Exploring vortioxetine combination with intranasal esketamine: A feasible alternative to SSRI/SNRI? - Insights from the REAL-ESK study

• Published in: Journal of affective disorders Vol. 367; pp. 583 - 588
• Main Authors: d’Andrea, Giacomo, Miuli, Andrea, Pettorruso, Mauro, Cavallotto, Clara, Marrangone, Carlotta, Cocco, Alessio, De Filippis, Sergio, Martiadis, Vassillis, Andriola, Ileana, Barlati, Stefano, Vita, Antonio, Dell'Osso, Bernardo Maria, Sensi, Stefano L., Di Lorenzo, Giorgio, Martinotti, Giovanni
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.12.2024
• Subjects: Administration, Intranasal; Adult; Antidepressive Agents - administration & dosage; Antidepressive Agents - therapeutic use; Depression; Depressive Disorder, Major - drug therapy; Depressive Disorder, Treatment-Resistant - drug therapy; Drug Therapy, Combination; Emotional blunting; ESK-NS; Female; Glutamate; Humans; Ketamine - administration & dosage; Ketamine - adverse effects; Male; Middle Aged; Psychiatric Status Rating Scales; Psychiatric/Mental Health; Selective Serotonin Reuptake Inhibitors - administration & dosage; Serotonin and Noradrenaline Reuptake Inhibitors - administration & dosage; Serotonin and Noradrenaline Reuptake Inhibitors - pharmacology; TRD; Treatment Outcome; Vortioxetine; Vortioxetine - administration & dosage; Depression; Glutamate; Emotional blunting; Vortioxetine; ESK-NS; TRD
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2024.09.004

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. •Esketamine nasal spray (ESK-NS) is a new treatment for TRD.•Standard-of-care combines ESK-NS with SSRIs or SNRIs.•We compared the effectiveness of Vortioxetine + ESK-NS vs. SSRI/SNRI + ESK-NS.•We found similar antidepressant effect with a better safety profile for Vortioxetine.•Vortioxetine + ESK-NS was more effective against emotional blunting.