Nelson J Craig, Mazure Carolyn M, Jatlow Peter I, Bowers Malcolm B, Price Lawrence H
Department of Psychiatry, University of California-San Francisco, 401 Parnassus Avenue, Box 0984-5, San Francisco, CA 94143, USA
Biol Psychiatry. 2004 Feb 1;55(3):296-300. doi: 10.1016/j.biopsych.2003.08.007.
Although several antidepressants are now available, all have limited efficacy and a delayed onset of action. The current study was undertaken as a proof of the concept that combining norepinephrine and serotonin reuptake inhibition would be more effective and act more rapidly than either drug alone.
Inpatients with nonpsychotic unipolar major depression and a Hamilton Depression Rating Scale (HAMD) score of at least 18 after 1 week of hospitalization without antidepressant medication were randomized to 6 weeks of treatment with fluoxetine (FLX) 20 mg/day, desipramine (DMI) adjusted to an adequate plasma level, or the combination of FLX 20 mg/day and DMI, given under double-blind conditions. Twenty-four-hour DMI levels were used to rapidly adjust DMI dose to achieve a therapeutic level and to anticipate the enzyme-inhibiting effects of FLX. Treatment-resistant patients were stratified. Patients were rated with the HAMD and the Montgomery-Asberg Depression Rating Scale (MADRS).
Thirty-nine patients began treatment. One patient withdrew consent. The DMI-FLX combination was significantly more likely to result in remission on the MADRS than either FLX or DMI alone [53.8% vs. 7.1% and 0%, respectively; chi(2)(2) = 13.49, p =.001]. The advantage for combined treatment was not explained by history of treatment resistance or by drug plasma concentrations. Rapid response, at 1 or 2 weeks, was neither statistically nor meaningfully greater with combined treatment.
This study supports the hypothesis that the combination of a noradrenergic and serotonergic agent is more likely to result in remission than either selective agent alone during a 6-week treatment period.
尽管目前有多种抗抑郁药可供使用，但它们的疗效都有限且起效延迟。本研究旨在验证一个概念，即去甲肾上腺素和5-羟色胺再摄取抑制联合使用比单独使用任何一种药物更有效且起效更快。
将住院1周且未服用抗抑郁药、汉密尔顿抑郁量表（HAMD）评分至少为18分的非精神病性单相重度抑郁症患者，在双盲条件下随机分为三组，分别接受为期6周的治疗：每日20毫克氟西汀（FLX）、根据血浆水平调整至合适剂量的地昔帕明（DMI），或每日20毫克FLX与DMI的联合用药。通过24小时DMI水平快速调整DMI剂量以达到治疗水平，并预测FLX的酶抑制作用。对难治性患者进行分层。使用HAMD和蒙哥马利-艾斯伯格抑郁量表（MADRS）对患者进行评分。
39名患者开始治疗。1名患者撤回同意。与单独使用FLX或DMI相比，DMI-FLX联合用药使MADRS评分达到缓解的可能性显著更高[分别为53.8%、7.1%和0%；卡方检验（2）（2）=13.49，p = 0.001]。联合治疗的优势无法通过既往难治性病史或药物血浆浓度来解释。联合治疗在1周或2周时的快速反应在统计学上和实际意义上均未显示出更大优势。
本研究支持以下假设，即在为期6周的治疗期间，去甲肾上腺素能和5-羟色胺能药物联合使用比单独使用任何一种选择性药物更有可能导致症状缓解。
