Impact of Treatment With Esketamine Nasal Spray in Patients With Treatment Resistant Depression and Comorbid Anxiety: A Post-hoc Pooled Analysis of the TRANSFORM 1 and 2 Trials

Purpose: To evaluate the impact of esketamine (ESK) nasal spray in patients with treatment-resistant depression (TRD) and comorbid anxiety.

Methods: This post-hoc pooled analysis included two 4-week, phase 3 studies that involved treatment with ESK plus a newly initiated antidepressant (ESK+AD) or placebo nasal spray plus a new antidepressant (AD+PBO). Patients with TRD with baseline comorbid anxiety were identified according to: presence of (1) anxious depression (total score ≥8 on Inventory of Depressive Symptomatology anxiety subscale); (2) comorbid anxiety disorder (Mini-International Neuropsychiatric Interview); or (3) anxious distress (DSM-5 major depressive disorder specifier). Response rates (≥50% reduction in Montgomery–Åsberg Depression Rating Scale total score) at Week 4 between ESK+AD and AD+PBO were compared using the Cochran-Mantel-Haenzsel (CMH) test. Logistic regression models were fit to examine whether observed treatment differences at Week 4 were dependent on presence/absence of comorbid anxiety.

Results: At baseline, 22.3% (126/564), 14.2% (80/565), and 72.9% (412/565) of patients had anxious depression, comorbid anxiety disorder, or anxious distress, respectively. At Day 28, 58.7% (182/310) of patients in the ESK+AD group achieved response in depression symptoms compared with 45.1% (94/208) of patients in AD+PBO group, with a statistically significant difference between treatment groups (p<0.001). A treatment-by-subgroup interaction terms analysis examined whether response differed between treatment groups based on presence of comorbid anxiety. No interaction terms met the a priori p<0.05 definition.

Conclusion: In patients with TRD, esketamine nasal spray plus a newly initiated antidepressant was generally an efficacious treatment regardless of whether patients had comorbid anxiety present at baseline.

This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.