Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression

Juan F. Cano; Rodrigo Nel Cordoba Rojas

doi:10.1056/NEJMoa2304145

Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression

Título traducido de la contribución: Aerosol nasal de esketamina versus quetiapina para la depresión resistente al tratamiento

Producción científica: Contribución a revista › Artículo de Investigación › revisión exhaustiva

194 Citas (Scopus)

Resumen

Antecedentes
En la depresión resistente al tratamiento, comúnmente definida como la falta de respuesta a dos o más tratamientos consecutivos durante el episodio depresivo actual, el porcentaje de pacientes con remisión es bajo y el porcentaje con recaída es alto. Se desconocen la eficacia y la seguridad del aerosol nasal de esketamina en comparación con el tratamiento de aumento con quetiapina de liberación prolongada, ambos en combinación con el tratamiento en curso con un inhibidor selectivo de la recaptación de serotonina (ISRS) o un inhibidor de la recaptación de serotonina-norepinefrina (IRSN), en pacientes con depresión resistente al tratamiento.

Métodos
En un ensayo abierto, simple ciego (sin que los evaluadores conocieran la asignación a los grupos), multicéntrico, de fase 3b, aleatorizado y controlado activamente, asignamos a los pacientes, en una proporción de 1:1, a recibir dosis flexibles (según el resumen de las características del producto) de esketamina en aerosol nasal (grupo esketamina) o quetiapina de liberación prolongada (grupo quetiapina), ambos en combinación con un ISRS o un IRSN. El criterio de valoración primario fue la remisión, definida como una puntuación de 10 o menos en la Montgomery-Åsberg Depression Rating Scale (MADRS), en la semana 8 (las puntuaciones oscilan entre 0 y 60, y las puntuaciones más altas indican una depresión más grave). El criterio de valoración secundario clave fue la ausencia de recaída en la semana 32 tras la remisión en la semana 8. Se incluyeron en el análisis todos los pacientes. Todos los pacientes fueron incluidos en el análisis; se consideró que los pacientes que interrumpieron el tratamiento del ensayo habían tenido un resultado desfavorable (es decir, se agruparon con los pacientes que no tuvieron remisión o que tuvieron una recaída). Los análisis de los criterios de valoración primarios y secundarios clave se ajustaron en función de la edad y el número de fracasos terapéuticos.

Resultados
En total, 336 pacientes fueron asignados al grupo de esketamina y 340 al grupo de quetiapina. Más pacientes en el grupo de esketamina que en el de quetiapina tuvieron remisión en la semana 8 (91 de 336 pacientes [27,1%] frente a 60 de 340 pacientes [17,6%]; P=0,003) y no tuvieron recaída hasta la semana 32 después de la remisión en la semana 8 (73 de 336 pacientes [21,7%] frente a 48 de 340 pacientes [14,1%]). Durante 32 semanas de seguimiento, el porcentaje de pacientes con remisión, el porcentaje de pacientes con una respuesta al tratamiento y el cambio en la puntuación MADRS desde el inicio favorecieron al aerosol nasal de esketamina. Los acontecimientos adversos fueron coherentes con los perfiles de seguridad establecidos de los tratamientos del ensayo.

Conclusiones
En pacientes con depresión resistente al tratamiento, el aerosol nasal de esketamina más un ISRS o IRSN fue superior a la quetiapina de liberación prolongada más un ISRS o IRSN con respecto a la remisión en la semana 8. (Financiado por Janssen EMEA; número de ClinicalTrials.gov de ESCAPE-TRD, NCT04338321).

Título traducido de la contribución	Aerosol nasal de esketamina versus quetiapina para la depresión resistente al tratamiento
Idioma original	Inglés estadounidense
Páginas (desde-hasta)	1298-1309
Número de páginas	12
Publicación	New England Journal of Medicine
Volumen	389
N.º	14
DOI	https://doi.org/10.1056/NEJMoa2304145
Estado	Publicada - oct 4 2023

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Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

ODS 3: Salud y bienestar

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Psiquiatría y salud mental

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10.1056/NEJMoa2304145

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@article{1f216ea9a3034741ac642ef6abf5f173,

title = "Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression",

abstract = "Background In treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments during the current depressive episode, the percentage of patients with remission is low and the percentage with relapse is high. The efficacy and safety of esketamine nasal spray as compared with extended-release quetiapine augmentation therapy, both in combination with ongoing treatment with a selective serotonin reuptake inhibitor (SSRI) or a serotonin{\textendash}norepinephrine reuptake inhibitor (SNRI), in patients with treatment-resistant depression are unknown. Methods In an open-label, single-blind (with raters unaware of group assignments), multicenter, phase 3b, randomized, active-controlled trial, we assigned patients, in a 1:1 ratio, to receive flexible doses (according to the summary of product characteristics) of esketamine nasal spray (esketamine group) or extended-release quetiapine (quetiapine group), both in combination with an SSRI or SNRI. The primary end point was remission, defined as a score of 10 or less on the Montgomery{\textendash}{\AA}sberg Depression Rating Scale (MADRS), at week 8 (scores range from 0 to 60, with higher scores indicating more severe depression). The key secondary end point was no relapse through week 32 after remission at week 8. All patients were included in the analysis; patients who discontinued the trial treatment were considered as having had an unfavorable outcome (i.e., they were grouped with patients who did not have remission or who had a relapse). Analyses of the primary and key secondary end points were adjusted for age and number of treatment failures. Results Overall, 336 patients were assigned to the esketamine group and 340 to the quetiapine group. More patients in the esketamine group than in the quetiapine group had remission at week 8 (91 of 336 patients [27.1\%] vs. 60 of 340 patients [17.6\%]; P=0.003) and had no relapse through week 32 after remission at week 8 (73 of 336 patients [21.7\%] vs. 48 of 340 patients [14.1\%]). Over 32 weeks of follow-up, the percentage of patients with remission, the percentage of patients with a treatment response, and the change in the MADRS score from baseline favored esketamine nasal spray. The adverse events were consistent with the established safety profiles of the trial treatments. Conclusions In patients with treatment-resistant depression, esketamine nasal spray plus an SSRI or SNRI was superior to extended-release quetiapine plus an SSRI or SNRI with respect to remission at week 8. (Funded by Janssen EMEA; ESCAPE-TRD ClinicalTrials.gov number, NCT04338321.)",

author = "Cano, \{Juan F.\} and \{Cordoba Rojas\}, \{Rodrigo Nel\}",

note = "https://www.nejm.org/doi/10.1056/NEJMoa2304145?url\_ver=Z39.88-2003\&rfr\_id=ori:rid:crossref.org\&rfr\_dat=cr\_pub\%20\%200pubmed",

year = "2023",

month = oct,

day = "4",

doi = "10.1056/NEJMoa2304145",

language = "English (US)",

volume = "389",

pages = "1298--1309",

journal = "New England Journal of Medicine",

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publisher = "Massachussetts Medical Society",

number = "14",

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TY - JOUR

T1 - Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression

AU - Cano, Juan F.

AU - Cordoba Rojas, Rodrigo Nel

N1 - https://www.nejm.org/doi/10.1056/NEJMoa2304145?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

PY - 2023/10/4

Y1 - 2023/10/4

N2 - Background In treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments during the current depressive episode, the percentage of patients with remission is low and the percentage with relapse is high. The efficacy and safety of esketamine nasal spray as compared with extended-release quetiapine augmentation therapy, both in combination with ongoing treatment with a selective serotonin reuptake inhibitor (SSRI) or a serotonin–norepinephrine reuptake inhibitor (SNRI), in patients with treatment-resistant depression are unknown. Methods In an open-label, single-blind (with raters unaware of group assignments), multicenter, phase 3b, randomized, active-controlled trial, we assigned patients, in a 1:1 ratio, to receive flexible doses (according to the summary of product characteristics) of esketamine nasal spray (esketamine group) or extended-release quetiapine (quetiapine group), both in combination with an SSRI or SNRI. The primary end point was remission, defined as a score of 10 or less on the Montgomery–Åsberg Depression Rating Scale (MADRS), at week 8 (scores range from 0 to 60, with higher scores indicating more severe depression). The key secondary end point was no relapse through week 32 after remission at week 8. All patients were included in the analysis; patients who discontinued the trial treatment were considered as having had an unfavorable outcome (i.e., they were grouped with patients who did not have remission or who had a relapse). Analyses of the primary and key secondary end points were adjusted for age and number of treatment failures. Results Overall, 336 patients were assigned to the esketamine group and 340 to the quetiapine group. More patients in the esketamine group than in the quetiapine group had remission at week 8 (91 of 336 patients [27.1%] vs. 60 of 340 patients [17.6%]; P=0.003) and had no relapse through week 32 after remission at week 8 (73 of 336 patients [21.7%] vs. 48 of 340 patients [14.1%]). Over 32 weeks of follow-up, the percentage of patients with remission, the percentage of patients with a treatment response, and the change in the MADRS score from baseline favored esketamine nasal spray. The adverse events were consistent with the established safety profiles of the trial treatments. Conclusions In patients with treatment-resistant depression, esketamine nasal spray plus an SSRI or SNRI was superior to extended-release quetiapine plus an SSRI or SNRI with respect to remission at week 8. (Funded by Janssen EMEA; ESCAPE-TRD ClinicalTrials.gov number, NCT04338321.)

AB - Background In treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments during the current depressive episode, the percentage of patients with remission is low and the percentage with relapse is high. The efficacy and safety of esketamine nasal spray as compared with extended-release quetiapine augmentation therapy, both in combination with ongoing treatment with a selective serotonin reuptake inhibitor (SSRI) or a serotonin–norepinephrine reuptake inhibitor (SNRI), in patients with treatment-resistant depression are unknown. Methods In an open-label, single-blind (with raters unaware of group assignments), multicenter, phase 3b, randomized, active-controlled trial, we assigned patients, in a 1:1 ratio, to receive flexible doses (according to the summary of product characteristics) of esketamine nasal spray (esketamine group) or extended-release quetiapine (quetiapine group), both in combination with an SSRI or SNRI. The primary end point was remission, defined as a score of 10 or less on the Montgomery–Åsberg Depression Rating Scale (MADRS), at week 8 (scores range from 0 to 60, with higher scores indicating more severe depression). The key secondary end point was no relapse through week 32 after remission at week 8. All patients were included in the analysis; patients who discontinued the trial treatment were considered as having had an unfavorable outcome (i.e., they were grouped with patients who did not have remission or who had a relapse). Analyses of the primary and key secondary end points were adjusted for age and number of treatment failures. Results Overall, 336 patients were assigned to the esketamine group and 340 to the quetiapine group. More patients in the esketamine group than in the quetiapine group had remission at week 8 (91 of 336 patients [27.1%] vs. 60 of 340 patients [17.6%]; P=0.003) and had no relapse through week 32 after remission at week 8 (73 of 336 patients [21.7%] vs. 48 of 340 patients [14.1%]). Over 32 weeks of follow-up, the percentage of patients with remission, the percentage of patients with a treatment response, and the change in the MADRS score from baseline favored esketamine nasal spray. The adverse events were consistent with the established safety profiles of the trial treatments. Conclusions In patients with treatment-resistant depression, esketamine nasal spray plus an SSRI or SNRI was superior to extended-release quetiapine plus an SSRI or SNRI with respect to remission at week 8. (Funded by Janssen EMEA; ESCAPE-TRD ClinicalTrials.gov number, NCT04338321.)

U2 - 10.1056/NEJMoa2304145

DO - 10.1056/NEJMoa2304145

M3 - Research Article

C2 - 37792613

SN - 0028-4793

VL - 389

SP - 1298

EP - 1309

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 14

ER -

Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression

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