Effects of esketamine nasal spray on depressive symptom severity in adults with treatment-resistant depression and associations between the Montgomery-Åsberg Depression Rating Scale and the 9-item Patient Health Questionnaire.

In adults with treatment-resistant depression, adding esketamine nasal spray to a newly initiated oral antidepressant led to greater improvement in depressive symptoms than oral antidepressant plus placebo spray. Across two short-term trials, the group receiving esketamine plus oral antidepressant showed a mean reduction of 12.8 points on the Patient Health Questionnaire-9 (PHQ-9) at 28 days, compared with 10.3 points in the placebo group, a statistically significant difference. 77.1% of patients in the esketamine group achieved a clinically meaningful improvement (at least a 6-point drop) versus 64% in the placebo group. In a separate relapse-prevention study, 57.3% of patients on esketamine plus oral antidepressant maintained remission (PHQ-9 score ≤4) versus 44.2% on oral antidepressant plus placebo. The self-reported PHQ-9 results aligned with clinician-rated Montgomery-Åsberg Depression Rating Scale scores.

Study at a glance

Abstract

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.