This post-approval, double-blind, placebo-controlled study (n=223, TRANSFORM-2) finds that those with comorbid anxiety (72%) responded just as well as those without anxiety to esketamine (56-84mg, 4 weeks, combined with SSRI) treatment.
Abstract
“Background: Comorbid anxiety is generally associated with poorer response to antidepressant treatment. This post hoc analysis explored the efficacy of esketamine plus an antidepressant in patients with treatment-resistant depression (TRD) with or without comorbid anxiety.
Methods: TRANSFORM-2, a double-blind, flexible-dose, 4-week study (NCT02418585), randomized adults with TRD to placebo or esketamine nasal spray, each with a newly-initiated oral antidepressant. Comorbid anxiety was defined as clinically noteworthy anxiety symptoms (7-item Generalized Anxiety Disorder scale [GAD-7] score ≥10) at screening and baseline or comorbid anxiety disorder diagnosis at screening. Treatment effect based on change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score, and response and remission were examined by presence/absence of comorbid anxiety using analysis of covariance and logistic regression models.
Results: Approximately 72% (162/223) of patients had baseline comorbid anxiety. Esketamine-treated patients with and without anxiety demonstrated significant reductions in MADRS (mean [SD] change from baseline at day 28: -21.0 [12.51] and -22.7 [11.98], respectively). Higher rates of response and remission, and a significantly greater decrease in MADRS score at day 28 were observed compared to antidepressant/placebo, regardless of comorbid anxiety (with anxiety: difference in LS means [95% CI] -4.2 [-8.1, -0.3]; without anxiety: -7.5 [-13.7, -1.3]). There was no significant interaction of treatment and comorbid anxiety (p = .371). Notably, in the antidepressant/placebo group improvement was similar in those with and without comorbid anxiety.
Conclusion: Post hoc data support efficacy of esketamine plus an oral antidepressant in patients with TRD, regardless of comorbid anxiety.”
Authors: Ella J. Daly, Ibrahim Turkoz, Giacomo Salvadore, Maggie Fedgchin, Dawn F. Ionescu, H. Lynn Starr, Stephane Borentain, Madhukar H. Trivedi, Michael E. Thase & Jaskaran B. Singh
Study details
Compounds studied
Ketamine
Topics studied
Anxiety
Depression
Study characteristics
Placebo-Controlled
Double-Blind
Randomized
Participants
223
Institutes
Institutes associated with this publication
Johnson & JohnsonOne of the largest pharmaceutical companies in the world, Johnson & Johnson are responsible for bringing esketamine to market in the form of Spravato.
Linked Research Papers
Notable research papers that build on or are influenced by this paper
Evaluation of Individual Items of the Patient Health Questionnaire (PHQ-9) and Montgomery-Asberg Depression Rating Scale (MADRS) in Adults with Treatment-Resistant Depression Treated with Esketamine Nasal Spray Combined with a New Oral AntidepressantThis posthoc analysis of the TRANSFORM-2 trial assessed the effects of esketamine plus an oral antidepressant (AD) using the Patient Health Questionnaire (PHQ-9) and Montgomery-Asberg Depression Rating Scale (MADRS). The odds of improving in those treated with esketamine plus AD were at least two times greater than with placebo plus AD.