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).

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.

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).

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.

ClinicalTrials.gov: NCT02417064, NCT02418585, NCT02493868.

旨在检查艾氯胺酮鼻喷雾剂 (ESK) 加新开始口服抗抑郁药 (OAD) 与 OAD 加安慰剂鼻喷雾剂 (PBO) 对蒙哥马利-阿斯伯格抑郁评定量表 (MADRS) 和 9 项患者健康问卷 (PHQ) 之间关联的影响-9) 患有难治性抑郁症 (TRD) 的成人患者的评分。

对来自 TRANSFORM-1 和 TRANSFORM-2（两项类似设计的随机主动对照 TRD 研究）和 SUSTAIN-1（复发预防研究）的数据进行了分析。使用协方差分析比较 PHQ-9 总分相对于基线的平均变化的组间差异。使用简单参数、非参数和多元回归模型评估 TRANSFORM-1/TRANSFORM-2 的 MADRS 和 PHQ-9 总分之间的关​​联。

在 TRANSFORM-1/TRANSFORM-2 中（ESK + OAD，n  = 343；OAD + PBO，n  = 222），ESK + OAD 的基线 PHQ-9 平均得分为 20.4，OAD + PBO（严重抑郁）为 20.6。第 28 天，在 PHQ-9 评分相对于基线的最小二乘平均变化 (SE) 方面观察到显着的组间差异（−12.8 [0.46] vs -10.3 [0.53]，P  < .001），并且在 PHQ-9 的临床显着变化中观察到显着的组间差异。 ESK + OAD 和 OAD + PBO 组分别为9 分（≥6 分；77.1% vs 64%，P < .001）。观察到 MADRS 和 PHQ-9 之间存在非线性关系；总分显示出随着时间的推移相关性不断增强。在 SUSTAIN-1 中，57.3% 接受 ESK + OAD 的患者 ( n  = 89) 与 44.2% 接受 OAD + PBO ( n  = 86) 的患者在维持治疗终点保留缓解状态 (PHQ-9 评分 ≤ 4) ( P =  . 044）。

在患有 TRD 的成人中，ESK + OAD 显着改善了抑郁症状的严重程度，并且与 OAD + PBO 相比，更多患者根据 PHQ-9 实现了抑郁症状的临床有意义的变化。 PHQ-9 的结果与临床医生评价的 MADRS 的结果一致。

ClinicalTrials.gov：NCT02417064、NCT02418585、NCT02493868。