Gerra Maria Lidia, Marchesi Carlo, Amat Jose A, Blier Pierre, Hellerstein David J, Stewart Jonathan W
Department of Neuroscience, Psychiatry Unit, University General Hospital, Braga Bldg, Via Gramsci 14, Parma, PR 43126, Italy
J Clin Psychiatry. 2014 Sep;75(9):e939-44. doi: 10.4088/JCP.14m09025.
This work tested the hypothesis that patients with high negative affectivity (NA) would have a better response to a serotonergic agent (escitalopram) than to one not thought to act directly on serotonin (bupropion).
Data from a study conducted between August 2007 and July 2011 were reanalyzed retrospectively. Patients (N = 245) meeting criteria for major depressive disorder (MDD), diagnosed with DSM-IV-TR, were randomly assigned to double-blind treatment with bupropion extended-release, escitalopram, or the combination. Negative affectivity score was estimated using the guilt, hostility/irritability, and fear/anxiety items of the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Rating Scale, the Quick Inventory of Depressive Symptoms, and the Social Adjustment Scale. We felt that these items captured published descriptions of the NA construct. A Clinical Global Impressions-Severity of Illness (CGI-S) score ≤ 2 defined response. Because combined treatment addressed both serotonin and non-serotonin systems, patients treated with both medications did not test the hypothesis and so were excluded from the analyses.
Analysis of covariance with treatment as a grouping variable, NA as covariate, and CGI-S as dependent variable showed a significant 2-way interaction between treatment and NA (F₁,₁₅₆ = 4.82, P < .03). In the low-NA group, response rates were similar between treatments (escitalopram: 28/42 [67%]; bupropion: 23/40 [58%]; NS), while there was a significant advantage for escitalopram in patients with high NA (escitalopram: 24/40 [60%]; bupropion = 14/41 [34%]; P = .017).
These data suggest that patients with high negative affectivity respond preferentially to antidepressants that selectively enhance serotonin neurotransmission. Although patients with low NA appear to benefit from serotonin enhancement as well, they also improved with bupropion, an antidepressant not thought to directly affect serotonin neurotransmission. These findings come from retrospective analyses using unproven approximation of NA, so no clinical inferences should be made before independent replication utilizing accepted NA measurement.
ClinicalTrials.gov identifier: NCT00519428.
本研究检验了以下假设，即高负性情绪（NA）患者对5-羟色胺能药物（艾司西酞普兰）的反应优于对一种被认为不直接作用于5-羟色胺的药物（安非他酮）的反应。
对2007年8月至2011年7月间进行的一项研究的数据进行回顾性重新分析。符合重度抑郁症（MDD）标准、根据《精神疾病诊断与统计手册》第四版修订版（DSM-IV-TR）诊断的患者（N = 245）被随机分配接受安非他酮缓释剂、艾司西酞普兰或两者联合的双盲治疗。使用汉密尔顿抑郁量表、蒙哥马利-阿斯伯格抑郁量表、抑郁症状快速量表和社会适应量表中的内疚、敌意/易怒和恐惧/焦虑项目来评估负性情绪得分。我们认为这些项目涵盖了已发表的关于NA结构的描述。临床总体印象-疾病严重程度（CGI-S）评分≤2定义为有反应。由于联合治疗涉及5-羟色胺和非5-羟色胺系统，接受两种药物治疗的患者未检验该假设，因此被排除在分析之外。
以治疗为分组变量、NA为协变量、CGI-S为因变量的协方差分析显示治疗与NA之间存在显著的双向交互作用（F₁,₁₅₆ = 4.82，P <.03）。在低NA组中，各治疗组的反应率相似（艾司西酞普兰：28/42 [67%]；安非他酮：23/40 [58%]；无显著性差异），而在高NA患者中，艾司西酞普兰有显著优势（艾司西酞普兰：24/40 [60%]；安非他酮 = 14/41 [34%]；P =.017）。
这些数据表明，高负性情绪患者对选择性增强5-羟色胺神经传递的抗抑郁药反应更佳。虽然低NA患者似乎也从5-羟色胺增强中获益，但他们使用安非他酮（一种被认为不直接影响5-羟色胺神经传递的抗抑郁药）也有改善。这些发现来自使用未经证实的NA近似值的回顾性分析，因此在利用公认的NA测量方法进行独立重复研究之前，不应进行临床推断。
ClinicalTrials.gov标识符：NCT00519428。
