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.
Comparable studies
Other randomized controlled trials on esketamine for anxiety, most cited first.
Citations in the library
Cited by 17
- Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis. American Journal of Psychiatry March 1, 2025
- Effects of intranasal (S)-ketamine on Veterans with co-morbid treatment-resistant depression and PTSD: A retrospective case series EClinicalMedicine May 7, 2022
- Assessment of health-related quality of life and health status in patients with treatment-resistant depression treated with esketamine nasal spray plus an oral antidepressant Health and Quality of Life Outcomes May 8, 2023
- Listening to music during intranasal (es)ketamine therapy in patients with treatment-resistant depression correlates with better tolerability and reduced anxiety Frontiers in Psychiatry January 23, 2024
- Registered clinical trials investigating ketamine and esketamine for treatment-resistant depression: A systematic review Journal of Psychedelic Studies January 16, 2023
and 12 more in the library
Cites 3
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) The International Journal of Neuropsychopharmacology July 9, 2019