Meaningful Change in Depression Symptoms Assessed with the Patient Health Questionnaire (PHQ-9) and Montgomery-Åsberg Depression Rating Scale (MADRS) Among Patients with Treatment Resistant Depression in Two, Randomized, Double-blind, Active-controlled Trials of Esketamine Nasal Spray Combined With a New Oral Antidepressant
Stacie Hudgens, Lysbeth Floden, Michael Blackowicz, Carol Jamieson, Vanina Popova, Maggie Fedgchin, Wayne C. Drevets, Kimberly Cooper, Rosanne Lane, Jaskaran Singh
Journal of Affective Disorders November 14, 2020 DOI: 10.1016/j.jad.2020.11.066 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Population | Patients with treatment resistant depression |
| Interventions | Esketamine nasal spray antidepressant |
| Duration | 28 days |
| Topics | Anxiety Depression Esketamine |
| Keywords | Depression economics Patient health questionnaire Rating scale Randomized controlled trial Clinical psychology Depressive symptoms Developmental psychology |
| Citations | 77 |
| Key findings | By Day 28, a significantly higher proportion of patients with TRD receiving esketamine/AD reached or exceeded the PHQ-9 meaningful change threshold of -6 points (86.5%) and the MADRS threshold of -10 points (78.2%) compared to placebo/AD (70% and 65.0%, respectively). |
Abstract
Patients with major depressive disorder who do not respond to ≥2 different pharmacological treatments within the current depressive episode are considered to have treatment resistant depression (TRD). This analysis determined meaningful change thresholds (MCT) of the Patient Health Questionnaire (PHQ-9) and Montgomery-Åsberg Depression Rating Scale (MADRS) using anchor-based methods and compared proportions of meaningful changes in patients with TRD across treatment groups from two Phase 3 trials for esketamine nasal spray (SPRAVATOTM). Data from two Phase 3 trials in patients with TRD, TRANSFORM-1 and -2, were used in this analysis. The MCTs for the PHQ-9 and MADRS were derived using a clinician global impression of severity anchor. Blinded probability density functions displayed score distributions between anchor categories. Proportions of meaningful response were compared between treatment groups using chi-square tests supported by unblinded cumulative distribution functions of change scores. Baseline scores were similar for the PHQ-9 and MADRS between the esketamine/antidepressant (AD) and AD/placebo groups. The most appropriate MCT on the PHQ-9 was -6 points. By Day 28, 86.5% of patients reached or exceeded the PHQ-9 MCT in the esketamine/AD group compared to 70% in the placebo/AD group. The most appropriate MCT for the MADRS was -10 points. By Day 28, 78.2% of patients reached or exceeded the MADRS MCT in the esketamine/AD group compared to 65.0% in the placebo/AD group. Individual-level meaningful change for the PHQ-9 and MADRS was effectively quantified using a clinical anchor to interpret efficacy from patients with TRD and their treating clinicians.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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A significantly higher proportion of patients receiving esketamine plus an antidepressant reached meaningful improvement thresholds on depression scales by Day 28 compared with placebo plus antidepressant.
Synthesized
Comparable studies
Other randomized controlled trials on esketamine for anxiety, most cited first.