):414-20. doi: 10.4088/jcp.v65n0318.
Benefit from selective serotonin reuptake inhibitor (SSRI) treatment in major depressive disorder (MDD) usually takes several weeks. Typically, a third of patients achieve remission and roughly half achieve response with acute treatment. This open-label study evaluated the efficacy and safety of modafinil treatment initiated with an SSRI in patients with MDD and fatigue.
Twenty-nine patients with DSM-IV MDD, free from antidepressant therapy (> or = 4 weeks), were administered modafinil (titrated to 200 mg/day) and fluoxetine or paroxetine (20 mg/day) for 6 weeks. Assessments included the 21-item Hamilton Rating Scale for Depression (HAM-D), Structured Interview Guide for the HAM-D (SIGH-D), Fatigue Severity Scale (FSS), and Epworth Sleepiness Scale (ESS). The SIGH-D ratings were videotaped and rated by an independent rater masked to the visit schedule. Data were collected from August 2002 through March 2003.
Modafinil combined with an SSRI at treatment initiation significantly improved mean total SIGH-D scores within 1 week (-9.3, p <.001), and this improvement was progressive throughout the study (-21.2 at week 6, p <.001). Forty-two percent (11 of 26) and 79% (19 of 24) of patients were responders, and 39% (10 of 26) and 58% (14 of 24) of patients were remitters (HAM-D) by week 2 and week 6, respectively. Adjunct modafinil rapidly and significantly reduced fatigue (FSS score reduction from baseline = 0.7 at week 1, p <.01) and improved wakefulness (ESS score reduction from baseline = 3.6 at week 1, p <.01). The combination caused few adverse events, with nausea and headache being the most common.
Modafinil combined with an SSRI at treatment initiation may enhance the onset and degree of symptom benefit in patients with MDD and fatigue. Treatment with adjunct modafinil was generally well tolerated, with most adverse effects being mild or moderate in severity.
在重度抑郁症（MDD）中，从选择性5-羟色胺再摄取抑制剂（SSRI）治疗中获益通常需要数周时间。通常，三分之一的患者在急性治疗后实现缓解，约一半患者实现反应。这项开放标签研究评估了在患有MDD和疲劳的患者中，起始使用SSRI时联合使用莫达非尼治疗的疗效和安全性。
29例符合《精神疾病诊断与统计手册》第四版（DSM-IV）标准的MDD患者，未接受过抗抑郁治疗（≥4周），给予莫达非尼（滴定至200毫克/天）和氟西汀或帕罗西汀（20毫克/天），为期6周。评估包括21项汉密尔顿抑郁评定量表（HAM-D）、HAM-D结构化访谈指南（SIGH-D）、疲劳严重程度量表（FSS）和爱泼华嗜睡量表（ESS）。SIGH-D评分进行录像，并由一名对访视计划不知情的独立评估者进行评分。数据收集时间为2002年8月至2003年3月。
起始治疗时莫达非尼联合SSRI可在1周内显著改善平均SIGH-D总分（-9.3，p<.001），且在整个研究过程中这种改善持续存在（第6周时为-21.2，p<.001）。分别有42%（26例中的11例）和79%（24例中的19例）的患者在第2周和第6周时为反应者，分别有39%（26例中的10例）和58%（24例中的14例）的患者在第2周和第6周时为缓解者（HAM-D）。联合使用莫达非尼可迅速且显著减轻疲劳（第1周时FSS评分较基线降低0.7，p<.01）并改善觉醒状态（第1周时ESS评分较基线降低3.6，p<.01）。该联合治疗引起的不良事件较少，最常见的是恶心和头痛。
起始治疗时莫达非尼联合SSRI可能会增强MDD和疲劳患者症状改善的起效速度和程度。联合使用莫达非尼治疗总体耐受性良好，大多数不良反应的严重程度为轻度或中度。
