Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis

<b>Background/Objective:</b> Major depressive disorder (MDD) is a common mental disorder, with a significant portion of patients developing treatment-resistant depression (TRD). Esketamine is an antagonist of the N-methyl-D-aspartate receptor indicated as a nasal spray in combination wit...

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Main Authors: Ilaria Ammendolia, Carmen Mannucci, Emanuela Esposito, Gioacchino Calapai, Mariaconcetta Currò, Paola Midiri, Cristina Mondello, Luigi Cardia, Fabrizio Calapai
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/5/702
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author Ilaria Ammendolia
Carmen Mannucci
Emanuela Esposito
Gioacchino Calapai
Mariaconcetta Currò
Paola Midiri
Cristina Mondello
Luigi Cardia
Fabrizio Calapai
author_facet Ilaria Ammendolia
Carmen Mannucci
Emanuela Esposito
Gioacchino Calapai
Mariaconcetta Currò
Paola Midiri
Cristina Mondello
Luigi Cardia
Fabrizio Calapai
author_sort Ilaria Ammendolia
collection DOAJ
description <b>Background/Objective:</b> Major depressive disorder (MDD) is a common mental disorder, with a significant portion of patients developing treatment-resistant depression (TRD). Esketamine is an antagonist of the N-methyl-D-aspartate receptor indicated as a nasal spray in combination with other antidepressants for adults with TRD. Signals of suspected adverse reactions (SARs) to esketamine from the EudraVigilance database in European countries were analyzed for a more defined safety profile of this drug in the real world. <b>Methods:</b> SARs to esketamine reported in the data system EudraVigilance were analyzed, and disproportionality analysis for adverse reactions indicating suicidality for esketamine, in comparison to the antidepressants fluoxetine and venlafaxine, was performed. <b>Results:</b> Increases in blood pressure (15.4%) and dissociation (15.0%) were the most frequently reported SARs. The sex distribution indicates the prevalence of women, except for increased blood pressure and completed suicide, which were signaled in men, while adults (18–64 years) and elders (65–85 years) were the ages with the largest number of reported adverse reactions to esketamine. The results indicate the existence of a potential increase in the risk of suicide in depressed patients taking esketamine when compared with fluoxetine and venlafaxine. <b>Conclusions:</b> Apart from carefulness due to the known limitations of pharmacovigilance research conducted by using data systems of spontaneous signals for SARs, the analysis of data points toward the need for greater attention being paid to the potential risk of suicide following the prescription of esketamine in depressed subjects. In this regard, as regulatory agencies also recommend, patients with a history of suicide-related events or those exhibiting a significant degree of suicidal ideation prior to beginning treatment should receive more careful monitoring during treatment.
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spelling doaj-art-bb91a22f72d84eb899f4b0ebdd8130452025-08-20T03:14:29ZengMDPI AGPharmaceuticals1424-82472025-05-0118570210.3390/ph18050702Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database AnalysisIlaria Ammendolia0Carmen Mannucci1Emanuela Esposito2Gioacchino Calapai3Mariaconcetta Currò4Paola Midiri5Cristina Mondello6Luigi Cardia7Fabrizio Calapai8Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, ItalyDepartment of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, 98122 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98122 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98122 Messina, ItalyDepartment of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, 98122 Messina, ItalyDepartment of Human Pathology of Adult and Childhood “Gaetano Barresi”, University of Messina, 98122 Messina, ItalyDepartment of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, 98122 Messina, Italy<b>Background/Objective:</b> Major depressive disorder (MDD) is a common mental disorder, with a significant portion of patients developing treatment-resistant depression (TRD). Esketamine is an antagonist of the N-methyl-D-aspartate receptor indicated as a nasal spray in combination with other antidepressants for adults with TRD. Signals of suspected adverse reactions (SARs) to esketamine from the EudraVigilance database in European countries were analyzed for a more defined safety profile of this drug in the real world. <b>Methods:</b> SARs to esketamine reported in the data system EudraVigilance were analyzed, and disproportionality analysis for adverse reactions indicating suicidality for esketamine, in comparison to the antidepressants fluoxetine and venlafaxine, was performed. <b>Results:</b> Increases in blood pressure (15.4%) and dissociation (15.0%) were the most frequently reported SARs. The sex distribution indicates the prevalence of women, except for increased blood pressure and completed suicide, which were signaled in men, while adults (18–64 years) and elders (65–85 years) were the ages with the largest number of reported adverse reactions to esketamine. The results indicate the existence of a potential increase in the risk of suicide in depressed patients taking esketamine when compared with fluoxetine and venlafaxine. <b>Conclusions:</b> Apart from carefulness due to the known limitations of pharmacovigilance research conducted by using data systems of spontaneous signals for SARs, the analysis of data points toward the need for greater attention being paid to the potential risk of suicide following the prescription of esketamine in depressed subjects. In this regard, as regulatory agencies also recommend, patients with a history of suicide-related events or those exhibiting a significant degree of suicidal ideation prior to beginning treatment should receive more careful monitoring during treatment.https://www.mdpi.com/1424-8247/18/5/702esketaminepharmacovigilanceadverse reactionsmajor depressive disordertreatment-resistant depressionsuicide
spellingShingle Ilaria Ammendolia
Carmen Mannucci
Emanuela Esposito
Gioacchino Calapai
Mariaconcetta Currò
Paola Midiri
Cristina Mondello
Luigi Cardia
Fabrizio Calapai
Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis
Pharmaceuticals
esketamine
pharmacovigilance
adverse reactions
major depressive disorder
treatment-resistant depression
suicide
title Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis
title_full Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis
title_fullStr Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis
title_full_unstemmed Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis
title_short Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis
title_sort safety profile and suicidality associated with the use of esketamine in the treatment of major depressive disorder in european countries an eudravigilance database analysis
topic esketamine
pharmacovigilance
adverse reactions
major depressive disorder
treatment-resistant depression
suicide
url https://www.mdpi.com/1424-8247/18/5/702
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