Exploring vortioxetine combination with intranasal esketamine: A feasible alternative to SSRI/SNRI? - Insights from the REAL-ESK study.
Giacomo d'Andrea, Andrea Miuli, Mauro Pettorruso, Clara Cavallotto, Carlotta Marrangone, Alessio Cocco, Sergio De Filippis, Vassillis Martiadis, Ileana Andriola, Stefano Barlati, Antonio Vita, Bernardo Maria Dell'Osso, Stefano L. Sensi, Giorgio Di Lorenzo, Giovanni Martinotti
Journal of Affective Disorders December 15, 2024 DOI: 10.1016/j.jad.2024.09.004 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Post-hoc analysis Randomized Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | TRD patients |
| Interventions | Vortioxetine Esketamine nasal spray |
| Duration | 3 months |
| Topics | Depression Esketamine |
| Keywords | Esk-ns Emotional blunting Glutamate Vortioxetine Depression treatment Treatment-resistant depression trd Antidepressants Mental health therapies Drug combinations |
| Citations | 6 |
| Key points | Vortioxetine plus ESK-NS was as effective as SSRI/SNRI plus ESK-NS in reducing depressive symptoms and showed a higher effect size in reducing emotional blunting at three months, with a better safety and tolerability profile. |
Abstract
Treatment-Resistant Depression (TRD) affects almost 30 % of patients with Major Depressive Disorder (MDD). Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD in combination with a Serotonin Specific Reuptake Inhibitor/SSRI or a Serotonin-Norepinephrine Reuptake Inhibitor/SNRI. There is a lack of studies investigating the effectiveness and safety of ESK-NS in combination with other oral antidepressants. To assess the efficacy of Vortioxetine plus ESK-NS in mitigating depressive symptoms and emotional blunting, as well as its tolerability in TRD subjects, compared to the standard-of-care of SSRI/SNRI plus ESK-NS. We conducted a post-hoc analysis of the REAL-ESK study. The study included twenty TRD patients, ten subjects taking Vortioxetine as the main oral antidepressant with ESK-NS, and ten subjects taking SSRI or SNRI with ESK-NS. Psychometric assessments (Montgomery-Åsberg Depression Rating Scale/MADRS, Brief Psychiatric Rating Scale/BPRS) were conducted at baseline(T0), one month(T1), and three months after the treatment initiation(T2). The combination of Vortioxetine and ESK-NS was as effective as the standard-of-care in reducing depressive symptoms, with a higher effect size in reducing emotional blunting at T2. The safety and tolerability profile of the Vortioxetine+ESK-NS combination appeared to be better, with a lower rate of treatment-emergent adverse events. The combination of Vortioxetine and ESK-NS may be a valuable alternative to the standard-of-care SSRI/SNRI plus ESK-NS in TRD patients, particularly regarding the reduction of emotional blunting and potentially a better safety and tolerability profile. Further randomized controlled trials with larger sample sizes and prospective designs are needed to confirm these findings.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cited by 5
- Patient Experience with Intranasal Esketamine in Treatment-Resistant Depression: Insights from a Multicentric Italian Study (REAL-ESKperience) Journal of Personalized Medicine April 1, 2025
- Esketamine Combined With SSRI or SNRI for Treatment-Resistant Depression. JAMA Psychiatry April 2, 2025
- Effectiveness of repeated Esketamine nasal spray administration on anhedonic symptoms in treatment-resistant bipolar and unipolar depression: A secondary analysis from the REAL-ESK study group. Psychiatry Research July 26, 2025
- Rapid treatment center for depression in China: constructive reflections and transnational implications. Frontiers in Psychiatry 2025
- Dimensional effect profiles in treatment-resistant depression: A naturalistic, prospective head-to-head comparison of arTMS, esketamine nasal spray, and oral brexpiprazole. Journal of Affective Disorders July 28, 2026
Cites 9
- 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
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II) The International Journal of Neuropsychopharmacology August 26, 2020
- Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment‐resistant depression Bipolar Disorders January 13, 2023
- Predicting outcome with Intranasal Esketamine treatment: A machine-learning, three-month study in Treatment-Resistant Depression (ESK-LEARNING) Psychiatry Research July 29, 2023
and 4 more in the library