目的:研究艾氯胺酮鼻喷雾剂(ESK)加口服抗抑郁药(OAD)与OAD加安慰剂鼻喷雾剂(PBO)对蒙哥马利-奥斯贝格抑郁量表(MADRS)和9项患者健康问卷(PHQ-9)评分在成人难治性抑郁症(TRD)中的相关性。
方法:来自TRANSFORM-1和TRANSFORM-2的数据(两个类似设计,随机化,分析了主动控制的TRD研究)和SUSTAIN-1(复发预防研究)。使用协方差分析比较PHQ-9总分从基线的平均变化的组差异。使用简单参数评估TRANSFORM-1/TRANSFORM-2的MADRS和PHQ-9总分之间的关联,非参数,和多元回归模型。
结果:在TRANSFORM-1/TRANSFORM-2(ESK+OAD,n=343;OAD+PBO,n=222),ESK+OAD的基线PHQ-9平均评分为20.4分,OAD+PBO(重度抑郁症)为20.6分.在第28天,PHQ-9评分与基线相比的最小二乘均值变化(SE)存在显着差异(-12.8[0.46]vs-10.3[0.53],P<.001)和PHQ-9评分的临床实质性变化(≥6分;77.1%vs64%,P<.001)在ESK+OAD和OAD+PBO组中,分别。观察到MADRS和PHQ-9之间的非线性关系;总分显示出随着时间的推移相关性增加。在SUSTAIN-1中,57.3%接受ESK+OAD(n=89)和44.2%接受OAD+PBO(n=86)的患者在维持治疗终点时保持缓解状态(PHQ-9评分≤4)(P=.044)。
结论:在患有TRD的成年人中,ESK+OAD显著改善抑郁症状的严重程度,与OAD+PBO相比,更多的患者根据PHQ-9在抑郁症状方面实现了有临床意义的变化。PHQ-9结果与临床医生评估的MADRS结果一致。
背景:ClinicalTrials.gov:NCT02417064,NCT02418585,NCT02493868。
OBJECTIVE: To examine the effect of esketamine nasal spray (ESK) plus newly initiated oral antidepressant (OAD) versus OAD plus placebo nasal spray (PBO) on the association between Montgomery-Åsberg Depression Rating Scale (MADRS) and 9-item Patient Health Questionnaire (PHQ-9) scores in adults with treatment-resistant depression (TRD).
METHODS: Data from TRANSFORM-1 and TRANSFORM-2 (two similarly designed, randomized, active-controlled TRD studies) and SUSTAIN-1 (relapse prevention study) were analyzed. Group differences for mean changes in PHQ-9 total score from baseline were compared using analysis of covariance. Associations between MADRS and PHQ-9 total scores from TRANSFORM-1/TRANSFORM-2 were assessed using simple parametric, nonparametric, and multiple regression models.
RESULTS: In TRANSFORM-1/TRANSFORM-2 (ESK + OAD, n = 343; OAD + PBO, n = 222), baseline PHQ-9 mean scores were 20.4 for ESK + OAD and 20.6 for OAD + PBO (severe depression). At day 28, significant group differences were observed in least squares mean change (SE) in PHQ-9 scores from baseline (-12.8 [0.46] vs -10.3 [0.53], P < .001) and in clinically substantial change in PHQ-9 scores (≥6 points; 77.1% vs 64%, P < .001) in ESK + OAD and OAD + PBO groups, respectively. A nonlinear relationship between MADRS and PHQ-9 was observed; total scores demonstrated increased correlation over time. In SUSTAIN-1, 57.3% of patients receiving ESK + OAD (n = 89) versus 44.2% receiving OAD + PBO (n = 86) retained remission status (PHQ-9 score ≤4) at maintenance treatment end point (P = .044).
CONCLUSIONS: In adults with TRD, ESK + OAD significantly improved severity of depressive symptoms, and more patients achieved clinically meaningful changes in depressive symptoms based on PHQ-9, versus OAD + PBO. PHQ-9 outcomes were consistent with those of clinician-rated MADRS.
BACKGROUND: ClinicalTrials.gov: NCT02417064, NCT02418585, NCT02493868.